National Library of Energy BETA

Sample records for rat rattus norvegicus

  1. Copyright 1998 Psychonomic Society, Inc. 76 Colonies of Norway rats (Rattus norvegicus) in large

    E-Print Network [OSTI]

    Timberlake, William D.

    Copyright 1998 Psychonomic Society, Inc. 76 Colonies of Norway rats (Rattus norvegicus) in large and landmark orientation contributed to foraging efficiency when Norway rats were presented with different

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

    E-Print Network [OSTI]

    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

  3. Thermoregulatory Behavior in Infant Norway Rats (Rattus norvegicus) and Syrian Golden Hamsters (Mesocricetus auratus)

    E-Print Network [OSTI]

    Thermoregulatory Behavior in Infant Norway Rats (Rattus norvegicus) and Syrian Golden Hamsters). In contrast to hamsters, infant Norway rats are capable of producing heat using brown adipose tissue (BAT

  4. 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

  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. Contributions of Endothermy to Huddling Behavior in Infant Norway Rats (Rattus norvegicus) and Syrian Golden Hamsters (Mesocricetus auratus)

    E-Print Network [OSTI]

    Contributions of Endothermy to Huddling Behavior in Infant Norway Rats (Rattus norvegicus little thermoregulatory benefit from the presence of multiple littermates. In contrast, infant Norway hamsters and Norway rats both produce altricial young that differ substan- tially in their thermoregulation

  7. Swimming in Flavored Water Leads to Avoidance of that Flavor in Laboratory Rats (Rattus Norvegicus)

    E-Print Network [OSTI]

    Nakajima, Sadahiko

    2015-01-01

    study. The rat-in-flavored-water procedure, thus, departsreviewed Swimming in Flavored Water Leads to Avoidance ofthat swam in the flavored water. A statistically reliable

  8. Effect of housing conditions on sex differences in spatial cognition in rats 

    E-Print Network [OSTI]

    Harris, Anjanette Patricia

    2009-01-01

    Male mammals typically outperform females in tests of spatial ability. However, in laboratory rats (Rattus norvegicus), from which the majority of data in support of this difference come, sex differences are not consistently ...

  9. 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.

    2010-01-14

    Rift Valley Fever Virus is a plebovirus that causes epidemics and epizootics in sub-Saharan African countries but has expanded to Egypt and the Arabian Peninsula. The laboratory rat (Rattus norvegicus) is susceptible to ...

  10. Zoology 109 (2006) 5465 Differential segmental growth of the vertebral column of the rat

    E-Print Network [OSTI]

    Bergmann, Philip J.

    2006-01-01

    ZOOLOGY Zoology 109 (2006) 54­65 Differential segmental growth of the vertebral column of the rat (Rattus norvegicus) Philip J. BergmannÃ, Amanda D. Melin, Anthony P. Russell Vertebrate Morphology the development of these organisms. We investigate the segmental and regional growth of the entire vertebral

  11. Comparative genome mapping of the deer mouse (Peromyscus maniculatus) reveals greater similarity to rat (Rattus norvegicus) than to the lab mouse (Mus musculus)

    E-Print Network [OSTI]

    Ramsdell, Clifton M; Lewandowski, Adrienne A; Glenn, Julie Weston; Vrana, Paul B; O'Neill, Rachel J; Dewey, Michael J

    2008-01-01

    The comprehensive mouse radiation hybrid map densely cross-link- age and radiation hybrid cell maps) [2]. As a result,radiation http://www.biomedcentral.com/1471-2148/8/65 hybrid maps

  12. CONTROLLING RODENTS IN COMMERCIAL POULTRY FACILITIES

    E-Print Network [OSTI]

    Pittendrigh, Barry

    mouse (Mus musculus), Norway rat (Rat- tus norvegicus), and roof rat (Rattus rattus) are commonly found magnify the expense. Conducting effective and efficient programs to control rodents in commercial poultry

  13. Effects of semi-natural environmental conditions on phenotypic plasticity in Rattus norvegicus

    E-Print Network [OSTI]

    Margerum, Lisa

    2013-01-01

    dark nest boxes, social interactions) could compensate for the negative effects of stress resulting in no net

  14. Anim. Behav., 1994,48, 1057-1062 Passage of time reduces effects of familiarity on social learning: functional

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    hypotheses about the functions that socially induced food prefer- ences might serve in natural circumstances: functional implications BENNETT G. GALEF, JR & ELAINE E. WHISKIN Department of Psychology, Mc, after a rat Rattus norvegicus has eaten a food for several days, it is resistant to social induction

  15. MAMMALIAN POSTNATAL GROWTH ESTIMATES: THE INFLUENCE OF WEANING ON THE CHOICE

    E-Print Network [OSTI]

    Bergmann, Philip J.

    of the postnatal growth of the vertebral column of the Norway rat (Rattus norvegicus), we recorded hind-foot length such as the skull and vertebral column. However, this measur for the comprehension of vertebrate population dynamics and life histories (Lu 2003; Moscarella and Aguilera 1999

  16. A new way to study teaching in animals: despite demonstrable benefits, rat dams do not teach their young what to eat

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    A new way to study teaching in animals: despite demonstrable benefits, rat dams do not teach taught are large. Here, we determined, first, whether Rattus novegicus dams would modify their food by mothers would be effective, if it occurred. We examined food choices of rat dams trained to eat one of two

  17. Control of rabbits to protect island birds from cat predation Franck Courchamp a,

    E-Print Network [OSTI]

    Courchamp, Franck

    notorious and harmful introduced predators are domestic cats Felis catus, rats Rattus spp. and mon- gooses

  18. 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 their sewer homes over their travel routes. These filthy rats may run over and contaminate your food, table

  19. Controlling Rats and Mice 

    E-Print Network [OSTI]

    Texas Wildlife Services

    2007-03-13

    House rats and mice eat and contaminate human and animal food, and they damage and destroy property. This leaflet explains how to identify rats and mice by their droppings, runways, food crumbs and noises. Various control methods are discussed....

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

    E-Print Network [OSTI]

    2007-01-01

    Pachyptila belcheri (Catry et al. 2003). Ship rats Rattus rattus, house mice Mus musculus and cats Felis catus have possibly been present on the island for at least 100 years and yet prions have been able

  1. Super Rat Poison Man

    E-Print Network [OSTI]

    Hacker, Randi; Tsutsui, William

    2007-04-04

    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...

  2. The Metabolism of Americium in the Rat

    E-Print Network [OSTI]

    Scott, K.G.

    2010-01-01

    A. J. Barber, J. G Hamilton, Metabolism of Plutonium inRats, Plutonium Project Record of the National Nuclearin the Rat (CH 3606) Plutonium Project Record of the

  3. Lubiprostone Stimulates Duodenal Bicarbonate Secretion in Rats

    E-Print Network [OSTI]

    Mizumori, Misa; Akiba, Yasutada; Kaunitz, Jonathan D.

