Sample records for rat rattus norvegicus

  1. Variations in the diet of introduced Norway rats (Rattus norvegicus) inferred using stable isotope analysis

    E-Print Network [OSTI]

    Jones, Ian L.

    Variations in the diet of introduced Norway rats (Rattus norvegicus) inferred using stable isotope predators; island ecosystem conservation; stable isotope analysis; Norway rats; diet. Correspondence Heather of introduced Norway rats Rattus norvegicus has raised concerns for the fate of the large least auklet Aethia

  2. Demography of auklets Aethia spp. in relation to introduced Norway rats Rattus norvegicus at Kiska

    E-Print Network [OSTI]

    Jones, Ian L.

    Demography of auklets Aethia spp. in relation to introduced Norway rats Rattus norvegicus at Kiska................................................................................................4 Norway Rat Abundance and Distribution .........................................................5................................................................................................6 Norway Rat Abundance and Distribution.........................................................7

  3. Maternal Responsiveness to Infant Norway Rat (Rattus norvegicus) Ultrasonic Vocalizations During the Maternal Behavior Cycle and After

    E-Print Network [OSTI]

    Maternal Responsiveness to Infant Norway Rat (Rattus norvegicus) Ultrasonic Vocalizations During environment, Norway rat (Rattus norvegicus) pups emit ultrasonic vocalizations that can elicit maternal search is particularly important in altricial species such as the Norway rat in which infants rely on the mother

  4. ECOLOGY OF NORWAY RATS (RATTUS NORVEGICUS) IN RELATION TO CONSERVATION AND MANAGEMENT OF SEABIRDS ON KISKA ISLAND,

    E-Print Network [OSTI]

    Jones, Ian L.

    ECOLOGY OF NORWAY RATS (RATTUS NORVEGICUS) IN RELATION TO CONSERVATION AND MANAGEMENT OF SEABIRDS to predation by introduced Norway rats (Rattus norvegicus). In 2001 and 2002 the auklet colony experienced the lowest reproductive success ever recorded for auklets. Norway rats have been suggested as the cause

  5. Stimulus Control of Maternal Responsiveness to Norway Rat (Rattus norvegicus) Pup Ultrasonic Vocalizations

    E-Print Network [OSTI]

    Stimulus Control of Maternal Responsiveness to Norway Rat (Rattus norvegicus) Pup Ultrasonic be considered a specialization of Norway rats and other small rodents. When removed from the nest and placed in a cool environment, infant Norway rats emit USVs. These vocalizations range from 30 to 50 k

  6. adult rats rattus: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 IMPACTS OF INTRODUCED NORWAY RATS (RATTUS NORVEGICUS) ON LEAST AUKLETS (AETHIA PUSILLA) BREEDING AT KISKA ISLAND,...

  7. albino rats rattus: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    most commonly used in research are believed to be domesticated albino strains of the Norway rat rattus nirvegicus. Rats like mice, belong to the order Rodentia Biology and...

  8. Marine Ornithology 41: 4148 (2013) Bond et al.: Crested Auklet survival with Norway Rats 41

    E-Print Network [OSTI]

    Jones, Ian L.

    Marine Ornithology 41: 41­48 (2013) Bond et al.: Crested Auklet survival with Norway Rats 41 in the Aleutians (Bailey 1993, Ebbert & Byrd 2002). Another introduced predator, the Norway rat Rattus norvegicus AND REPRODUCTIVE SUCCESS OF CRESTED AUKLETS AETHIA CRISTATELLA IN THE PRESENCE OF INTRODUCED NORWAY RATS RATTUS

  9. Impacts of the Norway Rat on the auklet breeding colony at Sirius Point, Kiska

    E-Print Network [OSTI]

    Jones, Ian L.

    Impacts of the Norway Rat on the auklet breeding colony at Sirius Point, Kiska Island, Alaska-3239 FAX: (709) 737-3018 e-mail: x19hlm@mun.ca #12;Major and Jones Impacts of the Norway Rat... 2 Fresh rat during World War II (Atkinson, 1985). It is believed that the Norway Rat (Rattus norvegicus

  10. Assessing the effects of Norway rats on auklet breeding success and survival at Sirius Point, Kiska

    E-Print Network [OSTI]

    Jones, Ian L.

    Assessing the effects of Norway rats on auklet breeding success and survival at Sirius Point, Kiska Introduction The presence of introduced Norway rats (Rattus norvegicus) has been implicated as a possible sightings of Norway rats at Sirius Point Colony during the late 1980s and early 1990s. Furthermore

  11. Impacts of the Norway Rat on the auklet breeding colony at Sirius Point, Kiska Island, Alaska in 2003

    E-Print Network [OSTI]

    Jones, Ian L.

    Impacts of the Norway Rat on the auklet breeding colony at Sirius Point, Kiska Island, Alaska of the Norway rat (Rattus norvegicus) onto Kiska Island, Aleutian Islands, Alaska, in the 1940s (Murie 1959 and to investigate the biology and demography of the Norway rat population. Moors and Atkinson (1984) suggested

  12. Genome sequence of the brown Norway rat yields insights into mammalian evolution

    SciTech Connect (OSTI)

    Gibbs, Richard A.; Weinstock, George M.; Metzker, Michael L.; Muzny, Donna M.; Sodergren, Erica J.; Scherer, Steven; Scott, Graham; Steffen, David; Worley, Kim C.; Burch, Paula E.; Okwuonu, Geoffrey; Hines, Sandra; Lewis, Lora; DeRamo, Christine; Delgado, Oliver; Dugan-Rocha, Shannon; Miner, George; Morgan, Margaret; Hawes, Alicia; Gill, Rachel; Holt, Robert A.; Adams, Mark D.; Amanatides, Peter G.; Baden-Tillson, Holly; Barnstead, Mary; Chin, Soo; Evans, Cheryl A.; Ferriera, Steven; Fosler, Carl; Glodek, Anna; Gu, Zhiping; Jennings, Don; Kraft, Cheryl L.; Nguyen, Trixie; Pfannkoch, Cynthia M.; Sitter, Cynthia; Sutton, Granger G.; Venter, J. Craig; Woodage, Trevor; Smith, Douglas; Lee, Hong-Maei; Gustafson, Erik; Cahill, Patrick; Kana, Arnold; Doucette-Stamm, Lynn; Weinstock, Keith; Fechtel, Kim; Weiss, Robert B.; Dunn, Diane M.; Green, Eric D.; Blakesley, Robert W.; Bouffard, Gerard G.; de Jong, Pieter J.; Osoegawa, Kazutoyo; Zhu, Baoli; Marra, Marco; Schein, Jacqueline; Bosdet, Ian; Fjell, Chris; Jones, Steven; Krzywinski, Martin; Mathewson, Carrie; Siddiqui, Asim; Wye, Natasja; McPherson, John; Zhao, Shaying; Fraser, Claire M.; Shetty, Jyoti; Shatsman, Sofiya; Geer, Keita; Chen, Yixin; Abramzon, Sofyia; Nierman, William C.; Havlak, Paul H.; Chen, Rui; Durbin, K. James; Egan, Amy; Ren, Yanru; Song, Xing-Zhi; Li, Bingshan; Liu, Yue; Qin, Xiang; Cawley, Simon; Cooney, A.J.; D'Souza, Lisa M.; Martin, Kirt; Wu, Jia Qian; Gonzalez-Garay, Manuel L.; Jackson, Andrew R.; Kalafus, Kenneth J.; McLeod, Michael P.; Milosavljevic, Aleksandar; Virk, Davinder; Volkov, Andrei; Wheeler, David A.; Zhang, Zhengdong; Bailey, Jeffrey A.; Eichler, Evan E.; Tuzun, Eray; Birney, Ewan; Mongin, Emmanuel; Ureta-Vidal, Abel; Woodwark, Cara; Zdobnov, Evgeny; Bork, Peer; Suyama, Mikita; Torrents, David; Alexandersson, Marina; Trask, Barbara J.; Young, Janet M.; et al.

    2004-02-02T23:59:59.000Z

    The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90 percent of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

  13. The laboratory rat strains most commonly used in research are believed to be domesticated albino strains of the Norway rat rattus nirvegicus. Rats like mice, belong to the order Rodentia

    E-Print Network [OSTI]

    Shihadeh, Alan

    and the nude rat. Uses Despite the fear that rats invoke in people they actually make quiet, gentle pets rate 70-115 Food consumption 5-6g/100g/d Water consumption 10-12ml/100g/d Breeding onset Male 65-110d

  14. albino rat cfn: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    most commonly used in research are believed to be domesticated albino strains of the Norway rat rattus nirvegicus. Rats like mice, belong to the order Rodentia Biology and...

  15. albino wistar rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    most commonly used in research are believed to be domesticated albino strains of the Norway rat rattus nirvegicus. Rats like mice, belong to the order Rodentia Biology and...

  16. albino rats exposed: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    most commonly used in research are believed to be domesticated albino strains of the Norway rat rattus nirvegicus. Rats like mice, belong to the order Rodentia Biology and...

  17. albino rat anatomical: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    most commonly used in research are believed to be domesticated albino strains of the Norway rat rattus nirvegicus. Rats like mice, belong to the order Rodentia Biology and...

  18. auklet ptychoramphus aleuticus: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to nestlings in order 9 Demography of auklets Aethia spp. in relation to introduced Norway rats Rattus norvegicus at Kiska Environmental Sciences and Ecology Websites Summary:...

  19. Least and Crested Auklet productivity and survival in relation to introduced Norway

    E-Print Network [OSTI]

    Jones, Ian L.

    Least and Crested Auklet productivity and survival in relation to introduced Norway Rats at Sirius and rats - Kiska 2004 2 Norway rats (Rattus norvegicus) were introduced to Kiska Island, western Aleutian was near normal (c. 50%) at Sirius Point in 2003 (Major and Jones 2003, Major 2004). Introduced Norway rats

  20. Genetic analysis of the endangered silver rice rat (Oryzomys palustris natator) and Lower Keys marsh rabbit (Sylvilagus palustris hefneri)

    E-Print Network [OSTI]

    Crouse, Amanda Louise

    2007-04-25T23:59:59.000Z

    al. 1996; U.S. Fish and Wildlife Service (USFWS) 1999). These include roadway mortalities (USFWS 1999; Harveson et al. 2004), increased predation by feral cats (Felis domesticus; Forys and Humphrey 1999), competition from black rats (Rattus rattus...; Mace 2004). In a conservation context, this means that management efforts are established on what is perceived, based on taxonomy, as the best way to preserve biological diversity. This is of even greater importance when the taxonomic status...

  1. DOI 10.1007/s10071-009-0218-z ORIGINAL PAPER

    E-Print Network [OSTI]

    Wilkinson, Gerald S.

    ; Cyanocitta cris- tata: Stephens et al. 2002; Rattus norvegicus: Rutte and Taborsky 2007, 2008). Carefully reciprocity (Rutte and Taborsky 2008; Hauser et al. 2003), and there is some experimental evidence

  2. RATS VERSUS PEOPLE Rats equal twice

    E-Print Network [OSTI]

    , ----= -, - paper car ton s, and wooden containers are easily damaged. #12;By Starting Fires Rats start fires by damaging the insu- lation of electric wiring. A survey of 39 cities showed that 530 fires were started

  3. Controlling Rats and Mice

    E-Print Network [OSTI]

    Texas Wildlife Services

    2007-03-13T23:59:59.000Z

    at least 18 inches off the ground. 18? 18? TCE?Wildlife Services P.O. Box 100410 ? San Antonio, Texas 78201-1710 Rat-proofing Whenever it can be accomplished at a rea- sonable cost, rat-proofing is recommended as the most permanent means of control...

  4. Super Rat Poison Man

    E-Print Network [OSTI]

    Hacker, Randi; Tsutsui, William

    2007-04-04T23:59:59.000Z

    Bob Square Tie. But Zheng Xiaoyu, the deposed head of China's State Food and Drug Administration begs to be excused. A rat poison manufacturer here in China applied for permission to name some of its products after him, partly because he's corrupt...

  5. Polar Biol (2007) 30:391394 DOI 10.1007/s00300-006-0204-8

    E-Print Network [OSTI]

    pairs of thin-billed prions nests despite the presence of introduced ship rats, house mice and feral Pachyptila belcheri (Catry et al. 2003). Ship rats Rattus rattus, house mice Mus musculus and cats Felis em Eco-Etologia, Rua Jardim do Tabaco 44, Lisboa 1149-041, Portugal e-mail: paulo.catry@netc.pt P

  6. Genome sequence of the Brown Norway rat yields insights into

    E-Print Network [OSTI]

    Pachter, Lior

    Genome sequence of the Brown Norway rat yields insights into mammalian evolution Rat Genome Norway (BN) rat strain. The sequence represents a high-quality `draft' covering over 90% of the genome

  7. Water Retrieval by Norway Rats: Behavior as Deduction

    E-Print Network [OSTI]

    Wallace, R J

    1998-01-01T23:59:59.000Z

    1948). Burrows and feeding of the Norway a radial Mammalogy,Object retrieval preferences of Norway rats: An evolutionaryinedible objects by Norway rats: Motivational interactions

  8. Ethanol Consumption by Rat Dams During Gestation,

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    Ethanol Consumption by Rat Dams During Gestation, Lactation and Weaning Increases Ethanol examined effects of ethanol consumption in rat dams during gestation, lactation, and weaning on voluntary ethanol consumption by their adolescent young. We found that exposure to an ethanol-ingesting dam

  9. Arginine metabolism in enterocytes of diabetic rats

    E-Print Network [OSTI]

    Morrow, Natalie Anne

    2002-01-01T23:59:59.000Z

    Diabetic rats and patients exhibit decreased plasma arginine concentrations. Arginine is important in numerous cellular pathways, including the synthesis of nitric oxide and the release of insulin from pancreatic ? cells. At present, little...

  10. Purification of sulfide oxidase from rat liver

    E-Print Network [OSTI]

    Pu, Lixia

    1994-01-01T23:59:59.000Z

    The present study represents an initial investigative effort to purify sulfide oxidase from rat liver. Two methods to determine sulfide oxidase activity have been established and both are based on measuring substrate disappearance of sulfide. Both...

  11. THE BEHAVIOR OF THE LABORATORY RAT

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    , Alaska, at 60 degrees North latitude, where rats feed on human garbage, to South Georgia Island, at 55 members that had survived their ini- tial contact with the poisoned bait and had learned to avoid eating

  12. Cardiopulmonary Function in RatsWith Lung Hemorrhage

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    Cardiopulmonary Function in RatsWith Lung Hemorrhage Induced by Pulsed Ultrasound Exposure Jeffery using superthreshold exposure conditions known to produce sig- nificant lung hemorrhage. Methods. In 1 in the left lung of each rat. In a second group of 6 rats, 5 foci of ultrasound-induced hemorrhage were

  13. Social Influences on Food Choices of Norway Rats and Mate Choices of Japanese Quail

    E-Print Network [OSTI]

    Galef, Jr., Bennett G.

    2001-01-01T23:59:59.000Z

    ecology and sociology of the Norway rat . Bethesda: U.S. De-food stealing by young Norway rats. Journal of Comparativesufficient diet by Norway rats. Journal of Comparative

  14. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption...

  15. E-Print Network 3.0 - adult rat liver Sample Search Results

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    from normal rat liver and incubated for 3 or 16 hours with increasing doses... of carbon tetrachloride (CCl4). Rat ... Source: Groningen, Rijksuniversiteit - Centre for...

  16. adult rat vestibular: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    stimulate cell proliferation in adult rat vestibular sensory epithelia, as does the infusion of transforming growth factor alpha (TGF ) plus insulin. We sought to determine...

  17. Suppressed serum prolactin in sinoaortic-denervated rats

    SciTech Connect (OSTI)

    Alexander, N.; Melmed, S.; Morris, M.

    1987-02-01T23:59:59.000Z

    The authors investigated the effect of arterial baroreceptor deafferentation on serum and pituitary prolactin (PRL) and on catecholamines in median eminence (ME) and anterior and posterior pituitaries. Male Wistar rats were sinoaortic denervated (SAD) or sham operated (SO). Three days after surgery serum prolactin, measured by radioimmunoassay, was suppressed in SAD rats, and dopamine (DA) and norepinephrine (NE) concentrations, measured by radioenzymatic or high-performance liquid chromatography electron capture methods, were significantly reduced in ME of SAD rats. Simultaneously, anterior pituitary of SAD rats had significant increases in both catecholamines, whereas posterior pituitary showed no changes. Four hours after surgery serum PRL was also reduced in SAD rats, but no changes in ME catecholamines were found. Mean arterial pressure (MAP) and heart rate were measured before and after injection of bromocriptine in SAD and SO rats 3 days after surgery. Bromocriptine markedly suppressed serum PRL in both groups and reduced MAP from 144 +/- 10 to 84 +/- 5 and from 116 +/- 2 to 99 +/- 3 in SAD and SO rats, respectively; heart rate was reduced in SAD rats. They conclude that the SAD rat is a model of hypertension with suppressed serum PRL and that interruption of arterial baroreceptor nerves suppresses PRL secretion probably by modulating tuberoinfundibular turnover of catecholamines.

  18. Chemical Renal Denervation in the Rat

    SciTech Connect (OSTI)

    Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

    2013-12-03T23:59:59.000Z

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 ?L of 10{sup ?5} M through 10{sup ?2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  19. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect (OSTI)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine, CA 92612 (United States); Fisher, Robyn L. [Vitron Inc., Tucson, AZ (United States); Vickers, Alison E.M., E-mail: vickers_alison@allergan.com [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine, CA 92612 (United States)

    2014-01-15T23:59:59.000Z

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 ?M) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1?, Il-1?, IL-6 and TNF? in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol at similar concentrations in vitro.

  20. A DELAYED NONLINEAR PBPK MODEL FOR GENISTEIN DOSIMETRY IN RATS

    E-Print Network [OSTI]

    A DELAYED NONLINEAR PBPK MODEL FOR GENISTEIN DOSIMETRY IN RATS #3; MICHAEL G. ZAGER y , HIEN T on laboratory animals and human volunteers [4], and critical literature reviews [32]. Phytoestrogens, a class endocrine-related e#11;ects such as reduced birth weight in rats and humans. In its conjugated form

  1. Measurement of Regional Lung Function in Rats Using Hyperpolarized 3

    E-Print Network [OSTI]

    Measurement of Regional Lung Function in Rats Using Hyperpolarized 3 Helium Dynamic MRI Ben T. Chen,* Anja C.S. Brau, and G. Allan Johnson Dynamic regional lung function was investigated in rats using by a constant flow ventila- tor. Based on regional differences in the behavior of inspired air, the lung

  2. Differential Expression of Cyclic Nucleotide Phosphodiesterases 4 in Developing Rat Lung Running Title: PDE4 in developing rat lung

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    1 Differential Expression of Cyclic Nucleotide Phosphodiesterases 4 in Developing Rat Lung Running Title: PDE4 in developing rat lung Emmanuel Lopez 1,2,3,4 , Pierre-Henri Jarreau 1,2,3,4 , Elodie Zana 1 Dynamics 239, 9 (2010) 2470-8" DOI : 10.1002/dvdy.22374 #12;2 Abstract During the perinatal period, lungs

  3. Toxicologic and biochemical effects of extracts from Karwinskia humboldtiana on the albino rat

    E-Print Network [OSTI]

    Wheeler, Michael Hugh

    1970-01-01T23:59:59.000Z

    Oral doses of coyotillo plant extract (Pe-1) given to rats of Group I-A. 12 Weight changes observed in rats following oral administration of coyotillo plant extract (Pe-l). Microscopic lesions observed in rats following oral administration... of coyotillo plant extract (Pe-l). Weight changes observed in rats following chronic oral administration of coyotillo plant extract (Cn-l). 37 Weight changes observed in rats following acute oral administration of coyotillo plant extract (Ch-l). 38...

  4. Acceleration of wound healing in young and aged rats 

    E-Print Network [OSTI]

    Maxwell, Bryan Douglas

    1996-01-01T23:59:59.000Z

    1. The effect of ACM on wound healing in young rats. . Page 15 2. The effect of ACM on wound healing in old, ad-lib rats . . . . . . . 17 3. The effect of ACM on wound healing in old, caloric-restricted rats . . . 4. The effect of old and young... group (AL) had been fed a laboratory diet ad libitum during their lifetime. The other group (CR) had been maintained on a calorie-restricted diet at a level of 60% of the food intake of the ad libitum-fed group. This decrease in caloric intake resulted...

  5. awake rats achieving: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Studies of Brain Function in Awake Rats CiteSeer Summary: Positron emission tomography (PET) is a non-invasive molecular imaging technique using positron-emitting radioisotopes to...

  6. AMPA-receptor mediated plasticity within the rat spinal cord

    E-Print Network [OSTI]

    Hoy, Kevin Corcoran

    2009-05-15T23:59:59.000Z

    AMPA-RECEPTOR MEDIATED PLASTICITY WITHIN THE RAT SPINAL CORD A Thesis by KEVIN CORCORAN HOY JR. Submited to the Ofice of Graduate Studies of Texas A&M University in partial fulfilment of the requirements... for the degre of MASTER OF SCIENCE August 2008 Major Subject: Psychology AMPA-RECEPTOR MEDIATED PLASTICITY WITHIN THE RAT SPINAL CORD A Thesis by KEVIN CORCORAN HOY JR. Submited to the Ofice of Graduate...

  7. Distribution of ochratoxin A in the pregnant rat

    E-Print Network [OSTI]

    Ballinger, Michael Brent

    1983-01-01T23:59:59.000Z

    . . . APPENDIX 1. SAFETY PROCEDURES. APPENDIX 2. BIOLOGICAL OXIDIZER PROCEDURES. . . APPENDIX 3. LIQUID SCINTILLATION COUNTING. . . . APPENDIX 4. PHARMACOKINETIC CALCULATIONS. . . . . VITA. 1V V1 V11 V111 3 4 12 26 27 27 27 28 29 33 35 54 57... 66 68 71 73 74 LIST OF TABLES Table Page 1 Pharmacokinetic parameters estimated from the serum radioactivity derived from 3H-ochratoxin A in pregnant rats. . 2 Excretion of 3H radioactivity by pregnant rats. . 38 39 3 Distribution...

  8. Arginine and Conjugated Linoleic Acid Reduce Fat Mass in Rats

    E-Print Network [OSTI]

    Nall, Jennifer L.

    2010-10-12T23:59:59.000Z

    ARGININE AND CONJUGATED LINOLEIC ACID REDUCE FAT MASS IN RATS A Thesis by JENNIFER LYNN NALL Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree... of MASTER OF SCIENCE May 2008 Major Subject: Nutrition ARGININE AND CONJUGATED LINOLEIC ACID REDUCE FAT MASS IN RATS A Thesis by JENNIFER LYNN NALL Submitted to the Office of Graduate Studies Texas A...

  9. Neuroendocrine effects of acute nickel chloride administration in rats

    SciTech Connect (OSTI)

    Clemons, G.K.; Garcia, J.F.

    1981-01-01T23:59:59.000Z

    An sc injection of nickel chloride (20 and 10 mg/kg) led to a profound and consistent increase of circulating prolactin (PRL) levels after 1 day and lasted for 4 days (p < 0.001) in male rats. Increases in insulin levels occurred 1 and 2 days postinjection. The nickel-induced PRL rise could be abolished by a simultaneous administration of 2-bromo-..cap alpha..-ergocryptine (CB 154). In vitro incubation of pituitaries from rats that received 20 mg/kg of nickel chloride 48 hr prior to sacrifice released more PRL into the culture medium, as well as contained more PRL in the final tissue than did the pituitaries from control animals. The hypothalamic extracts (HE) obtained from hypothalami of nickel-injected rats were tested also in vitro on normal rat pituitaries and the results showed that the HE from such rats released more PRL and therefore had less prolactin-inhibiting factor (PIF) than the HE obtained from control rats. The results show that nickel chloride has effects on the endocrine system that (a) last considerably longer than previously reported, (b) are mediated through the neuroendocrine system, and (c) instead of specifically inhibiting PRL secretion from the pituitary promote high circulating PRL levels lasting from 1 to 4 days.

  10. Systemic toxicity of dermally applied crude oils in rats

    SciTech Connect (OSTI)

    Feuston, M.H.; Mackerer, C.R.; Schreiner, C.A.; Hamilton, C.E. [Stonybrook Labs., Inc., Princeton, NJ (United States)] [Stonybrook Labs., Inc., Princeton, NJ (United States)

    1997-12-31T23:59:59.000Z

    Two crude oils, differing in viscosity (V) and nitrogen (N) and sulfur (S) content, were evaluated for systemic toxicity, In the Crude I (low V, low N, low S) study, the material was applied to the clipped backs of rats at dose levels of 0, 30, 125, and 500 mg/kg. In the Crude II (high V, high N, moderate S) study, the oil was applied similarly at the same dose levels. The crude oils were applied for 13 wk, 5 d/wk. Exposure sites were not occluded. Mean body weight gain (wk 1-14) was significantly reduced in male rats exposed to Crude II; body weight gain of all other animals was not adversely affected by treatment. An increase in absolute (A) and relative (R) liver weights and a decrease in A and R thymus weights were observed in male and female rats exposed to Crude II at 500 mg/kg; only liver weights (A and R) were adversely affected in male and female rats exposed to Crude I. In general, there was no consistent pattern of toxicity for serum chemistry endpoints; however, more parameters were adversely affected in Crude II-exposed female rats than in the other exposed groups. A consistent pattern of toxicity for hematology endpoints was observed among male rats exposed to Crude I and male and female rats exposed to Crude II. Parameters affected included: Crudes I and II, red blood cell count, hemoglobin, and hematocrit, Crude II, platelet count. Microscopic evaluation of tissues revealed the following treatment-related findings: Crude I, treated skin, thymus, and thyroid; Crude II, bone marrow, treated skin, thymus, and thyroid. The LOEL (lowest observable effect level) for skin irritation and systemic toxicity (based on marginal effects on the thyroid) for both crude oils was 30 mg/kg; effects were more numerous and more pronounced in animals exposed to Crude II. Systemic effects are probably related to concentrations of polycyclic aromatic compounds (PAC) found in crude oil.

  11. STABLE FREQUENCY RESPONSE TO VARYING STIMULUS INTENSITY IN A MODEL OF THE RAT OLFACTORY BULB

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    STABLE FREQUENCY RESPONSE TO VARYING STIMULUS INTENSITY IN A MODEL OF THE RAT OLFACTORY BULB Thomas Neurosciences et Systèmes sensoriels, CNRS UMR 5020, Lyon, France ABSTRACT In the rat olfactory bulb (OB), fast. Introduction The rat olfactory bulb (OB) is a rich and complex sensory processing system that shows stimulus

  12. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    SciTech Connect (OSTI)

    Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.

    1990-12-01T23:59:59.000Z

    Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

  13. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.; Boyd, P.J.; Hayden, B.K.; Evanoff, J.J.; Rommereim, R.L.

    1994-02-01T23:59:59.000Z

    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs. Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).

  14. The effect of fear on gregariousness and exploration in rats

    E-Print Network [OSTI]

    Anderson, Bergie Wayne

    1973-01-01T23:59:59.000Z

    ' "ms of the behavior occurring in the open field. Rats display three major behaviors in the open field; these are fear, exploration, and gregariousness. Research has shown that when a pMr of rats are placed into an open field, they display signs... them. The two variables were found to be positively correlated and significant at the 0. 05 level of con- fidence (r = . 16; df = 230). The analysis of variance of the combined fear scores, indicated a significant difference. between methods (F = 4...

  15. Original article Digestion and fermentation of proteins in rats fed

    E-Print Network [OSTI]

    Boyer, Edmond

    Original article Digestion and fermentation of proteins in rats fed keratin, albumin, cooked casein the hypothesis that cooking reduces the digestibility of casein, and increases the yield of bacterial me transfer and fermentation in the caecum. The caecal digestion of casein (cooked or not), ker- atin

  16. Facial Wiping in the Rat Fetus: Variation of Chemosensory

    E-Print Network [OSTI]

    Robinson, Scott R.

    how variation in stimulus parameters of lemon odor infusion (concentration, volume, and infusion time) affected the wiping response of E20 rat fetuses. Infusions of higher concentration or greater volume of stimulation. Intraoral infusion of chemosensory fluids with strong olfactory components, such as lemon extract

  17. Aardvark hunt in Kenya Gaten B. Rat}rUin

    E-Print Network [OSTI]

    I I i Aardvark hunt in Kenya Gaten B. Rat}rUin Dept of Omittrologr & Mamrnalogr, Catifomia Academy eactrirg science as a Peace Corps Volunteer at Mirogi $conOary Scnou in Sou*r Nyanza District or Kenya of Kenya in Nairobi. 14 #12;

  18. Effects of Methanol on the Retinal Function of Juvenile Rats

    E-Print Network [OSTI]

    Casanova, Christian

    Effects of Methanol on the Retinal Function of Juvenile Rats C. Plaziac1 , P. Lachapelle2 , C Received 18 April 2002; accepted 22 July 2002 Abstract We have investigated the effect of methanol exposure recorded prior to and up to 72 h after the administration of methanol. Data were compared to a control

  19. PROTECTIVE EFFECTS OF VERAPAMIL AGAINST HEXACHLOROBUTADIENE NEPHROTOXICITY IN RATS

    E-Print Network [OSTI]

    E. Moghtadai Khorasgani; K. Manochehri; M. Hosseini

    In order to evaluate the protective effect of verapamil against hexachlorobutadiene (HCBD) nephrotoxicity, 30 adult Wistar albino rats were divided into five equal groups, A, B, C, D and E and were given intra-peritonially corn oil (I ml/kg; control), HCBD (50 mg/kg), verapamil (50 µg/kg) with HCBD

  20. Inconclusive Experiment with Rats By Bill Menke, December 1, 2013

    E-Print Network [OSTI]

    Menke, William

    of genetically-modified corn. The Times article says: The editor of the journal, Food and Chemical Toxicology the paper's main result, that rats fed genetically-modified, herbicide-resistant corn have a higher incident was a bit disingenuous of him. I do find delicious the irony that Séralini's paper is critiquing genetically-modified

  1. Single Glucose Biofuel Cells Implanted in Rats Power Electronic Devices

    E-Print Network [OSTI]

    Boyer, Edmond

    Single Glucose Biofuel Cells Implanted in Rats Power Electronic Devices A. Zebda1,2 , S. Cosnier1 the first implanted glucose biofuel cell (GBFC) that is capable of generating sufficient power from a mammal further developments. Following recent developments in nano- and biotechnology, state-of-the-art biofuel

  2. Nitrogen sparing by 2-ketoisocaproate in parenterally fed rats

    SciTech Connect (OSTI)

    Yagi, M.; Matthews, D.E.; Walser, M. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-11-01T23:59:59.000Z

    In rats receiving total parenteral nutrition with or without sodium 2-ketoisocaproate (KIC; 2.48 g.kg-1.day-1), L-(1-{sup 13}C)leucine and (1-{sup 14}C)KIC were constantly infused for 6 h. CO{sub 2} production, {sup 14}CO{sub 2} production, {sup 13}CO{sub 2} enrichment, urinary urea nitrogen (N) plus ammonia N and total urinary N were measured. Whole body protein synthesis (S) was calculated in non-KIC-infused rats and also in unfed rats infused with (1-{sup 14}C)leucine from fractional oxidation of labeled leucine (1-F), where F is fractional utilization for protein synthesis, and urea N plus ammonia N excretion (C) as S = C x F/(1-F). Addition of KIC caused a significant reduction in N excretion and a significant improvement in N balance. Fractional oxidation of labeled KIC increased, whereas fractional utilization of labeled KIC for protein synthesis decreased, but the extent of incorporation of infused KIC into newly synthesized protein (as leucine) amounted to at least 40% of the total rate of leucine incorporation into newly synthesized whole body protein. We conclude that addition of KIC spares N in parenterally fed rats and becomes a major source of leucine for protein synthesis.

  3. adult rat brain: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    rat brain First Page Previous Page 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 Thyroid hormone regulates hippocampal...

  4. JET PROPULSION LAB 0 RAT 0 R Y

    E-Print Network [OSTI]

    Waliser, Duane E.

    JET PROPULSION LAB 0 RAT 0 R Y ANN U A L REP 0 R T #12;#12;------ - - ~ CON TEN T S DIRECTOR Administration for the penod January 1 through December 31, 1986. JET PROPULSION LABORATORY Califorrua Institute, Voyager 2 gave us our first close view of the distant giant Uranus, its complex rings, inclined magnetic

  5. Susceptibility of immature rats to seizures induced by unsymmetrical dimethylhydrazine

    E-Print Network [OSTI]

    Boyd, Dale Duaine

    1963-01-01T23:59:59.000Z

    . Bain. Convulsant hydrazides I. In vito and in vivo inhibition of vitamin B6 enzymes by convulsive hydrazides. J. Pharmacol. Exp. Ther. 119:255-262 (1957). 8. Baxter, C. F. , and E. Roberts. Elevation of gamma-aminobutyric acid in rat brain...

  6. Ultrastructure of Primary Afferent Terminals and Synapses in the Rat

    E-Print Network [OSTI]

    Hill, David L.

    Ultrastructure of Primary Afferent Terminals and Synapses in the Rat Nucleus of the Solitary Tract tympani (CT), and glossopharyngeal (IX) nerves terminate in overlapping patterns in the brainstem electron microscopy. Although all three nerves had features charac- teristic of excitatory nerve terminals

  7. Characterization and Mapping of the Gene Conferring Resistance to Rift Valley Fever Virus Hepatic Disease in WF.LEW Rats

    E-Print Network [OSTI]

    Callicott, Ralph J.

    2010-01-14T23:59:59.000Z

    168 271 164 218 243 142 154 268 168 271 164 218 243 142 D6Rat46 D6Rat68 D6Rat105 D6Rat74 D6Rat144 D6Rat135 D6Rat124 D6Rat116 D6Rat1 155 278 246 253 185 169 260 152 238 155 278 244 255 181 169 260... 220 242 181 349 134 177 256 132 131 160 165 216 242 181 349 134 177 256 132 133 148 159 220 248 203 349 126 175 246 138 171 160 163 214 248 203 349 126 175 246 138 171 160 163 214 248 203 349...

  8. Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium

    SciTech Connect (OSTI)

    Lee, S.S.; Girod, C.; Braillon, A.; Hadengue, A.; Lebrec, D.

    1986-08-01T23:59:59.000Z

    Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output and portal tributary blood flow. Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. The authors conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminated the hyperdynamic circulation.

  9. Regulation of Endothelial Phenotype in Rat Soleus Muscle Feed Arteries: Influence of Aging and Exercise Training

    E-Print Network [OSTI]

    Trott, Daniel Wayne

    2012-02-14T23:59:59.000Z

    arrival, rats were exercise trained (Ex) or remained sedentary (Sed) for 10-12 weeks. Thus, at the end of the training program, the ages of the young and old rats were 4-5 mo or 24-25 mo respectively. The resulting experimental design consisted... of four groups of rats: 1) young Sed (n = 10), 2) young Ex (n = 10), 3) old Sed (n = 10), and 4) old Ex (n = 10). To determine whether exogenous antioxidants produce exercise-like effects on aged SFA, a separate group of male Fischer 344 rats (4...

  10. Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats

    E-Print Network [OSTI]

    Schulteis, Gery; Liu, Jian

    2006-01-01T23:59:59.000Z

    stimulation reward: effects of ethanol. Alcohol Clin Exp Resstimulus produced by ethanol withdrawal. J Pharmacol Expthe "anxiogenic" response to ethanol withdrawal in the rat.

  11. 3D MRI of Non-Gaussian He Gas Diffusion in the Rat Lung. | EMSL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Results show that the non-Gaussian effects of ³He gas diffusion in healthy rat lungs are directly attributed to the anisotropic geometry of lung microstructure, and that...

  12. Effects of combined hyperoxia and cyclooxygenase inhibition in neonatal rat lungs

    E-Print Network [OSTI]

    2010-01-01T23:59:59.000Z

    K. Effect of indomethacin on lung development in postnatalinhibition & neonatal rat lungs the fetal ductus arteriosus.expression in human lungs of newborns with congenital

  13. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

    SciTech Connect (OSTI)

    Com, Emmanuelle, E-mail: emmanuelle.com@univ-rennes1.fr [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France) [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France); INSERM U625, Proteomics Core Facility Biogenouest, Rennes (France); Boitier, Eric; Marchandeau, Jean-Pierre [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France)] [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France); Brandenburg, Arnd [Genedata AG, Basel (Switzerland)] [Genedata AG, Basel (Switzerland); Schroeder, Susanne [Nycomed GmbH, Barsbüttel (Germany)] [Nycomed GmbH, Barsbüttel (Germany); Hoffmann, Dana; Mally, Angela [University of Würzburg, Department of Toxicology, University of Würzburg, Würzburg (Germany)] [University of Würzburg, Department of Toxicology, University of Würzburg, Würzburg (Germany); Gautier, Jean-Charles [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France)] [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France)

    2012-01-01T23:59:59.000Z

    Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ? Gentamicin induces renal tubular necrosis in rats. ? The mechanisms of gentamicin nephrotoxicity remain still elusive. ? Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ? Transcriptomic and proteomic data turned out to be complementary and are integrated. ? A more comprehensive putative model of nephrotoxicity of gentamicin is presented.

  14. Albumin extravasation rates in tissues of anesthetized and unanesthetized rats

    SciTech Connect (OSTI)

    Renkin, E.M.; Joyner, W.L.; Gustafson-Sgro, M.; Plopper, G.; Sibley, L.

    1989-05-01T23:59:59.000Z

    Bovine serum albumin (BSA) labeled with /sup 131/I was injected intravenously in chronically prepared, unanesthetized rats and into pentobarbital-anesthetized rats that had received 2 ml 5% BSA to help sustain plasma volume. Initial uptake rates (clearances) in skin, skeletal muscles, diaphragm, and heart (left ventricle) were measured over 1 h. BSA labeled with /sup 125/I was injected terminally to correct for intravascular /sup 131/I-BSA. Observed clearances were in the following order in both groups of animals: heart much greater than diaphragm approximately equal to skin greater than resting skeletal muscles. Differences between unanesthetized and anesthetized animals were small and inconsistently directed. Our results suggest that the lower albumin clearances reported in the literature for anesthetized rats are not the result of their immobility or any direct effect of anesthesia on albumin transport in these tissues. The lower transport rates appear to result indirectly from changes produced by anesthesia and/or surgery in controllable parameters such as plasma volume and intravascular protein mass.

  15. Bitumen fume-induced gene expression profile in rat lung

    SciTech Connect (OSTI)

    Gate, Laurent [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France)]. E-mail: laurent.gate@inrs.fr; Langlais, Cristina [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France); Micillino, Jean-Claude [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France); Nunge, Herve [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France); Bottin, Marie-Claire [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France); Wrobel, Richard [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France); Binet, Stephane [Institut National de Recherche et Securite, Avenue de Bourgogne, BP 27, 54501 Vandoeuvre Cedex (France)

    2006-08-15T23:59:59.000Z

    Exposure to bitumen fumes during paving and roofing activities may represent an occupational health risk. To date, most of the studies performed on the biological effect of asphalt fumes have been done with regard to their content in carcinogenic polycyclic aromatic hydrocarbons (PAH). In order to gain an additional insight into the mechanisms of action of bitumen fumes, we studied their pulmonary effects in rodents following inhalation using the microarray technology. Fisher 344 rats were exposed for 5 days, 6 h/day to bitumen fumes generated at road paving temperature (170 {sup o}C) using a nose-only exposition device. With the intention of studying the early transcriptional events induced by asphalt fumes, lung tissues were collected immediately following exposure and gene expression profiles in control and exposed rats were determined by using oligonucleotide microarrays. Data analysis revealed that genes involved in lung inflammatory response as well as genes associated with PAH metabolization and detoxification were highly expressed in bitumen-exposed animals. In addition, the expression of genes related to elastase activity and its inhibition which are associated with emphysema was also modulated. More interestingly genes coding for monoamine oxidases A and B involved in the metabolism of neurotransmitters and xenobiotics were downregulated in exposed rats. Altogether, these data give additional information concerning the bitumen fumes biological effects and would allow to better review the health effects of occupational asphalt fumes exposure.

  16. Auklet Demography and the Influence of Norway rats at Kiska Island report on results of monitoring to 2009

    E-Print Network [OSTI]

    Jones, Ian L.

    Auklet Demography and the Influence of Norway rats at Kiska Island ­ report on results METHODS 4 AUKLET PRODUCTIVITY 4 TIMING OF BREEDING 5 AUKLET SURVIVAL 6 NORWAY RAT ABUNDANCE 10 NORWAY RAT ABUNDANCE AND DISTRIBUTION 10 VEGETATION CHANGES 11 DISCUSSION 11 LEAST AUKLET

  17. Activation of orexin signal in basal forebrain facilitates the emergence from sevoflurane anesthesia in rat

    E-Print Network [OSTI]

    anesthesia in rat Hailong Dong 1 , Jiyuan Niu 1 , Binxiao Su, Zhenghua Zhu, Yan Lv, Yizhi Li, Lize Xiong t Orexinergic system may play an important role in the regulation of anesthesia­arousal. However, which region, induction and emergence time to sevoflurane anesthesia in rats. Either orexin-A or orexin-B was injected

  18. Relaxation Time Constants and Apparent Diffusion Coefficients of Rat Retina at 7 Tesla

    E-Print Network [OSTI]

    Duong, Timothy Q.

    Relaxation Time Constants and Apparent Diffusion Coefficients of Rat Retina at 7 Tesla Govind Nair* and ADC of the rat eyes were measured at 50 3 50 3 800 lm at 7 Tesla. Profiles of T1, T2, T2* and ADC

  19. Effect of Two Models of Intrauterine Growth Restriction on Alveolarization in Rat Lungs: Morphometric and Gene

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Effect of Two Models of Intrauterine Growth Restriction on Alveolarization in Rat Lungs L-NAME impairs lung development before alveolarization. Known growth factors involved in lung on Alveolarization in Rat Lungs: Morphometric and Gene Expression Analysis. PLoS ONE 8(11): e78326. doi:10

  20. Endogenous opioids and attenuated hypothalamic-pituitary-adrenal axis responses to immune challenge in pregnant rats 

    E-Print Network [OSTI]

    Russell, J. A.; Ochedalski, T; Meddle, S. L.; Ma, S.; Brunton, P. J.; Douglas, A. J.

    2005-01-01T23:59:59.000Z

    , but not pregnant, rats. However, naloxone infused directly into the PVN increased noradrenaline release after IL-1{beta} in pregnant rats. Thus, the HPA axis responses to immune signals are suppressed in pregnancy at the level of pPVN CRH neurons through an opioid...

  1. Experimental and theoretical studies of oxygen gradients in rat pial microvessels

    E-Print Network [OSTI]

    Popel, Aleksander S.

    no substantial impact on the transmural PO2 gradient. Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1597Experimental and theoretical studies of oxygen gradients in rat pial microvessels Maithili Sharan1 near cortical arterioles and transmural PO2 gradients in the pial arterioles of the rat. Under control

  2. The Effects of Alcohol and Age on Astrocytes In Female Rats Following an Inflammatory Stimulus

    E-Print Network [OSTI]

    Simpson, Ashley

    2009-09-30T23:59:59.000Z

    THE EFFECTS OF ALCOHOL AND AGE ON ASTROCYTES IN FEMALE RATS FOLLOWING AN INFLAMMATORY STIMULUS A Senior Scholars Thesis by ASHLEY NICOLE SIMPSON Submitted to the Office of Undergraduate Research Texas A...&M University In partial fulfillment of the requirements for the designation as UNDERGRADUATE RESEARCH SCHOLAR April 2006 Major: Biology THE EFFECTS OF ALCOHOL AND AGE ON ASTROCYTES IN FEMALE RATS FOLLOWING...