    2009-01-01

    using a non- absorbable ferrocyanide marker. Some rats wereindomethacin, sodium ferrocyanide ([Fe(CN) 6 ] 4- ), HEPES

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

    E-Print Network [OSTI]

    Payseur, Bret

    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

  5. Water Retrieval by Norway Rats: Behavior as Deduction

    E-Print Network [OSTI]

    Wallace, R J

    1998-01-01

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

  6. 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

  7. Arginine metabolism in enterocytes of diabetic rats 

    E-Print Network [OSTI]

    Morrow, Natalie Anne

    2002-01-01

    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...

  8. Trophic Garnishes: CatRat Interactions in an Urban Environment

    E-Print Network [OSTI]

    Holt, Robert D.

    they represent the majority of species. We characterized house cat (Felis catus) predation on wild Norway rats

  9. 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

  10. Purification of sulfide oxidase from rat liver 

    E-Print Network [OSTI]

    Pu, Lixia

    1994-01-01

    oxidase from rat liver has been isolated and purified by means of ammonium sulfate fractionation, anion-exchange chromatography, and size exclusion chromatography. The use of 80% saturation with ammonium sulfate at pH 7.2 provided an initial precipitation...

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

    E-Print Network [OSTI]

    Galef, Jr., Bennett G.

    2001-01-01

    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

  12. 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)

    2014-01-15

    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.

  13. 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

  14. Serum Levels of the Fetuin-Mineral Complex Correlate with Artery Calcification in the Rat*S

    E-Print Network [OSTI]

    Price, Paul A.

    Serum Levels of the Fetuin-Mineral Complex Correlate with Artery Calcification in the Rat- mineral complex in serum and vitamin D-induced artery calcification. The first experiment shows that there is a fetuin-mineral complex in the blood of rats in which extensive calcification of the artery media has been

  15. Early Detection of Oleic Acid-Induced Lung Injury in Rats Using 111In-Labeled Anti-Rat

    E-Print Network [OSTI]

    Terasaki, Mark

    Early Detection of Oleic Acid-Induced Lung Injury in Rats Using 111In-Labeled Anti of Radiology, VA Medical Center, Newington, Connecticut Previous study of the bleomycin-induced lung injury of 111In-aICAM-1 to detect inflammation in another ARDS lung injury model. Methods: 111In-labeled rat

  16. Acceleration of wound healing in young and aged rats 

    E-Print Network [OSTI]

    Maxwell, Bryan Douglas

    1996-01-01

    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...

  17. Experimental approaches to establish rat embryonic stem cells 

    E-Print Network [OSTI]

    Meek, Stephen Earl

    2011-06-27

    The rat has been an established experimental animal model within many areas of biological investigation for over one hundred years due to its size, breeding characteristics, and knowledge of its physiology and behaviour. ...

  18. RAT FR MIGRATION e.V. Integration und Illegalitt

    E-Print Network [OSTI]

    Kallenrode, May-Britt

    RAT FÜR MIGRATION e.V. (RfM) Integration und Illegalität in Deutschland herausgegeben von Klaus J >Festung EuropaMigration. Von Klaus J. Bade Resolution des Rates für Migration zum Problem der aufenthaltsrechtlichen Illegalität

  19. Mechanical properties of normotensive and hypertensive female rat carotid arteries 

    E-Print Network [OSTI]

    Smith, Katherine Elizabeth

    2002-01-01

    female rat carotid arteries to applied loads considering active and passive responses in the longitudinal and circumferential directions, and (3) to compare the female response in both groups to data available for males. The first objective provides...

  20. Lymphocyte depletion in peripheral blood of gamma irradiated rats 

    E-Print Network [OSTI]

    Goldin, Eric Michael

    1972-01-01

    LYMPHOCYTE DEPLETION IN PERIPHERAL BLOOD OF GAMMA IRRADIATED RATS A Thesis by ERIC MICHAEL GOLDIN Submitted to the Graduate College of Texas ABM University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE... December 1972 Major Subject: Nuclear Engineering (Health Physics) LYMPHOCYTE DEPLETION IN PERIPHERAL BLOOD OF GAMMA IRRADIATED RATS A Thesis by ERIC MICHAEL GOLDIN Approved as to sty1e and con ent by: ( hairman of Co it ee) (H of Depar ment...

  1. Structural and functional alterations associated with transformation in rat ovarian cell model systems 

    E-Print Network [OSTI]

    Echols, Jana Elizabeth

    1995-01-01

    In vitro cell model systems derived from rat granuloma cells were developed for the study of multistep ovarian carcinogenesis. Spontaneously immortalized rat granuloma cells (SIGC) were transfected with either the pSV3neo plasmid which contains...

  2. Inflammasome Sensor NLRP1 Controls Rat Macrophage Susceptibility to Toxoplasma gondii

    E-Print Network [OSTI]

    Cirelli, Kimberly

    Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring Toxoplasma resistance in rats was previously ...

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

    E-Print Network [OSTI]

    High-resolution imaging of vessels in the isolated rat brain M. F. Valverde Salzmann1 , N for the distribution of vessels in the rat brain. Angiography is able to use the blood flow in the brain of the living of this study was to obtain a full picture of vessels even down to relatively small size in the isolated rat

  4. ELECTRICAL STIMULATION REDUCES AGE RELATED ATROPHY AND WEAKNESS IN EDL MUSCLES OF RATS

    E-Print Network [OSTI]

    Dennis, Robert G.

    the atrophy and weakness. We electrically stimulated EDL muscles of adult and old rats during a 2 month period of denervation. The control muscles of old rats had declines in muscle mass and maximum force compared with adult control muscles. Denervated muscles of either adult or old rats had even larger declines. Stimulated

  5. 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.

    1990-12-01

    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.

  6. 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.

    1994-02-01

    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).

  7. Viability of adult rat skin following 13 Mev proton irradiation 

    E-Print Network [OSTI]

    Caraway, Bobby Lamar

    1966-01-01

    alteration resulting from total skin proton irradiation seemed to be dose related. Therefore, since the amount of tissue alteration seems to be dose-dependent, a hypothesis was developed that growth and viability of skin cells removed' by biopsy... rats each were subjected to total-skin proton irradiation of varying doses. The dose varied from 1300 rad in Group I to 200 rad in Group 1V. Two rats from each group served as controls and received no irradiation. Five days and 30 days...