  3. Research Report Effects of ethanol consumption by adult female rats on subsequent

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    Research Report Effects of ethanol consumption by adult female rats on subsequent consumption January 2004 Abstract We used a two-bottle choice test to measure voluntary ethanol consumption by adolescent rats that had lived with ethanol-consuming or water-consuming adult conspecifics. We found

  4. The harmful effects of late-onset alcohol consumption on cortical bone in aged rats

    E-Print Network [OSTI]

    Bowlin, Julie Lee

    2001-01-01T23:59:59.000Z

    This study looked at the effects of late-onset alcohol consumption for 8 weeks on the aged rat model (15 months old). Thirty 15 month old female Fisher 344 rats were divided into three diet groups: Alcohol (n=9), pair-fed (n=9), and pellet (n=6...

  5. Water balance in rats exposed to chronic centrifugation RUDY M. ORTIZ AND CHARLES E. WADE

    E-Print Network [OSTI]

    Ortiz, Rudy M.

    was observed, the lack of a change in %TBW among the three measurement periods or in water flux over the 12Water balance in rats exposed to chronic centrifugation RUDY M. ORTIZ AND CHARLES E. WADE Life; accepted in final form 22 February 2000 Ortiz, Rudy M., and Charles E. Wade. Water balance in rats exposed

  6. Prefrontal involvement in the regulation of emotion: convergence of rat and human studies

    E-Print Network [OSTI]

    Quirk, Gregory J.

    experiments designed to bridge human and rodent models of emotion regulation. Addresses 1 Department of prefrontal involvement of emotion regula- tion using rat and human models, and suggest future experimentsPrefrontal involvement in the regulation of emotion: convergence of rat and human studies Gregory J

  7. PMSG responsiveness during adult life after partial oogonia destruction with misulban in the rat embryo

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    sensitive to X-ray irradiation in the last period of division, i.e. about day 15 of pregnancy in the rat-month old female rats were bred under standard conditions of light (14 h light―10 h dark) and food

  8. Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment

    E-Print Network [OSTI]

    Lutchen, Kenneth

    Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase P. Ingenito, and Be´la Suki. Lung and alveolar wall elastic and hysteretic behavior in rats: effects behavior of the alveolar walls and the macroscopic mechanical properties of the whole lung in an in vivo

  9. Plasticity in the Rat Posterior Auditory Field Following Nucleus Basalis Stimulation

    E-Print Network [OSTI]

    Kilgard, Michael P.

    Plasticity in the Rat Posterior Auditory Field Following Nucleus Basalis Stimulation Amanda C. Plasticity in the rat posterior auditory field following nucleus basalis stimulation. J Neurophysiol 98: 253 have been shown to cause frequency-specific plasticity in both primary and secondary cortical areas

  10. Impedance measurements of ex vivo rat lung at different volumes of inflation

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    Impedance measurements of ex vivo rat lung at different volumes of inflation Michael L. Oelze that the occurrence of ultrasonically induced lung hemorrhage in rats was directly correlated to the level of lung inflation. In that study, it was hypothesized that the lung could be modeled as two components consisting

  11. Catheterization of the Hepatic Artery Via the Left Common Carotid Artery in Rats

    SciTech Connect (OSTI)

    Li Xiao [West China Hospital, Sichuan University, Department of Radiology (China); Wang Yixiang, J. [AstraZeneca R and D (United Kingdom); Zhou Xiangping [West China Hospital, Sichuan University, Department of Radiology (China)], E-mail: xiangpingzhou46@163.com; Guan Yongsong; Tang Chengwei [West China Hospital, Sichuan University, Department of Gastroenterology (China)

    2006-12-15T23:59:59.000Z

    The commonly used approach for rat hepatic artery catheterization is via the gastroduodenal artery, which is ligated after the procedure. A new method of rat hepatic artery catheterization via the left common carotid artery (LCCA) is described. The LCCA is repaired after catheterization. The catheterization procedures included the following: (1) opening the rat's abdominal cavity and exposing the portion of abdominal aorta at the level of the celiac trunk; (2) separating and exposing the LCCA; inserting a microguidewire and microcatheter set into the LCCA via an incision; after placement into the descending aorta, the microguidewire and microcatheter are maneuvered into the hepatic artery under direct vision; (3) after transcatheter therapy, the catheter is withdrawn and the incision at the LCCA is repaired. This technique was employed on 60 male Sprague-Dawley rats with diethylnitrosamine-induced liver cancer, using a 3F microguidewire and microcatheter set. Selective hepatic artery catheterization was successfully performed in 57 rats. One rat died during the operation and five rats died within 7 days after the procedure. It is envisaged that as experience increases, the catheterization success rate will increase and the death rate will decrease. A new approach for selective hepatic artery catheterization via the LCCA in rats is introduced, which makes repeat catheterization of this artery possible and allows large embolization particles to be delivered by using a 3F catheter.

  12. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    SciTech Connect (OSTI)

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01T23:59:59.000Z

    Acrolein, a member of reactive ?,?-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including ?-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  13. Blocking long term consolidation of extinction in rats with puromycin

    E-Print Network [OSTI]

    Broussard, William Joseph

    1972-01-01T23:59:59.000Z

    OF SCIBNC August 1972 )major Subject: Psychology BLOCKING LONG TERM CONSOLIDATION OF EXTINCTION IN RATS WI ' H PUROMYCIN A Thesis WILLIAM JOSEPH BROUSSARD Approved as to style and content by~ c'F, ~ g, Chairman of Co j. ttee H o e ar men Mem er..., snd Joseph . "lagyvary, this manuscript would have been considerably longer in taking shape. The author e. ,pecially wishes to call attention to his wife. If tolerance, patience, and encourageme. , t can be considered part of a higher education...

  14. The oncogenic action of ionizing radiation on rat skin

    SciTech Connect (OSTI)

    Burns, F.J.; Garte, S.J.

    1992-01-01T23:59:59.000Z

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/[mu]), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of [sup 14]C-thymidine. The return of these cells to S-phase a second time was detected by a second label ([sup 3]H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The [sup 14]C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with [sup 14]C increased after 42 hr and remained relatively constant thereafter.

  15. The effects of alcohol and irradiation on the albino rat 

    E-Print Network [OSTI]

    Klobukowski, Christopher John

    1963-01-01T23:59:59.000Z

    '&eight During the Test I'eriod. lh Combined. Daily Caloric Intake - Ca- lories per 100 Grams of 3ody Ueight. 17 Survival '?ata and Peak Death Days 3xpt. II. Surv1 vBI Data and Peek !3ea'l h Days Sxpte Ilia 3 j& Average Dody "? eights ( Pram... ~ ) ?" i rat Day I'ostirradiation. Average Pluid Intake (in millili gers) per 100 Grams of Dody Ueight, T~so Dave Pre-, Three ?Days Postirradiafion, "?S Average Percent ?ge of Total Caloric lntal:e per 100 Grams of 3od. , ? '?eight Supplied. 'by...

  16. Organization and evolution of the rat tyrosine hydroxylase gene

    SciTech Connect (OSTI)

    Brown, E.R.; Coker, G.T. III; O'Malley, K.L.

    1987-08-11T23:59:59.000Z

    This report describes the organization of the rat tyrosine hydroxylase (TH) gene and compares its structure with the human phenylalanine hydroxylase gene. Both genes are single copy and contain 13 exons separated by 12 introns. Remarkably, the positions of 10 out 12 intron/exon boundaries are identical for the two genes. These results support the idea that these hydroxylases genes are members of a gene family which has a common evolutionary origin. The authors predict that this ancestral gene would have encoded exons similar to those of TH prior to evolutionary drift to other members of this gene family.

  17. Effect of anesthesia on glucose production and utilization in rats

    SciTech Connect (OSTI)

    Penicaud, L.; Ferre, P.; Kande, J.; Leturque, A.; Issad, T.; Girard, J.

    1987-03-01T23:59:59.000Z

    This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using (3-/sup 3/H) glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-(1-/sup 3/H) deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain.

  18. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    SciTech Connect (OSTI)

    Bass, V. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gordon, C.J.; Jarema, K.A.; MacPhail, R.C. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Cascio, W.E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Phillips, P.M. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Ledbetter, A.D.; Schladweiler, M.C. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Andrews, D. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Miller, D. [Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC (United States); Doerfler, D.L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, U.P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2013-12-15T23:59:59.000Z

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased ?{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone metabolic effects are only slightly exacerbated in geriatric rats.

  19. A study of the nutritive value of sorghum grain with rats

    E-Print Network [OSTI]

    Dohm, Carolee Kathryn

    1969-01-01T23:59:59.000Z

    and Levels of Protein and Amino Acids Response of Rats Fed Sorghum Grain Basal Diets With Individual Supplemental Amino Acids Omitted I. imiting Amino Acids of Sorghum Grain Protein (Rartin) Determined by Chemical Analysis, Rat Growth and by Plasma... for the s?mino acid analysis. Experi???ent 1 The f?. rst e& perimcnt was ccnducted to obtain necessary pri- lin. inary irinmnatiori on the ability of sorghum grain alone nd supplemented with prot. ein or amino acids to promote growth of. i?eanling rats...

  20. The effect of Zoledronate treatment timing on lumbar and caudal vertebrae in ovariectomized rats

    E-Print Network [OSTI]

    Ruchelsman, Michal (Michal Aliza)

    2007-01-01T23:59:59.000Z

    Introduction: While there have been numerous studies demonstrating the effect of bisphosphonates in rats as either a preventative treatment or recovering treatment for osteoporosis, few have directly compared the two ...

  1. Skeletal Response to Simulated Microgravity Exposures and Exercise in the Adult Rat Model 

    E-Print Network [OSTI]

    Shirazi-Fard, Yasaman

    2013-04-29T23:59:59.000Z

    mass, structure, and integrity and not an accurate predictor of fracture risk. Therefore, it is essential to measure the mechanical properties of bone tissue directly using animal models. The hindlimb unloaded (HU) rat model is a well-established ground...

  2. Beneficial effects of dietary L-arginine supplementation to diabetic rats

    E-Print Network [OSTI]

    Kohli, Ripla

    2004-09-30T23:59:59.000Z

    Diabetic rats exhibit decrease in plasma arginine, NO synthesis and tetrahydrobiopterin in endothelial cells (EC). Treatment with L-arginine may be beneficial for enhancing NO synthesis in diseases associated with endothelial dysfunction. However...

  3. The impact of binge drinking on the young growing female rat skeleton

    E-Print Network [OSTI]

    Gallagher, Sharon Lee

    1997-01-01T23:59:59.000Z

    Previous research indicated that chronic alcohol consumption has a detrimental impact on the skeleton in both humans and alcohol-fed rats. The decreased bone mass seen in alcoholics increases their risk for fractures over time and likely contributes...

  4. E-Print Network 3.0 - anesthetized lactating rats Sample Search...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    in situ and force in the rat plantaris muscle during repeated Effect of lactate infusion on M... .physiology.orgDownloadedfrom 12;Effect of lactate infusion on M-wave...

  5. Effect of passive and active immunization against somatostatin in growing rats and cattle

    E-Print Network [OSTI]

    Lawrence, Mark Elliott

    1985-01-01T23:59:59.000Z

    found in other cells throughout the gastro- intestinal mucosa, usually in the midzone of the villi (Polak et al. , 1975). Somatostatin is found in hypothalamic as well as extrahypothalamic regions of the rat brain (Epelbaum et al. , 1977). Epelbaum...

  6. Dose Dependent Response to Cyclodextrin Infusion in a Rat Model of Verapamil Toxicity

    E-Print Network [OSTI]

    Mottram, Allan R.; Bryant, Sean M; Aks, Steven E

    2012-01-01T23:59:59.000Z

    time to asystole in rats infused with both verapamil Westernso that the total volume infused was the same across groups,respectively. The group infused with verapamil and SBE-CD in

  7. The impact of binge drinking on the young growing female rat skeleton 

    E-Print Network [OSTI]

    Gallagher, Sharon Lee

    1997-01-01T23:59:59.000Z

    Previous research indicated that chronic alcohol consumption has a detrimental impact on the skeleton in both humans and alcohol-fed rats. The decreased bone mass seen in alcoholics increases their risk for fractures over ...

  8. Quantification of Neuroepithelial Bodies and Their Innervation in Fawn-Hooded and Wistar Rat Lungs

    E-Print Network [OSTI]

    Burnstock, Geoffrey

    Quantification of Neuroepithelial Bodies and Their Innervation in Fawn-Hooded and Wistar Rat Lungs neuroendocrine system (DNES) of the lungs, the neuroendocrine cells of which have been shown to express

  9. Estimating cancellous bone properties of the rat from mechanical testing of the femoral neck 

    E-Print Network [OSTI]

    Groves, Jennifer Ann

    1998-01-01T23:59:59.000Z

    ESTIMATING CANCELLOIJS BONE PROPERTIES OF THE RAT FROM MECHANICAL TESTING OF THE FEMORAL NECK A Thesis by JENNIFER ANN GROVES Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE December 1998 Major Subject: Mechanical Engineering ESTIMATING CANCELLOUS BONE PROPERTIES OF THE RAT FROM MECHANICAL TESTING OF THE FEMORAL NECK A Thesis by JENNIFER ANN GROVES Submitted to Texas Ai8:M University...

  10. Absence of an inhibitory action of prolactin on plasma luteinizing hormone in ovariectomized rats

    E-Print Network [OSTI]

    Owens, Robert Ellis

    1977-01-01T23:59:59.000Z

    ABSENCE OF AN INHIBITORY ACTION OF PROLACTIN ON PLASMA LUTEINIZING HORMONE IN OVARIECTOMIZED RATS A Thesis by ROBERT ELLIS OWENS Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree... of MASTER OF SCIENCE August 1977 Major Subject: Physiology of Reproduction ABSENCE OF AN INHIBITORY ACTION OF PROLACTIN ON PLASMA LUTEINIZING HORMONE IN OVARIECTOMIZED RATS A Thesis by ROBERT ELLIS OWENS Approved as to style and content by: Chai man...

  11. 3-Methylhistidine excretion as an index of dietary protein adequacy in the rat

    E-Print Network [OSTI]

    Kirby, Rebecca Kay

    1980-01-01T23:59:59.000Z

    3-METHYLHISTIDINE EXCRETION AS AN INDEX OF DIETARY PROTEIiV ADEQUACY IN THE RAT A Thesis by REBECCA KAY KIRBY Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree of MASTER... OF SCIENCE August 1980 Major Subject: Biochemistry and Biophysics 3-METHYLHISTIDINE EXCRETION AS AN INDEX OF DIETARY PROTEIN ADEQUACY IN THE RAT A Thesis by REBECCA KAY KIRBY Approved as to style and content by: (Chairman of Committee) (Member...

  12. Sodium and potassium levels in the serum of acutely irradiated and non-irradiated rats

    E-Print Network [OSTI]

    Shepherd, David Preston

    1967-01-01T23:59:59.000Z

    SODIUM AND POTASSIUM LEVELS IN THE SERUM OF ACUTELY IRRADIATED AND NON-IRRADIATED RATS A Thesis By DAVID PRESTON SHEPHERD Submitted to the Graduate College of the Texas ARM University in partial fulfillment of the requirements for the degree... of MASTER OF SCIENCE August 1967 Major Subject: Zoology SODIUM AND POTASSIUM LEVELS IN THE SERUM OF ACUTELY IRRADIATED AND NON-IRRADIATED RATS A Thesis By DAVID PRESTON SHEPHERD Approved as to style and content by: (Chairman of Committee) (Head...

  13. The postnatal development of the sex organs in prenatally and early postnatally irradiated male albino rats

    E-Print Network [OSTI]

    Ricks, Robert Clinton

    1964-01-01T23:59:59.000Z

    THE POSTNATAL DEVELOPMENT OF THE SEX ORGANS IN PRENATALLY AND EARLY POSTNATALLY IRRADIATED MALE ALBINO RATS A Thesis By ROBERT C. RICKS Submitted to the Graduate College of the Texas ARM University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE August, 1964 Major Subject: Zoology THE POSTNATAL DEVELOPMENT OF THE SEX ORGANS IN PRENATALLY AND EARLY POSTNATALLY IRRADIATED MALE ALBINO RATS A Thesis By ROBERT C. RICKS Approved as to style and content by...

  14. Magnesium and pyridoxine intake and mineral content of selected tissues and physical development in rats

    E-Print Network [OSTI]

    Edgar, Susan Elaine

    1986-01-01T23:59:59.000Z

    MAGNESIUM AND PYRIDOXINE INTAKE MINERAL CONTENT OF SELECTED TISSUES PHYSICAL DEVELOPMENT IN RATS A Thesis by SU S AN ELA I NE EDGAR Submitted to the Graduate College of Texas A8rM University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE August 1986 Major Subject: Nutrition MAGNESIUM AND PYRIDOXINE INTAKE MINERAL CONTENT OF SELECTED TISSUES PHYS ICAL DEVELOPMENT IN RATS A Thesis by SUSAN ELAINE EDGAR Approved as to style and content by: 'KAREN...

  15. Effects of simulated microgravity on vasoconstrictor and mechanical properties of the rat abdominal aorta

    E-Print Network [OSTI]

    Papadopoulos, Anthony

    2002-01-01T23:59:59.000Z

    EFFECTS OF SIMULATED MICROGRAVITY ON VASOCONSTRICTOR AND MECHANICAL PROPERTIES OF THE RAT ABDOMINAL AORTA A Thesis by ANTHONY PAPADOPOULOS Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE August 2002 Major Subject: Biomedical Engineering EFFECTS OF SIMULATED MICROGRAVITY ON VASOCONSTRICTOR AND MECHANICAL PROPERTIES OF THE RAT ABDOMINAL AORTA A Thesis by ANTHONY PAPADOPOULOS Submitted...

  16. Copper induced osteopenia and its relationship to the development of postmenopausal osteoporosis in the rat

    E-Print Network [OSTI]

    Yee, Cindy Deann

    1992-01-01T23:59:59.000Z

    COPPER INDUCED OSTEOPENIA AND ITS RELATIONSHIP TO THE DEVELOPMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN THE RAT A Thesis CINDY DEANN YEE Submitted to the Office of Graduate Studies of Texas ASM University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE August 1992 Major Subject: Nutrition COPPER INDUCED OSTEOPENIA AND ITS RELATIONSHIP TO THE DEVELOPMENT OF POSTMENOPAUSAL OSTEOPOROSIS IN THE RAT A Thesis CINDY DEANN YEE Approved as to style and content...

  17. LES TYROSINASES CUTANES CHEZ LE RAT. MODIFICATIONS AU COURS DU DVELOPPEMENT

    E-Print Network [OSTI]

    Boyer, Edmond

    LES TYROSINASES CUTAN�ES CHEZ LE RAT. MODIFICATIONS AU COURS DU D�VELOPPEMENT ET PENDANT LE CYCLE Sciences appliquées, 69621 Villeurbanne 1 1 R�SUM� Nous avons effectué l'étude des tyrosinases de la peau chez le Rat. Ces tyrosinases sont mises en évidence, après électrophorèse par réaction de Dopa sur gel

  18. Magnesium deficiency and type of protein during gestation and lactation in rats 

    E-Print Network [OSTI]

    Holmes, Kathryn Ellen Hughes

    1988-01-01T23:59:59.000Z

    MAGNESIUM DEFICIENCY AND TYPE OF PROTEIN DURING GESTATION AND LACTATION IN RATS A Thesis by KATHRYN ELLEN HUGHES HOLMES Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirements for the degree... of MASTER OF SCIENCE August 1988 Major Subject: Nutrition MAGNESIUM DEFICIENCY AND TYPE OF PROTEIN DURING GESTATION AND LACTATION IN RATS A Thesis by KATHRYN ELLEN HUGHES HOLMES Approved as to style and content by: Karen S. Kubena (Chair...

  19. Systematics of the southern races of two species of kangaroo rats (Dipodomys compactus and D. ordi)

    E-Print Network [OSTI]

    Baumgardner, George D

    1979-01-01T23:59:59.000Z

    SYSTEMATICS OF THE SOUTHERN RACES OF TWO SPECIES OF KANGAROO RATS (DIPODOMYS COMPACTUS AND D. ORDI) A Thesis by GEORGE DAVIS BAUMGARDNER Submitted to the Graduate Colleqe of Texas A&M University in partial fulfillment o- the requirement... for the deqree of MASTER OF SCIENCE May 1979 Major Subject: Nildlife and Fisheries Sciences SYSTEMATICS OF THE SOUTHERN RACES OF TWO SPECIES OF KANGAROO RATS (DIPODOMYS COMPACTUS AND D. ORDI) A Thesis by GEORGE DAVIS BAUMGARDNER Approved as to style...

  20. Dose-Response Effect of Charged Carbon Beam on Normal Rat Retina Assessed by Electroretinography

    SciTech Connect (OSTI)

    Mizota, Atsushi, E-mail: mizota-a@med.teikyo-u.ac.j [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Department of Ophthalmology, Juntendo University Urayasu Hospital, Urayasu (Japan); Tanaka, Minoru [Department of Ophthalmology, Juntendo University Urayasu Hospital, Urayasu (Japan); Kubota, Mariko; Negishi, Hisanari [Department of Ophthalmology, National Hospital Organization Chiba Medical Center, Chiba (Japan); Watanabe, Emiko [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Tsuji, Hiroshi; Miyahara, Nobuyuki; Furusawa, Yoshiya [National Institute of Radiological Sciences, Chiba (Japan)

    2010-12-01T23:59:59.000Z

    Purpose: To compare the effects of carbon beam irradiation with those of proton beam irradiation on the physiology of the retina of rats. Methods and Materials: Eight-week-old Wister rats were used. The right eyes were irradiated with carbon beam (1, 2, 4, 8, and 16 Gy) or proton beam (4, 8, 16, and 24 Gy) with the rats under general anesthesia. Electroretinograms were recorded 1, 3, 6, and 12 months after the irradiation, and the amplitudes of the a and b waves were compared with those of control rats. Results: The amplitude of b waves was reduced more than that of a waves at lower irradiation doses with both types of irradiation. With carbon ion irradiation, the amplitudes of the b wave were significantly reduced after radiation doses of 8 and 16 Gy at 6 months and by radiation doses of 4, 8, and 16 Gy at 12 months. With proton beam irradiation, the b-wave amplitudes were significantly reduced after 16 and 24 Gy at 6 months and with doses of 8 Gy or greater at 12 months. For the maximum b-wave amplitude, a significant difference was observed in rats irradiated with carbon beams of 4 Gy or more and with proton beams of 8 Gy or more at 12 months after irradiation. Conclusions: These results indicate that carbon beam irradiation is about two times more damaging than proton beam irradiation on the rat retina at the same dose.

  1. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

    SciTech Connect (OSTI)

    Saeed, Noha M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt)] [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); El-Demerdash, Ebtehal [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)] [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Abdel-Rahman, Hanaa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt)] [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); Algandaby, Mardi M. [Department of Biology (Botany), Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia)] [Department of Biology (Botany), Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Al-Abbasi, Fahad A. [Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia)] [Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Abdel-Naim, Ashraf B., E-mail: abnaim@pharma.asu.edu.eg [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-10-01T23:59:59.000Z

    Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6). MP and EP decreased NF-?B expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ? Efficacy of MP and EP in combating inflammation was displayed in several models. ? MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ? MP and EP decreased TNF-? and IL-6 levels in experimental endotoxemia. ? MP and EP reduced NF-?B expression and histological changes in rat liver and lung. ? MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.

  2. Prolactin and aging: X-irradiated and estrogen-induced rat mammary tumorigenesis

    SciTech Connect (OSTI)

    Ito, A.; Naito, M.; Watanabe, H.; Yokoro, K.

    1984-07-01T23:59:59.000Z

    Both sexes of inbred WF rats at either 8 or 28-60 weeks of age were exposed to 200 rad whole-body radiation, 2.5 or 5.0 mg 17 beta-estradiol (E2), or both agents The female rats treated with E2 alone or with both X-rays and E2 at 8 weeks of age showed a high incidence of mammary carcinomas (MCA), a large increase in pituitary weight, and a rise in serum prolactin (PRL) levels. However, the same treatments to males did not induce MCA despite a moderate increase in both pituitary weight and serum PRL. Ovariectomy prior to E2 treatment failed to modify the occurrence of MCA or pituitary tumors. When X-rays and E2 were given to female rats at 28-60 weeks of age, pituitary weight, serum PRL levels, and the incidence of MCA were unaffected. When the E2 pellet was kept for the first 24 weeks and withdrawn during the last 12 weeks, the incidence of MCA, pituitary weight, and serum PRL was low. It was concluded that: 1) the pituitary glands of young female rats were susceptible to E2 treatment but were insensitive in older females, and 2) the occurrence of MCA in female rats appeared to be promoted by elevated PRL levels secreted by E2-induced pituitary tumors. Mammary tissue of male rats was less sensitive to PRL levels in the development of MCA.

  3. Ovariectomized Sprague-Dawley and Long-Evans rats release prolactin differently in response to estrogen

    SciTech Connect (OSTI)

    Lawson, D.M.; Sensui, N.; Gala, R.R.

    1984-01-30T23:59:59.000Z

    Mature female Sprague-Dawley (SD) and Long-Evans (LE) rats were ovariectomized (OVX), and given a single sc injection of either 25 or 100 ..mu..g polyestradiol phosphate (PEP); seven days later blood samples were withdrawn at two hour intervals from 1100 to 2100 hours to detect the presence of an afternoon surge of prolactin (PRL). Other groups of OVX rats of both strains also treated with PEP were sampled before and at 2, 5, 10 and 30 min after iv administration of 1 ..mu..g synthetic thyrotropin releasing hormone (TRH). Pituitary (AP) and uterine weights were determined following sacrifice one day after TRH treatment. The AP homogenates and plasma samples were assayed for PRL by radioimmunoassay. Rats of both strains had afternoon PRL surges and in both strains the magnitude and/or duration of the surges were enhanced by the higher dose of PEP. However, within each PEP dose LE rats released significantly more PRL during the surge than did SD drats. Rats of both strains also rleased PRL in response to TRH and this response was enhanced in both strains by the higher of the two doses of PEP. These data not only show that strain differences exist in estrogen-induced or mediated PRL release in the rat but also indicate that the differences are not uniform.

  4. Finite element analysis and computed tomography based structural rigidity analysis of rat tibia with simulated lytic defects

    E-Print Network [OSTI]

    Vaziri, Ashkan

    Finite element analysis and computed tomography based structural rigidity analysis of rat tibia) (Damron et al., 2003; Mirels, 1989). In contrast, Computed Tomography based Structural Rigidly Ana- lysis

  5. Ethanol seeking triggered by environmental context is attenuated by blocking dopamine D1 receptors in the nucleus accumbens core and shell in rats

    E-Print Network [OSTI]

    Chaudhri, Nadia; Sahuque, Lacey L.; Janak, Patricia H.

    2009-01-01T23:59:59.000Z

    self-administration when infused into either the NAc core ortest. As test rats were infused with saline and placed intotests where rats were infused with SCH 23390 (0, 0.006,

  6. Comparative Metabolism of Carbon Tetrachloride in Rats, Mice and Hamsters Using Gas Uptake and PBPK Modeling

    SciTech Connect (OSTI)

    Thrall, Karla D. (BATTELLE (PACIFIC NW LAB)); Vucelick, Mark E. (FLUOR HANFORD, INC); Gies, Richard A. (BATTELLE (PACIFIC NW LAB)); Zangar, Richard C. (BATTELLE (PACIFIC NW LAB)); Weitz, Karl K. (BATTELLE (PACIFIC NW LAB)); Poet, Torka S. (BATTELLE (PACIFIC NW LAB)); Springer, David L. (BATTELLE (PACIFIC NW LAB)); Grant, Donna M. (BATTELLE (PACIFIC NW LAB)); Benson, Janet M. (Inhalation Toxicology Research Institute)

    2000-08-25T23:59:59.000Z

    No study has comprehensively compared the rate of metabolism of carbon tetrachloride (CCl4) across species. Therefore, the in vivo metabolism of CCl4 was evaluated using groups of male animals (F344 rats, B6C3F1 mice, and Syrian hamsters) exposed to 40-1800 ppm CCl4 in a closed, recirculating gas-uptake system. For each species, an optimal fit of the family of uptake curves was obtained by adjusting Michaelis-Menten metabolic constants Km (affinity) and Vmax (capacity) using a physiologically based pharmacokinetic (PBPK) model. The results show that the mouse has a slightly higher capacity and lower affinity for metabolizing CCl4 compared to the rat, while the hamster has a higher capacity and lower affinity than either rat or mouse. A comparison of the Vmax to Km ratio, normalized for mg of liver protein (L/hr/mg) across species indicates that hamsters metabolize more CCl4 than either rats or mice, and should be more susceptible to CCl4-induced hepatotoxicity. These species comparisons were evaluated against toxicokinetic studies conducted in animals exposed by nose-only inhalation to 20 ppm 14C-labeled CCl4 for 4 hours. The toxicokinetic study results are consistent with the in vivo rates of metabolism, with rats eliminating less radioactivity associated with metabolism (14CO2 and urine/feces) and more radioactivity associated with the parent compound (radioactivity trapped on charcoal) compared to either hamsters or mice. The in vivo metabolic constants determined here, together with in vitro constants determined using rat, mouse, hamster and human liver microsomes, were used to estimate human in vivo metabolic rates of 1.49 mg/hr/kg body weight and 0.25 mg/L for Vmax and Km, respectively. Normalizing the rate of metabolism (Vmax/Km) by mg liver protein, the rate of metabolism of CCl4 differs across species, with hamster > mouse& > rat > human.

  7. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    SciTech Connect (OSTI)

    Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.go [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Twaddle, Nathan C.; Vanlandingham, Michelle [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Fisher, Jeffrey W. [Department of Environmental Health Sciences, College of Public Health, University of Georgia, Athens, GA 30602 (United States)

    2010-09-01T23:59:59.000Z

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  8. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    SciTech Connect (OSTI)

    Oller, Adriana R. [NiPERA, 2605 Meridian Parkway, Suite 200, Durham, NC 27713 (United States)], E-mail: aoller@nipera.org; Kirkpatrick, Daniel T.; Radovsky, Ann [WIL Research Laboratories, LLC, 1407 George Road, Ashland, OH 44805 8946 (United States); Bates, Hudson K. [NiPERA, 2605 Meridian Parkway, Suite 200, Durham, NC 27713 (United States)

    2008-12-01T23:59:59.000Z

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m{sup 3} nickel metal powder (MMAD = 1.8 {mu}m, GSD = 2.4 {mu}m) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m{sup 3} nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m{sup 3} was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m{sup 3} male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m{sup 3} females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies.

  9. In vitro dermal absorption of pyrethroid pesticides in human and rat skin

    SciTech Connect (OSTI)

    Hughes, Michael F., E-mail: hughes.michaelf@epa.go [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Edwards, Brenda C. [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2010-07-15T23:59:59.000Z

    Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flow-through diffusion cells, and radiolabeled bifenthrin, deltamethrin or cis-permethrin was applied in acetone to the skin. Fractions of receptor fluid were collected every 4 h. At 24 h, the skins were washed with soap and water to remove unabsorbed chemical. The skin was then solubilized. Two additional experiments were performed after washing the skin; the first was tape-stripping the skin and the second was the collection of receptor fluid for an additional 24 h. Receptor fluid, skin washes, tape strips and skin were analyzed for radioactivity. For rat skin, the wash removed 53-71% of the dose and 26-43% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid ranged from 1 to 5%. For human skin, the wash removed 71-83% of the dose and 14-25% remained in the skin. The cumulative percentage of the dose at 24 h in the receptor fluid was 1-2%. Tape-stripping removed 50-56% and 79-95% of the dose in rat and human skin, respectively, after the wash. From 24-48 h, 1-3% and about 1% of the dose diffused into the receptor fluid of rat and human skin, respectively. The pyrethroids bifenthrin, deltamethrin and cis-permethrin penetrated rat and human skin following dermal application in vitro. However, a skin wash removed 50% or more of the dose from rat and human skin. Rat skin was more permeable to the pyrethroids than human skin. Of the dose in skin, 50% or more was removed by tape-stripping, suggesting that permeation of pyrethroids into viable tissue could be impeded. The percentage of the dose absorbed into the receptor fluid was considerably less than the dose in rat and human skin. Therefore, consideration of the skin type used and fractions analyzed are important when using in vitro dermal absorption data for risk assessment.

  10. Dietary apigenin and naringenin protect against colon carcinogenesis by lowering high multiplicity aberrant crypt foci and enhancing apoptosis in azoxymethane-treated rats

    E-Print Network [OSTI]

    Leonardi, Tety

    2006-08-16T23:59:59.000Z

    investigated the potentially protective effects of four citrus flavonoids and one limonoid mixture against the promotion stage of chemically-induced colon cancer in rats. Male SD rats (n =60; 10 rats/group) were assigned to receive diets containing 0...

  11. Physiologically based Pharmacokinetic Modeling of 1,4-Dioxane in Rats, Mice, and Humans

    SciTech Connect (OSTI)

    Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.; Corley, Rick; Weber, Thomas J.; Locey, B. J.; Clarkson, Jacquelyn; Sager, S.; Gargas, M. L.

    2008-01-01T23:59:59.000Z

    ABSTRACT 1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver and kidney damage at sufficiently high exposure levels. Two physiologically-based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed:partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassays. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  12. Pancreatic hydrolases in cold-induced hyperphagia of rats fed a low or high-fat diet

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    -Bellevue, France. Summary. Rats fed either a low (2 p. 100) or high (40 p. 100)-fat diet were exposed to 22 or 5 °C consumption which entails increased digestive processes. The cold-adapted rat therefore provides containing 2.5 p. 100 lard supplemented with 0.4 p. 100 sunflower oil to provide the necessary unsaturated

  13. Methods for testing the strength of cancellous bone and tested method effects on cortical bone in the ovariectomized rat 

    E-Print Network [OSTI]

    Ruhmann, Sean Phillip

    1998-01-01T23:59:59.000Z

    In this study, two mechanical testing procedures were developed to test the strength of cancellous bone from the proximal tibia of the rat, the "punch method" and the "whole slice method". These were used to quantify the effect of ovariectomy on rat...

  14. A Novel Method for the Evaluation of Mechanical Properties of Cancellous Bone in the Rat Distal Femur 

    E-Print Network [OSTI]

    Lucas, Matthew W.

    2010-01-14T23:59:59.000Z

    .................................................................................................................. 35 3.7.1 Analysis of Mechanical Testing Data .............................................................. 35 3.7.2 Material Properties ........................................................................................... 37 3.7.3 Core....2 Osteoporosis and the Ovariectomized Rat Model .................................................... 5 2.3 Mechanical Testing of Cancellous Bone in Rats ..................................................... 5 2.3.1 Femoral Neck Testing...

  15. Characterization of the Bone Loss and Recovery Response at the Distal Femur Metaphysis of the Adult Male Hindlimb Unloaded Rat 

    E-Print Network [OSTI]

    Davis, Joshua Morgan

    2012-02-14T23:59:59.000Z

    Metaphysis of the Rat ....................................................................... 10 2.4 Mechanical Testing Methods for Rat Distal Femur Metaphysis ............................ 13 2.5 Reduced Platen Compression Mechanical Testing... ........................................................... 27 3.5 RPC Mechanical Testing and Analysis .................................................................... 30 3.6 Data Analysis .......................................................................................................... 32 4...

  16. Failure to find aversive marking of toxic foods by Norway rats BENNETT G. GALEF, JR, SHANNON PRETTY & ELAINE E. WHISKIN

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    Failure to find aversive marking of toxic foods by Norway rats BENNETT G. GALEF, JR, SHANNON PRETTY, not where or what they avoid eating. We discuss possible ultimate explanations for this failure of naive a rat dam is eating may enter her amni- otic fluid, and fetal exposure to such cues may enhance pups

  17. Methods for testing the strength of cancellous bone and tested method effects on cortical bone in the ovariectomized rat

    E-Print Network [OSTI]

    Ruhmann, Sean Phillip

    1998-01-01T23:59:59.000Z

    of the effect of two testing methods, torsion and three-point bending, on the mechanical strength of the rat femur and the changes in strength due to ovariectomy. From these tests, little change in cortical bone properties for the OVX rats compared to the Sham...

  18. The effects of exercise and dietary fat on calcium, magnesium, iron, and zinc on selected tissues in rats

    E-Print Network [OSTI]

    Nguyen, Thuy Huong

    1989-01-01T23:59:59.000Z

    and had a 12-hour photoperiod. Cages were lined with woodchip bedding, and stainless steel feeders were used. Design Following a three-day acclimation period, during which rats were fed the control diet, the rats were weighed and randomly assigned...

  19. Oxytocin receptors in the nucleus accumbens shell are involved in the consolidation of maternal memory in postpartum rats

    E-Print Network [OSTI]

    Sokolowski, Marla

    memory. In Experiment 1, postpartum female rats given 1 hour of maternal experience were infused, postpartum female rats were infused with either a high or low dose of OT into the NA shell after a 15-minute no significant differences between the females infused with OT and females treated with a vehicle infused

  20. Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    treatment in post- myocardial infarction failing heart rats Christophe ADAMY1,2,9 , Paul MULDER3,4,9 , Lara-MI failing heart rat Key words: chronic heart failure; glutathione; N-acetylcysteine; neutral, we showed that the left ventricle (LV) of human failing heart was depleted in total glutathione by 54

  1. Dual constrictor and dilator actions of ETB receptors in the rat renal microcirculation: interactions with ETA receptors

    E-Print Network [OSTI]

    Just, Armin

    Dual constrictor and dilator actions of ETB receptors in the rat renal microcirculation, and William J. Arendshorst. Dual constrictor and dilator actions of ETB receptors in the rat renal the combination of vasoconstrictor ETA and ETB receptors on smooth muscle cells and vasodilator ETB receptors

  2. The effect of alcohol on the bone growth spurt of rats at a time equivalent to adolescent females 

    E-Print Network [OSTI]

    Chaffin, Catherine Lee

    1997-01-01T23:59:59.000Z

    The objective of this study is to determine the effect of long-term alcohol consumption on the growth spurt in adolescent rats. Female Sprague-Dawley rats were fed one of three diets (alcohol, pair-fed or chow) for 3 months. ...

  3. Extracellular calcium sensing in rat aortic vascular smooth muscle cells

    SciTech Connect (OSTI)

    Smajilovic, Sanela [Laboratory of Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet (Denmark); Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen (Denmark); Hansen, Jakob Lerche [Laboratory of Molecular and Cellular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet (Denmark); Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen (Denmark); Christoffersen, Tue E.H. [Laboratory of Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet (Denmark); Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen (Denmark)] (and others)

    2006-10-06T23:59:59.000Z

    Extracellular calcium (Ca2+o) can act as a first messenger in many cell types through a G protein-coupled receptor, calcium-sensing receptor (CaR). It is still debated whether the CaR is expressed in vascular smooth muscle cells (VSMCs). Here, we report the expression of CaR mRNA and protein in rat aortic VSMCs and show that Ca2+o stimulates proliferation of the cells. The effects of Ca2+o were attenuated by pre-treatment with MAPK kinase 1 (MEK1) inhibitor, as well as an allosteric modulator, NPS 2390. Furthermore, stimulation of the VSMCs with Ca2+o-induced phosphorylation of ERK1/2, but surprisingly did not cause inositol phosphate accumulation. We were not able to conclusively state that the CaR mediates Ca2+o-induced cell proliferation. Rather, an additional calcium-sensing mechanism may exist. Our findings may be of importance with regard to atherosclerosis, an inflammatory disease characterized by abnormal proliferation of VSMCs and high local levels of calcium.

  4. Cardiovascular changes in unanesthetized and ketamine-anesthetized Sprague-Dawley rats exposed to 2. 8-GHz radiofrequency radiation

    SciTech Connect (OSTI)

    Jauchem, J.R.; Frei, M.R. (United States Air Force School of Aerospace Medicine, Brooks Air Force Base, TX (USA))

    1991-01-01T23:59:59.000Z

    Sprague-Dawley rats were exposed to 2.8-GHz radiofrequency radiation, first while unanesthetized and then while anesthetized with ketamine (150 mg/kg.I.M.). Irradiation at a power density of 60 mW/cm2 (whole-body average specific absorption rate of approximately 14 W/kg) was conducted for sufficient duration to increase colonic temperature from 38.5 to 39.5 degrees C. The time required for the temperature increase was significantly longer in the anesthetized state. During irradiation, heart rate increased significantly both with and without anesthesia, while mean arterial blood pressure increased only when the rats were unanesthetized. The heart rate increase in the anesthetized state contrasts with a lack of change in a previous study of Fischer rats. This difference between anesthetized Sprague-Dawley and Fischer rats should be considered when comparing cardiovascular data obtained from these two strains of rats.

  5. Application of synchrotron radiation computed microtomography for quantification of bone microstructure in human and rat bones

    SciTech Connect (OSTI)

    Parreiras Nogueira, Liebert; Barroso, Regina Cely; Pereira de Almeida, Andre; Braz, Delson; Almeida, Carlos Eduardo de; Borba de Andrade, Cherley; Tromba, Giuliana [Nuclear Instrumentation Laboratory / COPPE / UFRJ, P.O. Box 68509, 21945-970, Rio de Janeiro (Brazil); Physics Institute / State University of Rio de Janeiro, 20550-900, Rio de Janeiro (Brazil); Nuclear Instrumentation Laboratory / COPPE / UFRJ, P.O. Box 68509, 21945-970, Rio de Janeiro (Brazil); Laboratory of Radiological Sciences / State University of Rio de Janeiro, Rio de Janeiro (Brazil); Sincrotrone Trieste SCpA, Strada Statale S.S. 14 km 163.5, 34012 Basovizza, Trieste (Italy)

    2012-05-17T23:59:59.000Z

    This work aims to evaluate histomorphometric quantification by synchrotron radiation computed microto-mography in bones of human and rat specimens. Bones specimens are classified as normal and pathological (for human samples) and irradiated and non-irradiated samples (for rat ones). Human bones are specimens which were affected by some injury, or not. Rat bones are specimens which were irradiated, simulating radiotherapy procedures, or not. Images were obtained on SYRMEP beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. The system generated 14 {mu}m tomographic images. The quantification of bone structures were performed directly by the 3D rendered images using a home-made software. Resolution yielded was excellent what facilitate quantification of bone microstructures.

  6. Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease

    SciTech Connect (OSTI)

    Wolff, J.A.; Fisher, L.J.; Xu, L.; Jinnah, H.A.; Rosenberg, M.B.; Shimohama, S.; Gage, F.H. (Univ. of California School of Medicine, La Jolla (USA)); Langlais, P.J. (Univ. of California School of Medicine, La Jolla (USA) School of Medicine and Veterans Administration Medical Center, La Jolla (USA) San Diego State Univ., CA (USA)); Iuvone, P.M. (Emory Univ., Atlanta, GA (USA)); O'Malley, K.L. (Washington Univ. School of Medicine, St. Louis, MO (USA))

    1989-11-01T23:59:59.000Z

    Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell cultured medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.

  7. The urinary excretion of unchanged d-amphetamine by rats at ground level and at altitude

    E-Print Network [OSTI]

    Harwell, James Franklin

    1968-01-01T23:59:59.000Z

    divided into 3 equal groups. One group received ammonium chloride to acidify the urine, a second group received sodium bicarbonate to alkalinize the urine, and the third group received distilled water. Immediately after receiving the pretreatment... solutions each rat was in3ected subcutaneously with d-amphetamine sulfate at the rate of 3 mg/kg body weight. Each rat was put into a metabolic cage and a 4 hour urine sample was collected at ground level. After a rest period of at least 48 hours...

  8. Chronic cellular responses of rat skin to 13 Mev proton irradiation

    E-Print Network [OSTI]

    Hinkle, Donald King

    1966-01-01T23:59:59.000Z

    CHRONIC CELLULAR RESPONSES OF RAT SKIN TO 13 MEV PROTON IRRADIATION A Thesis by DONALD KING HINKLE, D. V. M. Submitted to the Graduate College of the Texas AErM University in partial fulfillment of the requirements for the degree of MASTER... OF SCIENCE August 1966 Major Subject: Laboratory Animal Medicine CHRONIC CELLULAR RESPONSES OF RAT SKIN TO 13 MEV PROTON IRRADIATION A Thesis by DONALD KING HINKLE, D. V. M. Submitted to the Graduate College of the Texas ARM University in partial...

  9. Effect of exercise training and dietary fat on rat adipose tissue lipolysis and morphology

    E-Print Network [OSTI]

    Neale, Sonia Barstad

    1989-01-01T23:59:59.000Z

    . , Colorado State University Co-Chairs of Advisory Committee: Dr. Karen S. Kubena Dr. Stephen B. Smith The effects of exercise training and dietary fat on lipolysis rate and adipocyte morphology of epididymal fat pads were studied. Male rats (5 wk old...-free. The diets were initiated when the rats were 4 wk old. Body weight (p&0. 001), fat pad weight (p&0. 001), and adipocyte diameter (p&0. 05) were significantly less in the exercised group than in the sedentary group. Adipocyte number was not significantly...

  10. Toxicity of polychlorinated diphenyl ethers in Hydra attenuata and in rat whole embryo culture

    E-Print Network [OSTI]

    Becker, Marion Carol

    1991-01-01T23:59:59.000Z

    TOXICITY OF POLYCHLORINATED DIPHENYL ETHERS IN HYDRA A?TENUATA AND IN RAT WHOLE EMBRYO CULTURE A Thesis by MARION CAROL BECKER Submitted to the Office of Graduate Studies of Texas A8cM University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE May 1991 Major Subject: Toxicology TOXICITY OF POLYCHLORINATED DIPHENYL ETHERS IN HYDRA A1TENUATA AND IN RAT WHOLE EMBRYO CULTURE by MARION CAROL BECKER Approved as to style and content by: Stephen H. S (Ca...

  11. Toxicity of polychlorinated diphenyl ethers in Hydra attenuata and in rat whole embryo culture 

    E-Print Network [OSTI]

    Becker, Marion Carol

    1991-01-01T23:59:59.000Z

    TOXICITY OF POLYCHLORINATED DIPHENYL ETHERS IN HYDRA A?TENUATA AND IN RAT WHOLE EMBRYO CULTURE A Thesis by MARION CAROL BECKER Submitted to the Office of Graduate Studies of Texas A8cM University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE May 1991 Major Subject: Toxicology TOXICITY OF POLYCHLORINATED DIPHENYL ETHERS IN HYDRA A1TENUATA AND IN RAT WHOLE EMBRYO CULTURE by MARION CAROL BECKER Approved as to style and content by: Stephen H. S (Ca...

  12. Testicular damage and regeneration in rats following low-level gamma irradiation

    E-Print Network [OSTI]

    Maxwell, Wesley Howard

    1974-01-01T23:59:59.000Z

    of these animals were examined using several recognized histological procedures. The sequential damage and recovezy of the germinal epithelium was s'tudied for S4 days post-irradiation. The lower dose rate (7 R/hr) resulted in temporari. ly arresting meiotic...- ation of the germinal epithelium of rats irradiated with 7 R/hr was seen by 84 days post-irradiation. However, this same time iv. was not sufficient for total recovery of the rats irradiated to a total dose of 1000 R, at 14 R/hr. ACKNOWLEDGEMENT...

  13. Magnesium and pyridoxine intake and mineral content of selected tissues and physical development in rats 

    E-Print Network [OSTI]

    Edgar, Susan Elaine

    1986-01-01T23:59:59.000Z

    lower f eed intake s than did rats from other dietary treatments. During lactation, dai ly feed consumpt ion was lower in an ima1 s depr ived of magnesium. Approximately 24 hr postpartum, in dams who consumed a magnesium-deficient diet, the heart... and kidney contained significantly more calcium, 150'% and 300% respectively. During lactation, mild magnesium restriction resulted in increased weight loss by dams and decreased weight gain by pupa. In the of f spring of rats dep1 et ed o f magnesium...

  14. 5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats

    E-Print Network [OSTI]

    Wurtman, Richard

    Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA c Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA Received 22 January 2003 deprivation and a standardized stress (tail pinch), and on plasma 5-HTP levels in humans. In rats, 5-HTP (3

  15. High-resolution imaging of vessels in the isolated rat brain M. F. Valverde Salzmann1

    E-Print Network [OSTI]

    for the distribution of vessels in the rat brain. Angiography is able to use the blood flow in the brain of the living into a test tube filled with fluorocarbon fluid for susceptibility matching. MR Images were acquired at a horizontal 16.4 T scanner with a homemade microstrip volume coil, using gradient echo sequences

  16. Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which

  17. Polycyclic Aromatic Hydrocarbons Present in Cigarette Smoke Cause Bone Loss in an Ovariectomized Rat Model

    E-Print Network [OSTI]

    Waldman, Stephen D.

    of epidemiological studies have suggested that cigarette smoking is a risk factor for osteoporosis. Benzo- (a and fragility seen in smoking-related osteoporosis. In this study four groups of 9-month-old Sprague-Dawley rats; Ovariectomy (ovx); Estrogen; Osteoporosis. Introduction Epidemiological studies have focused

  18. Some histological manifestations in the vitamin B b12 sdeficient newborn rat

    E-Print Network [OSTI]

    Jones, Carroll Christian

    1954-01-01T23:59:59.000Z

    &dna;, . and spieen 1n duced by a materw?l v1tamin Rl? deficiency 1? the ?suborn albino rat, 4 secondary porno a Ips to co"lpga e the '?Jot'. , +t dif faro loca bot'i&en the hearts, livorn and '. . Tdnevs of novborn offspring oi' v'to oin Q2 deficient mothers...

  19. Imaging Oxygen Consumption in Forepaw Somatosensory Stimulation in Rats Under Isoflurane Anesthesia

    E-Print Network [OSTI]

    Duong, Timothy Q.

    Imaging Oxygen Consumption in Forepaw Somatosensory Stimulation in Rats Under Isoflurane Anesthesia consumption, indicative of partial coupling of CBF and CMRO2. This study describes a useful forepaw. Following Fox et al.'s (2) initial study with positron emission tomography (PET), stimulus- evoked CMRO2

  20. Diffuse Optical Tomography of Cerebral Blood Flow, Oxygenation, and Metabolism in Rat During Focal Ischemia

    E-Print Network [OSTI]

    Yodh, Arjun G.

    of oxygen consumption (CMRO2). Temporary (60-minute) MCAO was performed on five rats. Ischemic changes--Cerebral metabolic rate of oxygen consumption. Diffuse optical tomography (DOT) of the brain is an attractive new complementary to those of magnetic resonance imaging (MRI) and positron emission tomog- raphy (PET), and holds

  1. anticoagulant-susceptible norway rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    anticoagulant-susceptible norway rats First Page Previous Page 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 Assessing the...

  2. Effects of Dietary Lead and Cholesterol Supplementation on Hemolysis in the Sprague-Dawley Rat1

    E-Print Network [OSTI]

    Moore, Paul A.

    Effects of Dietary Lead and Cholesterol Supplementation on Hemolysis in the Sprague-Dawley Rat1 has been observed in a number of organisms exposed to lead. Previous investigators have proposed into the serum. Lead-exposed fish have displayed depressed serum cholesterol and elevated serum protein

  3. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-11-01T23:59:59.000Z

    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

  4. JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR INCREASED EATING IN RATS DEPRIVED OF RUNNING'

    E-Print Network [OSTI]

    Premack, David

    JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR INCREASED EATING IN RATS DEPRIVED OF RUNNING of the wheel. When this outcome is coupled with the positive relation between food deprivation and running-and food depriva- tion is seen as a loss of eating rather than as a physiological state

  5. Dim Light at Night Increases Immune Function in Nile Grass Rats, a Diurnal Rodent

    E-Print Network [OSTI]

    Nelson, Randy J.

    Dim Light at Night Increases Immune Function in Nile Grass Rats, a Diurnal Rodent Laura K. Fonken lighting during the 20th century, human and nonhuman animals became exposed to high levels of light significant implications for certain ecological niches because of the important influence light exerts

  6. Effect of fermentable carbohydrates on volatile fatty acids, ammonia and mineral absorption in the rat caecum

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    intestine on caecal digestion and absorption have been studied in the rat. Even in diets lacking these carbo of the urea nitrogen was used in bacterial protein synthesis. Arteriovenous differences in the caecum showed, for which hydrolysing enzymes are lacking or poorly efficient in the small i ntesti ne. These carbohydrates

  7. A Glucose BioFuel Cell Implanted in Rats Philippe Cinquin1

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    A Glucose BioFuel Cell Implanted in Rats Philippe Cinquin1 *, Chantal Gondran2 , Fabien Giroud2 powerful ones, Glucose BioFuel Cells (GBFCs), are based on enzymes electrically wired by redox mediators applications. Citation: Cinquin P, Gondran C, Giroud F, Mazabrard S, Pellissier A, et al. (2010) A Glucose BioFuel

  8. Inositol lipid metabolism in vasopressin stimulated hepatocytes from rats infused with tumor necrosis factor

    SciTech Connect (OSTI)

    Spitzer, J.A.; Rodriguez de Turco, E.B. (Louisiana State Univ. Medical Center, New Orleans (USA))

    1989-05-30T23:59:59.000Z

    We studied the effect of i.v. infusion of human recombinant tumor necrosis factor alpha (rHuTNF alpha, Cetus, 15 micrograms/100 g bw over 3 h) on vasopressin (VP)-stimulated {sup 32}P-inositol lipid turnover and the release of {sup 3}H-inositol phosphates in isolated rat hepatocytes. The early VP-induced decrease (within 30 s) in {sup 32}P-phosphatidylinositol 4-phosphate and {sup 32}P-phosphatidylinositol 4,5-bisphosphate labeling was significantly reduced (-40%) and at the same time the uptake of {sup 32}P into phosphatidic acid was 50% lower than in saline-infused (matched control) rats. Within 5 min of VP-stimulation, lower {sup 32}P phosphatidylinositol (-40%) and higher {sup 32}P-phosphatidic acid (+30%) labeling were observed in rHuTNF alpha-infused rats. Infusion of rHuTNF alpha also affected the VP-induced release of {sup 3}H-inositol phosphates. The accumulation of {sup 3}H-inositol-labeled water soluble products was decreased by 25% and 17% at 30 s and 10 min, respectively. These data show that rHuTNF alpha mimics early perturbations induced by Escherichia coli endotoxin infusion in VP-stimulated inositol lipid metabolism in rat hepatocytes.

  9. acid-challenged rat stomach: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    acid-challenged rat stomach First Page Previous Page 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 Activities of amino acid...

  10. ALZHEIMER'S AMYLOID-BETA PEPTIDE INHIBITS SODIUM/CALCIUM EXCHANGE MEASURED IN RAT AND

    E-Print Network [OSTI]

    ALZHEIMER'S AMYLOID-BETA PEPTIDE INHIBITS SODIUM/CALCIUM EXCHANGE MEASURED IN RAT AND HUMAN BRAIN-beta1­40 (A 1­40) and A 25­35 reduced vesicular Ca2+ content. Both peptides produced a maximal reduction in Ca2+ content of approximately 50%. The peptides reduced Ca2+ content with similar potency and half

  11. UPTAKE OF [3H]-COLCHICINE INTO BRAIN AND LIVER OF MOUSE, RAT, AND CHICK

    E-Print Network [OSTI]

    Bennett, Edward L.

    2010-01-01T23:59:59.000Z

    by M.R. Rosenzweig and E.l. Bennett, Cambridge, MA: The MITJ.F. , D.W. landry, E.l. Bennett, and M.E. Jarvik. long-termRAT,AND CHICK Edward L. Bennett, Marie Hebert Alberti, and

  12. Imaging of Alcohol-Induced Dopamine Release in Rats: Preliminary Findings With

    E-Print Network [OSTI]

    Morris, Evan D,

    . Normandin: Yale PET Center, P.O. Box 208048, New Haven, CT 06520 *Correspondence to: Evan D. Morris, YaleImaging of Alcohol-Induced Dopamine Release in Rats: Preliminary Findings With [11 C]Raclopride PET positron emission tomography (PET). PET images were acquired in 44 alcohol-nai¨ve male Wistar and alcohol

  13. fMRI visualisation of transient activations in the rat olfactory bulb using short odour stimulations

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    fMRI visualisation of transient activations in the rat olfactory bulb using short odour in the olfactory bulb OB displays both spatial and temporal organization. The difficulty when assessing spatio of the olfactory bulb (OB). Hence, in this structure, the identity of odorants is associated with a unique spatial

  14. Increased severity of acute Trypanosoma brucei brucei infection in rats with alloxan-induced diabetes

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    -induced diabetes Ikechukwu Onyebuchi Igbokwea Sani Isaa Umma Kalsum Aliyub Hajja Gana Hamzab Tobias Egbe made diabetic by treatment with alloxan monohydrate (10 % solution, 100 mg/kg body weight). Ten diabetic and ten non-diabetic rats were intraperitoneally infected with the same infective doses

  15. Grid Cells and Theta as Oscillatory Interference: Electrophysiological Data From Freely Moving Rats

    E-Print Network [OSTI]

    Burgess, Neil

    Grid Cells and Theta as Oscillatory Interference: Electrophysiological Data From Freely Moving Rats, regular firing patterns by medial entorhinal cortical (mEC) grid cells in terms of the interference specific relationships between the intrinsic firing frequency and spa- tial scale of grid cell firing

  16. Regulation of Endothelial Phenotype in Rat Soleus Muscle Feed Arteries: Influence of Aging and Exercise Training 

    E-Print Network [OSTI]

    Trott, Daniel Wayne

    2012-02-14T23:59:59.000Z

    (AUC) was calculated using the trapezoidal method. Body composition and adiposity. The body mass of the rats was measured to the nearest 0.01 g and body composition was determined using dual-energy x-ray absorptiometry (Hologic QDR-1000/w DEXA...

  17. How Enrichment Affects Exploration Trade-Offs in Rats: Implications for Welfare and Well-Being

    E-Print Network [OSTI]

    Champagne, Frances A.

    How Enrichment Affects Exploration Trade-Offs in Rats: Implications for Welfare and Well-being and animal welfare, we designed a novel test of exploration behavior. Environmentally and socially enriched, 20 animals remained in enriched housing (enrichment-maintenance) while 40 animals were re

  18. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    SciTech Connect (OSTI)

    Feng, Shan-Li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)] [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Sun, Ming-Rui [Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001 (China)] [Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001 (China); Li, Ting-Ting; Yin, Xin [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)] [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Xu, Chang-Qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China)] [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Sun, Yi-Hua, E-mail: syh200415@126.com [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)] [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)

    2011-03-11T23:59:59.000Z

    Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3} increased the expression of TRPC3 mRNA and protein, which were reversed by SKF96365 but not by inhibitors of the L-type channels and the Na{sup +}/Ca{sup 2+} exchangers. However, GdCl{sub 3} had no obvious effect on the expression of TRPC1 protein. These results suggested that CaR stimulation induced activation of TRP channels and promoted the expression of TRPC3, but not TRPC1, that sustained the increased [Ca{sup 2+}]{sub i}.

  19. Plasma kinetics, tissue distribution, and cerebrocortical sources of reverse triiodothyronine in the rat

    SciTech Connect (OSTI)

    Obregon, M.J.; Larsen, P.R.; Silva, J.E.

    1985-06-01T23:59:59.000Z

    Studies in vitro have shown that rT3 is a potent and competitive inhibitor of T4 5'-deiodination (5'D). Recent studies in vivo have shown that cerebrocortical (Cx) T4 5'D-type II (5'D-II) activity (propylthiouracil (PTU) insensitive pathway), is reduced by T4 and rT3, the latter being more potent than T3 in Cx 5'D-II suppression. Some other reports had described rT3 production in rat brain as a very active pathway of thyroid hormone metabolism. To examine the possibility that rT3 plays a physiological role in regulating Cx 5'D-II, we have explored rT3 plasma kinetics, plasma to tissue exchange, and uptake by tissues in the rat, as well as the metabolic routes of degradation and the sources of rT3 in cerebral cortex (Cx). Plasma and tissue levels were assessed with tracer (/sup 125/I)rT3. Two main compartments were defined by plasma disappearance curves in euthyroid rats (K/sub 1/ = -6.2 h-1 and K/sub 2/ = -0.75 h-1). In Cx of euthyroid rats, (/sup 125/I)rT3 peaked 10 min after iv injection, tissue to plasma ratio being 0.016 +/- 0.004 (SE). In thyroidectomized rats, plasma and tissue (/sup 125/I)rT3 concentrations were higher than in euthyroid rats, except for the Cx that did not change. PTU caused further increases in all the tissues studied, except for the Cx and the pituitaries of thyroidectomized rats. From the effect of blocking 5'D-I with PTU or reducing its activity by making the animals hypothyroid, we concluded that 5'D-I accounts for most of the rT3 clearance from plasma. In contrast, in Cx and pituitary the levels of rT3 seem largely affected by 5'D-II activity. Since the latter results suggest that plasma rT3 does not play a major role in determining rT3 levels in these tissues, we explored the sources of rT3 in Cx using (/sup 125/I)T4. The (/sup 125/I)rT3 (T4) to (/sup 125/I)T4 ratio remained constant at 0.03 from 1 up to 5 h after injection of (/sup 125/I)T4.

  20. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    SciTech Connect (OSTI)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)] [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)] [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    2013-02-01T23:59:59.000Z

    Highlights: ? Propofol, as a model anesthetic drug, induced whole body insulin resistance. ? Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ? Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ? Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  1. Demonstration of lactogenic receptors in rat endocrine pancreases by quantitative autoradiography

    SciTech Connect (OSTI)

    Polak, M.; Scharfmann, R.; Ban, E.; Haour, F.; Postel-Vinay, M.C.; Czernichow, P. (National Institute of Health and Medical Research, Paris (France))

    1990-09-01T23:59:59.000Z

    A direct effect of growth hormone and/or prolactin on the growth of the pancreatic beta-cell has been proposed. This study assessed the presence of human growth hormone (hGH)-binding sites in male adult rat endocrine pancreas via quantitative autoradiography. The binding of 125I-labeled hGH was evaluated by receptor autoradiography on frozen-pancreas cryostat cut sections. The sections were incubated with 125I-hGH (10(-10) M) for 75 min at room temperature, and nonspecific binding was determined in the presence of excess native hGH (5 X 10(-7) M). The specificity of the binding was assessed in competition experiments with bovine GH and ovine prolactin. The autoradiograms were quantified with a computer-assisted image-processing system. The sections were then stained to visualize the endocrine islets. Nondiabetic control and streptozocin (STZ)-injected rats were used. Our results show that (1) there is specific binding of iodinated hGH in small areas of the pancreas, which appear as the Langerhans islets when the autoradiogram and the stained sections are superimposed; (2) the specificity of hGH binding in rat islets is lactogenic; (3) the density of the hGH-binding sites in the endocrine pancreas is estimated at 4.8 fmol/mg protein, with IC50 ranging from 0.98 to 2.50 nM; and (4) binding sites may be present on the beta-cell, because specific binding disappears in STZ-injected rats. In conclusion, by use of a quantitative autoradiographic technique, we provide evidence for the presence of lactogenic receptors on rat beta-cells.

  2. The role of constrictor prostanoids in the development of aortic coarctation-induced hypertension in male and female rats

    E-Print Network [OSTI]

    Baltzer, Wendy Irene

    2005-02-17T23:59:59.000Z

    function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent...

  3. Inactivation of the insular cortex increases anxiety-like behavior in rats : relevance to drug abuse and interoception

    E-Print Network [OSTI]

    Wolfe, Monica

    2011-01-01T23:59:59.000Z

    µl of lidocaine (or aCSF) was infused over the period of twocompared to vehicle-infused controls. It is important toplus maze. Specifically, rats infused with lidocaine showed

  4. Redescription of the enigmatic long-tailed rat Sigmodontomys aphrastus (Cricetidae: Sigmodontinae) with comments on taxonomy and natural history

    E-Print Network [OSTI]

    McCain, Christy M.; Timm, Robert M.; Weksler, Marcelo

    2007-08-01T23:59:59.000Z

    Sigmodontomys aphrastus, the long-tailed rat, is an exceedingly rare rodent species from montane regions of Central and South America of which very little is known ecologically or systematically. It has been variously ...

  5. Periadolescent oral manganese exposure affects conditioned place preference by cocaine and conditioned place aversion by lithium chloride in rats

    E-Print Network [OSTI]

    Lee, Samuel Ming Hin

    2013-02-22T23:59:59.000Z

    Manganese neurotoxicity compromises basal ganglia functions that could affect the limbic system and drug sensitivity. Male rats were orally exposed to manganese chloride (0, 100, 200 mg/kg/day Mn) for 15 days starting at postnatal day (PND) 28...

  6. Effect of dietary protein quality on fractional rates of muscle protein synthesis and catabolism in the rat

    E-Print Network [OSTI]

    Roeder, Richard Anthony

    1979-01-01T23:59:59.000Z

    EFFECT OF DIETARY PROTEIN QUALITY ON FRACTIONAL RATES OF MUSCLE PROTEIN SYNTHESIS AND CATABOLISM IN THE RAT A Thesis by RICHARD ANTHONY ROEDER Submitted to the Graduate College of Texas A8cM University in partial fulfillment... of the requirement for the degree of MASTER OF SCIENCE August 1979 Major Subject: Animal Nutrition EFFECT OF DIETARY PROTEIN QUALITY ON FRACTIONAL RATES OF MUSCLE PROTEIN SYNTHESIS AND CATABOLISM IN THE RAT A Thesis by RICHARD ANTHONY ROEDER Approved...

  7. A radiographic analysis of the effect of dietary fiber on transit time through the rat large intestine 

    E-Print Network [OSTI]

    Meacher, Mary Melanie

    1986-01-01T23:59:59.000Z

    A RADIOGRAPHIC ANALYSIS OF THE EFFECT OF DIETARY FIBER ON TRANSIT TIME THROUGH THE RAT LARGE INTESTINE A Thesis by MARY MELANIE MEACHER Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE August 1986 Major Subject. ' Nutrition A RADIOGRAPHIC ANALYSIS OF THE EFFECT OF DIETARY FIBER ON TRANSIT TIME THROUGH THB RAT LARGE INTESTINE A Thesis by MARY MELANIE MEACHER Approved as to style and content by...

  8. Effects of electrical brain stimulation on the temperature of interscapular brown adipose tissue in the adult rat

    E-Print Network [OSTI]

    Freeman, Patricia Hilliard

    1985-01-01T23:59:59.000Z

    EFFECTS OF ELECTRICAL BRAIN STIMULATI ON ON THE TEMPERATURE OF INTERSCAPULAR BROWN ADIPOSE TISSUE IN'THE ADULT RAT A Thesis by PATRICIA HILL IARD FREEMAN Submitted to the Graduate College of Texas ARM University in partial fulfillment... of the requirement for the degree of MASTER OF SCIENCE May 1985 Major Subject: Psychology EFFECTS OF ELECTRICAL BRAIN STIMULATION ON THE TEMPERATURE OF BROWN ADIPOSE TISSUE IN THE ADULT RAT A Thesis by PATRICIA HILL IARD FREEMAN Approved as to style...

  9. Opiate activity in the rat prefrontal cortex: modulation of ventral tegmental area dopaminergic influence on cortical efferent neurons

    E-Print Network [OSTI]

    St. Mary, John Steven

    1986-01-01T23:59:59.000Z

    OPIATE ACTIVITY IN THE RAT PREFRONTAL CORTEX: MODULATION OF VENTRAL TEGMENTAL AREA DOPAMINERGIC INFLUENCE ON CORTICAL EFFERENT NEURONS A Thesis by JOHN STEVEN ST. MARY Submitted to the Graduate College of Texas A&M University in partial... Thesis by JOHN STEVEN ST. MARY Approved as to style and content by: Steven Peterson (Chairman of Committee) Robert Matthews (- '" j'pj") Ger a ((~Fe g (Mem er) George Chion (Member) December 1986 ABSTRACT Opiate Activity in the Rat...

  10. An investigation of the potentiating effects of ethanol on a chronic exposure of rats to 1,1,1-trichloroethane

    E-Print Network [OSTI]

    Walker, DeWayne Harold

    1973-01-01T23:59:59.000Z

    AN INVESTIGATION OF THE POTENTIATING EFFECTS OF ETHANOL ON A CHRONIC EXPOSURE OF RATS TO 1, 1&I-TRICHLOROETHANE A Thesis by DEWAYNE HAROLD WALKER Submitted to the Graduate College of Texas AFM University in partial fulfillment... of the requirement for the degree of MASTER OF SCIENCE August 1973 Major Subject: Laboratory Animal Medicine AN INVESTIGATION OF THE POTENTIATING EFFECTS OF ETHANOL ON A CHRONIC EXPOSURE OF RATS TQ 1&1, 1-TRICHLOROETHANE A Thesis by DENAYNE HAROLD WALKER...

  11. Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs

    E-Print Network [OSTI]

    2013-01-01T23:59:59.000Z

    neonatal and adult rat lungs. Particle and Fibre Toxicologysensitivity of the postnatal lung to environmental insultsdevelopment of the human lung. Prog Clin Biol Res 1983, 140:

  12. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-? expression

    SciTech Connect (OSTI)

    Siddiqui, Shabeena [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India); Ahsan, Haseeb [Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi 110025 (India); Khan, Mohammad Rashid [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India); Siddiqui, Waseem A., E-mail: wasiddiqui01@gmail.com [Department of Biochemistry, Lipid Metabolism Laboratory, Jamia Hamdard (Hamdard University), New Delhi 110062 (India)

    2013-12-01T23:59:59.000Z

    Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-?, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-?, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-? (TGF-?) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-? to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. - Highlights: • The nephroprotective effect of TRF in type-2 diabetic rats was investigated. • Treatment with TRF improved glycemic status, lipid profile and renal functions in rats. • TRF down-regulated the expression of TGF-?, fibronectin and collagen in rats' kidney. • TRF ameliorated nephropathy by hypoglycemic, hypolipidemic and antioxidant activity. • Tocotrienols modulate the expression of TGF-? in DN in type-2 diabetic rats.

  13. Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

    SciTech Connect (OSTI)

    Vickers, Alison E.M., E-mail: vickers_alison@allergan.com [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States); Heale, Jason; Sinclair, John R.; Morris, Stephen; Rowe, Josh M. [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States)] [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States); Fisher, Robyn L. [Vitron Inc., Tucson, AZ (United States)] [Vitron Inc., Tucson, AZ (United States)

    2012-04-01T23:59:59.000Z

    Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ? 10 ?M MMI. Thyroid from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (? 15–84 ?M), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (? 10 ?M) and PTU (100 ?M). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ? 2-fold) and only at higher MMI concentrations (? 1500 ?M, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ? Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ? TPO inhibition by MMI or PTU altered hormone synthesis and release genes. ? Rat thyroid was more sensitive to the drug effects than human tissue.

  14. The effect of exercise and dietary fiber on the rate of gastrointestinal transit in the rat

    E-Print Network [OSTI]

    Dorr, Jerri Suzanne

    1987-01-01T23:59:59.000Z

    with cancer of the rectum. These data were compared to the life-time occupational physical exercise of 1, 43l patients with non-neoplastic, nondigestive diseases. Results indicate an increasing risk of colon cancer with increasing work years, proportion... cancer incidence, Several studies have reported changes in body composition that occur as a result of exercise (59, 67, 68). We found that the exercised rats weighed less than the non- exercised controls after they had been swimming for three weeks...

  15. Some histological manifestations in the early postnatal vitamin B?? deficient albino rat

    E-Print Network [OSTI]

    Johnson, Elmer Marshall

    1955-01-01T23:59:59.000Z

    rats were slightly smeller in sine. Ilistologically the cortex was reduced in thickness ?nd therefore in total volume There was a considerable increase in intercellular space which was often filled with connective tissue and sometimes blood..., The renal corpus- cles were characterised by an increase in the space between Bowman's capsule and the glomerulus (I~'ig, 7). The loops of Henle in the medul- lary region showed reduoed lumina. The convoluted tubules (pr obably due to the fatty...

  16. The Relation of Lime and Phosphoric Acid to the Growth and Bone Development of White Rats.

    E-Print Network [OSTI]

    Blum, J. K. (Joseph Kelly)

    1931-01-01T23:59:59.000Z

    LIBRARY, A & M COLLEGE. CAMPUS. TEXAS AGRICULTURAL EXPERIMENT STATION A. B. CONNER, DIRECTOR College Station, Brazos County, Texas BULLETIN NO. 441 DECEMBER, 1931 DIVISION OF CHEMISTRY The Relation of Lime and Phosphoric Acid to the Growth... and Bone Development of White Rats 2 ., .t .I* .-. /.' AGRICULTURAL AND MECHANICAL COLLEGE OF TEXAS--. .. T. 0. WALTON, President ..- STATION STAFF+ ADMINISTRATION: VETERINARY SCIENCE: A B. CONNER M S. Director *M. FRANCIS, D. V. M., Chief. R: E...

  17. The gestation-dependent variation in aflatoxin B? activation by rat liver microsomes 

    E-Print Network [OSTI]

    Wall, Florence Elizabeth

    1989-01-01T23:59:59.000Z

    Microsomes. (May t 989) Florence Elizabeth Wall, B. A. , Trinity University Chair of Advisory Committee: Dr. T. Rick Irvin The metabolic capacity of maternal rat liver microsomes to bioactivate a model teratogen, AFBt, was examined through a series... BCA (bicinchoninic acid) protein assay. . . . . . . . . . Microsomal metabolism assay . DNA isolation . Liquid scintillation counting . Sa/mone//a /mammalian-microsome mutagenicity assay Postimplantation embryo culture assay . . RESULTS Page...

  18. Effects of chronic cadmium exposure on the conditioned reinforcing properties of morphine and fentanyl in rats

    E-Print Network [OSTI]

    Miller, Dennis K

    1997-01-01T23:59:59.000Z

    &M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved as to style and content by: ck R. Nation (C ir of Committee) Gerald D. Frye (Member) Paul J. Wellman (Member) Paul J. Wellman (Head of Department... the metal (Nation, Livermore, Bratton, & Schenk, 1996). A similar attenuation was shown with repeated cocaine exposure--the development of locomotor sensitization. Rats that received chronic cadmium exposure required more cocaine administration sessions...

  19. Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

    SciTech Connect (OSTI)

    Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

    2009-01-30T23:59:59.000Z

    Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

  20. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    SciTech Connect (OSTI)

    Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

    2014-01-01T23:59:59.000Z

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1?, IL-6, and TNF-?), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron increased the levels of IL-1?, IL-6 and TNF-? in lung tissues at high altitudes. • Trolox alleviated the iron-induced histological and biochemical changes to the lungs.

  1. Metabolism of the geometric isomers of phosphamidon in insects and rats

    E-Print Network [OSTI]

    Grabbe, Rolland Ralph

    1966-01-01T23:59:59.000Z

    Metabolism of the Geometric Isomers of Phosphamldon ln Insects and Rats, Nay 1955. Rolland R, Grabbe, B. S. , Iowa State Dnlverslty Directed by: Dr. Don L, Bull Abstract Phosphamldon (2-chloro 2 dlethylcarbamoyl I methylvlnyl dimethyl phosphate) ls a... with phosphamldon that was radlolabeled either with C at the methyl-vinyl and carbonyl carbon atoms or with P 32 Slightly more N deethyl phosphamldon (2 ohloro 2-ethylcarbamoyl I-methylvlnyl dimethyl phosphate) was formed ln Insects treated with cls...

  2. A study of the effect of restricted diets in the male albino rat 

    E-Print Network [OSTI]

    Griffin, Travis Barton

    1961-01-01T23:59:59.000Z

    26 Sections of the Testes Stained with Hematwylin and Eosin 30 CHAPTER l INT RODUCT ION During the past 30 years there has been rr, uch invssti~tion of the various effects of low caloric intake upon laboratory anirrals, This has come about... in decreased growth rats due to decreased food %take, it becomes necessary to differentiate between the various effects and thereby account for those due to caloric decrease. The problem is very coxrplex and cannot becozr. s completely solved until...

  3. Increased activity of tyrosine hydroxylase in the cerebellum of the x-irradiated dystonic rat

    SciTech Connect (OSTI)

    Dopico, A.M.; Rios, H.; Mayo, J.; Zieher, L.M. (Departamentos de Biologia Celular e Histologia y de Farmacologia y Toxicologia, Facultad de Medicina, Universidad de Buenos Aires, (Argentina))

    1990-08-01T23:59:59.000Z

    The exposure of the cephalic end of rats to repeated doses of x-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 {plus minus} 4 ng/CE and 2.8 {plus minus} 1.5 ng/CE, respectively) and x-irradiated rats (17.1 {plus minus} 1 ng/CE and 8.3 {plus minus} 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally x-irradiated animals when compared to age-matched controls (16.4 {plus minus} 1.4 vs 6.32 {plus minus} 0.6 nmol CO2/h/mg prot., p less than 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 {plus minus} 23.8 vs 408.2 {plus minus} 21.5 nmol CO2/h/CE, p less than 0.01 (controls and x-treated, respectively). These results suggest that x-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.

  4. The effect of stress on the pulsatile pattern of luteinizing hormone in the ovariectomized rat

    E-Print Network [OSTI]

    Farr, Kathryn Louise

    1982-01-01T23:59:59.000Z

    as a model. The first objective of this study was to develop a method to accurately monitor the pattern of pituitary LH release in the ovari- ectomized rat, Using this method the second objective was to deter- mine the influence of two types... is attached to the anterior pituitary qland by the pituitary stalk. Within the pituitary stalk rests the vascular pathway that transports LHRH to the anterior pituitary. This unique vascular network is termed the hypothalamic-hypophysea1 portal system. 13...

  5. Rat lymphoma cell bioassay for prolactin: observations on its use and comparison with radioimmunoassay

    SciTech Connect (OSTI)

    Dawson, D.M.; Sensui, N.; Haisenleder, D.H.; Gala, R.R.

    1982-12-27T23:59:59.000Z

    The rat Nb/sub 2/ node lymphoma cell bioassay (BA) for prolactin (PRL) was validated for use in our laboratories. During the course of this validation we observed that rat prolactin (NIAMDD-RP-1) stimulated cell division by as much as 16.5 fold over the range of 0.04 to 40.0 ng/ml at the end of 72 hours of incubation. We also observed a dose related increase in the size of the lymphoma cells. Prolactin concentrations in rat plasma, serum, anterior pituitary (AP) homogenates and milk were measured by both radioimmunoassay (RIA) and BA. In individual BA's there was parallelism between samples and standard; but when several dilutions of the same plasma and pituitary homogenates were assayed repeatedly, higher PRL levels were consistently observed for the more concentrated samples. At low or moderate levels of plasma PRL there was excellent agreement between RIA and BA; however, at high levels plasma PRL bioactivity exceeded radioimmunoactivity by a small, but significant, amount. A comparison of pituitary PRL concentrations measured by RIA and BA were in good agreement when homogenization was done at pH 10.6. However, when homogenization was done at pH 7.6, slightly but significantly more PRL was extracted when assayed by BA than when assayed by RIA.

  6. TRIGEMINAL UPTAKE AND CLEARANCE OF INHALED MANGANESECHLORIDE IN RATS AND MICE

    SciTech Connect (OSTI)

    Lewis, J; Bench, G; Myers, O; Tinner, B; Staines, W; Barr, E; Divine, K K; Barrington, W; Karlsson, J

    2003-12-09T23:59:59.000Z

    Inhaled manganese (Mn) can enter the olfactory bulbs via the olfactory epithelium, and can then be further transported trans-synaptically to deeper brain structures. In addition to olfactory neurons, the nasal cavity is innervated by the maxillary division of the trigeminal nerve that projects to the spinal trigeminal nucleus. Direct uptake and transport of inhaled metal particles in the trigeminal system has not been investigated previously. We studied the uptake, deposition, and clearance of soluble Mn in the trigeminal system following nose-only inhalation of environmentally relevant concentrations. Rats and mice were exposed for 10 days (6 hours/day, 5 days/week) to air or MnCl2 aerosols containing 2.3 {+-} 1.3mg Mn/m{sup 3} with mass median aerodynamic diameter (MMAD) of 3.1 {+-} 1.4 {micro}m for rats and 2.0 {+-} 0.09 mg Mn/m{sup 3} MnCl{sup 2} with MMAD of 1.98 {+-} 0.12 {micro}m for mice. Mn concentrations in the trigeminal ganglia and spinal trigeminal nucleus were measured 2 hours (0 day), 7, 14, or 30 days post-exposure using Proton Induced X-ray Emission (PIXE). Manganese-exposed rats and mice showed statistically elevated levels of Mn in trigeminal ganglia 0, 7 and 14 days after the 10 day exposure period when compared to control animals. The Mn concentration gradually decreased over time with a clearance rate (t{sub 1/2}) of 7-8 days. Rats and mice were similar in both average accumulated Mn levels in trigeminal ganglia and in rates of clearance. We also found a small but significant elevation of Mn in the spinal trigeminal nucleus of mice 7 days post-exposure and in rats 0 and 7 days post-exposure. Our data demonstrate that the trigeminal nerve can serve as a pathway for entry of inhaled Mn to the brain in rodents following nose-only exposure and raise the question of whether entry of toxicants via this pathway may contribute to development of neurodegenerative diseases.

  7. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect (OSTI)

    Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Twaddle, Nathan C.; Vanlandingham, Michelle [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Brown, Ronald P. [Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2011-09-15T23:59:59.000Z

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral administration, and fetal age are critical in reducing exposures to the fetus. - Highlights: > Studies of BPA in rat tissues showed placental transfer and fetal metabolism. > Levels in fetus are similar to maternal tissues. > Fetal metabolism can reduce levels.

  8. Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity

    SciTech Connect (OSTI)

    Corley, R.A. [Battelle Pacific Northwest Division, Richland, WA 99352 (United States)], E-mail: rick.corley@pnl.gov; Wilson, D.M. [Dow Chemical Company, Midland, MI 48674 (United States); Hard, G.C. [Tairua, 2853 (New Zealand); Stebbins, K.E.; Bartels, M.J. [Dow Chemical Company, Midland, MI 48674 (United States); Soelberg, J.J. [Battelle Pacific Northwest Division, Richland, WA 99352 (United States); Dryzga, M.D. [Dow Chemical Company, Midland, MI 48674 (United States); Gingell, R. [Shell Oil Company, Houston, TX 77002 (United States); McMartin, K.E. [Louisiana State University Health Sciences Center, Shreveport, LA 71130 (United States); Snellings, W.M. [Dow Chemical Company, Midland, MI 48674 (United States)

    2008-04-15T23:59:59.000Z

    Male Wistar rats have been shown to be the most sensitive sex, strain and species to ethylene glycol-induced nephrotoxicity in subchronic studies. A chronic toxicity and dosimetry study was therefore conducted in male Wistar rats administered ethylene glycol via the diet at 0, 50, 150, 300, or 400 mg/kg/day for up to twelve months. Subgroups of animals were included for metabolite analysis and renal clearance studies to provide a quantitative basis for extrapolating dose-response relationships from this sensitive animal model in human health risk assessments. Mortality occurred in 5 of 20 rats at 300 mg/kg/day (days 111-221) and 4 of 20 rats at 400 mg/kg/day (days 43-193), with remaining rats at this dose euthanized early (day 203) due to excessive weight loss. Increased water consumption and urine volume with decreased specific gravity occurred at 300 mg/kg/day presumably due to osmotic diuresis. Calculi (calcium oxalate crystals) occurred in the bladder or renal pelvis at {>=} 300 mg/kg/day. Rats dying early at {>=} 300 mg/kg/day had transitional cell hyperplasia with inflammation and hemorrhage of the bladder wall. Crystal nephropathy (basophilic foci, tubule or pelvic dilatation, birefringent crystals in the pelvic fornix, or transitional cell hyperplasia) affected most rats at 300 mg/kg/day, all at 400 mg/kg/day, but none at {<=} 150 mg/kg/day. No significant differences in kidney oxalate levels, the metabolite responsible for renal toxicity, were observed among control, 50 and 150 mg/kg/day groups. At 300 and 400 mg/kg/day, oxalate levels increased proportionally with the nephrotoxicity score supporting the oxalate crystal-induced nephrotoxicity mode of action. No treatment-related effects on the renal clearance of intravenously infused {sup 3}H-inulin, a marker for glomerular filtration, and {sup 14}C-oxalic acid were observed in rats surviving 12 months of exposure to ethylene glycol up to 300 mg/kg/day. In studies with naive male Wistar and F344 rats (a less sensitive strain), a significant difference was observed in oxalate clearances between young rats (i.e. Wistar clearance < F344) but not in age-matched old rats. Regardless, the ratios of oxalate:inulin clearances in these two strains of rats, including those exposed to ethylene glycol, were all < 1, suggesting that a fraction of the filtered oxalate is reabsorbed. Other species, including humans, typically have clearance ratios > 1 and are more effective at clearing oxalic acid by both glomerular filtration and active secretion. Thus, the lower renal clearance and kidney accumulation of oxalates in male Wistar rats enhances their sensitivity, which will be a factor in human risk assessments. The benchmark dose values (BMD05, BMDL05) were 170 mg/kg/day and 150 mg/kg/day for nephropathy, and 170 mg/kg/day and 160 mg/kg/day for birefringent crystals, using incidence times severity data in each case. The NOAEL of 150 mg/kg/day is the same as that reported after 16-week exposure and appears to be a threshold dose below which no renal toxicity occurs, regardless of exposure duration.

  9. Physiology & Behavior, Vol. 26, pp. 783-786. Pergamon Press and Brain Research Pub!., 1981. Printed in the U.S.A. Preference for Natural Odors in Rat Pups

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    in the U.S.A. Preference for Natural Odors in Rat Pups: Implications of a Failure to Replicatel BENNETT G December 1980 GALEF, B. G., JR. Preference for natural odors in rat pups: Implications of a failure minor changes in the diet on which a rat dam is maintained can have profound effects

  10. PET Imaging of Brain 5-HT1A Receptors in Rat In Vivo with 18F-FCWAY and Improvement by

    E-Print Network [OSTI]

    Shen, Jun

    PET Imaging of Brain 5-HT1A Receptors in Rat In Vivo with 18F-FCWAY and Improvement by Successful)cyclohexanecarboxamide) is useful in clinical research with PET for measuring serotonin 1A (5-HT1A) re- ceptor densities in brain applicability to measuring brain regional 5-HT1A receptor densities. Methods: PET of rat head after

  11. Soluble epoxide hydrolase inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid is neuroprotective in rat model of

    E-Print Network [OSTI]

    Hammock, Bruce D.

    , and at 180 min after reperfusion. Neuroprotective effects of t-AUCB were evaluated in primary rat neuronal-AUCB may exert its neuroprotective effects by affecting multiple components of neurovascular unit including]-benzoic acid is neuroprotective in rat model of ischemic stroke Jafar Sadik B. Shaik,1 Muzamil Ahmad,3 Wenjin

  12. Highly accurate quantification of proton MR spectroscopy in rat brain in vivo at 16.4 T , D. Z. Balla1

    E-Print Network [OSTI]

    Highly accurate quantification of proton MR spectroscopy in rat brain in vivo at 16.4 T S-T. Hong1, Minnesota, United States Introduction Localized 1 H MR spectroscopy is an efficient tool capable Wistar rats that were anaesthetized by inhalation of 1.5-2 % concentration of isoflurane. All MR

  13. Control of the level of unusual estrogen-binding protein in rat liver by sex steroids and the pituitary

    SciTech Connect (OSTI)

    Smirnova, O.V.; Rozen, V.B.; Vishnyakova, T.G.