  8. Action potentials reliably invade axonal arbors of rat neocortical neurons

    E-Print Network [OSTI]

    Tank, David

    Action potentials reliably invade axonal arbors of rat neocortical neurons Charles L. Cox* , Winfried Denk§ , David W. Tank§ , and Karel Svoboda*¶ *Howard Hughes Medical Institute, Cold Spring Harbor, Murray Hill, NJ 07974 Communicated by James D. Watson, Cold Spring Harbor Laboratory, Cold Spring Harbor

  9. 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

  10. 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

  11. channels enable burst output in rat cerebellar Purkinje cells

    E-Print Network [OSTI]

    Turner, Ray

    to generate an appropriate spike output depends on a balance between membrane depolarizationsKv3 K+ channels enable burst output in rat cerebellar Purkinje cells B. E. McKay and R. W. Turner and the repolarizing actions of K+ currents. The high-voltage-activated Kv3 class of K+ channels repolarizes Na+ spikes

  12. 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

  13. 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

  14. 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

  15. Exercise training modulates apoptotic signaling in the aging rat heart 

    E-Print Network [OSTI]

    Kwak, Hyo Bum

    2005-11-01

    in the rate of apoptosis has been reported with aging in the rat left ventricle. In contrast, exercise training not only improves cardiac function, but also reduces the risk of heart disease. However, the ability of exercise training to modulate apoptotic...

  16. Neurotransmitter Modulation in Rat Hippocampus Via Extracranial Focal Electrical Stimulation

    E-Print Network [OSTI]

    Besio, Walter G.

    in developing countries. Besio et al. have been analyzing the effects of noninvasive transcranial focalNeurotransmitter Modulation in Rat Hippocampus Via Extracranial Focal Electrical Stimulation Besio electrical stimulation (TFS) for the control of seizures. The TFS has been very successful in controlling

  17. Modification of sympathetic neuronal function in the rat tail artery by dietary lipid treatment

    SciTech Connect (OSTI)

    Panek, R.L.; Dixon, W.R.; Rutledge, C.O.

    1985-06-01

    The effect of dietary lipid treatment on sympathetic neuronal function was examined in isolated perfused tail arteries of adult rats. The hypothesis that dietary manipulations alter the lipid environment of receptor proteins which may result in the perturbation of specific membrane-associated processes that regulate peripheral adrenergic neurotransmission in the vasculature was the basis for this investigation. In the present study, rats were fed semisynthetic diets enriched in either 16% coconut oil (saturated fat) or 16% sunflower oil (unsaturated fat). The field stimulation-evoked release of endogenous norepinephrine and total /sup 3/H was decreased significantly in rats receiving the coconut oil diet when compared to either sunflower oil- or standard lab chow-fed rats. Norepinephrine content in artery segments from coconut oil-treated rats was significantly higher compared to either sunflower oil- or standard lab chow-fed rats. Tail arteries from rats receiving the coconut oil diet displayed significantly lower perfusion pressure responses to nerve stimulation at all frequencies tested when compared to the sunflower oil- or standard lab chow-fed rats. Vasoconstrictor responses of perfused tail arteries exposed to exogenous norepinephrine resulted in an EC50 for norepinephrine that was not changed by the dietary treatment, but adult rats receiving the sunflower oil diet displayed a significantly greater maximum response to exogenous norepinephrine (10(-5) M) compared to arteries from either coconut oil- or standard lab chow-fed rats.

  18. 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

    1994-01-01

    Rats fed diets high in fat and sucrose exhibit varying degrees of obesity. Studies have sought to define differences between dietary-obese (DIO) rats and dietary-resistant (DR) rats which may contribute to the cause or ...

  19. Sex difference in the principal cytochrome P-450 for tributyltin metabolism in rats

    SciTech Connect (OSTI)

    Ohhira, Shuji [Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, Tochigi 321-0293 (Japan)]. E-mail: s-ohhira@dokkyomed.ac.jp; Enomoto, Mitsunori [Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, Tochigi 321-0293 (Japan); Matsui, Hisao [Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, Tochigi 321-0293 (Japan)

    2006-01-15

    Tributyltin is metabolized by cytochrome P-450 (CYP) system enzymes, and its metabolic fate may contribute to the toxicity of the chemical. In the present study, it is examined whether sex differences in the metabolism of tributyltin exist in rats. In addition, the in vivo and in vitro metabolism of tributyltin was investigated using rat hepatic CYP systems to confirm the principal CYP involved. A significant sex difference in metabolism occurred both in vivo and in vitro, suggesting that one of the CYPs responsible for tributyltin metabolism in rats is male specific or predominant at least. Eight cDNA-expressed rat CYPs, including typical phenobarbital (PB)-inducible forms and members of the CYP2C subfamily, were tested to determine their capability for tributyltin metabolism. Among the enzymes studied, a statistically significant dealkylation of tributyltin was mediated by CYP2C6 and 2C11. Furthermore, the sex difference in metabolism disappeared in vitro after anti-rat CYP2C11 antibody pretreatment because CYP2C11 is a major male-specific form in rats. These results indicate that CYP2C6 is the principal CYP for tributyltin metabolism in female rats, whereas CYP2C11 as well as 2C6 is involved in tributyltin metabolism in male rats, and it is suggested that CYP2C11 is responsible for the significant sex difference in the metabolism of tributyltin observed in rats.

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

    E-Print Network [OSTI]

    Schulteis, Gery; Liu, Jian

    2006-01-01

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

  1. PyRAT (python radiography analysis tool): overview

    SciTech Connect (OSTI)

    Armstrong, Jerawan C; Temple, Brian A; Buescher, Kevin L

    2011-01-14

    PyRAT was developed as a quantitative tool for robustly characterizing objects from radiographs to solve problems such as the hybrid nonlinear inverse problem. The optimization software library that was used is the nonsmooth optimization by MADS algorithm (NOMAD). Some of PyRAT's features are: (1) hybrid nonlinear inverse problem with calculated x-ray spectrum and detector response; (2) optimization based inversion approach with goal of identifying unknown object configurations - MVO problem; (3) using functionalities of Python libraries for radiographic image processing and analysis; (4) using the Tikhonov regularization method of linear inverse problem to recover partial information of object configurations; (5) using a priori knowledge of problem solutions to define feasible region and discrete neighbor for the MVO problem - initial data analysis + material library {yields} a priori knowledge; and (6) using the NOMAD (C++ version) software in the object.

  2. Non-essential amino acid metabolism in rats 

    E-Print Network [OSTI]

    Crooks, James Darrell

    1971-01-01

    -bound amino acids were studied' The amino acids studied were asparagine, aspartic acid, glutamine, glutamic acid, glycine, alanine, arginine, and praline. Growth rates of rats increased with increased levels of glutamate in the diet. Effects of level... of dietary glutamic acid on endogenous pool size;, of the free amino acids were studied. No consistent patterns were observed. The pool sizes of all but four of the free amino acids increased after the ingestion of a meal. Glucose levels decreased...

  3. PyRAT - python radiography analysis tool (u)

    SciTech Connect (OSTI)

    Temple, Brian A; Buescher, Kevin L; Armstrong, Jerawan C

    2011-01-14

    PyRAT is a radiography analysis tool used to reconstruction images of unknown 1-0 objects. The tool is written in Python and developed for use on LINUX and Windows platforms. The tool is capable of performing nonlinear inversions of the images with minimal manual interaction in the optimization process. The tool utilizes the NOMAD mixed variable optimization tool to perform the optimization.