    1986-02-01T23:59:59.000Z

    This paper studies the role of sex steriods and the pituitary in regulation of the unusual estrogen-binding protein (UEBP) level in male rat liver. The concentration of E/sub 2/-binding sites of UEBP in the liver cytosol was determined by measuring binding of a minimal addition of 2,4,6,7-tritium-E/sub 2/, with specific radioactivity of 98-100 Ci/mmole. Data on the effect of hypophysectomy on the UEBP level in the liver of different groups of rats are presented. The presence of comparable quantities of E/sub 2/ and androgens in rats of both sexes is evidence of the existence of a fine mechanism of combined regulation of the UEBP concentration under natural conditions that reflect changes in the absolute E/sub 2/ or androgen levels or in the ratio between them.

  14. Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human atrial appendage

    SciTech Connect (OSTI)

    Hamid, Q.; Wharton, J.; Terenghi, G.; Hassall, C.J.S.; Aimi, J.; Taylor, K.M.; Nakazato, H.; Dixon, J.E.; Burnstock, G.; Polak, J.M.

    1987-10-01T23:59:59.000Z

    The localization of mRNA encoding preproatrial natriuretic peptide was investigated in tissue sections and cultures of rat heart and in sections of human right atrial appendage using the technique of in situ hybridization with /sup 32/P- and /sup 35/S-labeled RNA probes. Rat atrial natriuretic peptide (ANP) transcripts were demonstrated in numerous atrial myocytes and, to a lesser extent, in ventricular myocytes in both tissue sections and newborn rat heart cultures. These findings are consistent with those obtained by RNA blot analysis of rat heart total RNA, indicating that a single prepro-ANP transcript of approx. 900 nucleotides was present in the ventricles as well as the atria. Using a /sup 35/S-labeled RNA probe for human ANP mRNA, ANP transcripts were also localized to the majority of myocytes in the human right atrial appendage. Only background levels of autoradiographic labeling were obtained when RNA probes identical to the coding sequence of rat or human ANP mRNA were used. A close correlation was found between the distribution of ANP immunoreactivity and prepro-ANP mRNA in these preparations. These results provide unequivocal evidence for the expression of the ANP gene in the rat ventricles, as well as the atria, because myocytes in these tissues have been established as the sites of both ANP localization and precursor biosynthesis. The combined use of cardiac cultures and in situ hybridization may be of value in future studies investigating the regulation of ANP synthesis in cardiac myocytes.

  15. RatBot: anti-enumeration peer-to-peer botnets

    SciTech Connect (OSTI)

    Yan, Guanhua [Los Alamos National Laboratory; Eidenbenz, Stephan [Los Alamos National Laboratory; Chen, Songqing [GEORGE MASON UNIV.

    2010-01-01T23:59:59.000Z

    Botnets have emerged as one of the most severe cyber threats in recent years. To obtain high resilience against a single point of failure, the new generation of botnets have adopted the peer-to-peer (P2P) structure. One critical question regarding these P2P botnets is: how big are they indeed? To address this question, researchers have proposed both actively crawling and passively monitoring methods to enumerate existing P2P botnets. In this work, we go further to explore the potential strategies that botnets may have to obfuscate their true sizes. Towards this end, this paper introduces RatBot, a P2P botnet that applies some statistical techniques to defeat existing P2P botnet enumeration methods. The key ideas of RatBot are two-fold: (1) there exist a fraction of bots that are indistinguishable from their fake identities, which are spoofing IP addresses they use to hide themselves; (2) we use a heavy-tailed distribution to generate the number of fake identities for each of these bots so that the sum of observed fake identities converges only slowly and thus has high variation. We use large-scale high-fidelity simulation to quantify the estimation errors under diverse settings, and the results show that a naive enumeration technique can overestimate the sizes of P2P botnets by one order of magnitude. We believe that our work reveals new challenges of accurately estimating the sizes of P2P botnets, and hope that it will raise the awareness of security practitioners with these challenges. We further suggest a few countermeasures that can potentially defeat RatBot's anti-enumeration scheme.

  16. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    SciTech Connect (OSTI)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa, E-mail: etyszkiewicz@wum.edu.pl

    2012-11-15T23:59:59.000Z

    The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ? Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ? Regional changes in levels of neurotransmitters in the brain have been identified. ? Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  17. Rat enterohepatic circulation and intestinal distribution of enterally infused thyroid hormones

    SciTech Connect (OSTI)

    DiStefano, J.J. III; Sternlicht, M.; Harris, D.R.

    1988-11-01T23:59:59.000Z

    The enterohepatic circulation (recycling), intestinal (gut) distribution, metabolism, and excretion of enterally infused thyroid hormones were studied in the intact rat under approximately normal physiological steady state conditions. Rats with 7-day osmotic minipumps implanted ip received constant intraduodenal infusions to steady state of very small trace doses of either 125I-labeled T3 (T3*) or T4 (T4*). Enterohepatic and other pathways remained open to normal function, and in particular, there was no biliary diversion or ligation. Complete feces and urine were collected daily, to assess daily distributions of radioactivity and establishment of the steady state, which occurred by day 3. On day 7, rats were anesthetized, blood was sampled, whole intestine and minipumps were removed, and the gut was separated into six segments. Fecal samples and the contents of each gut section were homogenized, ethanol extracted, evaporated, and reconstituted in NaOH for quantitative aqueous chromatography along with infusate, urine, and plasma samples, on Sephadex G-25 columns. No T3* or T4* was found in urine, but feces contained 39% of the T3* infused and 36% of the T4* infused in steady state. Statistically significant amounts of both T3* and T4* in systemic plasma on day 7 clearly indicated absorption of the hormones from the intestine, distinctly demonstrating an enterohepatic circulation of T3 and T4 under experimental conditions closely approximating the physiological steady state. This also establishes the intestine (with its contents) as an exchangeable hormone pool, physiologically internal to the system regulating thyroid hormones and their distribution. Gut contents contained 52 times more T3* and 4.34 times more T4* than corresponding plasma pools in steady state.

  18. The effects of a marginal intake of magnesium with soy protein concentrate on growth, gestation, and lactation in the rat 

    E-Print Network [OSTI]

    McLaughlin, Cynthia Anne

    1986-01-01T23:59:59.000Z

    THE EFFECTS OF A MARGINAL INTAKE OF MAGNESIUM WITH SOY PROTEIN CONCENTRATE ON GROWTH, GESTATION, AND LACTATION IN THE RAT A Thesis by CYNTHIA ANNE MCLAUGHLIN Submitted to the Graduate College of Texas A&M University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE May 19B6 Major Subject: Nutrrtion THE EFFECTS OF A MARGINAL INTAKE OF MAGNESIUM WITH SOY PROTEIN CONCENTRATE ON GROWTH, GESTATION, AND LACTATION IN THE RAT A Thesis by CYNTHIA ANNE MCLAUGHLIN Approved...

  19. Effect of dietary cysteine, methionine, and sterculic acid on fatty acid distribution in rat adipose tissue

    E-Print Network [OSTI]

    Brotze, Mary Frances

    1968-01-01T23:59:59.000Z

    . Statistical Anal sis The data were treated according to the analysis of variance for data with a single criterion of classifica- tion(24). Each of the ratios for the triglyceride frac- tion were analyzed as: Source oi Variation De rees of Freedom Total... ACIDS IN ADIPOSE TISSUE OF THE RAT B. Free Fatty Acid Fraction Group No. Sterculia f~oa ao 1 Methionine level in diet Cysteine level in diet 16/16:1 18/18:1 18/18:2 18:1/18:2 III IV VI VII VIII 0. 2 0. 2 0. 2 0. 2 low low high...

  20. Associative tolerance to nicotine analgesia in the rat: tail-flick and hot-plate assays

    E-Print Network [OSTI]

    Reynoso, Jose T.

    2000-01-01T23:59:59.000Z

    with amphetamine (2 or 3 mg/kg) before access to sweetened milk, and saline injection after access to the sweetened milk. Rats in the after group were administered an equal number of amphetamine and saline injections as the before group but in the reverse order... development. For instance, in order to develop tolerance to the anorectic effects of nicotine the organism must be allowed access to food during exposure to the drug. That is, the anorectic effects of nicotine represent a functional disturbance only when...

  1. Effect of dietary cysteine, methionine, and sterculic acid on fatty acid distribution in rat adipose tissue 

    E-Print Network [OSTI]

    Brotze, Mary Frances

    1968-01-01T23:59:59.000Z

    . Statistical Anal sis The data were treated according to the analysis of variance for data with a single criterion of classifica- tion(24). Each of the ratios for the triglyceride frac- tion were analyzed as: Source oi Variation De rees of Freedom Total... ACIDS IN ADIPOSE TISSUE OF THE RAT B. Free Fatty Acid Fraction Group No. Sterculia f~oa ao 1 Methionine level in diet Cysteine level in diet 16/16:1 18/18:1 18/18:2 18:1/18:2 III IV VI VII VIII 0. 2 0. 2 0. 2 0. 2 low low high...

  2. High affinity peptide histidine isoleucine-preferring receptors in rat liver

    SciTech Connect (OSTI)

    Paul, S.; Chou, J.; Kubota, E.

    1987-11-23T23:59:59.000Z

    Peptide Histidine Isoleucine (PHI) is generally considered a low affinity agonist for Vasoactive Intestinal Peptide (VIP) receptors. In this study, the authors investigated the presence of characteristics of (/sup 125/I)-PHI binding sites on rat liver membranes. Detergents at nonsolubilizing concentrations were included in the assay buffer to reduce adsorptive loss of PHI to acceptable levels and permit measurement of PHI-binding to receptors. Under these conditions, binding of PHI to liver membranes was time- and temperature-dependent, reversible and saturable. Unlabeled PHI was 9.7-fold more potent than VIP, and 357-fold more potent than secretin in displacing (/sup 125/I)-PHI binding. Scatchard analysis suggested the presence of two classes of PHI receptors, with Kd 27 pM and 512 pM. The data from (/sup 125/I)-PHI and (/sup 125/I)-VIP binding studies suggested that one class of receptors was PHI-preferring, and the other, equally reactive with PHI and VIP. The concentration of immunoreactive PHI, measured by radioimmunoassay, in blood from the hepatic portal vein of anesthetized rats was 2-fold higher than that from the hepatic vein, suggesting uptake of circulating PHI by the liver. 25 references, 3 figures, 1 table.

  3. EFFECTS OF ANESTHESIA ON NEURAL ACTIVITY IN THE PRIMARY VISUAL CORTEX OF THE RAT Benjamin L. White

    E-Print Network [OSTI]

    Fiser, József

    OF ANESTHESIA ON NEURAL ACTIVITY IN THE PRIMARY VISUAL CORTEX OF THE RAT Benjamin L. White andJózsef Fiser. Recordings were made in six stimulus conditions under four levels of isoflurane anesthesia. Recordings from the same cells across conditions and levels of isoflurane are compared here. Anesthesia ranged from deep

  4. Beacon Training in a Water Maze Can Facilitate and Compete With Subsequent Room Cue Learning in Rats

    E-Print Network [OSTI]

    Indiana University

    Beacon Training in a Water Maze Can Facilitate and Compete With Subsequent Room Cue Learning experiments in which rats completed a water-maze blocking procedure, experimental groups were trained to use location. A Room Test (landmarks and background cues only) showed that Stage 1 training with a fixed

  5. Influence of photoperiod on the time of parturition in the rat. III. Comparison of different daily light lengths with changes

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Influence of photoperiod on the time of parturition in the rat. III. Comparison of different daily light lengths with changes in light timing or light pulse given during darkness. M. J. BOSC Agnès to the light regime applied throughout pregnancy (day 1 : beginning of pregnancy). The majority of deliveries

  6. Hormonal regulation of Sertoli cell function in the rat V. HANSSON, K. PURVIS E. M. RITZN F. S. FRENCH

    E-Print Network [OSTI]

    Boyer, Edmond

    , there have until recently been few attempts to localize the FSH-sensitive target cells. In 1965 MurphyHormonal regulation of Sertoli cell function in the rat V. HANSSON, K. PURVIS E. M. RITZÃ?N F. S of Reproductive Biology, University of North Carolina, Chapel Hill, U. S. A. Summary. The Sertoli cell is the main

  7. The Effects of Nerve Growth Factor on Spatial Recent Memory in Aged Rats Persist after Discontinuation of Treatment

    E-Print Network [OSTI]

    Frick, Karyn M.

    21205 Nerve growth factor (NGF) infusion significantly reduces spatial recent memory deficits in aged examined. Four- and 22-month-old rats were tested preoper- atively, infused intraventricularly with recombinant human NGF or vehicle, and tested both during the 4 week infusion period and during the 4 weeks

  8. A study of the effect of mineralized cotton-seed meal on the growth of Albino rats

    E-Print Network [OSTI]

    Huebel, Leon William

    1934-01-01T23:59:59.000Z

    O. evicionos 2Mct ooy 10 per is a fscxto? Xn tho basil~ cd hceep~b~ indccpu~ of oopper~ but the latter plays a pccrt in oonvorting inorgenio iron into ho'. xoglobin Titus, Cave, anx( ~ stets that ~ee is benefioicl fox' hcexo globin buklning in rats etuxn...

  9. Overexpression of the gene for transmembrane 4 superfamily member 4 accelerates liver damage in rats treated with CCl4

    E-Print Network [OSTI]

    Tian, Weidong

    ; Carbon tetrachloride; Acute liver injury 1. Introduction Rat TM4SF4 (transmembrane 4 superfamily member 4). Abbreviations: TM4SF4, transmembrane 4 superfamily member 4; CCl4, carbon tetrachloride; ALT, alanine­13]. However, the in vivo function conferred by TM4SF4 is still largely unknown. Carbon tetrachloride (CCl4

  10. Cross-talk between the calcium-sensing receptor and the epidermal growth factor receptor in Rat-1 fibroblasts

    SciTech Connect (OSTI)

    Tomlins, Scott A.; Bollinger, Nikki; Creim, Jeffrey A.; Rodland, Karin D.

    2005-08-15T23:59:59.000Z

    The calcium-sensing receptor (CaR) is a G-protein coupled receptor that is activated by extracellular calcium (Ca2+o). Rat-1 fibroblasts have been shown to proliferate and increase ERK activity in response to elevation of [Ca2+]o, and these responses are dependent on functional CaR expression. In this report, we examined the role of cross-talk between the CaR and the epidermal growth factor receptor (EGFR) in mediating these responses in Rat-1 cells. This report shows that AG1478, a specific inhibitor of the EGFR kinase, significantly inhibits the increase in proliferation induced by elevated Ca2+o. Further, we show that AG1478 acts downstream or separately from G-protein subunit activation of phospholipase C. AG1478 significantly inhibits Ca2+o-stimulated ERK phosphorylation and in vitro kinase activity. A similar inhibition of ERK phosphorylation was observed in response to the inhibitor AG494. In addition, treatment with inhibitors of metalloproteases involved in shedding of membrane anchored EGF family ligands substantially inhibited the increase in ERK activation in response to elevated Ca2+o. This is consistent with the known expression of TGFa by Rat-1 cells. These results indicate that EGFR transactivation is an important component of the CaR mediated response to increased Ca2+o in Rat-1 fibroblasts, and most likely involves CaR-mediated induction of regulated proteolysis and ligand shedding.

  11. Characterization of the testicular cell types present in the rat by in vivo 31P magnetic resonance spectroscopy

    SciTech Connect (OSTI)

    van der Grond, J.; Van Pelt, A.M.; van Echteld, C.J.; Dijkstra, G.; Grootegoed, J.A.; de Rooij, D.G.; Mali, W.P. (Department of Radiodiagnosis, University of Utrecht (Netherlands))

    1991-07-01T23:59:59.000Z

    Testes of vitamin A-deficient Wistar rats before and after vitamin A replacement, of rats irradiated in utero, and of control rats were investigated by in vivo 31P magnetic resonance (MR) spectroscopy. The testicular phosphomonoester/ATP (PM/ATP) ratio ranged from 0.79 {plus minus} 0.05 for testes that contained only interstitial tissue and Sertoli cells to 1.64 {plus minus} 0.04 for testes in which spermatocytes were the most advanced cell types present. When new generations of spermatids entered the seminiferous epithelium, this ratio decreased. The testicular phosphodiester/ATP (PD/ATP) ratio amounted to 0.16 {plus minus} 0.06 for testes in which Sertoli cells, spermatogonia, or spermatocytes were the most advanced cell type present. When new generations of spermatids entered the seminiferous epithelium, the PD/ATP ratio rapidly increased and finally reached a value of 0.71 {plus minus} 0.06 for fully developed testes. Taken together, specific patterns of the PM/ATP ratio, the PD/ATP ratio, and pH were obtained that were correlated to the presence of spermatogonia, spermatocytes, round spermatids, and elongated spermatids or to the absence of spermatogenic cells. Hence, a good impression of the status of the seminiferous epithelium in the rat can be obtained by in vivo 31P MR spectroscopy.

  12. Clin Cancer Res . Author manuscript Enhanced survival and cure of F98 glioma-bearing rats following

    E-Print Network [OSTI]

    Boyer, Edmond

    ,FRé ID17, Biomedical Beamline2 ESRF , Grenoble,FR Department of Pathology3 Ohio State University glioma-bearing rats. Experimental Design Carboplatin (20 g/20 l) was administrated i.c. by CED to F98 ; administration & dosage ; Combined Modality Therapy ; Glioma ; drug therapy ; mortality ; pathology ; Humans

  13. Treatment with 8-OH-DPAT attenuates the weight loss associated with activity-based anorexia in female rats

    E-Print Network [OSTI]

    Hull, Elaine

    ) plays an important role in controlling food intake and regulating body weight. In addition, clinical). This animal model allows researchers to directly manipulate neuronal and endocrine systems that may the effects of pharmacological manipulation of the 5-HT system in female rats exposed to conditions

  14. Integrin Signaling at 2hr and 48hr Post-Eccentric Exercise in Heat Treated Rat Skeletal Muscle

    E-Print Network [OSTI]

    Graham, Zachary Aaron

    2010-07-28T23:59:59.000Z

    and refolding proteins and by maintain actin structures of the cellular membrane. Methods: Heat shocked (HS+EE) and non-heat shocked (EE) male Wistar rats performed a two hour downhill treadmill exercise. The soleus (SOL), vastus lateralis white (VLW) and red...

  15. Prostaglandin E2 regulates amyloid precursor protein expression via the EP2 receptor in cultured rat microglia

    E-Print Network [OSTI]

    Wurtman, Richard

    to be positively coupled to cAMP production. Stimulation of the EP2 receptor with butaprost increased APP) expression in cultured rat microglia. PGE2 treatment significantly increased the expression of APP with forskolin also increased APP expression. Co-treatment of microglia with PGE2 and the PKA inhibitor H- 89

  16. The secretion of prolactin (PRL) from pituitary lactotrophs of the rat is predominantly under inhibitory control exerted by

    E-Print Network [OSTI]

    Bertram, Richard

    The secretion of prolactin (PRL) from pituitary lactotrophs of the rat is predominantly under inhibitory control exerted by dopamine (DA) of hypothalamic origin (1). Other PRL-inhibit- ing substances from the Stojilkovic lab (3) and of this report. In addition to the PRL-inhibiting substances, a host

  17. Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    1 Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries : Diabetes impairs flow-mediated remodeling Address for Correspondence: Dr. Daniel Henrion, Pharm.D., Ph damages in type 2 diabetes. The capacity of the microcirculation to adapt or remodel in response

  18. Effects of naloxone and immobilization stress upon the pulsatile release of luteinizing hormone in the ovariectomized rat

    E-Print Network [OSTI]

    Crawford, Kimberly Ann

    1984-01-01T23:59:59.000Z

    of the hypothalamus and modulation of LHRH release. In the intact rat, early studies using morph' ne as a 0 agonist were the first to implicate EOs in the regula- tion of tne preovulatory LH surge (Packman and Rothchild, 1976; Pang et al. , 1977). The EOs were...

  19. Rat liver endothelial and Kupffer cell-mediated mutagenicity and polycyclic aromatic hydrocarbons and aflatoxin B sub 1

    SciTech Connect (OSTI)

    Steinberg, P.; Schlemper, B.; Molitor, E.; Platt, K.L.; Seidel, A.; Oesch, F. (Univ. of Mainz (West Germany))

    1990-08-01T23:59:59.000Z

    The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B{sub 1} (AFB{sub 1}) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB{sub 1} and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB{sub 1} showed a slight increase. BP and DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells form untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB{sub 1}. The reduced mutagenicity of AFB{sub 1} correlates with the decrease in the amount of 2{alpha}-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2{alpha}-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB{sub 1}. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activated several carcinogens to mutagenic metabolites.

  20. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    SciTech Connect (OSTI)

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel)] [Hebrew University Hadassah Medical School, Jerusalem (Israel); Shoshani-Dror, Dana [Hebrew University Hadassah Medical School, Jerusalem (Israel)] [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada)] [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel)] [Hebrew University Hadassah Medical School, Jerusalem (Israel); Weksler-Zangen, Sarah [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel)] [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States)] [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)] [Hebrew University Hadassah Medical School, Jerusalem (Israel)

    2012-12-01T23:59:59.000Z

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 ? among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ? High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ? Maternal copper blood levels directly correlated with fetal liver copper content ? Copper supplementation decreased embryonic resorption in the inbred strains ? Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ? Copper supplementation alleviated growth restriction and oxidative stress of liver.

  1. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    SciTech Connect (OSTI)

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01T23:59:59.000Z

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  2. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals

    SciTech Connect (OSTI)

    Lin, Tzu-Yu [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China) [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China); Department of Mechanical Engineering, Yuan Ze University, Taoyuan, 320, Taiwan (China); Lu, Cheng-Wei [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China)] [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China); Wang, Chia-Chuan; Lu, Jyh-Feng [School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China)] [School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China); Wang, Su-Jane, E-mail: med0003@mail.fju.edu.tw [Graduate Institute of Basic Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China) [Graduate Institute of Basic Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China); School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China)

    2012-09-01T23:59:59.000Z

    Hispidulin, a naturally occurring flavone, has been reported to have an antiepileptic profile. An excessive release of glutamate is considered to be related to neuropathology of epilepsy. We investigated whether hispidulin affected endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Hispidulin inhibited the release of glutamate evoked by the K{sup +} channel blocker 4-aminopyridine (4-AP). The effects of hispidulin on the evoked glutamate release were prevented by the chelation of extracellular Ca{sup 2+} ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect on hispidulin action. Hispidulin reduced the depolarization-induced increase in cytosolic free Ca{sup 2+} concentration ([Ca{sup 2+}]{sub C}), but did not alter 4-AP-mediated depolarization. Furthermore, the effect of hispidulin on evoked glutamate release was abolished by blocking the Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na{sup +}/Ca{sup 2+} exchange. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of hispidulin on evoked glutamate release. Western blot analyses showed that hispidulin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK; this decrease was also blocked by the MEK inhibitor. Moreover, the inhibition of glutamate release by hispidulin was strongly attenuated in mice without synapsin I. These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca{sup 2+} entry and ERK/synapsin I signaling pathway. -- Highlights: ? Hispidulin inhibited glutamate release from rat cerebrocortical synaptosomes. ? This action did not involve the participation of GABA{sub A} receptors. ? A decrease in the Ca{sup 2+} influx through Ca{sub v}2.2 and Ca{sub v}2.1 channels was involved. ? A role for the MAPK/ERK/synapsin I pathway in the action of hispidulin was suggested. ? This study provided further understanding of the mode of hispidulin action in the brain.

  3. PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION FOR A BINARY MIXTURE OF CHLORPYRIFOS AND DIAZINON IN THE RAT

    SciTech Connect (OSTI)

    Timchalk, Chuck; Poet, Torka S.; Hinman, Melissa N.; Busby, Andrea L.; Kousba, Ahmed A.

    2005-05-15T23:59:59.000Z

    Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE) by their oxon metabolites. The pharmacokinetic and pharmacodynamic impact of acute binary exposures to CPF and DZN in rats were evaluated in this study. Rats were orally administered CPF, DZN or a CPF/DZN mixture (0, 15, 30 or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12 and 24 h post-dosing, urine was also collected at 24 h. Chlorpyrifos, DZN and their respective metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP) were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBCs and plasma. Co-exposure to CPF/DZN at 15/15 mg/kg, did not appreciably alter the pharmacokinetics of CPF, DZN or their metabolites in blood; whereas, a 60/60 mg/kg dose resulted in a transient increase in Cmax, AUC, and decreased clearance of both compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and co-exposures. The overall potency for ChE inhibition was greater for CPF than DZN and the binary mixture response appeared to be strongly influenced by CPF. A comparison of the ChE binary response at the low dose (15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These are the first reported experiments we are aware of that characterize both the pharmacokinetic and pharmacodynamic interactions between CPF and DZN in the rat, and will be used to further develop a binary physiologically based pharmacokinetic and pharmacodynamic model for mixtures.

  4. Effect of HZE radiation and diets rich in fiber and n-3 poly unsaturated fatty acids (n-3 PUFA) on colon cancer in rats

    E-Print Network [OSTI]

    Glagolenko, Anna Anatolievna

    2006-08-16T23:59:59.000Z

    This study examines the carcinogenic effect of HZE radiation and protective effects of different types of diets against colon carcinogenesis in a rat model. The effect of HZE radiation on health state and colon cancer development was evaluated. HZE...

  5. Effect of HZE radiation and diets rich in fiber and n-3 poly unsaturated fatty acids (n-3 PUFA) on colon cancer in rats 

    E-Print Network [OSTI]

    Glagolenko, Anna Anatolievna

    2006-08-16T23:59:59.000Z

    This study examines the carcinogenic effect of HZE radiation and protective effects of different types of diets against colon carcinogenesis in a rat model. The effect of HZE radiation on health state and colon cancer development was evaluated. HZE...

  6. Characterization of the Femoral Neck Region’s Reponse to the Rat Hindlimb Unloading Model through Tomographic Scanning, Mechanical Testing and Estimated Strengths 

    E-Print Network [OSTI]

    Kupke, Joshua Scott

    2011-02-22T23:59:59.000Z

    quantitative computed tomography (pQCT), mechanical testing in two different loading conditions, and estimated strength indices. Adult male Sprague-Dawley rats (6-mo) were grouped into baseline (BL), ambulatory cage control (CC) and hindlimb unloaded (HU); HU...

  7. Cytokines and Toll-like receptor signaling pathways in the terminal ileum of hypoxic/hyperoxic neonatal rats: benefits of probiotics supplementation

    E-Print Network [OSTI]

    2012-01-01T23:59:59.000Z

    signaling pathways in the terminal ileum of hypoxic/to formula-feeding in the terminal ileum of neonatal rats.were determined in the terminal ileum. Data were compared to

  8. Luteinizing hormone signaling decreases cyclic GMP production in rat ovarian follicles by rapidly dephosphorylating the NPR2 guanylyl cyclase and by slowly decreasing its agonist CNP

    E-Print Network [OSTI]

    Terasaki, Mark

    Luteinizing hormone signaling decreases cyclic GMP production in rat ovarian follicles by rapidly),place on Millicell culture inserts No LH 20-30 min.LH Homogenize follicles,pellet crude membranes at 10,000 x g

  9. Delay Discounting in Lewis and Fischer 344 Rats: Implications for the Use of an Adjusting-amount Procedure to Detect Between-strain Differences

    E-Print Network [OSTI]

    Stein, Jeff S.

    2010-07-21T23:59:59.000Z

    Strain-related behavioral differences may facilitate investigation of the genetic and neurochemical determinants of delay discounting. Previous researchers report that Lewis rats make more impulsive choices than Fischer ...

  10. Lung tissue engineering : in vitro synthesis of lung tissue from neonatal and fetal rat lung cells cultured in a three-dimensional collagen matrix

    E-Print Network [OSTI]

    Chen, Patty P., 1981-

    2004-01-01T23:59:59.000Z

    The focus of this study was to investigate the histology of tissue formed when fetal (16-20 days gestation) and neonatal (2 days old) rat lung cells were grown in a collagen-glycosaminoglycan scaffold. This project employed ...

  11. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect (OSTI)

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China); Wen Fuqiang, E-mail: wenfuqiang.scu@gmail.co [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China)

    2010-05-15T23:59:59.000Z

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  12. In Situ Casting and Imaging of the Rat Airway Tree for Accurate 3D Reconstruction

    SciTech Connect (OSTI)

    Jacob, Rick E.; Colby, Sean M.; Kabilan, Senthil; Einstein, Daniel R.; Carson, James P.

    2013-08-01T23:59:59.000Z

    The use of anatomically accurate, animal-specific airway geometries is important for understanding and modeling the physiology of the respiratory system. One approach for acquiring detailed airway architecture is to create a bronchial cast of the conducting airways. However, typical casting procedures either do not faithfully preserve the in vivo branching angles, or produce rigid casts that when removed for imaging are fragile and thus easily damaged. We address these problems by creating an in situ bronchial cast of the conducting airways in rats that can be subsequently imaged in situ using 3D micro-CT imaging. We also demonstrate that deformations in airway branch angles resulting from the casting procedure are small, and that these angle deformations can be reversed through an interactive adjustment of the segmented cast geometry. Animal work was approved by the Institutional Animal Care and Use Committee of Pacific Northwest National Laboratory.

  13. Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

    SciTech Connect (OSTI)

    Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A; Kuznetsova, Jana V; Semyachkin-Glushkovskii, I A; Agafonov, Dmitry N; Tuchin, Valerii V

    2012-06-30T23:59:59.000Z

    The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects of speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.

  14. Evaluation of Radiation Dose Effects on Rat Bones Using Synchrotron Radiation Computed Microtomography

    SciTech Connect (OSTI)

    Nogueira, Liebert Parreiras; Braz, Delson [Nuclear Instrumentation Laboratory / COPPE / UFRJ, P.O. Box 68509, 21945-970, Rio de Janeiro (Brazil); Barroso, Regina Cely [Physics Institute / State University of Rio de Janeiro, 20550-900, Rio de Janeiro (Brazil); Almeida, Carlos Eduardo de; Andrade, Cherley Borba [Laboratory of Radiological Sciences / State University of Rio de Janeiro, Rio de Janeiro (Brazil); Tromba, Giuliana [Sincrotrone Trieste SCpA, Strada Statale S.S. 14 km 163.5, 34012 Basovizza, Trieste (Italy)

    2011-12-13T23:59:59.000Z

    In this work, we investigated the consequences of irradiation in the femora and ribs of rats submitted to radiation doses of 5 Gy. Three different sites in femur specimens (head, distal metaphysis and distal epiphysis) and one in ribs (ventral) were imaged using synchrotron radiation microcomputed tomography to assess trabecular bone microarchitecture. Histomorphometric quantification was calculated directly from the 3D microtomographic images using synchrotron radiation. The 3D microtomographic images were obtained at the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. A better understanding of the biological interactions that occur after exposure to photon radiation is needed in order to optimize therapeutic regimens and facilitate development and strategies that decrease radiation-induced side effects in humans. Results showed significant differences between irradiated and non-irradiated specimens, mostly in head and distal metaphysis bone sites.

  15. Wallerian degeneration demonstrated by magnetic resonance: spectroscopic measurements on peripheral nerve. [Rats

    SciTech Connect (OSTI)

    Jolesz, F.A.; Polak, J.F.; Ruenzel, P.W.; Adams, D.F.

    1984-07-01T23:59:59.000Z

    Wallerian degeneration of rat sciatic nerves was induced by nerve section. Fifteen days later the degenerated nerves were compared with the intact contralteral nerves from the same animal. Histological sections showed the changes typical of wallerian degeneration: axonal degeneration and secondary demyelination. The freshly dissected nerves were analyzed by magnetic resonance (MR) spectroscopy at 10 MHz, and the water content was determined by dehydration. In the degenerated nerves there was a marked prolongation of both T1 and T2 relaxation times, accompanied by an increase of water content. These results suggest that it should be possible to detect wallerian degeneration in MR images; this will have an important impact on neuropathological diagnosis of central and peripheral nervous system lesions.

  16. Increased contraction frequency in rat uterine strips treated in vitro with o,p prime -DDT

    SciTech Connect (OSTI)

    Juberg, D.R.; Loch-Caruso, R. (Univ. of Michigan, Ann Arbor (United States))

    1991-05-01T23:59:59.000Z

    Elevated levels of DDT and other organochlorine pesticides have been associated with spontaneous abortion and preterm birth in several species, including humans. Despite the prevalence of organochlorine pesticides in the environment, a mechanistic basis for this association has not been explored. Furthermore, while DDT has been associated with inhibition of calcium ATPases, altered gap junctional communication and electrophysiological changes, all of which could affect the excitation-contraction process characteristic of smooth muscle, direct effects of DDT on uterine smooth muscle have not been reported. This study was initiated to assess the direct effects of o,p{prime}-DDT (an estrogenic isomer present in the technical grade preparation) on pregnant rat uterine tissue.

  17. Autoradiographic localization of atrial natriuretic peptide receptor subtypes in rat kidney

    SciTech Connect (OSTI)

    Brown, J.; Salas, S.P.; Singleton, A.; Polak, J.M. (Univ. of Cambridge (England))

    1990-07-01T23:59:59.000Z

    The distribution of atrial natriuretic peptide (ANP) clearance receptors in rat kidney was investigated by in vitro autoradiography using des(Gln18,Ser19,Gly20,Leu21,Gly22)-ANP-(4- 23) (C-ANP) and 125I-Tyr0-ANP-(5-25) as relatively specific ligands of this receptor. Alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, outer medullary vasa recta bundles, and inner medulla. C-ANP (10 microM) inhibited greater than 60% of this glomerular binding but did not inhibit the binding of alpha-125I-ANP to medullary tissues. Alpha-125I-ANP also bound reversibly to the renal arteries up to the glomerulus. This arterial binding was only partly inhibited by 10 microM C-ANP. In the presence of 10 microM C-ANP, increasing concentrations of alpha-125I-ANP bound to a residue of glomerular sites with apparent dissociation constants of 0.82 +/- 0.16 to 2.73 +/- 1.20 nM at different cortical levels. 125I-Tyr0-ANP-(5-25) bound significantly to glomeruli and intrarenal arteries but not to vasa recta bundles or inner medulla. This glomerular binding also occurred with nanomolar dissociation constants. It was completely inhibited by 1 microM alpha-ANP and 10 microM C-ANP, but not by unrelated peptides such as gastrin. These results suggest that renal ANP clearance receptors are restricted in vivo to the glomeruli and renal arterial system of the rat.

  18. Endoplasmic reticulum stress is involved in arsenite-induced oxidative injury in rat brain

    SciTech Connect (OSTI)

    Lin, Anya M.Y. [Department of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chao, P.L.; Fang, S.F.; Chi, C.W. [Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan (China); Yang, C.H. [Department of Oncology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan (China)], E-mail: chihyang@ntu.edu.tw

    2007-10-15T23:59:59.000Z

    The mechanism underlying sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat brain. Arsenite was locally infused in the substantia nigra (SN) of anesthetized rat. Seven days after infusion, lipid peroxidation in the infused SN was elevated and dopamine level in the ipsilateral striatum was reduced in a concentration-dependent manner (0.3-5 nmol). Furthermore, local infusion of arsenite (5 nmol) decreased GSH content and increased expression of heat shock protein 70 and heme oxygenase-1 in the infused SN. Aggregation of {alpha}-synuclein, a putative pathological protein involved in several CNS neurodegenerative diseases, was elevated in the arsenite-infused SN. From the breakdown pattern of {alpha}-spectrin, both necrosis and apoptosis were involved in the arsenite-induced neurotoxicity. Pyknotic nuclei, cellular shrinkage and cytoplasmic disintegration, indicating necrosis, and TUNEL-positive cells and DNA ladder, indicating apoptosis was observed in the arsenite-infused SN. Arsenite-induced apoptosis was mediated via two different organelle pathways, mitochondria and endoplasmic reticulum (ER). For mitochondrial activation, cytosolic cytochrome c and caspase-3 levels were elevated in the arsenite-infused SN. In ER pathway, arsenite increased activating transcription factor-4, X-box binding protein 1, C/EBP homologues protein (CHOP) and cytosolic immunoglobulin binding protein levels. Moreover, arsenite reduced procaspase 12 levels, an ER-specific enzyme in the infused SN. Taken together, our study suggests that arsenite is capable of inducing oxidative injury in CNS. In addition to mitochondria, ER stress was involved in the arsenite-induced apoptosis. Arsenite-induced neurotoxicity clinically implies a pathophysiological role of arsenite in CNS neurodegeneration.

  19. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    SciTech Connect (OSTI)

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2006-03-01T23:59:59.000Z

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  20. Long-term survival and maturation of spinally grafted human fetal and embryonic stem cellderived neural precursors in implantable tacrolimus pellet- immunosuppressed ALS SOD1-G93A model rat

    E-Print Network [OSTI]

    Goldberg, Danielle S.

    2012-01-01T23:59:59.000Z

    after Tacrolimus releasable pellet implantation. Rats werein implantable tacrolimus pellet-immunosuppressed ALS SOD1-releasing Tacrolimus pellets……………………………. 12 3.2 Tolerability

  1. Dietary long-chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats

    E-Print Network [OSTI]

    Murray, Andrew J; Knight, Nicholas S; Little, Sarah E; Cochlin, Lowri E; Clements, Mary; Clarke, Kieran

    2011-08-01T23:59:59.000Z

    RESEARCH Open Access Dietary long-chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats Andrew J Murray*, Nicholas S Knight, Sarah E Little, Lowri E Cochlin, Mary Clements and Kieran Clarke... mitochondria were mea- sured using a Clark-type oxygen electrode (Strathkelvin Instruments Ltd, Glasgow, UK), as described previously [18]. The chambers were treated identically throughout the experiment, except that one contained 1 ?mol GDP added...

  2. Cross-talk between the calcium-sensing receptor and the epidermal growth factor receptor in Rat-1 fibroblasts

    SciTech Connect (OSTI)

    Tomlins, Scott A. [University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Bolllinger, Nikki [Biological Sciences Division, Battelle for the US DOE, PO Box 999, 790 Sixth Street, Richland, WA 99352 (United States); Creim, Jeffrey [Biological Sciences Division, Battelle for the US DOE, PO Box 999, 790 Sixth Street, Richland, WA 99352 (United States); Rodland, Karin D. [Biological Sciences Division, Battelle for the US DOE, PO Box 999, 790 Sixth Street, Richland, WA 99352 (United States)]. E-mail: Karin.rodland@pnl.gov

    2005-08-15T23:59:59.000Z

    The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that is activated by extracellular calcium (Ca {sub o} {sup 2+}). Rat-1 fibroblasts have been shown to proliferate and increase ERK activity in response to elevation of [Ca{sup 2+}] {sub o}, and these responses are dependent on functional CaR expression. In this report, we examined the role of cross-talk between the CaR and the epidermal growth factor receptor (EGFR) in mediating these responses in Rat-1 cells. This report shows that AG1478, a specific inhibitor of the EGFR kinase, significantly inhibits the increase in proliferation induced by elevated Ca {sub o} {sup 2+}. Furthermore, we show that AG1478 acts downstream or separately from G protein subunit activation of phospholipase C. AG1478 significantly inhibits Ca {sub o} {sup 2+}-stimulated ERK phosphorylation and in vitro kinase activity. A similar inhibition of ERK phosphorylation was observed in response to the inhibitor AG494. In addition, treatment with inhibitors of metalloproteases involved in shedding of membrane anchored EGF family ligands substantially inhibited the increase in ERK activation in response to elevated Ca {sub o} {sup 2+}. This is consistent with the known expression of TGF{alpha} by Rat-1 cells. These results indicate that EGFR transactivation is an important component of the CaR-mediated response to increased Ca {sub o} {sup 2+} in Rat-1 fibroblasts and most likely involves CaR-mediated induction of regulated proteolysis and ligand shedding.

  3. EFFECT OF DIETARY GLYCOMACROPEPTIDE AND CHOLESTEROL ON CORTICAL GANGLIOSIDE- AND GLYCOPROTEIN-BOUND N-ACETYLNEURAMINIC ACID IN YOUNG RATS

    E-Print Network [OSTI]

    Kary, Susan Ann

    2009-04-29T23:59:59.000Z

    , acylneuraminate pyruvate-lyase, is present in both bacteria and mammals. However, bacteria that express acylneuraminate pyruvate-lyase do not 8 synthesize Neu5Ac, and this enzyme is absent from mammalian tissues that continuously produce sialic acids (18... EFFECT OF DIETARY GLYCOMACROPEPTIDE AND CHOLESTEROL ON CORTICAL GANGLIOSIDE- AND GLYCOPROTEIN-BOUND N- ACETYLNEURAMINIC ACID IN YOUNG RATS by Susan A. Kary B.G.S., University of Kansas, 2006 Submitted to the graduate degree...

  4. The effects of exogenously administered pineal gland extract and melatonin on some reproductive aspects in the albino rat

    E-Print Network [OSTI]

    Hernandez-Perez, Milton John

    1967-01-01T23:59:59.000Z

    THE EFFECTS OF EXOGENOUSLY ADMINISTERED PINEAL GLAND EXTRACT AND MELATONIN ON SOME REPRODUCTIVE ASPECTS IN THE ALBINO RAT A Thesis by MILTON J. HERNANDEZ-PEREZ Submitted to the Graduate College of the Texas A&M University in partial... by MILTON J. HERNANDEZ-PEREZ Approved as to style and content by: (Chairman o'f Committee) (Head of Department) (Member) (Member) (Member) May 1967 ACKNOWLEDGEHENTS I sincerely thank Dr. George M. Krise, Dr. Sidney 0. Brown, and Dr. H. R. Crookshank...

  5. Metabolic Rate Constants for Hydroquinone in F344 Rat and Human Liver Isolated Hepatocytes: Application to a PBPK model.

    SciTech Connect (OSTI)

    Poet, Torka S.; Wu, Hong; English, J C.; Corley, Rick A.

    2004-11-15T23:59:59.000Z

    Hydroquinone (HQ) is an important industrial chemical that also occurs naturally in foods and in the leaves and bark of a number of plant species. Exposure of laboratory animals to HQ may result in a species-, sex-, and strain-specific nephrotoxicity. The sensitivity of male F344 vs. female F344 and Sprague-Dawley rats or B6C3F1 mice appears to be related to differences in the rates of formation and further metabolism of key nephrotoxic metabolites. Metabolic rate constants for the conversion of HQ through several metabolic steps to the mono-glutathione conjugate and subsequent detoxification via mercapturic acid were measured in suspension cultures of hepatocytes isolated from male F344 rats and humans. An in vitro mathematic kinetic model was used to analyze each metabolic step by simultaneously fitting the disappearance of each substrate and the appearance of subsequent metabolites. An iterative, nested approach was used whereby downstream metabolites were considered first and the model was constrained by the requirement that rate constants determined during analysis of individual metabolic steps must also satisfy the complete, integrated metabolism scheme, including competitive pathways. The results from this study indicated that the overall capacity for metabolism of HQ and its mono-glutathione conjugate is greater in hepatocytes from humans than those isolated from rats, suggesting a greater capacity for detoxification of the glutathione conjugates. Metabolic rate constants were applied to an existing physiologically based pharmacokinetic model and the model was used to predict total glutathione metabolites produced in the liver. The results showed that body burdens of these metabolites will be much higher in rats than humans.

  6. Short term effects of commercial polychlorinated biphenyl (PCB) mixtures and individual PCB congeners in female Sprague-Dawley rats

    E-Print Network [OSTI]

    Chen, Yu-Chyu

    1992-01-01T23:59:59.000Z

    fulfillment of the requirements for the degree of MASTER OF SCIENCE December 1992 Major subject: Toxicology SHORT TERM EFFECTS OF COMMERCIAL POLYCHLORINATED BIPHENYL (PCB) MIXTURES AND INDIVIDUAL PCB CONGENERS IN FEMALE SPRAGUE-DAWLEY RATS A Thesis... of isomers 3 12 24 42 46 42 24 12 3 1 209 This thesis followed the format and style of Toxicology and Applied Pharmacology. isomers and congeners in which there are differences with respect to the number of halogen atoms and their substitution...

  7. A Novel Method for the Evaluation of Mechanical Properties of Cancellous Bone in the Rat Distal Femur

    E-Print Network [OSTI]

    Lucas, Matthew W.

    2010-01-14T23:59:59.000Z

    Walton Lucas, B.S., Lipscomb University Co-Chairs of Advisory Committee: Dr. Harry Hogan Dr. Susan Bloomfield The mechanical properties of the cancellous bone in the laboratory rat animal model... the cortical shell for 50 slices in a region starting ~0.5 mm below the most proximal portion of the growth plate for each animal. Images were binarized (threshold of 100 on a 0-255 scale) and the following parameters were assessed for the three- dimensional...

  8. The effect of a prolonged magnesium restriction on the humoral immune response in maternal rats and their offspring 

    E-Print Network [OSTI]

    Cohill, Diane T

    1987-01-01T23:59:59.000Z

    and to observe alteration in these effects resulting from magnesium supplementation during gestation and lactation. Female weanling Sprague-Dawley rats were provided diets containing adequate (1200 mg Mg/kg diet) or inadequate (200 mg Mg/kg diet) magnesium...), was lower in the magnesium-restricted dams, In the group which had been magnesium restricted during growth but then received supplemental magnesium during gestation and lactation, dams had an improved immune r esponse; but pups did not lt was conc...

  9. The effects of exercise and dietary fat on calcium, magnesium, iron, and zinc on selected tissues in rats 

    E-Print Network [OSTI]

    Nguyen, Thuy Huong

    1989-01-01T23:59:59.000Z

    of the requirements for the degree MASTER OF SCIENCE December 1989 Major Subject: Nutrition THE EFFECTS OF EXERCISE AND DIETARY FAT ON CALCIUM, MAGNESIUM, IRON, AND ZINC ON SELECTED TISSUES IN RATS A Thesis by THUY HUONG NGUYEN Approved as to style... and content by: Karen S. ubena (Chair of Committee) L. yne Greene (Member) Barbara C. O' Brien (Member) Gary C. Smith (Head of Department) December 1989 ABSTRACT The Effects of Exercise and Dietary Fat on Calcium, Magnesium, Iron, and Zinc...

  10. The effects of a suboptimal intake of magnesium with soy protein concentrate on parturition, growth, and viability in the rat 

    E-Print Network [OSTI]

    Carson, Sonja D'Awn

    1985-01-01T23:59:59.000Z

    % casein or 20% soy concentrate as the protein source, and supplemented with 700 ppm, 650 ppm, 75 ppm or 0 ppm magnesium. The experiment was conducted from growth throughout lactation. Maternal performance postpartum was adversely affected by sub... prompted research of soy products (23). Few have reported on the effects of feeding rats a suboptimal level of magnesium in a diet based on casein or soy protein concentrate from weanling through gestation and lactation. The objectives of this study...

  11. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    SciTech Connect (OSTI)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03T23:59:59.000Z

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  12. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    SciTech Connect (OSTI)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1983-03-01T23:59:59.000Z

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD.

  13. Disrupted G{sub 1} to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    SciTech Connect (OSTI)

    Devi, Sachin S. [Department of Toxicology, School of Pharmacy, College of Health Sciences, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall no. 306, Monroe, LA 71209-0470 (United States); Mehendale, Harihara M. [Department of Toxicology, School of Pharmacy, College of Health Sciences, University of Louisiana at Monroe, 700 University Avenue, Sugar Hall no. 306, Monroe, LA 71209-0470 (United States)]. E-mail: mehendale@ulm.edu

    2005-09-01T23:59:59.000Z

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G{sub 0} to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G{sub 1} to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes.

  14. Cysteamine, zinc, and thiols modify detectability of rat pituitary prolactin: a comparison with effects on bovine prolactin suggests differences in hormone storage

    SciTech Connect (OSTI)

    Jacobs, L.S.; Lorenson, M.Y.

    1986-03-01T23:59:59.000Z

    Little is known about the structure of prolactin (PRL) within secretory granules. Evidence from our previous studies in bovine tissue preparations suggests that control of secretion may reside, in part, in the conversion of storage hormone to releasable PRL. The conversion can be monitored by measuring changes in immunodetectability since the oligomeric, storage form is poorly recognized by antisera raised against monomeric PRL. Since many investigators use rats to study the secretory process and changes in detectability of rat pituitary PRL occur during lactation (depletion-transformation), we undertook the present immunodetectability studies to gain insight into the storage structure of rat (r) PRL. Cysteamine and zinc inhibited tissue PRL immunoassayability in male rat pituitary homogenates and also in partially purified secretory granules as they had inhibited bovine (b) PRL; however, zinc inhibited the rodent hormone less potently than the bovine. In vitro incubation of rat tissue samples without additions resulted in increases in rPRL detectability of up to 84% after 180 minutes; such incubation of bovine samples had no significant effect. A striking additional difference between the species was that exposure to reduced glutathione (GSH), cysteine, homocysteine, mercaptoethanol, and dithiothreitol inhibited rPRL by up to 44%. This compared to thiol stimulation of bPRL by as much as 450%. The inhibitory GSH effect on rPRL was abolished when 0.5% sodium dodecyl sulfate (SDS) was included; in contrast, the stimulatory GSH effect on bPRL did not change with added SDS. SDS alone had no effect on rat homogenate PRL, and only increased rat granule rPRL by 23% compared to its ability to increase bPRL assayability by 44%.

  15. TCDD dysregulation of 13 AHR-target genes in rat liver

    SciTech Connect (OSTI)

    Watson, John D., E-mail: john.watson@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Prokopec, Stephenie D., E-mail: stephenie.prokopec@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Smith, Ashley B., E-mail: ashleyblaines@gmail.com [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Okey, Allan B., E-mail: allan.okey@utoronto.ca [Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio (Finland); Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki (Finland); Boutros, Paul C., E-mail: paul.boutros@oicr.on.ca [Ontario Institute for Cancer Research, Department of Informatics and Bio-computing Program, Toronto (Canada); Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2014-02-01T23:59:59.000Z

    Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long–Evans (Turku/AB; L–E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000 ?g/kg at 19 h after TCDD exposure and time points ranging from 1.5 to 384 h after exposure to 100 ?g/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose–response analysis, none had an ED{sub 50} equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10–100 fold higher, in at least one strain (Ahrr (L–E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L–E), Inmt (both), Nfe2l2 (L–E), Nqo1 (L–E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities. - Highlights: • NanoString measured hepatic mRNA molecules following TCDD treatment. • TCDD-sensitive Long–Evans and TCDD-resistant Han/Wistar rats were compared. • Time courses and dose responses were analyzed for AHR-core gene changes. • 7 genes displayed inter-strain mRNA differences at times after TCDD exposure. • 2 of the AHR-core genes had significant inter-strain differences in their TCDD ED{sub 50}.

  16. Effects of cysteamine on pituitary, MTTW15 tumor, and serum prolactin levels measured by rat lymphoma cell bioassay and radioimmunoassay

    SciTech Connect (OSTI)

    Parsons, J.A.; Peterson, E.K.; Hartfel, M.A.

    1984-05-01T23:59:59.000Z

    Cysteamine (CSH), a sulfhydryl compound, reduces both serum and anterior pituitary (AP) PRL measured by RIA. We have used the Nb2 lymphoma cell bioassay (BIO) for PRL to evaluate possible CSH-related changes in PRL levels in sera and tissues of male and MtTW15 mammosomatotropic tumor-bearing female rats. Experimental animals received a single sc injection of CSH (300 mg/kg), and samples were collected 0.5-24 h later. Since CSH and serum from CSH rats were toxic in BIO, samples were dialyzed before assay. All samples were evaluated for PRL and GH by RIA as well. A significant decrease (P less than 0.05) in BIO serum PRL was evident in male rats 0.5 h after CSH; levels remained low for 24 h. Serum PRL by RIA was significantly depressed at 4 h but not at 0.5 h or 24 h. PRL in AP extracts was decreased (60-90%) at all times by BIO and RIA. Significant decreases of BIO- and RIA-detectable PRL were recorded in serum and tissues (AP and tumors) at 4 h in tumor rats. Sequentially bled (0.5-4 h) CSH-treated tumor-bearing rats showed 50% and 80% reductions in serum PRL at 1 and 4 h by both BIO and RIA. CSH had no effect on GH levels in sera and tissues of any animal studied at any time interval. Our results substantiate earlier reports on CSH-induced decreases in RIA-detectable PRL. They show that such changes cannot be attributed to assay effects alone, as significant decreases in circulating and stored PRL (both AP and tumor) were evident by BIO. Results with tissue extracts were the most dramatic. They suggest an action of CSH or a metabolic intermediate with stored PRL which reduces both extractable PRL and hormone release. Such an effect of CSH on PRL extraction has been suggested by others. Whatever the mechanism, it appears to be relatively specific, since GH cells were not affected.

  17. Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

    SciTech Connect (OSTI)

    Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30T23:59:59.000Z

    Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF metabolism was not affected by repeated treatments with ethanol or both ethanol and nicotine. When compared with a previous study of nicotine and CPF exposure, there were no apparent additional exacerbating effects due to ethanol co-exposure.

  18. Delayed effects of neutron irradiation on central nervous system microvasculature in the rat

    SciTech Connect (OSTI)

    Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gordon, W.A.; Yates, A.J.; Gahbauer, R.A.; Barth, R.F.; Fairchild, R.G.

    1988-01-01T23:59:59.000Z

    Pathologic examination of a series of 14 patients with malignant gliomas treated with BNCT showed well demarcated zones of radiation damage characterized by coagulation necrosis. Beam attenuation was correlated with edema, loss of parenchymal elements, demyelination, leukocytosis, and peripheral gliosis. Vascular disturbances consisted of endothelial swelling, medial and adventitial proliferation, fibrin impregnation, frequent thrombosis, and perivascular inflammation. Radiation changes appeared to be acute and delayed. The outcome of the patients in this series was not significantly different from the natural course of the disease, even though two of the patients had no residual tumor detected at the time of autopsy. The intensity of the vascular changes raised a suspicion that boron may have sequestered in vessel walls, resulting in selectively high doses of radiation to these structures (Asbury et al., 1972), or that there may have been high blood concentrations of boron at the time of treatment. The potential limiting effects of a vascular ischemic reaction in Boron Neutron Capture Therapy (BNCT) prompted the following study to investigate the delayed response of microvascular structures in a rat model currently being used for pre-clinical investigations. 8 refs., 3 figs., 1 tab.

  19. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect (OSTI)

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15T23:59:59.000Z

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  20. Bisphenol-A rapidly enhanced passive avoidance memory and phosphorylation of NMDA receptor subunits in hippocampus of young rats

    SciTech Connect (OSTI)

    Xu Xiaohong, E-mail: xuxh63@zjnu.cn; Li Tao; Luo Qingqing; Hong Xing; Xie Lingdan; Tian Dong

    2011-09-01T23:59:59.000Z

    Bisphenol-A (BPA), an endocrine disruptor, is found to influence development of brain and behaviors in rodents. The previous study indicated that perinatal exposure to BPA impaired learning-memory and inhibited N-methyl-D-aspartate receptor (NMDAR) subunits expressions in hippocampus during the postnatal development in rats; and in cultured hippocampal neurons, BPA rapidly promotes dynamic changes in dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDAR subunit NR2B. In the present study, we examined the rapid effect of BPA on passive avoidance memory and NMDAR in the developing hippocampus of Sprague-Dawley rats at the age of postnatal day 18. The results showed that BPA or estradiol benzoate (EB) rapidly extended the latency to step down from the platform 1 h after footshock and increased the phosphorylation levels of NR1, NR2B, and mitogen-activated extracellular signal-regulated kinase (ERK) in hippocampus within 1 h. While 24 h after BPA or EB treatment, the improved memory and the increased phosphorylation levels of NR1, NR2B, ERK disappeared. Furthermore, pre-treatment with an estrogen receptors (ERs) antagonist, ICI182,780, or an ERK-activating kinase inhibitor, U0126, significantly attenuated EB- or BPA-induced phosphorylations of NR1, NR2B, and ERK within 1 h. These data suggest that BPA rapidly enhanced short-term passive avoidance memory in the developing rats. A non-genomic effect via ERs may mediate the modulation of the phosphorylation of NMDAR subunits NR1 and NR2B through ERK signaling pathway. - Highlights: > BPA rapidly extended the latency to step down from platform 1 h after footshock. > BPA rapidly increased pNR1, pNR2B, and pERK in hippocampus within 1 h. > ERs antagonist or MEK inhibitor attenuated BPA-induced pNR1, pNR2B, and pERK.

  1. Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen

    SciTech Connect (OSTI)

    Wang Jianling; Wang Gangduo; Ma Huaxian; Khan, M. Firoze, E-mail: mfkhan@utmb.edu

    2011-01-15T23:59:59.000Z

    Aniline exposure is associated with toxicity to the spleen leading to splenomegaly, hyperplasia, fibrosis and a variety of sarcomas of the spleen on chronic exposure. In earlier studies, we have shown that aniline exposure leads to iron overload, oxidative stress and activation of redox-sensitive transcription factors, which could regulate various genes leading to a tumorigenic response in the spleen. However, molecular mechanisms leading to aniline-induced cellular proliferation in the spleen remain largely unknown. This study was, therefore, undertaken on the regulation of G1 phase cell cycle proteins (cyclins), expression of cyclin-dependent kinases (CDKs), phosphorylation of retinoblastoma protein (pRB) and cell proliferation in the spleen, in an experimental condition preceding a tumorigenic response. Male SD rats were treated with aniline (0.5 mmol/kg/day via drinking water) for 30 days (controls received drinking water only), and splenocyte proliferation, protein expression of G1 phase cyclins, CDKs and pRB were measured. Aniline treatment resulted in significant increases in splenocyte proliferation, based on cell counts, cell proliferation markers including proliferating cell nuclear antigen (PCNA), nuclear Ki67 protein (Ki67) and minichromosome maintenance (MCM), MTT assay and flow cytometric analysis. Western blot analysis of splenocyte proteins from aniline-treated rats showed significantly increased expression of cyclins D1, D2, D3 and E, as compared to the controls. Similarly, real-time PCR analysis showed significantly increased mRNA expression for cyclins D1, D2, D3 and E in the spleens of aniline-treated rats. The overexpression of these cyclins was associated with increases in the expression of CDK4, CDK6, CDK2 as well as phosphorylation of pRB protein. Our data suggest that increased expression of cyclins, CDKs and phosphorylation of pRB protein could be critical in cell proliferation, and may contribute to aniline-induced tumorigenic response in the spleen.

  2. Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

    SciTech Connect (OSTI)

    Lash, Lawrence H. [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States)]. E-mail: l.h.lash@wayne.edu; Putt, David A. [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States); Hueni, Sarah E. [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States); Payton, Scott G. [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States); Zwickl, Joshua [Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201 (United States)

    2007-06-15T23:59:59.000Z

    Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg{sup 2+}) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg{sup 2+} increased expression of glutathione S-transferase-{alpha}1 (GST{alpha}1) but decreased expression of GST{alpha}2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI. Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg{sup 2+}. Pretreatment of human proximal tubular (hPT) cells with Hg{sup 2+} caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg{sup 2+} by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg{sup 2+} exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg{sup 2+}-induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg{sup 2+}, TRI, or DCVC are markedly altered by prior exposures.

  3. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    SciTech Connect (OSTI)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01T23:59:59.000Z

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ? We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ? We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ? The toxins decreased the liver's ability to uptake bile acid from the circulation. ? Oxidative stress induced by the toxins altered bile acid biosynthesis in the liver. ? Selected bile acids in the plasma and urine could be sensitive DILI biomarkers.

  4. Estimating changes in the mechanical properties of the femur in the adult and aged rat due to adult-onset alcohol consumption 

    E-Print Network [OSTI]

    Nguyen, Lyndon Phuoc

    2001-01-01T23:59:59.000Z

    in animals 15 and 19 months of age, which is comparable to the young adult and aged human. 2. 6 Relevant Research on the Mechanical Properties of Rat Bone Emphasis on safety in automotive, aircraft and aerospace engineering has lead to a growing interest... the second set (eight- week alcohol plus six-week cessation) only consisted of an alcohol and a pair-fed group. At eight weeks and again at fourteen weeks, the rats were sacrificed and the femurs were removed for mechanical testing. This is summarized...

  5. Comparison of benzo(a)pyrene metabolism and mutation induction in CHO cells using rat liver homogenate (S9) or Syrian hamster embryonic cell-mediated activation systems

    SciTech Connect (OSTI)

    Chen, D.J.; Okinaka, R.T.; Strniste, G.F.

    1981-01-01T23:59:59.000Z

    Mutagenesis in CHO cells has been studied by the addition of an ezymatically active liver homogenate (S9) fraction. However, the metabolism of procarcinogens, such as benzo(a)pyrene (B(a)P), by rat liver homogenate differs from that in intact cellular activation systems. Consequently, B(a)P-induced mutation frequencies in mammalian cells may vary when different activation systems are used. This study attempts to compare B(a)P metabolism and conjugation in rat liver homogenate (S9 preparation) and in Syrian hamster embryonic (SHE) cells. Furthermore, a CHO mutation assay incorporating either of the activation systems is being used to measure the mutation induction frequency.

  6. Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes

    SciTech Connect (OSTI)

    Sun, Yi-hua [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)] [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Yong-quan [Harbin Medical University, Harbin 150086 (China)] [Harbin Medical University, Harbin 150086 (China); Feng, Shan-li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)] [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Li, Bao-xin; Pan, Zhen-wei [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)] [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Xu, Chang-qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China)] [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Li, Ting-ting [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)] [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Yang, Bao-feng, E-mail: syh200415@yahoo.com.cn [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)] [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China)

    2010-04-16T23:59:59.000Z

    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca{sup 2+} stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca{sup 2+} imaging, we found that the depletion of ER/SR Ca{sup 2+} stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca{sup 2+} ([Ca{sup 2+}]{sub i}), followed by sustained increase depending on extracellular Ca{sup 2+}. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na{sup +}/Ca{sup 2+} exchanger inhibitors, inhibited [Ca{sup 2+}]{sub i} relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl{sub 3}) or by an increased extracellular Ca{sup 2+}([Ca{sup 2+}]{sub o}) increased the concentration of intracelluar Ca{sup 2+}, whereas, the sustained elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of SKF96365. Similarly, the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of extracellular Ca{sup 2+}. Western blot analysis showed that GdCl{sub 3} increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl{sub 3}. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca{sup 2+}-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis.

  7. The effect of a low dosage of parathion upon DRL performance and acquisition in the albino rat

    E-Print Network [OSTI]

    Thompson, Marion Stockton

    1971-01-01T23:59:59.000Z

    studied extensively. Prenatal effects studied by Al Hachim and Fink (1968) may be related to hormone factors since the f'etal environment is largely dependent upon various hormone levels of the mother for its stability. It was re- ported that rats... that this agent, when used in normal con- centrations for pest control, does not pose a significant threat to the integrity of small animal populations through adverse effects on complex behaviors. REFERENCES Al Hachim, G. M. , and Fink, G. B. , "The effect...

  8. Effects of phenylethanolamine N-methyltransferase inhibitors on uptake and release of norepinephrine and dopamine from rat brain

    SciTech Connect (OSTI)

    Liang, N.Y.; Hower, J.A.; Borchardt, R.T.

    1985-09-01T23:59:59.000Z

    Inhibitors of phenylethanolamine N-methyltransferase (PNMT) and amphetamine were evaluated for their effects on the uptake of (TH)-norepinephrine (TH-NE) and the release of endogenous NE and dopamine (DA) from chopped rat brain tissues. Unlike amphetamine, all of PNMT inhibitors tested produced only slight inhibition of (TH)-NE uptake into chopped cerebral cortex. 2,3-Dichloro-alpha-methylbenzylamine (DCMB) and 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF64139), but not 2-cyclooctyl-2-hydroxyethylamine (CONH) and 1-aminomethylcycloundecanol (CUNH) produced slight release of endogenous NE and DA from chopped hypothalami, but their effects were less pronounced than those produced by amphetamine.

  9. Effect of dietary magnesium and calcium on blood lipids and minerals in tissues in rats fed a high fat diet

    E-Print Network [OSTI]

    Conboy-Downs, Jean

    1991-01-01T23:59:59.000Z

    EFFECT OF DIETARY MAGNESIUM AND CALCIUM ON BLOOD LIPIDS AND MINERALS ZN TISSUES IN BATS FED A HIGH FAT DIET A Thesis by JEAN CONBOY-DONNS Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE May 1991 Major Subject: Nutrition EFFECT OF DIETARY MAGNESIUM AND CALCIUM ON BLOOD LIPZDS AND MZNERALS ZN TISSUES IN RATS FED A BIGS FAT DIET A Thesis by JEAN CONBOY-DOWNS Approved as to style...

  10. The effect of temperature and oxygen level on the production of testosterone, androstenedione and progesterone by rat testis in vitro

    E-Print Network [OSTI]

    Dudley, Peter Anthony

    1969-01-01T23:59:59.000Z

    THE EFFECT OF TEMPERATURE AND OXYGEN LEVEL ON THE PRODUCTION OF TESTOSTERONE, ANDROSTFNEDIONE AND PROGESTERONE BY RAT TESTIS IN VITRO A Thesis by PETER ANTHONY DUDLEY Submitted to the Graduate College of the Texas A%M University in partial... IN VITRO A Thesis by PETER ANTHONY DUDLEY Approved as to style and content by: (C irman of Committee) (Head of Department) &, 'Mcmbe r ) ' M c'm b e r ) AC KN OW LEDG MENTS The author i'eels extremely fortunate to have had as the chair- man...

  11. The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

    SciTech Connect (OSTI)

    Burns, F.J.; Garte, S.J.

    1992-12-31T23:59:59.000Z

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.

  12. Fermentation of pectin and cellulose to short chain fatty acids: a comparative study with humans, baboons, pigs, and rats

    E-Print Network [OSTI]

    Villalba, Leonilde Nonita

    1989-01-01T23:59:59.000Z

    digestibility to the human results. SCFA were measured using gas chromatography. The pH was measured before and after the fermentations. The percent fiber remaining after fermentation was assayed colorimetrically. The greatest interspecies differences were...%I@ W, W, '. '" yW~, t . . . M~~~)~ '1 r FERMENTATION OF PECTIN AND CELLULOSE TO SHORT CHAIN FATTY ACIDS: A COMPARATIVE STUDY WITH HUMANS, BABOONS, PIGS, AND RATS A Thesis by LEONILDE NONITA VILLALBA IL W I Z IJ Z 4 Z 4 2 5 V Z I...

  13. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

    SciTech Connect (OSTI)

    Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Buschbom, R. L.

    1989-05-01T23:59:59.000Z

    Occupational health standards have not been established for sulfur mustard (HD) [bis{2-chloroethyl)-sulfide) ' a strong alkylating agent with known mutagenic properties. Little, however, is known about the mutagenic activity of HD in mammalian species and data regarding the dominant lethal effects of HD are ambiguous. The purpose of this study was to determine the dominant lethal effect in male and female rats orally exposed to HD. The study was conducted in two phases; a female dominant lethal phase and a male dominant lethal phase. Sprague-Dawley rats of each sex were administered 0.08, 0.20, or 0.50 mg/kg HD in sesame oil 5 days/week for 10 weeks. For the female phase, treated or untreated males were mated with treated females and their fetuses were evaluated at approximately 14 days after copulation. For the male dominant lethal phase, treated males cohabited with untreated femal (during 5 days of each week for 10 weeks) and females were sacrificed for fetal evaluation 14 days after the midweek of cohabitation during each of the 10 weeks. The appearance and behavior of the rats were unremarkable throughout the experiment and there were no treatment-related deaths. Growth rates were reduced in both female and male rats treated with 0.50 mg/kg HD. Indicators of reproductive performance did not demonstrate significant female dominant lethal effects, although significant male dominant lethal effects were observed at 2 and 3 week post-exposure. These effects included increases of early fetal resorptions and preimplantation losses and decreases of total live embryo implants. These effects were most consistently observed at a dose of 0.50 mg/kg, but frequently occurred at the lower doses. Although no treatment-related effects on male reproductive organ weights or sperm motility were found, a significant increase in the percentage of abnormal sperm was detected in males exposed to 0. 50 mg/kg HD. The timing of these effects is consistent with an effect during the postmeiotic stages of spermatogenesis, possibly involving the generally sensitive spermatids.

  14. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    SciTech Connect (OSTI)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01T23:59:59.000Z

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were lesser affected. • The CB1 antagonist AM251 had no effect on chlorpyrifos but reduced parathion toxicity.

  15. Effect of dietary magnesium and calcium on blood lipids and minerals in tissues in rats fed a high fat diet 

    E-Print Network [OSTI]

    Conboy-Downs, Jean

    1991-01-01T23:59:59.000Z

    EFFECT OF DIETARY MAGNESIUM AND CALCIUM ON BLOOD LIPIDS AND MINERALS ZN TISSUES IN BATS FED A HIGH FAT DIET A Thesis by JEAN CONBOY-DONNS Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE May 1991 Major Subject: Nutrition EFFECT OF DIETARY MAGNESIUM AND CALCIUM ON BLOOD LIPZDS AND MZNERALS ZN TISSUES IN RATS FED A BIGS FAT DIET A Thesis by JEAN CONBOY-DOWNS Approved as to style...

  16. Effects of head-up tilt on mean arterial pressure, heart rate, and regional cardiac output distribution in aging rats

    E-Print Network [OSTI]

    Ramsey, Michael Wiechmann

    2006-04-12T23:59:59.000Z

    on Mean Arterial Pressure, Heart Rate, and Regional Cardiac Output Distribution in Aging Rats. (December 2005) Michael Wiechmann Ramsey, B.S.; M.A., Sam Houston State University Chair of Advisory Committee: Dr. Michael Delp Many senescent... to extend my gratitude to my friends as well as the faculty and staff that have supported me throughout my studies at Texas A&M University. Thanks also to Dr. Gary Oden who helped instill a love and appreciation of Exercise Physiology. A special thanks...

  17. Involvement of calcium-sensing receptor in ischemia/reperfusion-induced apoptosis in rat cardiomyocytes

    SciTech Connect (OSTI)

    Zhang Weihua [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Fu Songbin [Department of Genetics, Harbin Medical University, Harbin 150086 (China); Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086 (China); Lu Fanghao [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China)]. E-mail: lufanghao1973@yahoo.com.cn; Wu Bo [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Gong Dongmei [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Pan, Zhen-wei [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Lv Yanjie [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Zhao Yajun [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Li Quanfeng [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Wang Rui [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Department of Biology, Lakehead University, Thunder Bay, Ont., P7B5E1 (Canada); Yang Baofeng [Department of Pharmacology, Harbin Medical University, Harbin 150086 (China); Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086 (China); Xu Changqing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China) and Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086 (China)]. E-mail: xucq@163.com

    2006-09-08T23:59:59.000Z

    The calcium-sensing receptor (CaR) is a seven-transmembrane G-protein coupled receptor, which activates intracellular effectors, for example, it causes inositol phosphate (IP) accumulation to increase the release of intracellular calcium. Although intracellular calcium overload has been implicated in the cardiac ischemia/reperfusion (I/R)-induced apoptosis, the role of CaR in the induction of apoptosis has not been fully understood. This study tested the hypothesis that CaR is involved in I/R cardiomyocyte apoptosis by increasing [Ca{sup 2+}]{sub i}. The isolated rat hearts were subjected to 40-min ischemia followed by 2 h of reperfusion, meanwhile GdCl{sub 3} was added to reperfusion solution. The expression of CaR increased at the exposure to GdCl{sub 3} during I/R. By laser confocal microscopy, it was observed that the intracellular calcium was significantly increased and exhibited a collapsed {delta}{psi} {sub m}, as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolcarbocyanine iodide (JC-1) during reperfusion with GdCl{sub 3}. Furthermore, the number of apoptotic cells was significantly increased as shown by TUNEL assay. Typical apoptotic cells were observed with transmission electron microscopy in I/R with GdCl{sub 3} but not in the control group. The expression of cytosolic cytochrome c and activated caspase-9 and caspase-3 was significantly increased whereas the expression of mitochondrial cytochrome c significantly decreased in I/R with GdCl{sub 3} in comparison to the control. In conclusion, these results suggest that CaR is involved in the induction of cardiomyocyte apoptosis during ischemia/reperfusion through activation of cytochrome c-caspase-3 signaling pathway.

  18. Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats

    SciTech Connect (OSTI)

    Abbott, F.V.; Palmour, R.M.

    1988-01-01T23:59:59.000Z

    The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced and increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catelepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of (/sup 3/H)-etorphine, (/sup 3/H)-dihydromorphine and (/sup 3/H)-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with K/sub i/ values of about 30 nM, as compared to morphine K/sub i/ values of about 3 nM.

  19. Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

    SciTech Connect (OSTI)

    Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30T23:59:59.000Z

    Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

  20. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect (OSTI)

    Ronco, Ana Maria, E-mail: amronco@inta.cl [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Saez, Daniel [Faculty of Veterinary Medicine, University of Chile, Casilla 138-11, Santiago (Chile); Hirsch, Sandra [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Zepeda, Ramiro [Faculty of Medicine, University of Chile, Casilla 138-11, Santiago (Chile); Llanos, Miguel N. [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile)

    2011-03-01T23:59:59.000Z

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  1. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    SciTech Connect (OSTI)

    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15T23:59:59.000Z

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-?), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  2. Olfactory deprivation increases dopamine D2 receptor density in the rat olfactory bulb

    SciTech Connect (OSTI)

    Guthrie, K.M.; Pullara, J.M.; Marshall, J.F.; Leon, M. (University of California, Irvine (USA))

    1991-05-01T23:59:59.000Z

    Unilateral olfactory deprivation during postnatal development results in significant anatomical and neurochemical changes in the deprived olfactory bulb. Perhaps the most dramatic neurochemical change is the loss of dopaminergic expression by neurons of the glomerular region. The authors describe here the effects of early olfactory deprivation on other elements of the bulb dopaminergic system, namely the dopamine receptors of the olfactory bulb. Rat pups had a single naris occluded on postnatal day 2 (PN2). On PN20 or PN60, animals were sacrificed and the bulbs were examined for catecholamine levels or D2 and D1 dopamine receptor binding. Receptor densities were quantified by in vitro autoradiography using the tritiated antagonists spiperone (D2) and SCH23390 (D1). Dopamine uptake sites were similarly examined using tritiated mazindol. No significant specific labeling of D1 or mazindol sites was observed in the olfactory bulbs of control or experimental animals at either age. Normal animals displayed prominent labeling of D2 sites in the glomerular and nerve layers. After 60 days of deprivation, deprived bulbs exhibited an average increase in D2 receptor density of 32%. As determined by Scatchard analysis, the mean values for Kd and Bmax were 0.134 nM and 293 fmol/mg protein in normal bulbs, and 0.136 nM and 403 fmol/mg protein in deprived bulbs. The results suggest that, as in the neostriatum, dopamine depletion in the olfactory bulb leads to an upregulation of D2 receptor sites. This change may represent an attempt by the system to adapt neurochemically to reduced dopaminergic activity and thereby maintain bulb function.

  3. Stimulation of dopamine synthesis and activation of tyrosine hydroxylase by phorbol diesters in rat striatum

    SciTech Connect (OSTI)

    Onali, P.; Olianas, M.C.

    1987-03-23T23:59:59.000Z

    In rat striatal synaptosomes, 4..beta..-phorbol 12-myristate 13-acetate (PMA) and 4 ..beta..-phorbol 12,13-dibutyrate (PDBu), two activators of Ca/sup 2 +/-phospholipid-dependent protein kinase (protein kinase C) increased dopamine (DA) synthesis measured by following the release of /sup 14/CO/sub 2/ from L-(1-/sup 14/C) tyrosine. Maximal stimulation (21-28% increase of basal rate) was produced by 0.5 ..mu..M PMA and 1 ..mu..M PDBu. 4 ..beta..-Phorbol and 4 ..beta..-phorbol 13-acetate, which are not activators of protein kinase C, were ineffective at 1 ..mu..M. PMA did not change the release of /sup 14/CO/sub 2/ from L-(1-/sup 14/C)DOPA. Addition of 1 mM EGTA to a Ca/sup 2 +/-free incubation medium failed to affect PMA stimulation. KCl (60 mM) enhanced DA synthesis by 25%. Exposure of synaptosomes to either PMA or PDBu prior to KCl addition resulted in a more than additive increase (80-100%) of DA synthesis. A similar synergistic effect was observed when the phorbol diesters were combined with either veratridine or d-amphetamine but not with forskolin and dibutyryl cyclic AMP. Pretreatment of striatal synaptosomes with phorbol diesters produced an activation of tyrosine hydroxylase (TH) associated with a 60% increase of the Vmax and a decrease of the Km for the pterine cofactor 6-methyl-5,6,7,8-tetrahydropterin. These results indicate that protein kinase C participates in the regulation of striatal TH in situ and that its activation may act synergistically with DA releasing agents in stimulating DA synthesis. 37 references, 3 figures, 3 tables.

  4. Immunization with FSH? fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

    SciTech Connect (OSTI)

    Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen, E-mail: liven@nwu.edu.cn; Chen, Fulin, E-mail: chenfl@nwu.edu.cn

    2013-05-03T23:59:59.000Z

    Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal ? and ? estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSH? fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSH? antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.

  5. Neuropeptide Y-like immunoreactivity in rat cranial parasympathetic neurons: coexistence with vasoactive intestinal peptide and choline acetyltransferase

    SciTech Connect (OSTI)

    Leblanc, G.C.; Trimmer, B.A.; Landis, S.C.

    1987-05-01T23:59:59.000Z

    Neuropeptide Y (NPY) is widely distributed in the sympathetic nervous system, where it is colocalized with norepinephrine. The authors report here that NPY-immunoreactive neurons are also abundant in three cranial parasympathetic ganglia, the otic, sphenopalatine, and ciliary, in the rat measured by radioimmunoassay. High-performance liquid chromatographic analysis of the immunoreactive material present in the otic ganglion indicates that this material is very similar to porcine NPY and indistinguishable from the NPY-like immunoreactivity present in rat sympathetic neurons. These findings raise the possibility that NPY acts as a neuromodulator in the parasympathetic as well as the sympathetic nervous system. In contrast to what had been observed for sympathetic neurons, NPY-immunoreactive neurons in cranial parasympathetic ganglia do not contain detectable catecholamines or tyrosine hydroxylase immunoreactivity, and many do contain immunoreactivity for vasoactive intestinal peptide and/or choline acetyltransferase. These findings suggest that there is no simple rule governing coexpression of NPY with norepinephrine, acetylcholine, or vasoactive intestinal peptide in autonomic neurons. Further, while functional studies have indicated that NPY exerts actions on the peripheral vasculature which are antagonistic to those of acetylcholine and vasoactive intestinal peptide, the present results raise the possibility that these three substances may have complementary effects on other target tissues.

  6. Cell Detection in Knife-Edge Scanning Microscopy Images of Nissl-stained Mouse and Rat Brain Samples Using Random Forests

    E-Print Network [OSTI]

    Lal Das, Shashwat

    2014-11-26T23:59:59.000Z

    Microscopy has developed into a very powerful medium for studying the brain. The Knife-Edge Scanning Microscope (KESM), for example, is capable of imaging whole rat and mouse brains in three dimensions, and produces over 1.5 terabytes of images per...

  7. Localized In Vivo 1H NMR Detection of Neurotransmitter Labeling in Rat Brain During Infusion of [1-13C] D-Glucose

    E-Print Network [OSTI]

    Jegelka, Stefanie

    Localized In Vivo 1H NMR Detection of Neurotransmitter Labeling in Rat Brain During Infusion of [1 infusions of 13C-labeled glucose. Magn Reson Med 41:1077­1083, 1999. 1999 Wiley-Liss, Inc. Key words] glucose infusion In vivo 13C NMR spectroscopy with localization is emerg- ing as an important tool

  8. INteRNatIONal BuSINeSS BuSINeSS adMINIStRatION Students will gain critical insights into business operations

    E-Print Network [OSTI]

    Maxwell, Bruce D.

    MINORS INteRNatIONal BuSINeSS BuSINeSS adMINIStRatION Students will gain critical insights into business operations and strategy from accounting, finance, management and marketing coursework. The Business Administration Minor will provide students with fundamental knowledge and exposure to key business

  9. Simultaneous determination of aromatic acid metabolites of styrene and styrene-oxide in rat urine by gas chromatography -flame ionisation detection

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    to quantitatively analyze styrene, styrene-oxide, ethylbenzene and toluene metabolites in urines samples from rats exposed by inhalation to these compounds at levels close to the occupational threshold limit values of biological monitoring for workers exposed to styrene or related compounds. Keywords: Styrene; styrene

  10. Effects on food intake following stimulation of alpha1- and alpha2-adrenoceptors within the hypothalamic paraventricular nucleus of dietary-obese and dietary-resistant rats

    E-Print Network [OSTI]

    McMahon, Lance Richard

    1994-01-01T23:59:59.000Z

    -obesity) following intra-PVN injections of the adrenergic compounds norepinephrine (25 nmol), cirazoline (10, 20, and 30 nmol), and phenylpropanolamine (160 nmol) . Experiment 2 investigates food intake of DIO-prone and DR-prone rats (pre-obesity) following intra...

  11. Role of MMP2, MMP3 and MMP9 in the development of breast cancer brain and lung metastasis in a syngeneic rat model

    E-Print Network [OSTI]

    Mendes, Odete Rodrigues

    2005-11-01T23:59:59.000Z

    In order to study the expression of MMP2, MMP 3 and MMP9 in breast cancer brain and lung metastasis, we used a syngeneic rat model of distant metastasis of ENU1564, a carcinogen-induced mammary adenocarcinoma cell line. At six weeks post inoculation...

  12. Estimating changes in the mechanical properties of the femur in the adult and aged rat due to adult-onset alcohol consumption

    E-Print Network [OSTI]

    Nguyen, Lyndon Phuoc

    2001-01-01T23:59:59.000Z

    Numerous studies have shown that alcohol has a disturbing effect on the mechanical properties of the skeleton. To determine whether alcohol has a deleterious effect on the adult skeleton, fifty-four, nine-month old, female Sprague-Dawley rats were...

  13. Technical Aspects of an Impact Acceleration Traumatic Brain Injury Rat Model with Potential Suitability for both Microdialysis and PtiO2

    E-Print Network [OSTI]

    Boyer, Edmond

    molecules are now conceivable to ameliorate severe head-injury treatment. Keywords: Traumatic Brain Injury of anaesthesia and/or neuroprotection, a traumatic brain injury (TBI) animal model, similar to human head injury1 Technical Aspects of an Impact Acceleration Traumatic Brain Injury Rat Model with Potential

  14. Nuclear Instruments and Methods in Physics Research A 527 (2004) 166170 RatCAP: a small, head-mounted PET tomograph for imaging

    E-Print Network [OSTI]

    electronics, as well as studies with live animals to evaluate their behavior when using the device. of an awake rat. This device will permit neurophysiological studies to be carried out on small animals without of the animal. In order to minimize the weight of the ring, and to keep all of the front end readout electronics

  15. Cholinesterase inhibition and acetylcholine accumulation following intracerebral administration of paraoxon in rats

    SciTech Connect (OSTI)

    Ray, A.; Liu, J.; Karanth, S. [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74075 (United States); Gao, Y.; Brimijoin, S. [Department of Molecular Pharmacology, Mayo Clinic, Rochester, MN (United States); Pope, C. [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74075 (United States)], E-mail: carey.pope@okstate.edu

    2009-05-01T23:59:59.000Z

    We evaluated the inhibition of striatal cholinesterase activity following intracerebral administration of paraoxon assaying activity either in tissue homogenates ex vivo or by substrate hydrolysis in situ. Artificial cerebrospinal fluid (aCSF) or paraoxon in aCSF was infused unilaterally (0.5 {mu}l/min for 2 h) and ipsilateral and contralateral striata were harvested for ChE assay ex vivo. High paraoxon concentrations were needed to inhibit ipsilateral striatal cholinesterase activity (no inhibition at < 0.1 mM; 27% at 0.1 mM; 79% at 1 mM paraoxon). With 3 mM paraoxon infusion, substantial ChE inhibition was also noted in contralateral striatum. ChE histochemistry generally confirmed these concentration- and side-dependent effects. Microdialysates collected for up to 4 h after paraoxon infusion inhibited ChE activity when added to striatal homogenate, suggesting prolonged efflux of paraoxon. Since paraoxon efflux could complicate acetylcholine analysis, we evaluated the effects of paraoxon (0, 0.03, 0.1, 1, 10 or 100 {mu}M, 1.5 {mu}l/min for 45 min) administered by reverse dialysis through a microdialysis probe. ChE activity was then monitored in situ by perfusing the colorimetric substrate acetylthiocholine through the same probe and measuring product (thiocholine) in dialysates. Concentration-dependent inhibition was noted but reached a plateau of about 70% at 1 {mu}M and higher concentrations. Striatal acetylcholine was below the detection limit at all times with 0.1 {mu}M paraoxon but was transiently elevated (0.5-1.5 h) with 10 {mu}M paraoxon. In vivo paraoxon (0.4 mg/kg, sc) in adult rats elicited about 90% striatal ChE inhibition measured ex vivo, but only about 10% inhibition measured in situ. Histochemical analyses revealed intense AChE and glial fibrillary acidic protein staining near the cannula track, suggesting proliferation of inflammatory cells/glia. The findings suggest that ex vivo and in situ cholinesterase assays can provide very different views into enzyme-inhibitor interactions. Furthermore, the proliferation/migration of cells containing high amounts of cholinesterase just adjacent to a dialysis probe could affect the recovery and thus detection of extracellular acetylcholine in microdialysis studies.

  16. Lead and nickel alter the cardiorenal actions of endothelin in the rat

    SciTech Connect (OSTI)

    Novak, J.; Banks, R.O. [Univ. of Cincinnati College of Medicine, OH (United States)

    1995-02-01T23:59:59.000Z

    In the current study, we have determined to what extent lead and nickel alter the cardiorenal actions of endothelin in pentobarbital anesthetized female rates. One hour following surgery, 3 x 15-min renal clearances were collected and endothelin (ET)-1 was infused iv at 100 ng/kg/min for 30 min during which time an additional two clearances was collected. Lead (infused as lead acetate throughout the experiment) at 4.8 nmoles/min and 24 nmoles/min significantly attenuated the ET-induced increase in mean arterial pressure (MAP); lead infused at 0.48 nmoles/min had no effect. An ET-induced decrease in the glomerular filtration rate (GFR) in control rats was completely blocked by the higher doses of Pb{sup 2+}. By contrast, Pb{sup 2+} had no effect on angiotensin II or norepinephrine induced increases in MAP. In additional experiments, calcium chloride was infused at 500 nmoles/min for 105 min, then Ca{sup 2+} + Pb{sup 2+} (4.8 nmoles/min) were infused for another 105 min; in these experiments, there was no Pb{sup 2+}-induced inhibition of the MAP response to endothelin: the GFR response to the peptide remained blocked. NiCl{sub 2} reduced the ET-induced increase in MAP only at 24 nmoles/min; at 4.8 and 24 nmoles/min, nickel attentuated the decrease in GFR induced by ET. Finally, Ca{sup 2+} infusion had no effect on the inhibition by Ni{sup 2+} of the GFR response to ET. These data illustrate that (i) lead inhibits the cardiorenal actions of endothelin; (ii) a Ca{sup 2+}-related process is involved the systemic but not the renal component of this inhibition; (iii) since the heavy metal does not affect angiotensin II or nonrepinephrine-induced increases in MAP, the inhibition by lead of the systemic response is relatively specific for endothelin; and (iv) nickel also inhibits the renal response to the peptide but higher doses are required to inhibit the systemic response. 35 refs., 4 figs., 2 tabs.