  4. Proposal to Sequence an Organism of Unique Interest for Research on Aging: Heterocephalus glaber, the Naked Mole-Rat

    E-Print Network [OSTI]

    de Magalhães, João Pedro

    , the Naked Mole-Rat João Pedro de Magalhães1 , John M. Sedivy2 , Caleb E. Finch3 , Steven N. Austad4, we propose the genome sequencing of a unique long-lived organism, the naked mole-rat (Heterocephalus

  5. Synaptic Plasticity and NO-cGMP-PKG Signaling Regulate Pre-and Postsynaptic Alterations at Rat Lateral

    E-Print Network [OSTI]

    Schafe, Glenn

    in the lateral amygdala (LA) within 24 hrs following training. Further, we show that rats given intra-LA infusion immunoreactivity in the LA, while those rats infused with the PKG activator 8-Br-cGMP exhibit a significant increase in these proteins in the LA. In contrast, rats given intra-LA infusion of the NO scavenger c

  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. Preferential Cell Migration to Rat Organ Lysates for Studies of Chemotactic Factors in Cancer Metastases

    E-Print Network [OSTI]

    Chiao, Jung-Chih

    migration of cells from the primary to the secondary in the process of metastasis of cancer althoughPreferential Cell Migration to Rat Organ Lysates for Studies of Chemotactic Factors in Cancer the molecular mechanisms are not clear. This study investigated cell migration in response to rat organ lysates

  8. 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

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

    E-Print Network [OSTI]

    Alencar, Adriano Mesquita

    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

  10. A 3-D mathematical model to identify organ-specific risks in rats during thermal stress

    E-Print Network [OSTI]

    outcomes associated with heat stress is critical for effective management and mitigation of injury, which in a rat exposed to heat stress in an attempt to understand the correlation between heat load core temperature measurements in control and heat-stressed rats and other published experimental data

  11. 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

  12. Comparative demography of black rat snakes (Elaphe obsoleta) in Ontario and Maryland

    E-Print Network [OSTI]

    Blouin-Demers, Gabriel

    #12;Comparative demography of black rat snakes (Elaphe obsoleta) in Ontario and Maryland Gabriel. Demographic data collected from 1981 to 1998 in Ontario (ON; 583 males and 588 females) and from 1942 to 1976 season (ON % 135 days, MD % 190 days), rat snakes of both sexes from Ontario had lower and more variable

  13. Ontogeny of NMDA receptor-mediated morphine tolerance in the postnatal rat

    E-Print Network [OSTI]

    Barr, Gordon A.

    . On the other hand, in agreement with the adult data, NOS inhibitors suppress withdrawal in the 7-day-old rat of morphine tolerance in adult rats. But NMDA receptors undergo dramatic change during the first few weeks antagonists MK-801 and dextromethorphan on the development of morphine tolerance in 7-, 14-, and 21-day-old

  14. THRESHOLD ESTIMATES OF ULTRASOUND-INDUCED LUNG HEMORRHAGE IN ADULT RATS: ROLE OF PULSE DURATION

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    THRESHOLD ESTIMATES OF ULTRASOUND-INDUCED LUNG HEMORRHAGE IN ADULT RATS: ROLE OF PULSE DURATION W-induced lung hemorrhage has been estimated as a function of pulse duration (PD) in adult rats. A total of 220, there were five in situ (at the lung surface) peak rarefactional pressures. For PDs of 1.3, 4.4, 8.2, and 11

  15. Lesion Resolution Following Exposure of Rat Lung to Pulsed Ultrasound James F. Zachary,1

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    Lesion Resolution Following Exposure of Rat Lung to Pulsed Ultrasound James F. Zachary,1 Leon A ultrasound-induced lung hemorrhage in mice, rats, rabbits, monkeys, and pigs. This study characterized the temporal reparative (healing) responses in lung fol- lowing the induction of lesions by pulsed ultrasound

  16. 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

  17. ARTICLE IN PRESS Oxalate, calcium and ash intake and excretion balances in fat sand rats

    E-Print Network [OSTI]

    Vatnick, Itzick

    ARTICLE IN PRESS Oxalate, calcium and ash intake and excretion balances in fat sand rats (Psammomys and other inorganic matter (ash) intake and excretion in fat sand rats feeding on two different diets/3 of the ash content. In animals feeding on both diets, 65­80% of the oxalate ingested did not appear in urine

  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. Keystone rodent interactions: prairie dogs and kangaroo rats structure the biotic composition of a desertified grassland

    E-Print Network [OSTI]

    Davidson, Ana

    Keystone rodent interactions: prairie dogs and kangaroo rats structure the biotic composition. Keystone rodent interactions: prairie dogs and kangaroo rats structure the biotic composition of a desertified grass- land. Á Ecography 29: 755Á765. Understanding the interactive effects of multiple keystone

  20. Behavioral Assays to Study Sensorimotor Deficit and Recovery in Rats Following Middle Cerebral Artery Occlusion 

    E-Print Network [OSTI]

    Roman-Cruz, Glorian M.

    2010-07-14

    being ovariectomized via a gradual release pellet and the other did not receive an estrogen treatment. All the rats then went through a stroke surgery 3 weeks after the ovariectomy surgery. Before the stroke surgery, all rats also went through training...

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

    E-Print Network [OSTI]

    Bowlin, Julie Lee

    2001-01-01

    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...

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

    SciTech Connect (OSTI)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    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.

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

    E-Print Network [OSTI]

    Klobukowski, Christopher John

    1963-01-01

    '&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...

  4. Effect of co-exposure and cadmium in rats

    SciTech Connect (OSTI)

    Tandon, S.K.; Tewari, P.C.

    1987-10-01

    Metabolism and toxicity of heavy metals may be influenced by certain factors such as protein malnutrition, essential element deficiency or alcoholism. Ethanol has been found to enhance the absorption of lead in body and alcoholics have been reported to be more susceptible to lead intoxication. As alcoholism may be common among industry workers and a significant section of population, who may be exposed to cadmium, it was considered of interest to investigate the influence of ethanol-cadmium co-exposure on cadmium sensitive hepatic, renal and serum enzymes, tissue accumulation of cadmium, essential trace element status and cadmium induced hepatic metallothione in synthesis in rats.