  17. Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

    SciTech Connect (OSTI)

    Yu, Yunli, E-mail: chrisyu1255@yahoo.com.cn [Department of Pharmaceutics, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China) [Department of Pharmaceutics, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Wang, Xinting, E-mail: wxinting1986@yahoo.com.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Can, E-mail: ltsan@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Yao, Dan, E-mail: erinyao@126.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China) [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Shanghai Institute of Materia Medica, Shanghai 201203 (China); Hu, Mengyue, E-mail: juliahmy@126.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia, E-mail: ljbzd@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Hu, Nan, E-mail: hn_324@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Li, E-mail: liulee@cpu.edu.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Xiaodong, E-mail: xdliu@cpu.edu.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)] [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)

    2013-02-01T23:59:59.000Z

    Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-day gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K{sub ATP} channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. -- Highlights: ? Gatifloxacin induced hyperglycemia both in diabetic rats and normal rats. ? Gatifloxacin enhanced GLP-1 secretion but inhibited insulin secretion in rats. ? Long-term exposure to high GLP-1 inhibited insulin secretion and biosynthesis. ? GLP-1 over-secretion may be involved in gatifloxacin-induced hyperglycemia.

  18. High-resolution time-of-flight mass spectrometry fingerprinting of metabolites from cecum and distal colon contents of rats fed resistant starch

    SciTech Connect (OSTI)

    Anderson, Timothy J. [Ames Laboratory; Jones, Roger W. [Ames Laboratory; Ai, Yongfeng [Iowa State University; Houk, Robert S. [Ames Laboratory; Jane, Jay-lin [Iowa State University; Zhao, Yinsheng [Iowa State University; Birt, Diane F. [Iowa State University; McClelland, John F. [Ames Laboratory

    2013-12-04T23:59:59.000Z

    Time-of-flight mass spectrometry along with statistical analysis was utilized to study metabolic profiles among rats fed resistant starch (RS) diets. Fischer 344 rats were fed four starch diets consisting of 55 % (w/w, dbs) starch. A control starch diet consisting of corn starch was compared against three RS diets. The RS diets were high-amylose corn starch (HA7), HA7 chemically modified with octenyl succinic anhydride, and stearic-acid-complexed HA7 starch. A subgroup received antibiotic treatment to determine if perturbations in the gut microbiome were long lasting. A second subgroup was treated with azoxymethane (AOM), a carcinogen. At the end of the 8-week study, cecal and distal colon content samples were collected from the sacrificed rats. Metabolites were extracted from cecal and distal colon samples into acetonitrile. The extracts were then analyzed on an accurate-mass time-of-flight mass spectrometer to obtain their metabolic profile. The data were analyzed using partial least-squares discriminant analysis (PLS-DA). The PLS-DA analysis utilized a training set and verification set to classify samples within diet and treatment groups. PLS-DA could reliably differentiate the diet treatments for both cecal and distal colon samples. The PLS-DA analyses of the antibiotic and no antibiotic-treated subgroups were well classified for cecal samples and modestly separated for distal colon samples. PLS-DA analysis had limited success separating distal colon samples for rats given AOM from those not treated; the cecal samples from AOM had very poor classification. Mass spectrometry profiling coupled with PLS-DA can readily classify metabolite differences among rats given RS diets.

  19. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    SciTech Connect (OSTI)

    Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

    2013-12-01T23:59:59.000Z

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2?-, 3?-cyclic-nucleotide-3?-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. • The retina exhibits diminished neurotrophin levels and cellular differentiation. • The toxic effect is apoptotic.

  20. Characterization of the In Vitro Kinetic Interaction of Chlorpyrifos-Oxon with Rat Salivary Cholinesterase: A Potential Biomonitoring Matrix

    SciTech Connect (OSTI)

    Kousba, Ahmed A. (BATTELLE (PACIFIC NW LAB)); Poet, Torka S. (BATTELLE (PACIFIC NW LAB)); Timchalk, Charles (Pacific Northwest National Laboratory)

    2003-02-12T23:59:59.000Z

    Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). The primary mechanism of action for CPF involves the inhibition of acetylcholinesterase (AChE) by the active metabolite, CPF-oxon, with subsequent accumulation of acetylcholine (ACh) resulting in a wide range of neutotoxicity. CPF-oxon, can likewise inhibit other non-target cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker of exposure/response. Biological monitoring for OPs has focused on measuring parent chemical or metabolite in blood and urine or blood ChE inhibition. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure; however, there are a limited number of studies exploring its use for OPs. To evaluate the use of salivary ChE as a biological monitor for OP exposure, the current study characterized salivary ChE activity in Sprague-Dawley rats through its comparison with brain and plasma ChE using BW284C51 and iso-OMPA as selective inhibitors of AChE and BuChE, respectively. The study also estimated the kinetic constants describing BuChE interaction with CPF-oxon. A modified Ellman assay in conjunction with pharmacodynamic (PD) modeling was used to characterize the in vitro titration of diluted rat salivary ChE enzyme with CPF-oxon. The results indicated that, more than 95% of rat salivary ChE activity was associated with BuChE activity, total BuChE active site concentration was 0.0012 0.00013 nmol/ml saliva, reactivation rate constant (Kr) was 0.068 0.008 h-1 and inhibitory (Ki) rate constant of 8.825 and 9.80 nM-1h-1 determined experimentally and using model optimization respectively. These study results would be helpful for further evaluating the potential utility of salivary ChE as a practical tool for biological monitor of OP exposures.

  1. SOME EFFECTS OF CYPROTERONE ACETATE ON EPIDIDYMAL FUNCTION IN RATS. — T. D. GLOVER, D. J. BLACK, J. C. SHENTON, P. BOYD. Univer-T. D. GLOVER, D. J. BLACK J. C. SHENTON P. BOYD. Univer-

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    SOME EFFECTS OF CYPROTERONE ACETATE ON EPIDIDYMAL FUNCTION IN RATS. — T. D. GLOVER, D. J. BLACK, J. C. SHENTON, P. BOYD. Univer-T. D. GLOVER, D. J. BLACK J. C. SHENTON P. BOYD. Univer- site de

  2. Evaluation of the developmental toxicity of cyclopiazonic acid using H?y?d?r?a? a?t?t?e?n?u?a?t?a? and postimplantation rat whole embryo bioassays

    E-Print Network [OSTI]

    Dryden, Catherine Jeane.?

    1991-01-01T23:59:59.000Z

    EVALUATION OF THE DEVELOPMENTAL TOXICITY OF CYCLOPIAZONIC ACID USING HYDRA ATTENUATA AND POSTIMPLANTATION RAT WHOLE EMBRYO BIOASSAYS A Thesis by CATHERINE JEANE' DRYDEN Submitted to the Office of Graduate Studies of Texas A&M University... in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE May 1991 Major Subject: Food Science and Technology EVALUATION OF THE DEVELOPMENTAL TOXICITY OF CYCLOPIAZONIC ACID USING HYDRA A?TENUATA AND POSTIMPLANTATION RAT WHOLE EMBRYO...

  3. Evaluation of the developmental toxicity of cyclopiazonic acid using H?y?d?r?a? a?t?t?e?n?u?a?t?a? and postimplantation rat whole embryo bioassays 

    E-Print Network [OSTI]

    Dryden, Catherine Jeane.?

    1991-01-01T23:59:59.000Z

    EVALUATION OF THE DEVELOPMENTAL TOXICITY OF CYCLOPIAZONIC ACID USING HYDRA ATTENUATA AND POSTIMPLANTATION RAT WHOLE EMBRYO BIOASSAYS A Thesis by CATHERINE JEANE' DRYDEN Submitted to the Office of Graduate Studies of Texas A&M University... in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE May 1991 Major Subject: Food Science and Technology EVALUATION OF THE DEVELOPMENTAL TOXICITY OF CYCLOPIAZONIC ACID USING HYDRA A?TENUATA AND POSTIMPLANTATION RAT WHOLE EMBRYO...

  4. Prolactin-stimulated ornithine decarboxylase induction in rat hepatocytes: Coupling to diacylglycerol generation and protein kinase C

    SciTech Connect (OSTI)

    Buckley, A.R.; Buckley, D.J. (Kirksville College of Osteopathic Medicine, MO (USA))

    1991-01-01T23:59:59.000Z

    The trophic effects of prolactin (PRL) in rat liver have been linked to activation of protein kinase C (PKC). Since alterations in PKC activity imply its activation by 1,2-diacylglycerol (DAG), we tested whether PRL treatment stimulated DAG generation coupled to induction of a growth response in primary hepatocytes. Addition of PRL to hepatocyte cultures significantly increased ({sup 3}H)-glycerol incorporation into DAG within 5 minutes which was followed by a loss of cytosolic PKC activity by 10 minutes. Prolactin also significantly enhanced radiolabel incorporation into triacylglycerol and phospholipids within 10 minutes and induced ODC activity at 6 hours. Therefore, prolactin-stimulated alterations in PKC activity are preceded by enhanced DAG generation. Moreover, these events appear to be coupled to PRL-stimulated entry of hepatocytes into cell cycle.

  5. Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

    SciTech Connect (OSTI)

    Wu, Jiamin; Wu, Kewen; Lin, Feng; Luo, Qing; Yang, Li; Shi, Yisong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China)] [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China)] [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Sung, Kuo-Li Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China) [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412 (United States)

    2013-11-08T23:59:59.000Z

    Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.

  6. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect (OSTI)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-01-15T23:59:59.000Z

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause the adaptive change of glucocorticoid-IGF1 axis.

  7. Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs)

    SciTech Connect (OSTI)

    Ostrow, Lyle W., E-mail: lostrow1@jhmi.edu [Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States); Suchyna, Thomas M.; Sachs, Frederick [Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States)] [Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

    2011-06-24T23:59:59.000Z

    Highlights: {yields} Endothelin-1 expression by adult rat astrocytes correlates with cell proliferation. {yields} Stretch-induced ET-1 is inhibited by GsMtx-4, a specific inhibitor of Ca{sup 2+} permeant SACs. {yields} The less specific SAC inhibitor streptomycin also inhibits ET-1 secretion. {yields} Stretch-induced ET-1 production depends on a calcium influx. {yields} SAC pharmacology may provide a new class of therapeutic agents for CNS pathology. -- Abstract: The expression of endothelins (ETs) and ET-receptors is often upregulated in brain pathology. ET-1, a potent vasoconstrictor, also inhibits the expression of astrocyte glutamate transporters and is mitogenic for astrocytes, glioma cells, neurons, and brain capillary endothelia. We have previously shown that mechanical stress stimulates ET-1 production by adult rat astrocytes. We now show in adult astrocytes that ET-1 production is driven by calcium influx through stretch-activated ion channels (SACs) and the ET-1 production correlates with cell proliferation. Mechanical stimulation using biaxial stretch (<20%) of a rubber substrate increased ET-1 secretion, and 4 {mu}M GsMTx-4 (a specific inhibitor of SACs) inhibited secretion by 30%. GsMTx-4 did not alter basal ET-1 levels in the absence of stretch. Decreasing the calcium influx by lowering extracellular calcium also inhibited stretch-induced ET-1 secretion without effecting ET-1 secretion in unstretched controls. Furthermore, inhibiting SACs with the less specific inhibitor streptomycin also inhibited stretch-induced ET-1 secretion. The data can be explained with a simple model in which ET-1 secretion depends on an internal Ca{sup 2+} threshold. This coupling of mechanical stress to the astrocyte endothelin system through SACs has treatment implications, since all pathology deforms the surrounding parenchyma.

  8. Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats

    SciTech Connect (OSTI)

    Banu, Sakhila K. [Reproductive Endocrinology and Cell Signaling Laboratory, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States); Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States); Interdisciplinary Faculties of Toxicology and Reproductive Biology, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States)], E-mail: skbanu@cvm.tamu.edu; Samuel, Jawahar B. [Department of Zoology, St. John's College, Palayamkottai, 627 002 (India); Arosh, Joe A. [Reproductive Endocrinology and Cell Signaling Laboratory, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States); Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States); Burghardt, Robert C. [Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States); Interdisciplinary Faculties of Toxicology and Reproductive Biology, Texas A and M University, TAMU 4458, College Station, Texas 77843 (United States); Aruldhas, Michael M. [Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113 (India)], E-mail: aruldhasmm@yahoo.com

    2008-10-15T23:59:59.000Z

    Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 {mu}M (IC{sub 50}) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17{beta}-HSD-1, 17{beta}-HSD-2, FSHR, LHR, ER{alpha} and ER{beta}. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity.

  9. Effects of polychlorinated biphenyl (PCB) on regulation of thyroid-, growth-, and neurochemically related developmental processes in young rats

    SciTech Connect (OSTI)

    Juarez de Ku, L.M.

    1992-01-01T23:59:59.000Z

    Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than or in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.

  10. Technical Report TR_003 Technical report produced for

    E-Print Network [OSTI]

    ........................................................................................................12 3.2.5 Norway pout .......................................................................................................17 3.2.15 Norway lobster (Nephrops norvegicus).....................................................17

  11. Combination of /sup 60/Co. gamma. -radiation, misonidazole, and maltose tetrapalmitate in the treatment of Dunning prostatic tumor in the rat

    SciTech Connect (OSTI)

    Pageau, R.; Nigam, V.N.; Fisher, G.J.; Brailovsky, C.A.; Fathi, M.A.; Corcos, J.; Tahan, T.W.; Elhilali, M.M.

    1985-08-01T23:59:59.000Z

    Maltose tetrapalmitate (MTP), a synthetic nontoxic immunoadjuvant, the radiosensitizer misonidazole (MISO), and /sup 60/Co ..gamma..-radiation, alone or in combination, were used in the management of Dunning prostatic tumor in the rat. Nine groups of 10 rats each were used to assess the efficacy of various therapeutic modalities. Tumor growth rates and animal survival times were determined for each group. Radiation was more effective when combined with MTP, but the adjuvant must be present when radiation is given for synergism to occur. MISO was as effective as MTP when used with radiation, but combining them cancels out their individual effects. In a clinical situation it would be advantageous to use separately the synergisms existing between MISO and radiation on the one hand and MTP and radiation on the other hand.

  12. Concentrations of trace and other elements in the organs of wild rats and birds from the Northern Guinea savanna of Nigeria

    SciTech Connect (OSTI)

    Kapu, M.M.; Schaeffer, D.J. (Univ. of Illinois, Urbana (United States)); Akanya, H.O. (Federal Univ. of Technology, Minna (Nigeria)); Ega, R.A.; Olofu, E.O.; Balarabe, M.L. (Ahmadu Bello Univ., Zaria (Nigeria)); Chafe, U.M. (Usmanu Danfodiyo Univ., Sokota (Nigeria))

    1991-01-01T23:59:59.000Z

    In regions of human activities, where metal enter local aquatic ecosystems from the atmosphere and through wastewater outfalls, metal concentrations in food chains can exceed natural background levels and be above the threshold levels for sensitive species. Accordingly, metal levels in the organs and tissues of livestock and wildlife have been extensively studied. However, there are no reports of metal concentrations in the organs and tissues of wild animals from the Northern Guinea savanna of Nigeria. The mole rat (Africanthus niloticus, L) and village weaver bird (Ploceus cucullatus, L) contribute significantly to farm crop losses from sowing to harvest. Because there are no industries capable of causing metal contamination in the study area, the present study was undertaken to determine the natural baseline levels of metals for wild rats and birds from this environment.

  13. Electron microscopic observations of the adrenal cortical cells of young albino rats after near-lethal doses of chronic gamma irradiation

    E-Print Network [OSTI]

    Riggs, James C

    1968-01-01T23:59:59.000Z

    8. Section of normal spongiocyte indicating the position of an endothelial cell io relation to cortical cells 31 9. Cortical cells from an irradiated animal 33 10. Tubular cristae mitochondriales from an irradiated animal 35 11. Vacuolatioo...ELECTRON MICROSCOPIC OBSERVATIONS OP THE ADRENAL CORTICAL CELLS OF YOUNG ALBINO RATS AFTER NEAR-LETHAL DOSES OP CHRONIC GAK'IA IRRADIATION A Thesis by JAMES CRAIG RIGGS Submitted to the Graduate College of the Texas A&M University...

  14. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    SciTech Connect (OSTI)

    Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-01-15T23:59:59.000Z

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NF?B in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NF?B translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ? Taurine controls blood glucose via protection of pancreatic ? cells in diabetic rat. ? Taurine controls blood glucose via increasing the insulin level in diabetic rat. ? Taurine improves cardiac AKT/GLUT4 signaling pathways in diabetic conditions. ? Taurine exerts antioxidant, antihyperlipidemic and antiinflammatory activities. ? It protects cardiac apoptosis by regulating Bcl2 family and caspase 9/3 proteins.

  15. Threshold of trichloroethylene contamination in maternal drinking waters affecting fetal heart development in the rat. Environ Health Perspect 111(3):289?292

    E-Print Network [OSTI]

    Paula D. Johnson; Stanley J. Goldberg; Mary Z. Mays; Brenda V. Dawson

    2003-01-01T23:59:59.000Z

    Halogenated hydrocarbons such as trichloroethylene (TCE) are among the most common water supply contaminants in the United States and abroad. Epidemiologic studies have found an association but not a cause-and-effect relation between halogenated hydrocarbon contamination and increased incidence of congenital cardiac malformations or other defective birth outcomes. Avian and rat studies demonstrated statistically significant increases in the number of congenital cardiac malformations in those treated with high doses of TCE, either via intrauterine pump or in maternal drinking water, compared with controls. This study attempts to determine if there is a threshold dose exposure to TCE above which the developing heart is more likely to be affected. Sprague-Dawley rats were randomly placed in test groups and exposed to various concentrations of TCE (2.5 ppb, 250 ppb, 1.5 ppm, 1,100 ppm) in drinking water or distilled water (control group) throughout pregnancy. The percentage of abnormal hearts in the treated groups ranged from 0 to 10.48%, with controls having 2.1 % abnormal hearts, and the number of litters with fetuses with abnormal hearts ranged from 0 to 66.7%, and the control percentage was 16.4%. The data from this study indicate not only that there is a statistically significant probability overall of a dose response to increasing levels of TCE exposure, but also that this trend begins to manifest at relatively low levels of exposure (i.e., < 250 ppb). Maternal rats exposed to more than this level of TCE during pregnancy showed an associated increased incidence of cardiac malformations in their developing rat fetuses. Key words: cardiac malformations, cardiac teratogenicity, environmental contaminants, halogenated hydrocarbon, heart defects, heart development, TCE, trichloroethylene. Environ Health Perspect 111:289–292 (2003). doi:10.1289/ehp.5125 available via

  16. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    SciTech Connect (OSTI)

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28T23:59:59.000Z

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  17. Single voxel MR spectroscopy with echo times below 2 ms at 16.4 T in the rat brain: first in vivo results D. Z. Balla1

    E-Print Network [OSTI]

    results D. Z. Balla1 , S-T. Hong1 , G. Shajan1 , R. Pohmann1 , and K. Ugurbil1,2 1 High-Field MR Center for Magnetic Resonance Research, Minneapolis, Minnesota, United States Introduction In vivo 1H MR spectroscopySingle voxel MR spectroscopy with echo times below 2 ms at 16.4 T in the rat brain: first in vivo

  18. D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-?B and PKC signaling

    SciTech Connect (OSTI)

    Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

    2013-02-15T23:59:59.000Z

    Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic ?-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renal injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-?B and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ? Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ? D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ? It restores intra-cellular antioxidant machineries and kidney apoptosis. ? DSL reduces hyperglycemia-mediated oxidative stress via NF-kB and PKC signaling. ? DSL may act as a beneficial agent in hyperglycemia induced renal disorder.

  19. Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration

    SciTech Connect (OSTI)

    Osawa, Hiroyuki [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Ohnishi, Hirohide [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan)]. E-mail: hohnishi@jichi.ac.jp; Takano, Koji [Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo 113-8655 (Japan); Noguti, Takasi [Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo 113-8655 (Japan); Mashima, Hirosato [Department of Gastroenterology, University of Tokyo School of Medicine, Tokyo 113-8655 (Japan); Hoshino, Hiroko [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Kita, Hiroto [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Sato, Kiichi [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Matsui, Hirofumi [Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8576 (Japan); Sugano, Kentaro [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan)

    2006-06-02T23:59:59.000Z

    Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca{sup 2+}]{sub i}). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca{sup 2+}]{sub i}, activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system.

  20. Modulation of rat testes lipid composition by hormones: Effect of PRL (prolactin) and hCG (human chorionic gonadotropin)

    SciTech Connect (OSTI)

    Sebokova, E.; Wierzbicki, A.; Clandinin, M.T. (Univ. of Alberta, Edmonton (Canada))

    1988-10-01T23:59:59.000Z

    The effect of prolactin (PRL) and human chorionic gonadotropin (hCG) administration for 7 days on the composition and function of rat testicular plasma membrane was investigated. Refractory state in Leydig cells desensitized by hCG decreased the binding capacity for {sup 125}I-labeled hCG and also luteinizing hormone (LH)-induced adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) and testosterone production. In testicular membranes of hCG-treated animals, a depletion of cholesterol and an increase in total phospholipid content was observed after gonadotropin injection, thereby decreasing the cholesterol-to-phospholipid ratio. Injection of high doses of PRL had no effect on the binding capacity or affinity of the LH-hCG receptor but decreased the response of Leydig cells to LH in terms of cAMP and testosterone synthesis. PRL also increased total and esterified cholesterol and decreased free cholesterol and membrane phospholipid content. The fatty acid composition of testicular lipids was significantly and selectively influenced by both hormonal treatments. These observations suggest that metabolism of cholesterol and long-chain polyunsaturated fatty acids in testicular tissue is affected by chorionic gonadotropin and PRL and may provide the mechanism for regulating steroidogenic functions.

  1. Beta-adrenergic modulation of the release of atrial natriuretic factor from rat cardiac atria in vitro

    SciTech Connect (OSTI)

    Brown, A.; Imada, T.; Takayanagi, B.; Inagami, T.

    1986-03-01T23:59:59.000Z

    Several stimulatory factors for the release of atrial natriuretic factor, such as atrial stretch, atrial pacing and vasopressin, have been reported. We studied the effects of the adrenergic nervous system on the release of ANF using an in vitro perfusion system. Right and left atria from Sprague-Dawley rats were quartered and perfused with Krebs-Ringer bicarbonate solution gassed with 95% CO/sub 2//5% O/sub 2/ at 37/sup 0/C. Perfusate factions were collected every 2 minutes. Fractions were collected 20 minutes before and for 2 hours during the administration of test agents. ANF was measured by radioimmunoassay. Within 10 minutes of exposure to 10/sup -6/M isoproterenol, ANF secretion fell to less than 50% of its baseline level. However, beta agonists showed a stimulatory effect of 4-5 fold. Carbachol, in a concentration of 10/sup -2/M was used to demonstrate the viability of the atria exposed to isoproterenol, and produced a stimulation of ANF release of 4-6 times the basal level. The adrenergic nervous system can modulate ANF release in vitro. Further studies are being performed with selective beta agonists and antagonists to elucidate these results.

  2. Early postnatal maternal separation causes alterations in the expression of ?3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    SciTech Connect (OSTI)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan)] [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan)] [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan)] [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan)] [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan)] [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan)] [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)] [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06T23:59:59.000Z

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of ?3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), ?3-adrenergic receptor (?3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through ?3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the ?3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  3. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    SciTech Connect (OSTI)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15T23:59:59.000Z

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  4. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    SciTech Connect (OSTI)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-04-01T23:59:59.000Z

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

  5. o-p?-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats

    SciTech Connect (OSTI)

    Kwekel, Joshua C.; Forgacs, Agnes L. [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States); Williams, Kurt J. [Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI (United States); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States)

    2013-12-15T23:59:59.000Z

    1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p?-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p?-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague–Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p?-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p?-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy. - Highlights: • o,p?-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats. • o,p?-DDT and EE have different kinetics in uterine wet weight induction. • o,p?-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice. • 1256 genes were differentially expressed by both ligands in both species. • Only 51 genes had species-specific uterine expression.

  6. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    SciTech Connect (OSTI)

    Marín-Prida, Javier [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Pavón-Fuentes, Nancy [International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba); Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R. [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Delgado-Roche, Liván [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pardo-Andreu, Gilberto L. [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Polentarutti, Nadia [Istituto Clinico Humanitas (IRCCS), Rozzano (Italy); Riva, Federica [Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy); Pentón-Arias, Eduardo [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pentón-Rol, Giselle [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)

    2013-10-01T23:59:59.000Z

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  7. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    SciTech Connect (OSTI)

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)] [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India); Selvam, Govindan Sadasivam, E-mail: drselvamgsbiochem@rediffmail.com [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)

    2012-11-23T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be used as a potential treatment method to alleviate the late diabetic complications.

  8. The use of labeled leucine in establishing the time of allanto-chorionic fusion in the female albino rat with reference to implantation

    E-Print Network [OSTI]

    Rutledge, James Edward

    1966-01-01T23:59:59.000Z

    THE USE OF LABELED LEUCINE IN ESTABLISHING THE TIME OF ALLANTO-CHORIONIC FUSION IN THE FEMALE ALBINO RA T WIT H RE FERE NC E T 0 IM PLANTA T I ON A Thesis By JAMES EDWARD RUTLEDGE Submitted to the Graduate College of the Texas ASSAM... University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE January 1966 Major Subject: Physiology of Reproduction THE USE OF LABELED LEUCINE IN ESTABLISHING THE TIME OF ALLANTO- CHORIONIC FUSION IN THE FEMALE ALBINO RAT...

  9. The bulking effect of dietary fiber in the rat large intestine: an in vivo study of cellulose, guar, pectin, wheat bran and oat bran

    E-Print Network [OSTI]

    Gazzaniga, Jeanne Marie

    1985-01-01T23:59:59.000Z

    THE BULKING EFFECT OF DIETARY FIBER IN THE RAT LARGE INTESTINE: AN IN VIVO STUDY OF CELLULOSE, GUAR, PECTIN, WHEAT BRAN AND OAT BRAN A Thesis by JEANNE MARIE GAZZANIGA Submitted to the Graduate College of Texas A&M University in partial... JEANNE MARIE GAZZANIGA Approved as to style and content by: o~P L sc J nne R. Lupton (Chair of Committee) Karen S. Kubena (Member) ayne Suter (Member) G. C. Smith (Head of Department) December 1985 ABSTRACT The Bulking Effect of Dietary Fiber...

  10. DDT (2,2,bis(p-chlorophenyl) 1,1,1-trichloroethane) induced structural changes in adrenal glands of rats

    SciTech Connect (OSTI)

    Chowdhury, A.R.; Gautam, A.K.; Venkatakrishna-Bhatt, H. (National Institute of Occupational Health, Ahmedabad (India))

    1990-08-01T23:59:59.000Z

    Oldest chlorinated hydrocarbon insecticide, DDT was used widely to control pest and vector borne diseases in developing countries. Malaria and vector borne diseases can be econometrically controlled by DDT. Chronic and acute exposures to DDT result in systemic disorders in human as well as this confirmed in animals. Experimental study revealed that DDT caused the structural and functional changes in thyroid and reproductive system. The effects of DDT on adrenal glands are not well documented. Therefore this experimental investigation was undertaken to evaluate the histomorphological changes of adrenal gland after the treatment with DDT in rats.

  11. Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPAR{alpha} agonist WY14643 in rat hepatocytes

    SciTech Connect (OSTI)

    Wieneke, N.; Neuschaefer-Rube, F. [University of Potsdam, Institute of Nutrition Science, Biochemistry of Nutrition, Arthur-Scheunert-Allee 114-116, D14558 Nuthetal (Germany); Bode, L.M. [University of Potsdam, Institute of Nutrition Science, Food Chemistry, Arthur-Scheunert-Allee 114-116, D14558 Nuthetal (Germany); Kuna, M. [University of Potsdam, Institute of Nutrition Science, Biochemistry of Nutrition, Arthur-Scheunert-Allee 114-116, D14558 Nuthetal (Germany); Andres, J. [Charite - Campus Benjamin Franklin, Department of Endocrinology, Diabetes and Nutrition, Hindenburgdamm 30, 12200 Berlin (Germany); Carnevali, L.C. [Universidade de Sao Paulo, Departamento de Biologia Celular e Desenvolvimento, Instituto de Ciencias Biomedicas, Sao Paulo, SP (Brazil); Hirsch-Ernst, K.I. [Georg-August-Universitaet Goettingen, Institute of Pharmakology and Toxikology, Molekular Pharmakology, Robert-Koch-Str. 40, D-37075 Goettingen (Germany); Pueschel, G.P. [University of Potsdam, Institute of Nutrition Science, Biochemistry of Nutrition, Arthur-Scheunert-Allee 114-116, D14558 Nuthetal (Germany)], E-mail: gpuesche@uni-potsdam.de

    2009-10-01T23:59:59.000Z

    Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feedback-controlled regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase II enzymes of xenobiotic metabolism. We have recently shown, that PPAR{alpha} agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPAR{alpha} agonist could enhance the phenobarbital-dependent acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPAR{alpha} agonist WY14643 to a larger extent than after induction with either compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UGT1A10. The PPAR{alpha}-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-induced reduction in energy expenditure by fatty acids as natural PPAR{alpha} ligands. The synergism of the PPAR{alpha} agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics.

  12. Quantified regional and laminar distribution of the noradrenaline innervation in the anterior half of the adult rat cerebral cortex

    SciTech Connect (OSTI)

    Audet, M.A.; Doucet, G.; Oleskevich, S.; Descarries, L.

    1988-08-15T23:59:59.000Z

    The regional and laminar distribution of the noradrenaline (NA) innervation in the adult rat cerebral cortex was quantified in radioautographs of semithin sections from whole hemisphere slices incubated with tritiated catecholamines and a monoamine oxidase inhibitor. Uptake-labeled axonal varicosities (aggregates of silver grains) were counted with the help of a computerized image analyzer in seven cytoarchitectonic areas of the rostral half of the cortex: Cg3, rostral AID, Cg2, Fr1, Par1, caudal AID, and Pir (prepiriform) according to Zilles's nomenclature. Both dopamine (DA) and NA terminals were detected after incubation with (3H)DA and citalopram or with (3H)NA alone. In the presence of desipramine (DMI), DA terminals alone were demonstrated; the number of NA terminals was then obtained by subtraction from counts in adjacent slices incubated with or without DMI. These counts suggested that DA and NA varicosities were fully visualized only after labeling with their respective tritiated amine. Similar numbers of labeled NA varicosities as inferred after (3H)NA incubation with or without DMI were observed after (3H)NA incubation in the presence of benztropine (BZ). This indicated that NA terminals were then maximally detected to the exclusion of the DA ones, and the latter approach was adopted for the acquisition of normative data. Since the average diameter of the labeled NA varicosities was known from earlier measurements in electron microscope radioautographs, the initial counts of labeled sites/mm2 of histological section could be expressed as numbers of varicosities/mm3 of tissue following a double correction for incomplete detection at the chosen duration of radioautographic exposure and section thickness.

  13. The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

    SciTech Connect (OSTI)

    McInturf, S.M. [Naval Medical Research Unit at Dayton (NAMRU), Wright Patterson Air Force Base, OH (United States); Bekkedal, M.Y.V. [Two Steps Forward, LLC, Sun Prairie, WI (United States); Wilfong, E. [U.S. Naval Academy, 572M Holloway Road, Annapolis, MD (United States); Arfsten, D. [Navy Drug Screening Laboratory P.O. Box 113, Naval Air Station Jacksonville, FL (United States); Chapman, G. [Naval Medical Research Unit at Dayton (NAMRU), Wright Patterson Air Force Base, OH (United States); Gunasekar, P.G., E-mail: palur.gunasekar@wpafb.af.mil [Naval Medical Research Unit at Dayton (NAMRU), Wright Patterson Air Force Base, OH (United States)

    2011-07-15T23:59:59.000Z

    The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distress vocalizations were elevated in F{sub 1} offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F{sub 1} females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P{sub 0} animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.

  14. Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

    SciTech Connect (OSTI)

    Hussein, Jabeen [Department of Pediatrics, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); Farkas, Svetlana [Department of Pediatrics, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); MacKinnon, Yolanda [Department of Pediatrics, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); Ariano, Robert E. [Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba (Canada); Sitar, Daniel S. [Departments of Internal Medicine and, Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba (Canada); Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba (Canada); Hasan, Shabih U. [Department of Pediatrics, Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada)]. E-mail: hasans@ucalgary.ca

    2007-01-01T23:59:59.000Z

    Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers.

  15. Studies on the subcommissural organ area in the rat: the effects aldosterone infused into the central nervous system

    SciTech Connect (OSTI)

    Dundore, R.L.

    1985-01-01T23:59:59.000Z

    D-aldosterone (5 ng/..mu..l/hr) was infused for six days into the area of the subcommissural organ (SCO) of conscious rats to test the hypothesis that the SCO and the adrenal zona glomerulosa are related functionally in a negative feedback manner. Aldosterone increased urinary sodium loss and the sodium/potassium ratio. These effects still occurred when cannulae were displaced caudally up to 1 mm from the targeted SCO area. Aldosterone decreased the cross-sectional area of the adrenal medulla without affecting chromaffin cell density. Adrenal content of corticosterone was increased. These effects were highly dependent upon proper cannula placement and were not observed when the tip of the cannula was not in contact with the cerebrospinal fluid of the pineal recess over the rostral two-thirds of the SCO. Aldosterone infused intracerebroventricularly (ivt) into a lateral ventricle had no effect on sodium excretion, adrenal corticosterone concentration or adrenal morphology. After the infusion of radiolabelled aldosterone into the SCO area, the majority of the radioactivity was restricted to an area about 1-2 mm in diameter from the SCO. Iron-dextran injected intraperiotoneally did not accumulate in the SCO; therefore, the blood-brain barrier is intact. It is concluded that the effects of aldosterone were dependent upon the area of the brain in which it was infused. Aldosterone increased sodium excretion by an action in the SCO and/or adjacent structures. A relationship between mineralocorticoids and the adrenal modulla mediated by the SCO is also postulated. With regard to the blood-brain and brain-CSF barriers, the SCO more closely resembles general brain tissue than other circumventricular organs.

  16. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

    SciTech Connect (OSTI)

    Xu, Ying [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)] [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Nie, Ling [Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)] [Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Yin, Yang-Guang [Emergency Department, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)] [Emergency Department, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)] [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhou, Shi-Wen, E-mail: Zhoushiwen1956@yahoo.cn [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)] [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)

    2012-03-15T23:59:59.000Z

    Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 ?M) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ??m, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ? We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ? We find that the nephroprotective effects of resveratrol relate with mitochondria. ? The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

  17. The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells

    SciTech Connect (OSTI)

    Secondo, Agnese [Department of Neuroscience, Section of Pharmacology, University of Naples 'Federico II', Via S. Pansini, 5, 80131 Naples (Italy); De Mizio, Mariarosaria; Zirpoli, Laura; Santillo, Mariarosaria [Department of Neuroscience, Section of Physiology, University of Naples 'Federico II', Via S. Pansini, 5, 80131 Naples (Italy); Mondola, Paolo [Department of Neuroscience, Section of Physiology, University of Naples 'Federico II', Via S. Pansini, 5, 80131 Naples (Italy)], E-mail: mondola@unina.it

    2008-11-07T23:59:59.000Z

    The Cu-Zn superoxide dismutase (SOD1) belongs to a family of isoenzymes that are able to dismutate the oxygen superoxide in hydrogen peroxide and molecular oxygen. This enzyme is secreted by many cellular lines and it is also released trough a calcium-dependent depolarization mechanism involving SNARE protein SNAP 25. Using rat pituitary GH3 cells that express muscarinic receptors we found that SOD1 inhibits P-ERK1/2 pathway trough an interaction with muscarinic M1 receptor. This effect is strengthened by oxotremorine, a muscarinic M agonist and partially reverted by pyrenzepine, an antagonist of M1 receptor; moreover this effect is independent from increased intracellular calcium concentration induced by SOD1. Finally, P-ERK1/2 inhibition was accompanied by the reduction of GH3 cell proliferation. These data indicate that SOD1 beside the well studied antioxidant properties can be considered as a neuromodulator able to affect mitogen-activated protein kinase in rat pituitary cells trough a M1 muscarinic receptor.

  18. Etude biochimique et morphologique des particules lipoprotiques de la lymphe intestinale de rat au cours de l'absorption d'acide olique ou de son isomre trans, l'acide tadique,

    E-Print Network [OSTI]

    Boyer, Edmond

    , iso- mère trans de l'acide oléique. On infuse dans une anse intestinale de rat, 90 Ilmoles d'absorption se situe au cours de la seconde demi-heure qui suit l'infusion du régime « acide olëique» (37 + 3

  19. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    SciTech Connect (OSTI)

    Choi, Dong-Hee [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of) [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Medical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of)] [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Lim, Jeong Hoon [Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of) [Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of); Rehabilitation Medicine, Division of Neurology, Department of Medicine, National University Hospital, National University Health System (Singapore); Lee, Jongmin, E-mail: leej@kuh.ac.kr [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of) [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2012-06-01T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer 710 nm wavelength light (LED) has a protective effect in the stroke animal model. Black-Right-Pointing-Pointer We determined the effects of LED irradiation in vitro stroke model. Black-Right-Pointing-Pointer LED treatment promotes the neurite outgrowth through MAPK activation. Black-Right-Pointing-Pointer The level of synaptic markers significantly increased with LED treatment. Black-Right-Pointing-Pointer LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm{sup 2} and 50 mW/cm{sup 2}) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p < 0.05). Conclusion: Our data suggest that LED treatment may promote synaptogenesis through MAPK activation and subsequently protect cell death in the in vitro stroke model.

  20. Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

    SciTech Connect (OSTI)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2014-01-15T23:59:59.000Z

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. - Highlights: • DMBA increases Cx37 and Cx43 expression prior to follicle loss. • During follicle loss both Cx37 and Cx43 expressions are reduced. • CX43 protein is absent in follicle remnants lacking an oocyte.

  1. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    SciTech Connect (OSTI)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan) [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)] [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan) [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)] [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06T23:59:59.000Z

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  2. DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation

    SciTech Connect (OSTI)

    Li, C.-C.; Lii, C.-K.; Liu, K.-L. [Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Yang, J.-J. [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Chen, H.-W. [Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China)], E-mail: hawwen@csmu.edu.tw

    2007-12-15T23:59:59.000Z

    The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation by n-6 and n-3 PUFAs of PB-induced CYP 2B1 expression in rat primary hepatocytes. We used 100 {mu}M arachidonic acid, linoleic acid, eicosapentaenoic acid, and DHA to test this hypothesis. PB triggered the translocation of CAR from the cytosol into the nucleus in a dose-dependent and time-dependent manner in our hepatocyte system, and the CAR distribution in rat primary hepatocytes was significantly affected by DHA. DHA treatment decreased PB-inducible accumulation of CAR in the nuclear fraction and increased it in the cytosolic fraction in a dose-dependent manner. The down-regulation of CYP 2B1 expression by DHA occurred in a dose-dependent manner, and a similar pattern was found for the nuclear accumulation of CAR. The results of immunoprecipitation showed a CAR/RXR heterodimer bound to nuclear receptor binding site 1 (NR-1) of the PB-responsive enhancer module (PBREM) of the CYP 2B1gene. The EMSA results showed that PB-induced CAR binding to NR-1 was attenuated by DHA. Taken together, these results suggest that attenuation of CAR translocation and decreased subsequent binding to NR-1 are involved in DHA's down-regulation of PB-induced CYP 2B1 expression.

  3. Inhalation anesthesia in experimental radiotherapy: a reliable and time-saving system for multifractionation studies in a clinical department. [Rats; Mice

    SciTech Connect (OSTI)

    Ang, K.K. (Univ. Hospital, Leuven, Belgium); Van Der Kogel, A.J.; Van Der Schueren, E.

    1982-01-01T23:59:59.000Z

    An inhalation anesthesia system has been employed to overcome several of the limitations associated wih the use of sodium pentobarbital and other i.p. administered anesthetics in experimental radiotherapy. The described method is reliable and time-saving. The depth and duration of anesthesia are easily controllable. Only 4 deaths have occurred with more than 6000 animal exposures. The use of polystyrene jigs is shown to provide adequate thermal isolation. Oxygen as a carrier of the anesthetic agent is expected to prevent a reduced tissue oxygenation and its radiobiologial consequences. The whole system is constructed as a mobile unit in which up to 16 mice or rats can be anesthetized simultaneously and irradiated in a single field with clinical treatment equipment during short time intervals between patient irradiations. The described advantages of this method make it specially suited for experiments with protracted fractionation schedules.

  4. Enhancement of Raman Light Scattering in Dye-Labeled Rat Glioma Cells by Langmuir-Blodgett CNT-Bundles Arranged on Metal-Containing Conducting Polymer Film

    E-Print Network [OSTI]

    Egorov, A S; Grushevskaya, H V; Krot, V I; Krylova, N G; Lipnevich, I V; Orekhovskaya, T I; Shulitsky, B G

    2015-01-01T23:59:59.000Z

    We have fabricated layered nanocomposite consisting of a nanoporous anodic alumina sublayer (AOA), an ultrathin metal-containing polymer Langmuir-Blodgett (LB) film coating AOA, and multi-walled carbon nanotube (MCNT) - bundles which are arranged on the LB-film. MCNTs were preliminarily chemically modified by carboxyl groups and functionalized by stearic acid. We have experimentally observed an enhancement of Raman light scattering on surface plasmons in the LB-monolayers. This enhancement is due to charge and energy transfer. We demonstrate that propidium iodide (PI) fluorescence is quenched by the MCNT-bundles. A method of two-dimensional system imaging based on the MCNT-enhanced Raman spectroscopy has been proposed. This method has been applied to visualize focal adhesion sites on membranes of living PI-labeled rat glioma cells.

  5. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    SciTech Connect (OSTI)

    Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)] [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikata, Kenichi [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan) [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)] [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Usui, Hitomi Kataoka [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)] [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Makino, Hirofumi [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)] [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)

    2014-01-17T23:59:59.000Z

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-?B (NF-?B) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.

  6. The In Vivo Quantitation of Diazinon, chlorpyrifos, and Their Major Metabolites in Rat Blood for the Refinement of a Physiologically-Based Pharmacokinetic/Pharmacodynamic Models

    SciTech Connect (OSTI)

    Busby, A.; Kousba, A.; Timchalk, C.

    2004-01-01T23:59:59.000Z

    Chlorpyrifos (CPF)(O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate, CAS 2921-88-2), and diazinon (DZN)(O,O-diethyl-O-2-isopropyl-4-methyl-6-pyrimidyl thiophosphate, CAS 333-41-5) are commonly encountered organophosphorus insecticides whose oxon metabolites (CPF-oxon and DZN-oxon) have the ability to strongly inhibit acetylcholinesterase, an enzyme responsible for the breakdown of acetylcholine at nerve synapses. Chlorpyrifos-oxon and DZN-oxon are highly unstable compounds that degrade via hepatic, peripheral blood, and intestinal metabolism to the more stable metabolites, TCP (3,5,6-trichloro-2-pyridinol, CAS not assigned) and IMHP (2-isopropyl-6-methyl-4-pyrimidinol, CAS 2814-20-2), respectively. Studies have been performed to understand and model the chronic and acute toxic effects of CPF and DZN individually but little is known about their combined effects. The purpose of this study was to improve physiologically based pharmacokinetic/ pharmacodynamic (PBPK/PD) computational models by quantifying concentrations of CPF and DZN and their metabolites TCP and IMHP in whole rat blood, following exposure to the chemicals individually or as a mixture. Male Sprague-Dawley rats were orally dosed with 60 mg/kg of CPF, DZN, or a mixture of these two pesticides. When administered individually DZN and CPF were seen to reach their maximum concentration at ~3 hours post-dosing. When given as a mixture, both DZN and CPF peak blood concentrations were not achieved until ~6 hours post-dosing and the calculated blood area under the curve (AUC) for both chemicals exceeded those calculated following the single dose. Blood concentrations of IMHP and TCP correlated with these findings. It is proposed that the higher AUC obtained for both CPF and DZN as a mixture resulted from competition for the same metabolic enzyme systems.

  7. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

    SciTech Connect (OSTI)

    Yogi, Alvaro; Callera, Glaucia E. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada)] [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Mecawi, André S. [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil)] [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Batalhão, Marcelo E.; Carnio, Evelin C. [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil)] [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil); Antunes-Rodrigues, José [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil)] [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Queiroz, Regina H. [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil)] [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil); Touyz, Rhian M. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada)] [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)

    2012-11-01T23:59:59.000Z

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase?mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ? Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ? RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation. ? Translocation of p47phox and MAPKs phosphorylation are downstream effectors. ? Acute ethanol consumption increases the risk for acute vascular injury.

  8. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    SciTech Connect (OSTI)

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    2013-10-15T23:59:59.000Z

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

  9. Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat: Evidence for a role of oxidative stress via activation of CAR, PXR and PPAR signaling pathways

    SciTech Connect (OSTI)

    Kakehashi, Anna, E-mail: anna@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Hagiwara, Akihiro; Imai, Norio [DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113 (Japan); Nagano, Kasuke [Nagano Toxicologic-Pathology Consulting, Ochiai, Hadano, Kanagawa 257-0025 (Japan); Nishimaki, Fukumi [Biofuel Assessment Group, New Fuels Dept., Japan Petroleum Energy Center (JPEC), 4-3-9 Toranomon, Minato-ku, Tokyo 105-0001 (Japan); Banton, Marcy [Toxicology and Risk Assessment, LyondellBasell Industries, LyondellBasell Corporate HSE/Product Safety, One Houston Center, Suite 700, 1221 McKinney Street, Houston, TX 770 10 (United States); Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0011 (Japan); Wanibuchi, Hideki [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2013-12-01T23:59:59.000Z

    To elucidate possible mode of action (MOA) and human relevance of hepatotumorigenicity in rats for ethyl tertiary-butyl ether (ETBE), male F344 rats were administered ETBE at doses of 0, 150 and 1000 mg/kg body weight twice a day by gavage for 1 and 2 weeks. For comparison, non-genotoxic carcinogen phenobarbital (PB) was applied at a dose of 500 ppm in diet. Significant increase of P450 total content and hydroxyl radical levels by low, high doses of ETBE and PB treatments at weeks 1 and 2, and 8-OHdG formation at week 2, accompanied accumulation of CYP2B1/2B2, CYP3A1/3A2 and CYP2C6, and downregulation of DNA oxoguanine glycosylase 1, induction of apoptosis and cell cycle arrest in hepatocytes, respectively. Up-regulation of CYP2E1 and CYP1A1 at weeks 1 and 2, and peroxisome proliferation at week 2 were found in high dose ETBE group. Results of proteome analysis predicted activation of upstream regulators of gene expression altered by ETBE including constitutive androstane receptor (CAR), pregnane-X-receptor (PXR) and peroxisome proliferator-activated receptors (PPARs). These results indicate that the MOA of ETBE hepatotumorigenicity in rats may be related to induction of oxidative stress, 8-OHdG formation, subsequent cell cycle arrest, and apoptosis, suggesting regenerative cell proliferation after week 2, predominantly via activation of CAR and PXR nuclear receptors by a mechanism similar to that of PB, and differentially by activation of PPARs. The MOA for ETBE hepatotumorigenicity in rats is unlikely to be relevant to humans. - Highlights: • We focus on MOA and human relevance of hepatotumorigenicity in rats for ETBE. • ETBE was administered to F344 rats for 1 and 2 weeks. • Oxidative stress formation, proliferation and apoptosis in the liver are analyzed. • ETBE-induced changes of gene and protein expression in the liver are examined. • The effects are compared with those induced by non-genotoxic carcinogen PB.

  10. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect (OSTI)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15T23:59:59.000Z

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased inflammatory cells and IgE, but the others did not. • The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. • Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

  11. Identification of the human ERK gene as a putative receptor tyrosine kinase and its chromosomal localization to 1p36.1: A comparative mapping of human, mouse, and rat chromosomes

    SciTech Connect (OSTI)

    Saito, Toshiyuki; Matsuda, Yoichi; Hori, Tada-aki [National Institute of Radiological Sciences, Chiba (Japan)] [and others] [National Institute of Radiological Sciences, Chiba (Japan); and others

    1995-03-20T23:59:59.000Z

    From a newly determined cDNA sequence of the human ERK gene, a highly hydrophobic portion was identified upstream of the putative tyrosine kinase domain. This is the first evidence that the ERK protein possesses a receptor-like membrane-spanning structure. Fluorescence in situ hybridization analysis of R-banded metaphase chromosomes revealed that the ERK gene is located in chromosome region 1p36.1. This locus is near the frequent translocation breakpoint or deletion region of neuroblastoma and some other cancers. A comparative mapping study of the mouse and rat homologues indicated that each counterpart maps to the mouse chromosome 4D2.2-D3 and rat chromosome 5q36.13 regions, both of which have conserved linkage homology to human chromosome 1p. 15 refs., 2 figs.

  12. A triple-resonant RF coil setup for 1H, 23Na and 39K MR imaging of the rat brain at 9.4T M. A. Augath1,2

    E-Print Network [OSTI]

    A triple-resonant RF coil setup for 1H, 23Na and 39K MR imaging of the rat brain at 9.4T M. A. Augath1,2 , P. Heiler1 , S. Kirsch1 , and L. R. Schad1 1 Computer Assisted Clinical Medicine, Faculty concentrations of 23 Na and 39 K offers a very promising approach in clinical diagnostics. For MR imaging of both

  13. Excretion of radioactivity following the intraperitoneal administration of /sup 14/C-DDT, /sup 14/C-DDD, /sup 14/C-DDE and /sup 14/C-DDMU to the rat and Japanese Quail

    SciTech Connect (OSTI)

    Fawcett, S.C. (Univ. of Surrey, Guildford, England); Bunyan, P.J.; Huson, L.W.; King, L.J.; Stanley, P.I.

    1981-09-01T23:59:59.000Z

    A study in progress to examine the metabolic fate of DDT in birds and mammals is discussed. The first phase of the study, which is reported in this article, has been to establish the rate of excretion of ratioactivity following the intraperitoneal administrations of /sup 14/C-DDT, /sup 14/C-DDE, /sup 14/C-DDD, and /sup 14/C-DDMU to male rats and male Japanese quail. The mean values from the three animals in each experimental group for the amount of radioactivity excreted daily are given, and it was found that the rats excreted the radioactivity administered as DDT, DDD, and DDE substantially faster than did the quail. DDMU was excreted relatively rapidly and at similar rates. This finding suggests that apparent differences in the rates of excretion of DDT by birds and mammals probably arise from differences in the conversion of DDT to DDD or DDE or in the degradation of these metabolites to DDMU. The Japanese quail differ from the rats in excreting substantial amounts of unchanged DDT, DDE, and DDD, which probably reflects the inability of the Japanese quail to readily metabolise these compounds.

  14. Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells

    SciTech Connect (OSTI)

    Luo, Chunxia [Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)] [Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Yi, Bin, E-mail: yibin1974@163.com [Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China) [Department of Anesthesia, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Bai, Li [Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China)] [Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Xia, Yongzhi [Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)] [Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wang, Guansong; Qian, Guisheng [Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China)] [Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Feng, Hua [Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)] [Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2010-07-02T23:59:59.000Z

    Recent findings identify the role of proliferation of pulmonary artery smooth muscle cells (PASMCs) in pulmonary vascular remodeling. Phosphoinositide 3 kinase (PI3K) and serine/threonine kinase (Akt) proteins are expressed in vascular smooth muscle cells. In addition, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been identified as a negative regulator of cytokine signaling that inhibits the PI3K-Akt pathway. However, little is known about the role of PTEN/Akt signaling in hypoxia-associated vascular remodeling. In this study, we found that hypoxia-induced the expression of Akt1 mRNA and phosphorylated protein by at least twofold in rat PASMCs. Phospho-PTEN significantly decreased in the nuclei of PASMCs after hypoxic stimulation. After forcing over-expression of PTEN by adenovirus-mediated PTEN (Ad-PTEN) transfection, the expression of phospho-Akt1 was significantly suppressed in PASMCs at all time-points measured. Additionally, we showed here that hypoxia increased proliferation of PASMCs by nearly twofold and over-expression of PTEN significantly inhibited hypoxia-induced PASMCs proliferation. These findings suggest that phospho-PTEN loss in the nuclei of PASMCs under hypoxic conditions may be the major cause of aberrant activation of Akt1 and may, therefore, play an important role in hypoxia-associated pulmonary arterial remodeling. Finally, the fact that transfection with Ad-PTEN inhibits the phosphorylation of Akt1 in PASMCs suggests a potential therapeutic effect on hypoxia-associated pulmonary arterial remodeling.

  15. Positive regulation of the Egr-1/osteopontin positive feedback loop in rat vascular smooth muscle cells by TGF-{beta}, ERK, JNK, and p38 MAPK signaling

    SciTech Connect (OSTI)

    Yu, Hong-Wei; Liu, Qi-Feng [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China)] [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China); Liu, Gui-Nan, E-mail: guinanliu@hotmail.com [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China)] [Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping Block, Shenyang, 110001 Liaoning Province (China)

    2010-05-28T23:59:59.000Z

    Previous studies identified a positive feedback loop in rat vascular smooth muscle cells (VSMCs) in which early growth response factor-1 (Egr-1) binds to the osteopontin (OPN) promoter and upregulates OPN expression, and OPN upregulates Egr-1 expression via the extracellular signal-regulated protein kinase (ERK) signaling pathway. The current study examined whether transforming growth factor-{beta} (TGF-{beta}) activity contributes to Egr-1 binding to the OPN promoter, and whether other signaling pathways act downstream of OPN to regulate Egr-1 expression. ChIP assays using an anti-Egr-1 antibody showed that amplification of the OPN promoter sequence decreased in TGF-{beta} DNA enzyme-transfected VSMCs relative to control VSMCs. Treatment of VSMCs with PD98059 (ERK inhibitor), SP600125 (JNK inhibitor), or SB203580 (p38 MAPK inhibitor) significantly inhibited OPN-induced Egr-1 expression, and PD98059 treatment was associated with the most significant decrease in Egr-1 expression. OPN-stimulated VSMC cell migration was inhibited by SP600125 or SB203580, but not by PD98059. Furthermore, MTT assays showed that OPN-mediated cell proliferation was inhibited by PD98059, but not by SP600125 or SB203580. Taken together, the results of the current study show that Egr-1 binding to the OPN promoter is positively regulated by TGF-{beta}, and that the p38 MAPK, JNK, and ERK pathways are involved in OPN-mediated Egr-1 upregulation.

  16. MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma

    SciTech Connect (OSTI)

    Marin-Kuan, M. [Nestle Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)], E-mail: maricel.marin-kuan@rdls.nestle.com; Nestler, S. [Nephro-Urology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1E 1EH (United Kingdom); Department of Environmental Science and Technology, Imperial College London, London SW7 2AZ (United Kingdom); Verguet, C.; Bezencon, C.; Piguet, D.; Delatour, T. [Nestle Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland); Mantle, P. [Department of Environmental Science and Technology, Imperial College London, London SW7 2AZ (United Kingdom); Cavin, C.; Schilter, B. [Nestle Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

    2007-10-15T23:59:59.000Z

    Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA over 7 days, 21 days and 12 months were analysed for various cell signalling proteins known to be potentially involved in chemical carcinogenicity. OTA was found to increase the phosphorylation of atypical-PKC. This was correlated with a selective downstream activation of the MAP-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) and of their substrates ELK1/2 and p90RSK. Moreover, analysis of effectors acting upstream of PKC indicated a possible mobilisation of the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic activity associated with enhanced HDAC3 protein expression was also observed. These findings are potentially relevant with respect to the understanding of OTA nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to play a role in tumour development. Furthermore, PKC and the MEK-ERK MAP-kinase pathways are known to play important roles in cell proliferation, cell survival, anti-apoptotic activity and renal cancer development.

  17. Effect of short-term exposure to dichlorvos on synaptic plasticity of rat hippocampal slices: Involvement of acylpeptide hydrolase and {alpha}{sub 7} nicotinic receptors

    SciTech Connect (OSTI)

    Olmos, Cristina; Sandoval, Rodrigo [Laboratory of Environmental Neurotoxicology, Department of Biomedical Sciences, Faculty of Medicine, Universidad Catolica del Norte, Larrondo 1281, 178-1421 Coquimbo (Chile); Rozas, Carlos [Laboratory of Neurosciences, Department of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Alameda 3363, Santiago (Chile); Navarro, Sebastian [Laboratory of Environmental Neurotoxicology, Department of Biomedical Sciences, Faculty of Medicine, Universidad Catolica del Norte, Larrondo 1281, 178-1421 Coquimbo (Chile); Wyneken, Ursula [Laboratory of Neurosciences, Faculty of Medicine, Universidad de Los Andes, San Carlos de Apoquindo 2200, Santiago (Chile); Zeise, Marc [School of Psychology, Faculty of Humanities, University of Santiago de Chile, Alameda 3363, Santiago (Chile); Morales, Bernardo [Laboratory of Neurosciences, Department of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Alameda 3363, Santiago (Chile); Pancetti, Floria [Laboratory of Environmental Neurotoxicology, Department of Biomedical Sciences, Faculty of Medicine, Universidad Catolica del Norte, Larrondo 1281, 178-1421 Coquimbo (Chile)], E-mail: pancetti@ucn.cl

    2009-07-01T23:59:59.000Z

    Dichlorvos is the active molecule of the pro-drug metrifonate used to revert the cognitive deficits associated with Alzheimer's disease. A few years ago it was reported that dichlorvos inhibits the enzyme acylpeptide hydrolase at lower doses than those necessary to inhibit acetylcholinesterase to the same extent. Therefore, the aim of our investigation was to test the hypothesis that dichlorvos can enhance synaptic efficacy through a mechanism that involves acylpeptide hydrolase instead of acetylcholinesterase inhibition. We used long-term potentiation induced in rat hippocampal slices as a model of synaptic plasticity. Our results indicate that short-term exposures (20 min) to 50 {mu}M dichlorvos enhance long-term potentiation in about 200% compared to the control condition. This effect is correlated with approximately 60% inhibition of acylpeptide hydrolase activity, whereas acetylcholinesterase activity remains unaffected. Paired-pulse facilitation and inhibition experiments indicate that dichlorvos does not have any presynaptic effect in the CA3 {yields} CA1 pathway nor affect gabaergic interneurons. Interestingly, the application of 100 nM methyllicaconitine, an {alpha}{sub 7} nicotinic receptor antagonist, blocked the enhancing effect of dichlorvos on long-term potentiation. These results indicate that under the exposure conditions described above, dichlorvos enhances long-term potentiation through a postsynaptic mechanism that involves (a) the inhibition of the enzyme acylpeptide hydrolase and (b) the modulation of {alpha}{sub 7} nicotinic receptors.

  18. 4-Hydroxyestradiol is conjugated with thiols primarily at C-2: evidence from regiospecific displacement of tritium by rat liver microsomes or tyrosinase

    SciTech Connect (OSTI)

    Jellinck, P.H.

    1988-03-01T23:59:59.000Z

    4-Hydroxyestradiol bearing a 3H label specifically at C-2 was prepared chemically and incubated with male rat liver microsomes or mushroom tyrosinase. A very high proportion (80-90%) of the 3H was displaced from the labeled steroid when either glutathione or N-acetylcysteine was present, and tyrosinase was shown not to require NADPH as cofactor for this reaction. In either case, only negligible amounts (less than 3%) of the 3H radioactivity were found associated with water-soluble adducts in contrast to 3H-labeled 2-hydroxyestradiol, which gave rise to about 25% of such products. The effect of ascorbic acid on the microsomal reaction with regiospecifically labeled estradiol, 2-hydroxyestradiol, and 4-hydroxyestradiol was also investigated, and the results are discussed in terms of the reactivity at different carbon atoms in ring A of the catechol estrogens. All the evidence points to conjugation of 4-hydroxyestradiol with glutathione or N-acetylcysteine at C-2 but not C-1 of this highly reactive catechol estrogen. Measuring the displacement of 3H as 3H2O from specific positions in the steroid ring provides a useful and sensitive method to assess the formation of adducts in cases where their isolation and characterization is particularly difficult.

  19. Differences in folate?protein interactions result in differing inhibition of native rat liver and recombinant glycine N-methyltransferase by 5-methyltetrahydrofolate

    SciTech Connect (OSTI)

    Luka, Zigmund; Pakhomova, Svetlana; Loukachevitch, Lioudmila V.; Newcomer, Marcia E.; Wagner, Conrad (Vanderbilt); (LSU)

    2012-06-27T23:59:59.000Z

    Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. In mammalian liver it reduces S-adenosylmethionine levels by using it to methylate glycine, producing N-methylglycine (sarcosine) and S-adenosylhomocysteine. GNMT is inhibited by binding two molecules of 5-methyltetrahydrofolate (mono- or polyglutamate forms) per tetramer of the active enzyme. Inhibition is sensitive to the status of the N-terminal valine of GNMT and to polyglutamation of the folate inhibitor. It is inhibited by pentaglutamate form more efficiently compared to monoglutamate form. The native rat liver GNMT contains an acetylated N-terminal valine and is inhibited much more efficiently compared to the recombinant protein expressed in E. coli where the N-terminus is not acetylated. In this work we used a protein crystallography approach to evaluate the structural basis for these differences. We show that in the folate-GNMT complexes with the native enzyme, two folate molecules establish three and four hydrogen bonds with the protein. In the folate-recombinant GNMT complex only one hydrogen bond is established. This difference results in more effective inhibition by folate of the native liver GNMT activity compared to the recombinant enzyme.

  20. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

    SciTech Connect (OSTI)

    Martel, C.; Labrie, C.; Dupont, E.; Couet, J.; Trudel, C.; Rheaume, E.; Simard, J.; Luu-The, V.; Pelletier, G.; Labrie, F. (CHUL Research Center, Quebec (Canada))

    1990-12-01T23:59:59.000Z

    The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.

  1. Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex

    SciTech Connect (OSTI)

    Zlender, Vilim [Unit of Toxicology, Institute for Medical Research and Occupational Health, Zagreb (Croatia); Breljak, Davorka; Ljubojevic, Marija [Molecular Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10001, Zagreb (Croatia); Flajs, Dubravka [Unit of Toxicology, Institute for Medical Research and Occupational Health, Zagreb (Croatia); Balen, Daniela; Brzica, Hrvoje [Molecular Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10001, Zagreb (Croatia); Domijan, Ana-Marija; Peraica, Maja; Fuchs, Radovan [Unit of Toxicology, Institute for Medical Research and Occupational Health, Zagreb (Croatia); Anzai, Naohiko [Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo (Japan); Sabolic, Ivan [Molecular Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10001, Zagreb (Croatia)], E-mail: sabolic@imi.hr

    2009-09-15T23:59:59.000Z

    Mycotoxin ochratoxin A (OTA) is nephrotoxic in various animal species. In rodents, OTA intoxication impairs various proximal tubule (PT) functions, including secretion of p-aminohippurate (PAH), possibly via affecting the renal organic anion (OA) transporters (Oat). However, an effect of OTA on the activity/expression of specific Oats in the mammalian kidney has not been reported. In this work, male rats were gavaged various doses of OTA every 2nd day for 10 days, and in their kidneys we studied: tubule integrity by microscopy, abundance of basolateral (rOat1, rOat3) and brush-border (rOat2, rOat5) rOat proteins by immunochemical methods, and expression of rOats mRNA by RT-PCR. The OTA treatment caused: a) dose-dependent damage of the cells in S3 segments of medullary rays, b) dual effect upon rOats in PT: low doses (50-250 {mu}g OTA/kg b.m.) upregulated the abundance of all rOats, while a high dose (500 {mu}g OTA/kg b.m.) downregulated the abundance of rOat1, and c) unchanged mRNA expression for all rOats at low OTA doses, and its downregulation at high OTA dose. Changes in the expression of renal Oats were associated with enhanced OTA accumulation in tissue and excretion in urine, whereas the indicators of oxidative stress either remained unchanged (malondialdehyde, glutathione, 8-hydroxydeoxyguanosine) or became deranged (microtubules). While OTA accumulation and downregulation of rOats in the kidney are consistent with the previously reported impaired renal PAH secretion in rodents intoxicated with high OTA doses, the post-transcriptional upregulation of Oats at low OTA doses may contribute to OTA accumulation and development of nephrotoxicity.

  2. Repair of O sup 6 -ethylguanine in DNA protects rat 208F cells from tumorigenic conversion by N-ethyl-N-nitrosourea

    SciTech Connect (OSTI)

    Thomale, J.; Huh, Namho; Nehls, P.; Eberle, G.; Rajewsky, M.F. (Univ. of Essen Medical School (West Germany))

    1990-12-01T23:59:59.000Z

    O{sup 6}-Ethylguanine (O{sup 6}-EtGua) is one of about a dozen different alkylation products formed in the DNA of cells exposed to the alkylating N-nitroso carcinogen N-ethyl-N-nitrosourea (EtNU). The authors have evaluated selectively the relative capacity of cells for the specific enzymatic repair of O{sup 6}-EtGua as a determinant for the probability of malignant conversion. Eleven O{sup 6}-EtGua-repair-proficient (R{sup +}) variant subclones were isolated from the O{sup 6}-EtGua-repair-deficient (R{sup {minus}}) clonal rat fibroblast line 208F by selection for resistance to 1,3-bis-(2-chloroethyl)-1-nitrosourea. Contrary to the 208F wild-type cells, all variants expressed O{sup 6}-methylguanine-DNA methyltransferase activity, while both kinds of cells were deficient for repair of the DNA ethylation products O{sup 2}- and O{sup 4}-ethylthymine. After exposure to EtNU cells were analyzed for the formation of piled-up foci in monolayer culture and of anchorage-independent colonies in semisolid agar medium. No significant differences in the frequencies of piled-up foci were found between wild-type and variant cells after exposure to the major reactive metabolite of benzo(a)pyrene, (+)-7{beta},8{alpha}-dihydroxy-9,10{alpha}-epoxy7,8,9,10{alpha}-tetrahydrobenzo(a)pyrene, for which stable binding to guanine O{sup 6} in cellular DNA has not been observed. The relative capacity of cells for repair of O{sup 6}-alkylguanine is, therefore, a critical determinant for their risk of malignant conversion by N-nitroso carcinogens.

  3. Autoradiographic localization of sigma receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine

    SciTech Connect (OSTI)

    Gundlach, A.L.; Largent, B.L.; Snyder, S.H.

    1986-06-01T23:59:59.000Z

    (+)3H-3-PPP ((+)3H-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine) binds with high affinity to brain membranes with a pharmacological profile consistent with that of sigma receptors. The distribution of (+)3H-3-PPP binding sites in brain and spinal cord of both guinea pig and rat has been determined by in vitro autoradiography with binding densities quantitated by computer-assisted densitometry. (+)3H-3-PPP binding to slide-mounted brain sections is saturable and displays high affinity and a pharmacological specificity very similar to sites labeled in homogenates. (+)3H-3-PPP binding sites are heterogeneously distributed. Highest concentrations of binding sites occur in spinal cord, particularly the ventral horn and dorsal root ganglia; the pons-medulla, associated with the cranial nerve and pontine nuclei and throughout the brain stem reticular formation; the cerebellum, over the Purkinje cell layer; the midbrain, particularly the central gray and red nucleus; and hippocampus, over the pyramidal cell layer. Lowest levels are seen in the basal ganglia and parts of the thalamus, while all other areas, including hypothalamus and cerebral cortex, exhibit moderate grain densities. Quinolinic acid-induced lesions of the hippocampus indicate that (+)3H-3-PPP labels hippocampal pyramidal cells and granule cells in the dentate gyrus. Intrastriatal injection of ibotenic acid dramatically reduces (+)3H-3-PPP binding in this area, while injection of 6-hydroxydopamine produces a relatively slight decrease. The distribution of (+)3H-3-PPP binding sites does not correlate with the receptor distribution of any recognized neurotransmitter or neuropeptide, including dopamine. However, there is a notable similarity between the distribution of (+)3H-3-PPP sites and high-affinity binding sites for psychotomimetic opioids, such as the benzomorphan (+)SKF 10,047.

  4. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    SciTech Connect (OSTI)

    Tsirulnikov, Kirill; Abuladze, Natalia [Department of Medicine, University of California at Los Angeles, CA 90095 (United States)] [Department of Medicine, University of California at Los Angeles, CA 90095 (United States); Bragin, Anatol [Department of Neurology, University of California at Los Angeles, CA 90095 (United States) [Department of Neurology, University of California at Los Angeles, CA 90095 (United States); Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Faull, Kym [Brain Research Institute, University of California at Los Angeles, CA 90095 (United States) [Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095 (United States); Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 (United States); Cascio, Duilio [Institute of Genomics and Proteomics, University of California at Los Angeles, CA 90095 (United States)] [Institute of Genomics and Proteomics, University of California at Los Angeles, CA 90095 (United States); Damoiseaux, Robert; Schibler, Matthew J. [California NanoSystems Institute, University of California at Los Angeles, CA 90095 (United States)] [California NanoSystems Institute, University of California at Los Angeles, CA 90095 (United States); Pushkin, Alexander, E-mail: apushkin@mednet.ucla.edu [Department of Medicine, University of California at Los Angeles, CA 90095 (United States)] [Department of Medicine, University of California at Los Angeles, CA 90095 (United States)

    2012-09-15T23:59:59.000Z

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by ?-lyase. The enzymes of the GSH-conjugation pathway and ?-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a ?-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  5. Modeling sickle cell vasoocculsion in the rat leg: Quantification of trapped sickle cells and correlation with sup 31 P metabolic and sup 1 H magnetic resonance imaging changes

    SciTech Connect (OSTI)

    Fabry, M.E.; Rajanayagam, V.; Fine, E.; Holland, S.; Gore, J.C.; Nagel, R.L.; Kaul, D.K. (Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY (USA))

    1989-05-01T23:59:59.000Z

    The authors have developed an animal model to elucidate the acute effects of perfusion abnormalities on muscle metabolism induced by different density-defined classes of erythrocytes isolated from sickle cell anemia patients. Technetium-99m ({sup 99m}Tc)-labeled, saline-washed normal (AA), homozygous sickle (SS), or high-density SS (SS4) erythrocytes were injected into the femoral artery of the rat and quantitative {sup 99m}Tc imaging, {sup 31}P magnetic resonance spectroscopy by surface coil at 2 teslas, and {sup 1}H magnetic resonance imaging at 0.15 tesla were performed. Between 5 and 25 {mu}l of SS4 cells was trapped in the microcirculation of the thigh. In contrast, fewer SS discocytes (SS2) or AA cells were trapped. After injection of SS4 cells an initial increase in inorganic phosphate was observed in the region of the thigh served by the femoral artery, intracellular pH decreased, and subsequently the proton relaxation time T{sub 1} reached a broad maximum at 18-28 hr. When T{sub 1} obtained at this time was plotted against the volume of cells trapped, an increase of T{sub 1} over the control value of 411 {plus minus} 48 msec was found that was proportional to the number of cells trapped. They conclude that the densest SS cells are most effective at producing vasoocclusion. The extent of the change detected by {sup 1}H magnetic resonance imaging is dependent on the amount of cells trapped in the microcirculation and the magnitude of the initial increase of inorganic phosphate.

  6. Arsenite reduces insulin secretion in rat pancreatic {beta}-cells by decreasing the calcium-dependent calpain-10 proteolysis of SNAP-25

    SciTech Connect (OSTI)

    Diaz-Villasenor, Andrea [Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (Mexico); Burns, Anna L. [Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (Mexico); Facultad de Medicina, Universidad Nacional Autonoma de Mexico (Mexico); Salazar, Ana Maria; Sordo, Monserrat [Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (Mexico); Hiriart, Marcia [Department of Biophysics, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico (Mexico); Cebrian, Mariano E. [Section of Environmental Toxicology, CINVESTAV, IPN (Mexico); Ostrosky-Wegman, Patricia [Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (Mexico)], E-mail: ostrosky@servidor.unam.mx

    2008-09-15T23:59:59.000Z

    An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic {beta}-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca{sup 2+}]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 {mu}M). The global activity of calpains increased with 2 {mu}M arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 {mu}M arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the {beta} cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca{sup 2+}]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion.

  7. Tyrosine hydroxylase is activated and phosphorylated at different sites in rat pheochromocytoma PC 12 cells treated with phorbol ester and forskolin

    SciTech Connect (OSTI)

    Tachikawa, E.; Tank, A.W.; Weiner, D.H.; Mosimann, W.F.; Yanagihara, N.; Weiner, N.

    1986-03-01T23:59:59.000Z

    The effects of phorbol ester (4..beta..-phorbol, 12..beta..-myristate, 13..cap alpha..-acetate; TPA), an activator of Ca/sup + +//phospholipid-dependent protein kinase (PK-C), and forskolin, which stimulates adenylate cyclase and cyclic AMP-dependent protein kinase (cAMP-PK), on the activation and phosphorylation of tyrosine hydroxylase (TH) in rat pheochromocytoma (PC 12) cells were examined. Incubation of the cells with TPA (0.01-1 ..mu..M) or forskolin (0.01-0.1 ..mu..M) produces increases in activation and phosphorylation of TH in a concentration-dependent manner. The stimulatory effects of TPA are dependent on extracellular Ca/sup + +/ and are inhibited by pretreatment of the cells with trifluoperazine (TFP). The effects of forskolin are independent of Ca/sup + +/ and are not inhibited by TFP. In cells treated with forskolin, the time course of the increase in cAMP correlates with the increases in TH activity and phosphorylation. cAMP levels do not increase in cells treated with TPA. There is an increase in the phosphorylation of only one tryptic phosphopeptide derived from TH in cells treated with either forskolin or TPA. The peptide phosphorylated in TPA-treated cells exhibits different elution characteristics on HPLC from that in forskolin-treated cells. The authors conclude that TH in PC 12 cells is phosphorylated on different sites by cAMP-PK and PK-C. Phosphorylation of either of these sites is associated with enzyme activation.

  8. {gamma}-aminobutyric acid{sub A} (GABA{sub A}) receptor regulates ERK1/2 phosphorylation in rat hippocampus in high doses of Methyl Tert-Butyl Ether (MTBE)-induced impairment of spatial memory

    SciTech Connect (OSTI)

    Zheng Gang; Zhang Wenbin [Department of Occupational and Environmental Health, School of Public Health and Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032 (China); Zhang Yun [465 Hospital, Jilin Medical College, Jilin 132001 (China); Chen Yaoming; Liu Mingchao; Yao Ting; Yang Yanxia; Zhao Fang [Department of Occupational and Environmental Health, School of Public Health and Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032 (China); Li Jingxia; Huang Chuanshu [Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987 (United States); Luo Wenjing [Department of Occupational and Environmental Health, School of Public Health and Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032 (China)], E-mail: luowenj@fmmu.edu.cn; Chen Jingyuan [Department of Occupational and Environmental Health, School of Public Health and Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032 (China)], E-mail: jy_chen@fmmu.edu.cn

    2009-04-15T23:59:59.000Z

    Experimental and occupational exposure to Methyl Tert-Butyl Ether (MTBE) has been reported to induce neurotoxicological and neurobehavioral effects, such as headache, nausea, dizziness, and disorientation, etc. However, the molecular mechanisms involved in MTBE-induced neurotoxicity are still not well understood. In the present study, we investigated the effects of MTBE on spatial memory and the expression and function of GABA{sub A} receptor in the hippocampus. Our results demonstrated that intraventricular injection of MTBE impaired the performance of the rats in a Morris water maze task, and significantly increased the expression of GABA{sub A} receptor {alpha}1 subunit in the hippocampus. The phosphorylation of ERK1/2 decreased after the MTBE injection. Furthermore, the decreased ability of learning and the reduction of phosphorylated ERK1/2 level of the MTBE-treated rats was partly reversed by bicuculline injected 30 min before the training. These results suggested that MTBE exposure could result in impaired spatial memory. GABA{sub A} receptor may play an important role in the MTBE-induced impairment of learning and memory by regulating the phosphorylation of ERK in the hippocampus.

  9. Effets de l'administration chronique d'insuline sur la prise alimentaire et le gain de poids chez le rat, par Christiane LARUE-ACHAGIOTIS, J. LE MAGNEN, Collge de France, 11 placeChristiane LARUE-ACHAGIOTIS, J. LE MAGNEN Collge de France, 11 place

    E-Print Network [OSTI]

    Boyer, Edmond

    intraventricular insulin infusion reduces food intake and body weight in rats. Abstr. Soc. Neurosci. 7, 655. Vanderweele D. A., Pi-Sunyer, F. X., Novin D., Bush M. J., 1980. Chronic insulin infusion suppresses food Kay L. D., Porte Jr. D., 1979. Chronic intra-cerebroventricular infusion of insulin reduces food

  10. Role of the nuclear xenobiotic receptors CAR and PXR in induction of cytochromes P450 by non-dioxinlike polychlorinated biphenyls in cultured rat hepatocytes

    SciTech Connect (OSTI)

    Gährs, Maike; Roos, Robert [University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schroedinger-Str. 52, D-67663 Kaiserslautern (Germany); Andersson, Patrik L. [Umeå University, Department of Chemistry, Linnaeus väg 6, SE-901 87 Umeå (Sweden); Schrenk, Dieter, E-mail: schrenk@rhrk.uni-kl.de [University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schroedinger-Str. 52, D-67663 Kaiserslautern (Germany)

    2013-10-01T23:59:59.000Z

    Polychlorinated biphenyls (PCBs) are among the most ubiquitously detectable ‘persistent organic pollutants’. In contrast to ‘dioxinlike’ (DL) PCBs, less is known about the molecular mode of action of the larger group of the ‘non-dioxinlike’ (NDL) PCBs. Owing to the life-long exposure of the human population, a carcinogenic, i.e., tumor-promoting potency of NDL-PCBs has to be considered in human risk assessment. A major problem in risk assessment of NDL-PCBs is dioxin-like impurities that can occur in commercially available NDL-PCB standards. In the present study, we analyzed the induction of CYP2B1 and CYP3A1 in primary rat hepatocytes using a number of highly purified NDL-PCBs with various degrees of chlorination and substitution patterns. Induction of these enzymes is mediated by the nuclear xenobiotic receptors CAR (Constitutive androstane receptor) and PXR (Pregnane X receptor). For CYP2B1 induction, concentration–response analysis revealed a very narrow window of EC{sub 50} estimates, being in the range of 1–4 ?M for PCBs 28 and 52, and between 0.4 and 1 ?M for PCBs 101, 138, 153 and 180. CYP3A1 induction was less sensitive to NDL-PCBs, the most pronounced induction being achieved at 100 ?M with the higher chlorinated congeners. Using okadaic acid and small interfering RNAs targeting CAR and PXR, we could demonstrate that CAR plays a major role and PXR a minor role in NDL-PCB-driven induction of CYPs, both effects showing no stringent structure–activity relationship. As the only obvious relevant determinant, the degree of chlorination was found to be positively correlated with the inducing potency of the congeners. - Highlights: • We analyzed six highly purified NDL-PCBs for CYP2B1 and CYP3A1 expression. • CAR plays a major, PXR a minor role in NDL-PCB-driven induction of CYPs. • The degree of chlorination seems to be the major parameter for the inducing potency. • There exists a competition between CAR and PXR. • Activated PXR may antagonize CAR binding to the CYP2B1 promoter.

  11. Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1

    SciTech Connect (OSTI)

    Liu, Qi-Feng [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)] [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Yu, Hong-Wei [Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001 (China)] [Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001 (China); You, Lu; Liu, Ming-Xin [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)] [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Li, Ke-Yan [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China) [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001 (China); Tao, Gui-Zhou, E-mail: guizhoutao-@hotmail.com [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)] [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)

    2013-09-20T23:59:59.000Z

    Highlights: •The mechanism underlying the effects of Apelin-13 on VSMC was investigated. •Apelin-13 induced VSMC migration, proliferation and Egr-1 and OPN upregulation. •These effects were inhibited by the Egr-1 specific deoxyribozyme, ED5. •The effects of Apelin-13 on VSMC are mediated via Egr-1 upregulation. •These data will help in attempts to prevent and treat vascular remodeling diseases. -- Abstract: Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration. We hypothesized that the role of Apelin-13 is mediated via upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin-13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT-PCR and Western blotting, respectively. Results showed that, Apelin-13 upregulated the expression of Egr-1. Furthermore, treatment with the extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23 DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13-induced migration and proliferation of VSMCs using transwell and MTT assays, respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13-induced OPN upregulation. The results of this study indicated that Apelin-13 upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr-1. These results will provide an important theoretical and experimental basis for the control of inappropriate remodeling of vessel walls, and will hopefully lead to the prevention and treatment of vascular remodeling diseases.

  12. D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway

    SciTech Connect (OSTI)

    Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India)] [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)] [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India)] [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

    2011-12-15T23:59:59.000Z

    Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D-saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20-120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic {beta}-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic {beta}-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. Highlights: Black-Right-Pointing-Pointer Oxidative stress is suggested as a key event in the pathogenesis of diabetes. Black-Right-Pointing-Pointer D-saccharic acid 1,4-lactone (DSL) reduces the alloxan-induced diabetes mellitus. Black-Right-Pointing-Pointer DSL normalizes cellular antioxidant machineries disturbed due to alloxan toxicity. Black-Right-Pointing-Pointer DSL inhibits pancreatic {beta}-cells apoptosis via mitochondria-dependent pathway. Black-Right-Pointing-Pointer DSL could be a promising approach for the treatment of diabetes mellitus.

  13. Persistent fibrosis in the liver of choline-deficient and iron-supplemented L-amino acid-defined diet-induced nonalcoholic steatohepatitis rat due to continuing oxidative stress after choline supplementation

    SciTech Connect (OSTI)

    Takeuchi-Yorimoto, Ayano, E-mail: ayano.takeuchi@astellas.com [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Noto, Takahisa [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan); Yamada, Atsushi [Drug Safety Research Division, Astellas Research Technologies Co., Ltd., Osaka 532-8514 (Japan); Miyamae, Yoichi; Oishi, Yuji; Matsumoto, Masahiro [Drug Safety Research Labs, Astellas Pharma Inc., Osaka 532-8514 (Japan)

    2013-05-01T23:59:59.000Z

    Nonalcoholic steatohepatitis (NASH) is characterized by combined pathology of steatosis, lobular inflammation, fibrosis, and hepatocellular degeneration, with systemic symptoms of diabetes or hyperlipidemia, all in the absence of alcohol abuse. Given the therapeutic importance and conflicting findings regarding the potential for healing the histopathologic features of NASH in humans, particularly fibrosis, we investigated the reversibility of NASH-related findings in Wistar rats fed a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet for 12 weeks, with a recovery period of 7 weeks, during which the diets were switched to a choline-sufficient and iron-supplemented L-amino acid-defined (CSAA) one. Analysis showed that steatosis and inflammation were significantly resolved by the end of the recovery period, along with decreases in AST and ALT activities within 4 weeks. In contrast, fibrosis remained even after the recovery period, to an extent similar to that in continuously CDAA-fed animals. Real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical investigations revealed that expression of some factors indicating oxidative stress (CYP2E1, 4-HNE, and iNOS) were elevated, whereas catalase and SOD1 were decreased, and a hypoxic state and CD34-positive neovascularization were evident even after the recovery period, although the fibrogenesis pathway by activated ?-SMA-positive hepatic stellate cells via TGF-? and TIMPs decreased to the CSAA group level. In conclusion, persistent fibrosis was noted after the recovery period of 7 weeks, possibly due to sustained hypoxia and oxidative stress supposedly caused by capillarization. Otherwise, histopathological features of steatosis and inflammation, as well as serum AST and ALT activities, were recovered. - Highlights: ? NASH-like liver lesions are induced in rats by feeding a CDAA diet. ? Steatosis and lobular inflammation are resolved after switching to a CSAA diet. ? Fibrosis is sustained, possibly due to continuing hypoxia and oxidative stress.

  14. 3{alpha}-6{alpha}-Dihydroxy-7{alpha}-fluoro-5{beta}-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17{alpha}-ethynyl-estradiol-induced cholestasis in rats

    SciTech Connect (OSTI)

    Clerici, Carlo [Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale Universita degli Studi di Perugia, 06122 Perugia (Italy)]. E-mail: clerici@unipg.it; Castellani, Danilo [Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale Universita degli Studi di Perugia, 06122 Perugia (Italy); Asciutti, Stefania [Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale Universita degli Studi di Perugia, 06122 Perugia (Italy); Pellicciari, Roberto [Istituto di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, via del Liceo, 06123 Perugia (Italy); Setchell, Kenneth D.R. [Division of Pathology, Clinical Mass Spectrometry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States)]|[Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229 (United States); O'Connell, Nancy C. [Division of Pathology, Clinical Mass Spectrometry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 (United States)]|[Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229 (United States); Sadeghpour, Bahman; Camaioni, Emidio [Istituto di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, via del Liceo, 06123 Perugia (Italy); Fiorucci, Stefano; Renga, Barbara; Nardi, Elisabetta; Sabatino, Giuseppe; Clementi, Mattia; Giuliano, Vittorio; Baldoni, Monia; Orlandi, Stefano; Mazzocchi, Alessandro; Morelli, Antonio; Morelli, Olivia [Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale Universita degli Studi di Perugia, 06122 Perugia (Italy)

    2006-07-15T23:59:59.000Z

    3{alpha}-6{alpha}-Dihydroxy-7{alpha}-fluoro-5{beta}-cholanoate (UPF-680), the 7{alpha}-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17{alpha}-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 {mu}mol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO{sub 3} {sup -}), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO{sub 3} {sup -} output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na{sup +} taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease.

  15. Ultrastructural development of the rat corpus luteum

    E-Print Network [OSTI]

    Bailey, John Franklin

    1971-01-01T23:59:59.000Z

    ' -GCL ttlrcughoLL't r and in concci -ated focal points, in the cytoclasm. The c-. "ccnt=ationls took on the conf igLLration of -whorls 3, 1?' "Je e;. i1?i?n tile nate Dale, Oilee, 1/ie pa'raSOI&e were ?lost numerous 4-6 days after ovLllati on, but i.... er. The buffer u' ilizec. was s-colli- dine Cock solut! on which . ;as prepared as 2. 67 ca. ts s-coll c i!6 & 9 part, hyd rochlor ic acid, ? nd BG. "j3 part" distilled water. Sucrose was added to th. 's fixative-buffer solution at the rate of 0...