  5. SU-E-T-492: Implementing a Method for Brain Irradiation in Rats Utilizing a Commercially Available Radiosurgery Irradiator

    SciTech Connect (OSTI)

    Cates, J; Drzymala, R

    2014-06-01

    Purpose: The purpose of the study was to implement a method for accurate rat brain irradiation using the Gamma Knife Perfexion unit. The system needed to be repeatable, efficient, and dosimetrically and spatially accurate. Methods: A platform (“rat holder”) was made such that it is attachable to the Leskell Gamma Knife G Frame. The rat holder utilizes two ear bars contacting bony anatomy and a front tooth bar to secure the rat. The rat holder fits inside of the Leskell localizer box, which utilizes fiducial markers to register with the GammaPlan planning system. This method allows for accurate, repeatable setup.A cylindrical phantom was made so that film can be placed axially in the phantom. We then acquired CT image sets of the rat holder and localizer box with both a rat and the phantom. Three treatment plans were created: a plan on the rat CT dataset, a phantom plan with the same prescription dose as the rat plan, and a phantom plan with the same delivery time as the rat plan. Results: Film analysis from the phantom showed that our setup is spatially accurate and repeatable. It is also dosimetrically accurate, with an difference between predicted and measured dose of 2.9%. Film analysis with prescription dose equal between rat and phantom plans showed a difference of 3.8%, showing that our phantom is a good representation of the rat for dosimetry purposes, allowing for +/- 3mm diameter variation. Film analysis with treatment time equal showed an error of 2.6%, which means we can deliver a prescription dose within 3% accuracy. Conclusion: Our method for irradiation of rat brain has been shown to be repeatable, efficient, and accurate, both dosimetrically and spatially. We can treat a large number of rats efficiently while delivering prescription doses within 3% at millimeter level accuracy.

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

    SciTech Connect (OSTI)

    Bass, V.; Gordon, C.J.; Jarema, K.A.; MacPhail, R.C.; Cascio, W.E.; Phillips, P.M.; Ledbetter, A.D.; Schladweiler, M.C.; Andrews, D.; Miller, D.; Doerfler, D.L.; Kodavanti, U.P.

    2013-12-15

    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.

  7. Secondary structure of rat and human amylin across force fields

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi -cheng; de Pablo, Juan J.; Paci, Emanuele

    2015-07-29

    The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, ?-helices, and ?-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin wasmore »determined as a function of ?-helix and ?-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards ?-hairpins, while CHARMM22/CMAP predicts structures that are overly ?-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable dynamic pathways that facilitate the formation of aggregates and, eventually, amyloid fibrils.« less

  8. The effect of moderate alcohol intake on bone mineral density of ovariectomized rats 

    E-Print Network [OSTI]

    Shipley, Debra Lynn

    1997-01-01

    groups had access to rat chow and distilled water ad libitim. Ovariectomized animals had increased weight and decreased femur density and bone volume per total volume. They also had decreased total trubecular area, trabecular area and number as well...

  9. Cardiac dysfunction in the ZDF rat: Possible mechanisms and benefits of exercise

    E-Print Network [OSTI]

    VanHoose, Lisa

    2011-12-31

    heart disease include left ventricular hypertrophy, diastolic and systolic dysfunction, and diabetic cardiac autonomic neuropathy, which are regularly observed at varying severities in persons with type 2 diabetes. The Zucker diabetic fatty (ZDF) rat has...

  10. Function and acuity of the rat vibrissa system during texture discrimination

    E-Print Network [OSTI]

    Morita, Takeshi

    2008-01-01

    cortex underlying texture discrimination. PLoS Biol 5, e305.of vibrissal tactile discrimination in the rat. J NeurosciMice can learn roughness discrimination with vibrissae in a

  11. Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel 

    E-Print Network [OSTI]

    Wilson, John 1988-

    2012-11-15

    physiologic geometries obtained from confocal images of a rat mesenteric lymphatic vessel to determine the characteristics of NO transport in the lymphatic flow regime. Both steady and unsteady analyses were performed. Steady models were simulated...

  12. 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

  13. 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.

    2005-01-01

    In late pregnant rats, the hypothalamic-pituitary-adrenal (HPA) axis is hyporesponsive to psychogenic stressors. Here, we investigated attenuated HPA responses to an immune challenge and a role for endogenous opioids. ACTH ...

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

    E-Print Network [OSTI]

    Kohli, Ripla

    2004-09-30

    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...

  15. Electrical, molecular and behavioral effects of interictal spiking in the rat Daniel T. Barkmeier b

    E-Print Network [OSTI]

    Hua, Jing

    interictal spiking in rats. Methods: A single injection of tetanus toxin into somatosensory cortex generated activation and plasticity gene induction as is seen in the human interictal state. Increasing spike frequency

  16. Impact of Ghrelin Receptor Antagonism on Nicotine and Cocaine Drug Reactivity in Rats 

    E-Print Network [OSTI]

    Clifford, Patrick Shane

    2013-05-01

    Ghrelin is a 28 amino acid peptide that interacts with ghrelin receptors (GHS-Rs) to modulate brain reinforcement circuits. Systemic ghrelin infusions augment cocaine (COC) stimulated locomotion and conditioned place preference (CPP) in rats...

  17. Tissue magnesium and calcium concentration in relation to magnesium and calcium intake in rats 

    E-Print Network [OSTI]

    Pinkham, Carrie Stanton

    1987-01-01

    TISSUE MAGNESIUM AND CALCIUM CONCENTRATION IN RELATION TO MAGNESIUM AND CALCIUM INTAKE IN RATS A Thesis by CARRIE STANTON PINKRAM Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirerrents... for the degree of MASTER OF SCIENCE August 1987 Major Subject: Nutrition TISSUE MAGNESIUM AND CALCIUM CONCENTRATION IN RELATION TO MAGNESIUM AND CALCIUM INTAKE IN RATS A Thesis by CARRIE STANTON PINKHAM Approved as to style and content by: Karen S...

  18. The Lower Keys marsh rabbit and silver rice rat: steps toward recovery 

    E-Print Network [OSTI]

    Perry, Neil Desmond

    2006-10-30

    -1 LOWER KEYS MARSH RABBIT AND THE SILVER RICE RAT: STEPS TOWARDS RECOVERY A Thesis by NEIL DESMOND PERRY 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 2006 Major Subject: Wildlife and Fisheries Sciences LOWER KEYS MARSH RABBIT AND THE SILVER RICE RAT: STEPS TOWARDS RECOVERY A Thesis by NEIL DESMOND PERRY Submitted to the Office...

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

    E-Print Network [OSTI]

    Yee, Cindy Deann

    1992-01-01

    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...

  20. Antimuscarinic effects of chloroquine in rat pancreatic acini

    SciTech Connect (OSTI)

    Habara, Y.; Williams, J.A.; Hootman, S.R.

    1986-06-13

    Chloroquine inhibited carbachol-induced amylase release in a dose-dependent fashion in rat pancreatic acini; cholecystokinin- and bombesin-induced secretory responses were almost unchanged by the antimalarial drug. The inhibition of carbachol-induced amylase release by chloroquine was competitive in nature with a K/sub i/ of 11.7 ..mu..M. Chloroquine also inhibited (/sup 3/H)N-methylscopolamine binding to acinar muscarinic receptors. The IC/sub 50/ for chloroquine inhibition of (/sup 3/H)N-methylscopolamine binding was lower than that for carbachol or the other antimalarial drugs, quinine and quinidine. These results demonstrate that chloroquine is a muscarinic receptor antagonist in the exocrine pancreas.

  1. Automated whole-genome multiple alignment of rat, mouse, and human

    SciTech Connect (OSTI)

    Brudno, Michael; Poliakov, Alexander; Salamov, Asaf; Cooper, Gregory M.; Sidow, Arend; Rubin, Edward M.; Solovyev, Victor; Batzoglou, Serafim; Dubchak, Inna

    2004-07-04

    We have built a whole genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline which combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment, and consists of two main steps: (1) alignment of the mouse and rat genomes; and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human and 97% of all alignments with human sequence > 100kb agree with a three-way synteny map built independently using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment; and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.

  2. Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

    SciTech Connect (OSTI)

    Boeckner, L.S.; Kies, C.

    1986-03-05

    The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10/sup -6/ was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study.

  3. ATTRACTIVENESS OF CARBON DISULFIDE TO WILD NORWAY RATS J. RUSSELL MASON, U.S. Deparunent of Agriculture, Animal and Plant Health Inspection Service, Denver Wildlife

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    that carbon disulfide (CSz) and carbonyl sulfide were present on the breath of rats in rela- tively high

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

    SciTech Connect (OSTI)

    Hughes, Michael F.; Edwards, Brenda C.

    2010-07-15

    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.

  5. Effect of Age and Exercise on the Viscoelastic Properties of Rat Tail Tendon accepted version, Annals of Biomedical Engineering 41, (6), 1120-1128 (2013).

    E-Print Network [OSTI]

    Lakes, Roderic

    2013-01-01

    old rats were used to provide an adult control, while a group of 3 month old rats provided a young but not direct loading from the exercise regimen. Twenty-four month old rats underwent one of three treadmill, no #12;investigations lend conclusive evidence of a link between old age and changes in viscoelasticity

  6. 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

    2006-08-16

    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...

  7. The role of hepatic mitochondria in the regulation of glucose metabolism in BHE rats

    SciTech Connect (OSTI)

    Kim, M.J.C.

    1988-01-01

    The interacting effects of dietary fat source and thyroxine treatment on the hepatic mitochondrial function and glucose metabolism were studied. In the first study, three different sources of dietary fatty acids and thyroxine treatment were used to investigate the hepatic mitochondrial thermotropic behavior in two strains of rat. The NIDDM BHE and Sprague-Dawley rats were used. Feeding coconut oil increased serum T{sub 4} levels and T{sub 4} treatment increased serum T{sub 3} levels in the BHE rats. In the mitochondria from BHE rats fed coconut oil and treated with T{sub 4}, the transition temperature disappeared due to a decoupling of succinate supported respiration. This was not observed in the Sprague-Dawley rats. In the second study, two different sources of dietary fat and T{sub 4} treatment were used to investigate hepatic mitochondrial function. Coconut oil feeding increased Ca{sup ++}Mg{sup ++}ATPase and Mg{sup ++}ATPase. T{sub 4} treatment had potentiated this effect. T{sub 4} increased the malate-aspartate shuttle and {alpha}-glycerophosphate shuttle activities. In the third study, the glucose turnover rate from D-({sup 14}C-U)/(6-{sup 3}H)-glucose and gluconeogeneis from L-({sup 14}C-U)-alanine was examined. Dietary fat or T{sub 4} did not affect the glucose mass. T{sub 4} increased the irreversible fractional glucose turnover rate.

  8. 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

    1998-01-01

    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...

  9. 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

    2012-02-14

    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...

  10. Real-Time Imaging of Perivascular Transport of Nanoparticles During Convection-Enhanced Delivery in the Rat Cortex

    E-Print Network [OSTI]

    Schaffer, Chris B.

    , and nanoparticles infused into neural tissue localize in the perivascular spaces of blood vessels within the brain-time distribution of nanoparticles infused in the cortex of live, anesthetized rats via CED. Fluorescent nanoparticles of 24 and 100 nm nominal diameters were infused into rat cortex through microfluidic probes. We

  11. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    SciTech Connect (OSTI)

    Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan) [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan) [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan)] [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)] [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan)] [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan) [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan)] [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)] [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan)] [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.

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

    E-Print Network [OSTI]

    Edgar, Susan Elaine

    1986-01-01

    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...

  13. Forskolin- and dihydroalprenolol (DHA) binding sites and adenylate cyclase activity in heart of rats fed diets containing different oils

    SciTech Connect (OSTI)

    Alam, S.Q.; Ren, Y.F.; Alam, B.S.

    1987-05-01

    The purpose of the present investigation was to determine if dietary lipids can induce changes in the adenylate cyclase system in rat heart. Three groups of male young Sprague-Dawley rats were fed for 6 weeks diets containing 10% corn oil (I), 8% coconut oil + 2% corn oil (II) or 10% menhaden oil (III). Adenylate cyclase activity (basal, fluoride-, isoproterenol-, and forskolin-stimulated) was higher in heart homogenates of rats in group III than in the other two groups. Concentration of the (/sup 3/H)-forskolin binding sites in the cardiac membranes were significantly higher in rats fed menhaden oil. The values (pmol/mg protein) were 4.8 +/- 0.2 (I), 4.5 +/- 0.7 (II) and 8.4 +/- 0.5 (III). There was no significant difference in the affinity of the forskolin binding sites among the 3 dietary groups. When measured at different concentrations of forskolin, the adenylate cyclase activity in cardiac membranes of rats fed menhaden oil was higher than in the other 2 groups. Concentrations of the (/sup 3/H)DHA binding sites were slightly higher but their affinity was lower in cardiac membranes of rats fed menhaden oil. The results suggest that diets containing fish oil increase the concentration of the forskolin binding sites and may also affect the characteristics of the ..beta..-adrenergic receptor in rat heart.

  14. 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

  15. Sex and species differences in spatial memory in food-storing kangaroo rats

    E-Print Network [OSTI]

    Jacobs, Lucia

    did not differentially affect recovery in the two species of kangaroo rats, unlike previous studies recovery. Female performance was significantly impaired by the absence of local landmarks, while male persistence. Using a touch-screen to simulate a feeder array, coal tits, Periparus ater, show greater mem- ory

  16. LEARNING IND MOTIVATION (1974) 5, 231-247 Instrumental and Contingent Saccharin Licking in Rats

    E-Print Network [OSTI]

    Timberlake, William D.

    1974-01-01

    LEARNING IND MOTIVATION (1974) 5, 231-247 Instrumental and Contingent Saccharin Licking in Rats!/ Instrumental licking of .4% saccharin solution was increased by the contingent opportunity to lick a less in instrumental responding. The results support the hypothesis that instrumental responding will increase

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

    E-Print Network [OSTI]

    Papadopoulos, Anthony

    2002-01-01

    aminoguanidine (0.3mM). Active and passive stress-stretch relations were investigated by an extension response. Maximal tension developed in response to NE and AVP was less in aortic rings from HU rats, and the iNOS inhibitor did not normalize this difference...