  16. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan

    2008-01-01T23:59:59.000Z

    Figure 2 shows simulations of learning of weight for cue A (a previous simulation of sequential learning based on thesimulations are in good agreement with experimental findings. Keywords: Bayesian inference; model selection; sequential causal learning;

  17. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Hongjing Lu; Randall R. Rojas; Tom Beckers; Alan Yuille

    2011-01-01T23:59:59.000Z

    Figure 2 shows simulations of learning of weight for cue A (a previous simulation of sequential learning based on thesimulations are in good agreement with experimental findings. Keywords: Bayesian inference; model selection; sequential causal learning;

  18. Rat Trachea Dose Distribution Model Using MCNPTM

    E-Print Network [OSTI]

    Almanza, Christian

    2010-01-15T23:59:59.000Z

    of 10 statistical checks for the estimated answer for the tally fluctuation chart (tfc) bin of tally 6 tfc bin --mean-- ---------relative error--------- ----variance of the variance---- --figure of merit-- - pdf... =============================================================================== ==================================================== results of 10 statistical checks for the estimated answer for the tally fluctuation chart (tfc) bin of tally 8 tfc bin --mean-- ---------relative error--------- ----variance of the variance---- --figure of merit-- - pdf...

  19. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan

    2008-01-01T23:59:59.000Z

    selection, to a human experiment that employed pretraining (group (white) in human experiment by Beckers et al. (2005).set used for the human experiments, we increased the

  20. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Hongjing Lu; Randall R. Rojas; Tom Beckers; Alan Yuille

    2011-01-01T23:59:59.000Z

    selection, to a human experiment that employed pretraining (group (white) in human experiment by Beckers et al. (2005).set used for the human experiments, we increased the

  1. Ultrastructural development of the rat corpus luteum 

    E-Print Network [OSTI]

    Bailey, John Franklin

    1971-01-01T23:59:59.000Z

    ' -GCL ttlrcughoLL't r and in concci -ated focal points, in the cytoclasm. The c-. "ccnt=ationls took on the conf igLLration of -whorls 3, 1?' "Je e;. i1?i?n tile nate Dale, Oilee, 1/ie pa'raSOI&e were ?lost numerous 4-6 days after ovLllati on, but i.... er. The buffer u' ilizec. was s-colli- dine Cock solut! on which . ;as prepared as 2. 67 ca. ts s-coll c i!6 & 9 part, hyd rochlor ic acid, ? nd BG. "j3 part" distilled water. Sucrose was added to th. 's fixative-buffer solution at the rate of 0...

  2. The Rat’s not for Turning: Dissociating the Psychological Components of Cognitive Inflexibility

    E-Print Network [OSTI]

    Nilsson, Simon R.O.; Alsiö, Johan; Somerville, Elizabeth M.; Clifton, Peter G.

    2015-01-01T23:59:59.000Z

    , attentional set-shifting is more cognitively challenging than reversal learning. This was initially attributed to the partial positive reinforcement of a previously rewarded stimulus after the attentional set shift (Buss, 1953); but this hypothesis... was falsified by studies demonstrating that attentional set-shifting is more difficult than reversal learning even after controlling for partial reinforcement (Buss, 1956; Harrow and Friedman, 1958; Kendler and D'Amato, 1955). Yet it should be noted...

  3. Methamphetamine self-administration in rats developmentally exposed to lead

    E-Print Network [OSTI]

    Rocha, Angelica

    2009-05-15T23:59:59.000Z

    Methamphetamine is gaining mainstream popularity across the United States at the same time that lead exposure remains at elevated levels. Perinatal (gestation/lactation) lead exposure has been found to modify the reward efficacy of various drugs...

  4. awake behaving rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    temporal response, and spatial resolution of IRON fMRI in awake, behaving monkeys at 3 Tesla MIT - DSpace Summary: The main goal of this thesis was to systematically characterize...

  5. aged male rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Locker Half Male Varun Aggarwala Daniel Stringer Noah Benson John Philbin Michael Campbell Michael Nathan Lawrence Brown Theodor Oxholm John Jackson Jeffrey Haymaker Keith...

  6. adolescent male rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Locker Half Male Varun Aggarwala Daniel Stringer Noah Benson John Philbin Michael Campbell Michael Nathan Lawrence Brown Theodor Oxholm John Jackson Jeffrey Haymaker Keith...

  7. adult male rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Locker Half Male Varun Aggarwala Daniel Stringer Noah Benson John Philbin Michael Campbell Michael Nathan Lawrence Brown Theodor Oxholm John Jackson Jeffrey Haymaker Keith...

  8. adult male rat: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Locker Half Male Varun Aggarwala Daniel Stringer Noah Benson John Philbin Michael Campbell Michael Nathan Lawrence Brown Theodor Oxholm John Jackson Jeffrey Haymaker Keith...

  9. anesthetized male rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Locker Half Male Varun Aggarwala Daniel Stringer Noah Benson John Philbin Michael Campbell Michael Nathan Lawrence Brown Theodor Oxholm John Jackson Jeffrey Haymaker Keith...

  10. aging male rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Locker Half Male Varun Aggarwala Daniel Stringer Noah Benson John Philbin Michael Campbell Michael Nathan Lawrence Brown Theodor Oxholm John Jackson Jeffrey Haymaker Keith...

  11. adolescent female rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    authors 48 Female Leadership Raises Aspirations and Educational Attainment for Girls: A Policy Experiment in India MIT - DSpace Summary: Exploiting a randomized natural...

  12. african multimammate rat: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    African horse sickness (AHS) is a serious, often fatal, arthropod-borne viral disease of horses and mules. The mortality rate can be as high as 95 % in some forms of this disease....

  13. Genetical genomic determinants of alcohol consumption in rats and humans

    E-Print Network [OSTI]

    2009-01-01T23:59:59.000Z

    total of 31,379 (quality controltotal was divided by 30 to obtain the daily average. Quality Control

  14. Population dynamics of the cotton rat (genus Sigmodon

    E-Print Network [OSTI]

    Inglis, Jack Morton

    1955-01-01T23:59:59.000Z

    ie doeesdbe4 in the towt, iaAher eowee of infasaahhsas tho teak etndiees swyCreo esne diameefea et thie point, la Psbreary 195ls sa aaLo and tea foaelo eAton rato mse ineleeod in e aLa by eesen feet, tesh4Qa eego, %de iswloesssa eoneiete4 of ~ lae... of the gs?nai ~ hs& ns oewr. k foa eyeeios eith flan~@ming~ Largo sos&Lings sash ss ysseioa fleeer es& batten ensL 4 sero able 4e gmee ia this typo bst nseaQg it sse bassa see&a& peeped alone Whish ws fbnn& those, TLN asst Wai&stieaUp &iws?o typo oa tbs...

  15. Behavioral contrast and local rate-of-response in rats

    E-Print Network [OSTI]

    Dreyfus, Leon Richard

    1976-01-01T23:59:59.000Z

    to maintain the proper perspective throughout the years. vi TABLE OF CONTENTS INTRODUCTION AND REVIEW OF THE LITERATURE METHODS Page ~Sb ~~~At Procedure 10 RESULTS DISCUSSION 12 18 Conclusions REFERENCES VITA 21 23 26 vii LIST OF FIGURES.... The frequency of reinforcement was determined by variable-interval (VI) schedules in which reinforcement is available after a variable period of time providing a key-peck occurs after the time has elapsed. Variable- interval schedules are typically specified...

  16. Mechanical properties of normotensive and hypertensive female rat carotid arteries

    E-Print Network [OSTI]

    Smith, Katherine Elizabeth

    2002-01-01T23:59:59.000Z

    drawing of the layers of the arterial wall (IM, an A denote iniima, media, and adventitia, respectively); B. Cross-sectional muscular artery histology (The Elebrew University of Jerusalem, 1997) Tortuous inner layer is the internal elastic lamina, which... divides the intima and the media. The darker middle layer with circumferentially oriented smooth muscle cells is the media, and lighter outer layer is the adventitia. d This thesis follows the style and format of Journal of Biomechanics. constantly...

  17. Recent Advances in Genetics of the Spontaneously Hypertensive Rat

    E-Print Network [OSTI]

    Pravenec, Michal; Kurtz, Theodore W.

    2010-01-01T23:59:59.000Z

    of blood pressure and hypertension. Nat Genet 2009, 41:677–identifies STK39 as a hypertension susceptibility gene. Procfactors in spontaneous hypertension. J Clin Invest 1999,

  18. Population dynamics of the cotton rat (genus Sigmodon 

    E-Print Network [OSTI]

    Inglis, Jack Morton

    1955-01-01T23:59:59.000Z

    setdmdeel Oellege hsIfillaesdI of the map gwydgeeaa4e SN' the degiee od' keLsccngh~at ie dee aeey ye?pm? eitboui ?hoes aeeieteew tba etcctp eouM lech a?eh ef ~4 valse Lt bee~ %?abaca of ~ y grade?is aewittWC Qro J Jo sperry Oai art Oe Bc OeghapC ?CO dae... ~ e ~ ~ e ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 14 COM ON(5fiiOO 1%flllQNO ~ ~ ~ e t ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 17 AK+ bObi4 ~ ~ ~ ~ ~ ~ ~ e ~ e ~ ~ e ~ ~ ~ ~ ~ e ~ ~ ~ ~ 22 804 @g4f ~iOOO ~ ~ ~ ~ ~ ~ e ~ ~ ~ ~ e t ~ ~ ~ ~ ~ 26 Xe4taetjoa ef Oeer OIkl he4...

  19. Hemorrhagic stress effects on blood in irradiated rats

    E-Print Network [OSTI]

    Elissalde, Marcel Howell

    1966-01-01T23:59:59.000Z

    conditions the leukocyte, platelet and reticulo- cyte counts in the circulating blood of the human are back to norsml within two weeks following hemorrhage (26). Because of the gradual readjustment of circulatory volume and the general vasoconstriction...

  20. Of pungency, pain, and naked mole rats: chili peppers revisited

    E-Print Network [OSTI]

    Borges, Renee M

    to the chili pepper genus Capsicum within the plant family Solanaceae. The family is also known for species that produce powerful alkaloids such as nicotine (tobacco) and atropine (Atropa). This is the same family considerable survival value since they signal the presence of extreme external and internal threats; internally

  1. Quantifying non-axial deformations in rat myocardium

    E-Print Network [OSTI]

    Aghassibake, Kristina Diane

    2005-02-17T23:59:59.000Z

    comprise the sarcomere, the fundamental unit of contraction. The sarcomere 4 is bounded on both sides by the Z line, which is the structural backbone of the actin filaments (Opie, 2004). Fig. 1. Diagram of myofilament arrangement in striated muscle... shortens the sarcomere and is thought to be the fundamental mechanism of muscle contraction. Relaxation occurs when, in the presence of ATP, the myosin heads detach from the actin filaments and resume their un-flexed configuration (Opie, 2004). 6...

  2. Acute Hyperglycemia Worsens Hepatic Ischemia/Reperfusion Injury in Rats

    E-Print Network [OSTI]

    Behrends, Matthias; Martinez-Palli, Graciela; Niemann, Claus U.; Cohen, Sara; Ramachandran, Rageshree; Hirose, Ryutaro

    2010-01-01T23:59:59.000Z

    Rodgers CD, Locke M. Altered heat stress response followingHSP70 activation by heat stress, 23 although subsequentrats following heat stress. 24 Further interventional

  3. Propofol and sevoflurane induce distinct burst suppression patterns in rats

    E-Print Network [OSTI]

    Westover, M. Brandon

    Burst suppression is an EEG pattern characterized by alternating periods of high-amplitude activity (bursts) and relatively low amplitude activity (suppressions). Burst suppression can arise from several different pathological ...

  4. Meeting the oxygen requirements of an isolated perfused rat liver

    E-Print Network [OSTI]

    Izamis, Maria-Louisa, 1979-

    2006-01-01T23:59:59.000Z

    Liver perfusion systems can be used as organ culture platforms for metabolic, genetic and systems engineering, tissue regeneration, pharmacokinetics, organ storage and marginal donor reconditioning for transplantation. The ...

  5. Rat Behavioral Thermoregulation Integrates With Nonshivering Thermogenesis During Postnatal Development

    E-Print Network [OSTI]

    and on a thermocline, as early as the 1st week of postnatal life, and these pups can also produce heat metabolically mediated metabolism of brown adipose tissue (BAT). BAT is well formed in newborns and functions shortly thermogenesis. In the present study, 2-, 7-, and 14-day-old pups were observed on a thermal gradient following

  6. Arginine and Conjugated Linoleic Acid Reduce Fat Mass in Rats 

    E-Print Network [OSTI]

    Nall, Jennifer L.

    2010-10-12T23:59:59.000Z

    &M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved by: Chair of Committee, Stephen B. Smith Committee Members, John Bauer Guoyao Wu Chair of Nutrition Faculty, Stephen... may be due to effects on the metabolism of muscle, liver, and adipose tissue. v DEDICATION This thesis is dedicated to my parents, who have provided me with unconditional love, guidance...

  7. The effects of alcohol and irradiation on the albino rat

    E-Print Network [OSTI]

    Klobukowski, Christopher John

    1963-01-01T23:59:59.000Z

    , Cole and i'. ilia reported that Lifi mice x;her pretxeeted. '. "! th ~ntrapcri toneal injection: of ethanol . nd iz'radiated with doses of X-rays xanging i'rom 600r to g00r (51350 is 620r for this strain) were protected from radiation by a xeduction... administered either orally, (paterson, 1951), or by intrsperitoneal injection, (Cole, 1952; Cole, 1955& praslidka, 1956), anc was given in acute doses. All experiment, showed ;. ome protect' ve effect. 5 ~ -'alcohol administered costirrad3. H, tion...

  8. anaesthetized female rat: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    a 16-mg lead or a control solution for 30 days... Rocha, Angelica 2009-05-15 55 Perception of Conspecific Female Pheromone Stimulates Female Calling in an Arctiid Moth,...

  9. adult rats subjected: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the idea of creating a subjectivity classifier that uses lists of subjective nouns learned by bootstrapping algorithms. The goal of our research is to develop a system that can...

  10. Radiobiology of normal rat lung in Boron Neutron Capture Therapy

    E-Print Network [OSTI]

    Kiger, Jingli Liu

    2006-01-01T23:59:59.000Z

    Boron Neutron Capture Therapy (BNCT) is a binary cancer radiation therapy that utilizes biochemical tumor cell targeting and provides a mixed field of high and low Linear Energy Transfer (LET) radiation with differing ...

  11. aged rat erectile: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    98504-3144 An age-length key (ALK) is the tra- ditional method for estimating age-stage length samples for relatively costly age determination (age subsamplel. Age...

  12. adult rats fed: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Websites Summary: mover speed is variable, such as in wind turbines. For variable speed operation one of the machine's stator windings is connected to the fixed frequency...

  13. EFFECT OF DIETARY CHOLESTEROL ON BRAIN CHOLESTEROL IN DEVELOPING RATS

    E-Print Network [OSTI]

    Gottipati, Bhavana Sindhu

    2008-04-29T23:59:59.000Z

    at the beginning of this project and Melanie Curtis, MS, for her help and support in the lab. Finally, I would like to thank my husband Madhu Narra, MD, MS, for his support and encouragement...

  14. Melatonin modulates intercellular communication among immortalized rat suprachiasmatic nucleus cells

    E-Print Network [OSTI]

    Cox, Kimberly Yvonne

    2009-05-15T23:59:59.000Z

    , the influence of melatonin on calcium waves was studied in the presence of endogenously accumulated or exogenously supplemented ATP. 12 CHAPTER II MATERIALS AND METHODS Cell culture Cultures of SCN2.2 cells were grown on laminin-coated culture dishes (60... to cross gap junctions when introduced intracellularly. The dye solution was supplemented with melatonin or CBX as appropriate. Confluent cells on glass-bottom dishes were then damaged with a fresh, sterile scalpel blade or a pulled glass pipette tip...

  15. The role of spatial context in rat vision

    E-Print Network [OSTI]

    Meier, Philip Martin

    2011-01-01T23:59:59.000Z

    J. M. (1994). Human luminance pattern-vision mechanisms:A. , & Peli, E. (2001). Luminance artifacts of cathode-raysurround contrast and luminance did not reliably influence

  16. adolescent rats anxiety: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    social anxiety in 47 high trait social anxiety (HTSA) and 50 low trait social anxiety (LTSA) participants using an impromptu speech paradigm. We assessed anxiety experience,...

  17. abrasion tool rat: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    CMP Based on the Contact Mechanics of Pad, Abrasives, and Wafer Diner. Published October 7, 2009. Chemical mechanical polishing CMP is a polishing method commonly used...

  18. Exercise training modulates apoptotic signaling in the aging rat heart

    E-Print Network [OSTI]

    Kwak, Hyo Bum

    2005-11-01T23:59:59.000Z

    Aging is characterized by a progressive decline in cardiac function. A critical contributor to the age-related impairment in heart function is the loss of cardiac myocytes through ??apoptosis??, or programmed cell death. A dramatic increase...

  19. Endogenous Peptide Discovery of the Rat Circadian Clock

    E-Print Network [OSTI]

    Gillette, Martha U.

    rhythms, pain, hunger, feeding, and body weight regulation (1­4). Neuropeptides are produced from larger at ultrahigh mass accuracy (16) with a software pipeline designed for neuropeptide discovery. We use

  20. The role of spatial context in rat vision

    E-Print Network [OSTI]

    Meier, Philip Martin

    2011-01-01T23:59:59.000Z

    2007) to control standard OpenGL capable graphics cards (2007) to control standard OpenGL capable graphics cards (

  1. adult rats relationship: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    division that places the Judith H Robins; Patricia A Mclenachan; Matthew J Phillips; Bennet J Mccomish; Elizabeth Matisoo-smith; Howard A Ross 34 Neurogenesis in the dentate...

  2. atrophic fetal rat: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    compared with untreated TPTX mothers or sham-operated normal females. The treated (+ 1.6- 2.0 g) occurred at term with doses ranging from 0.05 to 0.25 Lgkg of body weight ;...

  3. Lymphocyte depletion in peripheral blood of gamma irradiated rats

    E-Print Network [OSTI]

    Goldin, Eric Michael

    1972-01-01T23:59:59.000Z

    38. F. H. Hager, A study of the effect of partial-body irradiation on the early reduction of circulating lymphocytes. (Thesis) Texas AKM University, 1969. 39. G. D'Angelo and M. Lacombe, A practical diluent for electz onic white cell counts. Amer...

  4. adult rats tested: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 3 Thyroid hormone...

  5. adult rat central: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 3 Thyroid hormone...

  6. adult rat myenteric: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  7. adult rats efeito: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  8. adult rat optic: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  9. adult rats relate: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 3 Thyroid hormone...

  10. adult rats potential: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  11. adult rat sacral: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  12. adult rats neuroprotection: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  13. adult rat type: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  14. adult rat left: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thesis By BOBBY IAMAR CARAWAY Approved as to yle and content by: (Cha rman of Committee) (Head of Department) (Coordinator... Caraway, Bobby Lamar 1966-01-01 2 Thyroid hormone...

  15. The influence of biotin on reproduction in the white rat

    E-Print Network [OSTI]

    Cooper, William Anderson

    1957-01-01T23:59:59.000Z

    ???fi ?G?i ???? ????G?? ???i???G?? ???? ???? ?G??? ?? ????? ???? ???i???A???G? G? ?i??G?????G? ??? ?G?Ai????f ???G???f???i? ?? ??G?????i? ????i?? ???? ??? ???i????i?? 9 ??Y405?7? ?6? ?4Y3r?? Y?G ?G???i? G? ?i??fi ????i ???? ?i?i ??i? ?? ???? ?????? l...?i???f?? ??? ???ff ?? ?G?? ???i? ??? ??? ??f?G??i? ??G??? ??? ?G????? ??? ??i ?i??????A G?i ??? ???ffi? ???? ??i f???i?????i ?G???i??? ? ?G??f G? ?? ?i?G????G?? G?????i? ?? ??i ?? ????iA???i? ?i??fi? G? ???? A?G??? l?G? ?i?G?? ?????A? ??i ?G???Gf ?i...

  16. adult rat lung: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biology and Medicine Websites Summary: . The correlation between LS alterations and airway obstruction in asthma has long been recognized in clinical). The LS signals were...

  17. adult rat ventricular: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    pattern, although some minor discrepancies were observed in the morphology of the 12-lead electrocardiogram. Keywords: Bidomain theory, hybrid model, anisotropy, ventricles,...

  18. Non-essential amino acid metabolism in rats

    E-Print Network [OSTI]

    Crooks, James Darrell

    1971-01-01T23:59:59.000Z

    -ketoglutarate by glutamic dehydrogenase is a major route of synthesis of glutamic acid (15, 33) . This path- way provides for the entrance of ammonia nitrogen into the amino acid pool (34) ~ The nitrogen can be distributed to the amino acids by the transamination... of ammonia in the mammal have been discussed. Due to this close relationship, glutamine can be derived from any compound forming glutamic acid (31, 35) . This is demonstrated by the synthesis of its carbon skeleton from aspartic acid (34), asparagine (29...

  19. Molecular Aspects of the Regulation of Female Sexual Behavior

    E-Print Network [OSTI]

    Christensen, Amy

    2012-01-01T23:59:59.000Z

    from Charles River (Portage, MI). Upon arrival, rats werepurchased (Charles River, Portage, MI). Upon arrival, rats

  20. Special Publication No. 3, Ticks And Tickborne Diseases, I. Genera And Species of Ticks, Part 1. Genera A-G

    E-Print Network [OSTI]

    Doss, Mildred A.; Farr, Marion M.; Roach, Katharine F.; Anastos, George

    1974-01-01T23:59:59.000Z

    River, Belgian Congo, Euxerus erythropus maestus; Paiata, Liberia, Papio cynocephalus; Kilosa, Tanganyika Territory) Darling, S. T., ( 1912N), 71-73 (Cathartes aura, Lep- todeira albofusca, Mus norvegicus; Panama City) Dinnik, J. ?., Walker, J... americana, Bos taurus; Panama) Faust, E. C., (1929A), 27-44 (dogs; China) da Fonseca, F., (1954c), 93-167 (Myrmecophaga t. tridactyla; Brazil) da Fonseca, F., [1959c], 99-186 (Monodelphys domes- tica; Brazil) da Fonseca, F., (1960?), 89-144 (Dasyprocta...

  1. Guide to A Successful Rat's Mouth Tailgate This guide was developed to assist student organizations in the Organized Student Tailgate Area (Rat's Mouth).

    E-Print Network [OSTI]

    Fernandez, Eduardo

    all of your trash and recycling, including charcoal, to appropriately designated receptacles. Food of equipment requiring power should be battery operated. As a reminder, amplified sound is not permitted here

  2. Dose Dependent Response to Cyclodextrin Infusion in a Rat Model of Verapamil Toxicity

    E-Print Network [OSTI]

    Mottram, Allan R.; Bryant, Sean M; Aks, Steven E

    2012-01-01T23:59:59.000Z

    ketamine and diazepam anesthesia followed by verapamilblockade following anesthesia. 2,3 Cyclodextrin moleculesfor induction only, maintained anesthesia with ketamine and

  3. Estimating cancellous bone properties of the rat from mechanical testing of the femoral neck

    E-Print Network [OSTI]

    Groves, Jennifer Ann

    1998-01-01T23:59:59.000Z

    ), moment can be related to stress by; (2-23) M =f cr?ydA 24 eutral surface Y Figure 2. 10. a. ) Stress distribution through the cross section of an elastic-perfectly plastic material in bending (Crandall et al. 1978). b. ) Stress-strain curvefor... and strain are still linearly related by s = ay/E and by substitution: (2-27) a, K= ? = Also, the yield curvature, Ky call be found from equatloll (2 5) wllel'e M: My so: (2-28) M?2cr, El Eh 26 Combining (2-27) and (2-28) gives: (2-29) h k, 2e Using...

  4. Acquisition of cocaine and heroin self-administration in rats developmentally exposed to lead

    E-Print Network [OSTI]

    Rocha, Angelica

    2005-08-29T23:59:59.000Z

    (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) heroin self-administration and cocaine self-administration using an automated procedure that included both Pavlovian and operant components. Methods: For Experiment 1...

  5. accelerated-senescence oxys rats: Topics by E-print Network

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    process Engineering Websites Summary: such as medical devices, steel and chemical manufacturing, and most recently carbon capture on a large scale. Presently, a widely discussed...

  6. The inability of rats to synthesize linoleic acid from cis-2-octenoic acid

    E-Print Network [OSTI]

    Anderson, Robert Eugene

    1965-01-01T23:59:59.000Z

    as Determined by GLC c id Glutar ic Ad-iyic Pimelic Suberic Azelaic Relative mount 6. 82j- 5. 97 2. 00 13. 00 72. 23 18:2 cid 5, 8 6, 9 7, 10 8, 11 9~12 Konoenoic Precursor Oleic Palmitoleic l. Average of the products of three oxidations...-liquid chromatography. . . . Preparative gas-liquid chrp atography. . . Preparative thin-layer chromatography. . . 10 Oxidation oi' l8:2 eaters Determination of weights. Deter ination of radioactivity. . Results and Discussion. Chromatographic separations. 14...

  7. The effects of radiation on spermatogenesis in the albino rat as determined by semen analysis

    E-Print Network [OSTI]

    Lawson, Rommon Loy

    1964-01-01T23:59:59.000Z

    AND ANIMAL RESTRAINT 10 V. EffECTS OF VARIOUS LEVELS OF ACUTE AND CHRONIC RADIATION ON SPERM VOLUME, TOTAL SPERM COUNT, PER CENT MOTILITY, PER CENT LIVE AND NORMAL SPERM, AND PER CENT ABNORMAL SPERM. . . . . . . . . . . . 17 VI. DISCUSSION..., and Probes 14 6. Complete Equipment Used 14 7. Collecting Platform 8. Animal in Collecting Position. 15 9. Effect of Radiation on Weight Changes (Acute). 23 10. Effect of Radiation on Packed Cell Volume (Acute) 11. Removing Copulation Plug from Glans...

  8. Cortical Plasticity and Behavioral Recovery Following Focal Lesion to Primary Motor Cortex in Adult Rats

    E-Print Network [OSTI]

    Nishibe, Mariko

    2012-05-31T23:59:59.000Z

    and how to take advantage of neural plasticity to maximize the functional outcome. Rodent models are most often used not only for studying the role of motor cortex in motor skill learning but also in neurodegenerative research. To further elucidate...

  9. CONTRIBUTIONS OF THE INPUT SIGNAL AND PRIOR ACTIVATION HISTORY TO THE DISCHAGE BEHAVIOR OF RAT MOTONEURONES

    E-Print Network [OSTI]

    Percival, Don

    transmitted down their own axons. The probability of spike occurrence in the postsynaptic cell depends: motoneurones, spike-evoking currents, autoregressive-moving-average (ARMA) model Section ii. Cell Physiology of excitability by partial removal of sodium inactivation. Alternatively, this feature could simply reflect

  10. Substructure within the dorsal lateral geniculate nucleus of the pigmented rat

    E-Print Network [OSTI]

    Discenza, Claire B.

    2011-01-01T23:59:59.000Z

    Journal of Vision. Montero, V. M. (1991). A quantitativethresholds. Journal of Vision. Montero, V. M. , Brugge, J.Hamos et al. , 1985; Montero, 1991), and retains many

  11. Orthotopic ovarian allografts in rats with respect to endocrinologic and gametogenic function

    E-Print Network [OSTI]

    Turner, Sandra Scarborough

    1968-01-01T23:59:59.000Z

    ovaries from dogs to rabbits. Foa (1900) appears to have been the first to study allografts of fetal ovarian tissues. He found that grafts to immature hosts survived for a longer period than did grafts to mature hosts. It appears quite likely that many..., sometimes including the bursa and part of the oviduct. From this he concluded that the ovary may regenerate de novo from the old stalk or even from the peritoneum in mice. Two prominent investigators in this field, Krohn (1955) and Woodruff (1960), throw...

  12. The Lower Keys marsh rabbit and silver rice rat: steps toward recovery

    E-Print Network [OSTI]

    Perry, Neil Desmond

    2006-10-30T23:59:59.000Z

    salt-marsh zones (Negus et al. 1961, Goodyear 1987, Forys and Humphrey 1999a). Over the past 40 years, many of these areas were converted to ocean-side canal-based human developments. Though habitat destruction has been largely thwarted by recent...

  13. Multivariate analysis of transcriptional changes following restoration of SERCA2a levels in failing rat hearts

    E-Print Network [OSTI]

    Tabchy, Adel B. (Adel Bassam), 1976-

    2004-01-01T23:59:59.000Z

    We have identified the genes responsible for SERCA2a-induced reversal of heart failure, the leading cause of morbidity and mortality in the United States and developed countries. We have previously shown that restoration ...

  14. Detection and characterization of rat hepatic stellate cells in a 3-dimensional, perfused, liver bioreactor

    E-Print Network [OSTI]

    Wack, Kathryn E. (Kathryn Eilleen), 1978-

    2004-01-01T23:59:59.000Z

    One of the major challenges in liver research today lay in the understanding of the complex relationship between liver structure and function. The highly orchestrated events that take place in the liver to maintain homeostasis ...

  15. THE KINETICS OF REVERSIBLE-SEQUESTRATION OF LEUKOCYTES BY THE ISOLATED PERFUSED RAT LUNG

    E-Print Network [OSTI]

    Goliaei, Bahrain.

    2010-01-01T23:59:59.000Z

    Granulocytes. , c. II. The Lung . . Material and Method . A.1954). "Role of Am. J. the Lungs in Regulation of the WhiteJ. R. ; eds. (1977). of the Lung. Marcel Dekker, Inc. , New

  16. The quantification of oxygen toxicity by the technique of cellulose acetate electrophoresis of rat serum proteins

    E-Print Network [OSTI]

    Barker, Marcia Wagner

    1979-01-01T23:59:59.000Z

    symptoms of atelectasis, pulmonary edema, congestion and consolidation of the lungs, alveoli filled with a granular fibrillar exudate, and a general pneumonic condition. Therefore, pulmonary pathology associated with oxygen toxicity has been termed... the epithelial cells of the lungs are in direct contact with the changes in partial pressures of oxygen. Exposure to oxygen at increased partial pressures has had some dramatic effects on the circulatory system, such as increased osmotic fragility (96, 105...

  17. Return of the Rat: Biologically-Inspired Robotic Exploration and Navigation*

    E-Print Network [OSTI]

    Weitzenfeld, Alfredo

    Ramírez and Alfredo Weitzenfeld Ridel Instituto Tecnológico Autónomo de México (ITAM) Computer Engineering abarrera@itam.mx, alfredo@itam.mx .Abstract ­ In this paper we present a biologically- inspired robotic is partially supported by collaboration projects UC MEXUS CONACYT (ITAM ­ UCSC), LAFMI CONACYT (ITAM ­ ISC

  18. Stimuli from Conspecifics Influence Brain Mast Cell Population in Male Rats

    E-Print Network [OSTI]

    Silver, Rae

    is not static, but changes with the behav- ioral and physiological state of the animal. In this study, we tested the paraventricular nucleus, anterior nuclear group, or mediodorsal, ventroposterior, or medial geniculate nuclei the paren- chyma along the blood vessels of several dorsal thalamic nuclei (Dropp, 1972, 1976; Theoharides

  19. Skeletal Response to Simulated Microgravity Exposures and Exercise in the Adult Rat Model

    E-Print Network [OSTI]

    Shirazi-Fard, Yasaman

    2013-04-29T23:59:59.000Z

    .28 * HU 8.44 ? 0.09 7.46 ? 0.10 *? 8.08 ? 0.11 ? 8.63 ? 0.15 8.82 ? 0.28 AC 2.45 ? 0.08 2.57 ? 0.09 2.38 ? 0.10 * 2.33 ? 0.12 * 2.06 ? 0.20 * HU 2.38 ? 0.07 2.30 ? 0.07 *? 2.28 ? 0.08 ? 2.37 ? 0.09 2.34 ? 0.12 AC 616.42 ? 4.12 619.43 ? 4.11 629.15 ? 5..., bone mass at this site will recovery faster and more completely than will bone density and cortical area, and they will all recover before and/or more than bone strength does. We also aimed to characterize loss and long-term recovery of mechanical...

  20. The Effects of Multiple Unloading Exposures on Bone Properties in the Femur of Adult Male Rats

    E-Print Network [OSTI]

    Morgan, Derrick Scott

    2012-07-16T23:59:59.000Z

    (AC, normal weight-bearing cage activity), 1HU7 (unloaded for 1 month starting at 7 months of age and allowed to recover for 3 months), 1HU10 (normal cage activity until 10 months of age, unloaded for 1 month, recovered for 2 months), and 2HU10...

  1. Local functional input to neurons in deep layers of rat visual cortex

    E-Print Network [OSTI]

    Zarrinpar, Amir

    2006-01-01T23:59:59.000Z

    cortex. J Neurosci 26:4394-4405. Sawatari A, Callaway EM (frontal cortex. J Neurosci 26:4394-4405. Nowak LG, Azouz R,

  2. Monetary Policy and Household Mobility: The Effects of Mortgage Interest Rats.

    E-Print Network [OSTI]

    Quigley, John M.

    2005-01-01T23:59:59.000Z

    W01-001, January Quigley, John M. and Daniel Weinberg, “Mac. Citation: Quigley, John M. , (2001) "Monetary Policy1989: 282-294. Quigley, John M. , “Interest Rate Variation,

  3. The Effects of Multiple Unloading Exposures on Bone Properties in the Femur of Adult Male Rats 

    E-Print Network [OSTI]

    Morgan, Derrick Scott

    2012-07-16T23:59:59.000Z

    quantitative computed tomography (pQCT) scanner was used to collect densitometric and geometric properties at the right and left femoral neck and at the left femoral midshaft. Mechanical testing (axial and lateral compression of the femoral neck and 3pt bending...

  4. Correlating mechanical properties of cancellous bone in the rat with various density measures 

    E-Print Network [OSTI]

    Ramaswamy, Ramya

    2004-09-30T23:59:59.000Z

    , and to correlate the mechanical properties of the rodent cancellous bone with the various density measures. Analytical studies were made to assess the effect of the size and shape of the platen based on the values from mechanical testing of the cancellous bone...

  5. The effect of food restriction and simulated microgravity on the rat skeleton 

    E-Print Network [OSTI]

    Currado, Alicia Anne

    2002-01-01T23:59:59.000Z

    that 1 month of HLS causes structural changes within bone sooner than food restriction, without concomitant changes in bone strength. Food restriction may take longer to affect bone structurally, but does exhibit whole-body biochemical changes after 1...

  6. The effects of dietary phenylalanine supplementation on ochratoxicosis in normal and partially nephrectomized rats

    E-Print Network [OSTI]

    Parker, Roger William

    1983-01-01T23:59:59.000Z

    ), and mice (creppy, et al. , 1980; Klinkert et al. , 1981) when phenylalanine is administered simultaneously. The excess phenyl alanine was gi ven parenteral ly to the mice. No studies of OA toxicity in the presence of excess dietary phenyl alanine have...

  7. Characterizing strain in the proximal rat tibia during electrical muscle stimulation

    E-Print Network [OSTI]

    Vyvial, Brent Aron

    2007-09-17T23:59:59.000Z

    simulated resistive exercise countermeasure to attenuate this bone loss. I sought to determine the relationship between strain measured at the antero-medial aspect of the proximal diaphysis of tibia and plantar-flexor torque measured at the ankle during...

  8. Structural and functional alterations associated with transformation in rat ovarian cell model systems

    E-Print Network [OSTI]

    Echols, Jana Elizabeth

    1995-01-01T23:59:59.000Z

    reagents were purchased from Sigma Chemical Co. (St. Louis, MO). Tissue culture flasks and dishes were obtained from Corning Inc. (Oneonta, NY). Lab-Tek slides and LUX permanox dishes were obtained from Nunc (Naperville, IL). Bacto- agar was purchased... negative control, leaving pSV2neoineu as the experimental transfection. Briefly, 2 x 10' SIGC (passage 20) were plated onto 60mm culture dishes and allowed to grow 48 hours. Then 2 ug of plasmid DNA and 5 ul of Lipofectin together with 200 ul serum...

  9. The effects of bicuculline on cocaine self-administration in male rats developmentally exposed to lead

    E-Print Network [OSTI]

    Valles, Rodrigo, Jr.

    2004-09-30T23:59:59.000Z

    to the backplate at one end, the other end of the leash was connected to a 20 single channel fluid swivel [22 ga] (Instech Labs, Plymouth Meeting, PA). The swivel design permitted an interlock with separate connecting arms located in the home cage and operant... test chambers. The hinged arm allowed for a range of movement in either the home cage or test chamber. A .02 ID catheter continued from the top of the swivel to an infusion pump (Razel Scientific Instruments; Stamford, CT) that controlled the solution...

  10. Effects of stress odors on escape-avoidance learning in rats

    E-Print Network [OSTI]

    Sears, Judy Embry

    1975-01-01T23:59:59.000Z

    the other' was not. Prefer ence for odors was noted by differential rates of lever pressing in a free-operant test. One exper iment (Long and Tapp, 1967) demonstrated a preference for the odor of amyl acetate to unodo-. ized air. Later studies showed...

  11. protein were dramatically reduced in the colonic mucosa of GF vs CV rats (respec-

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    the enzyme. Influence of dietary proteins on colonic cell proliferation and luminal polyamine metabolism. K-dependent but was apparently unaffected by the sodium gradient. Excess of unlabeled long chain fatty acids led to a 27

  12. Dietary L-arginine supplementation reduces fat mass in diet-induced obese rats 

    E-Print Network [OSTI]

    Jobgen, Wenjuan Shi

    2009-06-02T23:59:59.000Z

    in response to the arginine treatment. Subsequent experiments were conducted with cell models to define the direct effects of arginine on energy-substrate metabolism in insulin-sensitive cells. In BNL CL.2 mouse hepatocytes, C2C12 mouse myotubes and 3T3-L1...

  13. Macrophage Polarization And Nitric Oxide Mechanisms In Lymphatic Dysfunction In A Rat Model Of Metabolic Syndrome 

    E-Print Network [OSTI]

    Zawieja, Scott D

    2014-12-10T23:59:59.000Z

    Metabolic syndrome (MetSyn) is the clustering of multiple metabolic disorders that further increase the risk for cardiovascular disease and has been recently linked to poor lymphatic function. The lymphatic system plays a crucial role in maintaining...

  14. Nanofabricated collagen-inspired synthetic elastomers for primary rat hepatocyte culture

    E-Print Network [OSTI]

    Bettinger, Christopher J.

    Synthetic substrates that mimic the properties of extracellular matrix proteins hold significant promise for use in systems designed for tissue engineering applications. In this report, we designed a synthetic polymeric ...

  15. Overexpression of CREB in the Nucleus Accumbens Shell Increases Cocaine Reinforcement in Self-Administering Rats

    E-Print Network [OSTI]

    Larson, Erin B.

    Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought to reduce the positive hedonic effects of passive ...

  16. The Encapsulation of Rat Aortic Smooth Muscle Cells Within Porous Scaffold

    E-Print Network [OSTI]

    Iacob, Alexandra

    2009-09-30T23:59:59.000Z

    :4881-4893, 2006. 27 ? CONTACT INFORMATION Name: Alexandra Iacob Address: c/o Dr. Mariah Hahn Department of Chemical Engineering Texas A&M University College Station, Texas 77843 Email Address: sandra_iacob@yahoo.com...

  17. Effects of dietary fat, fiber and carcinogen on fecal diacylglcyerols in the rat

    E-Print Network [OSTI]

    Pickering, Jennifer Sharon

    1996-01-01T23:59:59.000Z

    colonic mucosal cell proliferation, our data offer insight into a mechanism by which diet may modify the risk of colon cancer development....

  18. DNMT1-mediated PTEN hypermethylation confers hepatic stellate cell activation and liver fibrogenesis in rats

    SciTech Connect (OSTI)

    Bian, Er-Bao; Huang, Cheng; Ma, Tao-Tao; Tao, Hui; Zhang, Hui; Cheng, Chang; Lv, Xiong-Wen; Li, Jun, E-mail: hunkahmu@126.com

    2012-10-01T23:59:59.000Z

    Hepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is a negative regulator of this process. PTEN promoter hypermethylation is a major epigenetic silencing mechanism in tumors. The present study aimed to investigate whether PTEN promoter methylation was involved in HSC activation and liver fibrosis. Treatment of activated HSCs with the DNA methylation inhibitor 5-aza-2?-deoxycytidine (5-azadC) decreased aberrant hypermethylation of the PTEN gene promoter and prevented the loss of PTEN expression that occurred during HSC activation. Silencing DNA methyltransferase 1 (DNMT1) gene also decreased the PTEN gene promoter methylation and upregulated the PTEN gene expression in activated HSC-T6 cells. In addition, knockdown of DNMT1 inhibited the activation of both ERK and AKT pathways in HSC-T6 cells. These results suggest that DNMT1-mediated PTEN hypermethylation caused the loss of PTEN expression, followed by the activation of the PI3K/AKT and ERK pathways, resulting in HSC activation. Highlights: ? PTEN methylation status and loss of PTEN expression ? DNMT1 mediated PTEN hypermethylation. ? Hypermethylation of PTEN contributes to the activation of ERK and AKT pathways.

  19. Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia

    E-Print Network [OSTI]

    Boyer, Edmond

    Recent studies demonstrate that bisphosphonates suppress bone resorption by leading to apoptosis of the osteoclast and inhibiting the differentiation to mature osteoclasts. The influence of bisphosphonates on bone and stimulate osteoblast proliferation and differentiation in vitro, leading to increased bone formation

  20. In Vitro Rat Hepatic and Intestinal Metabolism of the Organophosphate Pesticides Chlorpyrifos and Diazinon

    SciTech Connect (OSTI)

    Poet, Torka S. (BATTELLE (PACIFIC NW LAB)); Wu, Hong (BATTELLE (PACIFIC NW LAB)); Kousba, Ahmed A. (BATTELLE (PACIFIC NW LAB)); Timchalk, Charles (Pacific Northwest National Laboratory)

    2003-04-01T23:59:59.000Z

    Chlorpyrifos (CPF) and diazinon (DZN) are thionophosphorus organophosphate, insecticides; their toxicity is mediated through CYP450 metabolism to CPF-oxon and DZN-oxon, respectively. Conversely, CYP450s also detoxify these OPs to trichloropyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), respectively. In addition, A-esterase metabolism of CPF- and DZN-oxon also form TCP and IMHP. This study evaluated the role intestinal and hepatic metabolism may play in the first-pass elimination of CPF and DZN. Similar CYP450- and A-esterase-mediated metabolic profiles were demonstrated in microsomes from liver or isolated intestinal enterocytes. In enterocyte microsomes, the CYP450 metabolic efficiency (Vmax/Km) for metabolism to the oxon metabolites was~5-fold greater for CPF than DZN. Compared on a per nmol P450 basis, the Vmax for CPF in enterocytes was~2-3 times higher than in liver microsomes for the production of CPF-oxon and TCP. The affinity (Km) for the metabolism of CPF to CPF-oxon was comparable in liver and enterocyte microsomes, however the enterocyte Km for TCP production was higher (lower affinity). The smaller volume of intestine, lower amount of CYP450, and higher Km for TCP in the enterocyte microsomes, resulted in a lower catalytic efficiency (2 and 62 times) than in liver for oxon and TCP. A-esterase-mediated metabolism of CPF- and DZN-oxon was also demonstrated in liver and enterocyte microsomes. Although A-esterase affinity for the substrates were comparable in hepatic and enterocyte microsomes, the Vmax were 48 - to 275-fold, in the liver. These results suggest that intestinal metabolism may impact first-pass metabolism of CPF and DZN, especially following low-dose oral exposures.