  18. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    SciTech Connect (OSTI)

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

    1989-01-01

    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 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. 31 refs., 6 figs., 19 tabs.

  19. 0 50 100 150 FIGURE 3. The arctangent distribution t to the rat cancer data.

    E-Print Network [OSTI]

    Leemis, Larry

    , New York, NY. GEHAN, E. A. (1965). \\A Generalized Wilcoxon Test for Comparing Arbitrarily Singly- Censored Samples." Biometrika 52, pp. 203{223. KECECIOGLU, D. (1991). Reliability Engineering Handbook of the distribution's heavy right tail. Cox and Snell (1981, page 169) present data on life span of rats who have been

  20. Cytokine-induced Neutrophil Chemoattractant Mediates Neutrophil Influx in Immune Complex Glomerulonephritis in Rat

    E-Print Network [OSTI]

    Trask, Barbara Crippes

    Glomerulonephritis in Rat Xiaobo Wu, Arthur J. Wittwer,* Linda S. Carr,* Barbara A. Crippes, * Joseph E. De B. Lefkowith, M.D., Box 8045, Divi- sion of Rheumatology, Washington University School of Medicine that these mediators may have pleotrophic effects (1-4). Very little is known, in fact, about the participation

  1. The effects of ethanol on strychnine sensitive glycine receptors in the rat basolateral amygdala 

    E-Print Network [OSTI]

    Botting, Shaleen Kaye

    2000-01-01

    to measure the anxiolytic and anxiogenic effects of chronic ethanol ingestion and withdrawal. In these tests we found that both the ethanol and control rats displayed a slightly greater interest in exploring the dark side of the box, while the ethanol...

  2. Osmotic Regulation of Estrogen Receptor-in Rat Vasopressin and Oxytocin Neurons

    E-Print Network [OSTI]

    Betz, William J.

    Osmotic Regulation of Estrogen Receptor- in Rat Vasopressin and Oxytocin Neurons Suwit J. Somponpun)- . In contrast, only 7.5% of oxytocin (OT) MNCs express ER- . We examined the osmotic regulation of ER- mMNCs.ImmunocytochemistrydemonstratedthatthedecreaseinER- mRNAwastranslatedintodepletionof receptor protein content in hyper-osmotic animals. Numerous MNCs

  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.

    1988-11-01

    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. Passive spatial and temporal integration of excitatory synaptic inputs in cerebellar Purkinje cells of young rats

    E-Print Network [OSTI]

    Passive spatial and temporal integration of excitatory synaptic inputs in cerebellar Purkinje cells linearly independent of the spatial and temporal separation of inputs. Summation of inputs in a passive. Keywords: Dendritic integration; Parallel fiber; Excitation; Timing; Synchrony; Rat Based on a passive

  5. Altered neurochemical levels in the rat brain following chronic nicotine Sara Falasca a

    E-Print Network [OSTI]

    Chronic nicotine Prefrontal cortex Dorsal striatum Hypothalamus A B S T R A C T Converging evidence shows as glutamate and gamma aminobutyric acid in the rat prefrontal cortex, dorsal striatum and hypothalamus. We of carnitine in the hypothalamus (26.59%, p

  6. Involvement of growth factors and their receptors in radon-induced rat lung tumors

    SciTech Connect (OSTI)

    Leung, F.C.; Dagle, G.E.; Cross, F.T. [Pacific Northwest Lab., Richland, WA (United States)

    1992-12-31

    In this paper we examine the role of growth factors (GF) and their receptors (GFR) in radon-induced rat lung tumors. Inhalation exposure of radon and its daughters induced lung tumors in rats, but the molecule/cellular mechanisms are not known. Recent evidence suggests that GF/GFR play a critical role in the growth and development of lung cancer in humans and animals. We have developed immunocytochemical methods for identifying sites of production and action of GF/GFR at the cellular level; for example, the avidin-biotin horseradish peroxidase technique. In radon-induced rat epidermoid carcinomas, epidermal growth factor (EGF), EGF-receptors (EGF-R), transforming growth factor alpha (TGF-{alpha}), and bombesin were found to be abnormally expressed. These abnormal expressions, mainly associated with epidermoid carcinomas of the lung, were not found in any other lung tumor types. Our data suggest that EGF, EGF-R, TGF-{alpha}, and bombesin are involved in radon oncogenesis in rat lungs, especially in epidermoid carcinomas, possibly through the autocrine/paracrine pathway.

  7. 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

  8. Running Title: Intraspinal stimulation caudal to spinal cord transections in rats.

    E-Print Network [OSTI]

    Prochazka, Arthur

    coordination and weight-bearing sufficient for locomotion. These results support the main assumption, including the restoration of hindlimb weight-bearing and coordinated locomotion (Cheng et al. 1996; Coumans spinalized rats do not recover weight-bearing locomotion spontaneously (Basso et al. 1996), though they may

  9. Effect of pulse polarity and energy on ultrasound-induced lung hemorrhage in adult rats

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    Effect of pulse polarity and energy on ultrasound-induced lung hemorrhage in adult rats Leon A the role of inertial cavitation in ultrasound-induced lung hemorrhage by examining the effect of pulse polarity at a common in situ at the lung surface peak rarefactional pressure pr(in situ) and at a common

  10. 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

  11. The Encapsulation of Rat Aortic Smooth Muscle Cells Within Porous Scaffold 

    E-Print Network [OSTI]

    Iacob, Alexandra

    2009-09-30

    Growing rat aortic smooth muscle cells (RASMC) in vitro has posed numerous difficulties in the past. Smooth muscle cells are known to need a three-dimensional (3-D) structure, neighboring cells, space to allow for elongation and media to encourage...

  12. Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

    SciTech Connect (OSTI)

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

    1988-08-01

    Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 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 O 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 and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

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

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    , Maiduguri, Nigeria b Department of Biochemistry, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria (Received 6 January 1998; accepted 20 July 1998) Abstract-Twenty rats were [191. Recently, low dietary energy nutrition in animals was reported to increase the severity

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

    E-Print Network [OSTI]

    Miller, Dennis K

    1997-01-01

    as determined on a pre-test. In Experiment 1. control and cadmium-exposed rats received 0, 0.6, 1.25, 2.5. or 5 mg/kg morphine sulfate (ip) for 4 days, and vehicle only for 4 days. Control animals showed a preference for the drug-paired side at 1.25, 2.5. and 5...

  15. 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

  16. Measurement of Cerebral Glucose Metabolic Rates in the Anesthetized Rat by Dynamic

    E-Print Network [OSTI]

    Smith, Carolyn Beebe

    - thetized rats with the ATLAS (Advanced Technology Laboratory Animal Scanner) small animal PET scanner and biochemical processes, and it does so with minimal invasiveness. The spatial resolution of typical PETF-FDG, the ATLAS Small Animal PET Scanner, and Arterial Blood Sampling Kazuaki Shimoji, MD1; Laura

  17. 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.

    1985-06-01

    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.

  18. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    SciTech Connect (OSTI)

    Dickerson, Sarah M.; Cunningham, Stephanie L. [Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712 (United States); Gore, Andrea C., E-mail: andrea.gore@mail.utexas.edu [Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712 (United States); Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712 (United States); Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712 (United States)

    2011-04-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor {alpha} (ER{alpha}) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ER{alpha}, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA{sub B} receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGF{alpha}. Collectively, these results suggest that the disrupted sexual differentiation of the POA by prenatal EDC exposures is already evident as early as the day after birth, effects that may change the trajectory of postnatal development and compromise adult reproductive function.

  19. 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

    2005-02-17

    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...

  20. Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.

    E-Print Network [OSTI]

    2014-01-01

    filtration rate using FITC-inulin. Am J Physiol 1999;276:rate by single-bolus inulin: a comparison of estimationanalogues on glomerular inulin space of isolated rats renal

  1. Investigating the modulation of neonatal rat facial motoneurone excitability by monoamine neurotransmitters: Postsynaptic mechanisms and presynaptic modulation of glutamate release. 

    E-Print Network [OSTI]

    Perkins, Emma M

    2007-01-01

    The activity patterns of 5-HT-releasing neurons can be positively correlated with behavioural state and motor function and the central 5-HT system modulates motor activity at the cellular level. The rat facial motor ...

  2. Rats in Virtual Space: The development and implementation of a multimodal virtual reality system for small animals

    E-Print Network [OSTI]

    Aharoni, Daniel Benjamin

    2013-01-01

    recent years. A light weight Styrofoam sphere is placed in aa 24 inch diameter hollow Styrofoam sphere, Figure 2.2: Flowtreadmill for rats. The Styrofoam sphere is constructed from

  3. Prospective grading of neoplastic change in rat esophagus epithelium using angle-resolved low-coherence interferometry

    E-Print Network [OSTI]

    Wax, Adam

    Angle-resolved low-coherence interferometry (a/LCI) is used to obtain quantitative, depth-resolved nuclear morphology measurements. We compare the average diameter and texture of cell nuclei in rat esophagus epithelial ...

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

    E-Print Network [OSTI]

    Lucas, Matthew W.

    2010-01-14

    The mechanical properties of the cancellous bone in the laboratory rat animal model are of great interest to the research community for the evaluation of treatments for osteoporosis. Cancellous bone responds rapidly and ...

  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

    2013-02-22

    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. 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

    2007-08-01

    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 ...

  7. Single whole-body exposure to sarin vapor in rats: Long-term neuronal and behavioral deficits

    SciTech Connect (OSTI)

    Grauer, Ettie [Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona (Israel)], E-mail: ettieg@iibr.gov.il; Chapman, Shira; Rabinovitz, Ishai; Raveh, Lily; Weissman, Ben-Avi; Kadar, Tamar; Allon, Nahum [Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona (Israel)

    2008-03-01

    Freely moving rats were exposed to sarin vapor (34.2 {+-} 0.8 {mu}g/l) for 10 min. Mortality at 24 h was 35% and toxic sings in the surviving rats ranged from sever (prolonged convulsions) through moderate to almost no overt signs. Some of the surviving rats developed delayed, intermittent convulsions. All rats were evaluated for long-term functional deficits in comparison to air-exposed control rats. Histological analysis revealed typical cell loss at 1 week post inhalation exposure. Neuronal inflammation was demonstrated by a 20-fold increase in prostaglandin (PGE{sub 2}) levels 24 h following exposure that markedly decreased 6 days later. An additional, delayed increase in PGE{sub 2} was detected at 1 month and continued to increase for up to 6 months post exposure. Glial activation following neural damage was demonstrated by an elevated level of peripheral benzodiazepine receptors (PBR) seen in the brain 4 and 6 months after exposure. At the same time muscarinic receptors were unaffected. Six weeks, four and six months post exposure behavioral evaluations were performed. In the open field, sarin-exposed rats showed a significant increase in overall activity with no habituation over days. In a working memory paradigm in the water maze, these same rats showed impaired working and reference memory processes with no recovery. Our data suggest long lasting impairment of brain functions in surviving rats following a single sarin exposure. Animals that seem to fully recover from the exposure, and even animals that initially show no toxicity signs, developed some adverse neural changes with time.

  8. Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

    SciTech Connect (OSTI)

    Hershock, D.; Vogel, W.H. (Thomas Jefferson Univ., Philadelphia, PA (USA))

    1989-02-09

    Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regular diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.

  9. CYP3A Mediated Ketamine Metabolism is Severely Impaired in Liver S9 Fractions from Aging Sprague Dawley Rats

    E-Print Network [OSTI]

    Raphael Santamaria; Marie-Chantal Giroux; Pascal Vachon; Francis Beaudry

    2015-09-25

    Ketamine is widely used in veterinary medicine and in medicine. Ketamine is metabolized to its active metabolite norketamine principally by liver CYP3A. Drug metabolism alterations during aging have severe consequences particularly in anesthesiology and very few studies on older animals were conducted for ketamine. The objective of the present study is to assess the influence of aging on CYP3A metabolism of ketamine. Liver S9 fractions from 3, 6, 12 and 18 month old male Sprague Dawley rats were prepared and Michaelis-Menten parameters were determined for primary metabolic pathways. The derived maximum enzyme velocity (i.e. Vmax) suggests a rapid saturation of the CYP3A enzyme active sites in liver S9 fractions of 18-month old rats. Observed Vmax for Liver S9 fractions from 3, 6 and 12 month old male Sprague Dawley rats were 2.39 (+-0.23), 2.61 (+-0.18), and 2.07 (+-0.07) respectively compared to 0.68 (+-0.02) for Liver S9 fractions from 18 month old male Sprague Dawley rats. Interestingly, we observed a 6 to 7 fold change in the derived Km when comparing Liver S9 fractions from 18 month old male Sprague Dawley rats with Liver S9 fractions from younger rats. Our results suggest that rat CYP3A enzyme undergoes conformational changes with age particularly in our geriatric group (e.g. 18 month rats) leading significant decrease in the rate of formation of norketamine. Moreover, our results strongly suggest a severe impairment of CYP3A ketamine mediated metabolism.

  10. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

    SciTech Connect (OSTI)

    Milesi-Halle, Alessandra [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham 611, Little Rock, AR 72205 (United States); Hendrickson, Howard P. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham 611, Little Rock, AR 72205 (United States); Laurenzana, Elizabeth M. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham 611, Little Rock, AR 72205 (United States); Gentry, W. Brooks [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham 611, Little Rock, AR 72205 (United States); Department of Anesthesiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Owens, S. Michael [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham 611, Little Rock, AR 72205 (United States)]. E-mail: mowens@uams.edu

    2005-12-15

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats.

  11. Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

    E-Print Network [OSTI]

    2010-01-01

    EGS: Designed human hypothalamus/ neurohypophysis studies,1b receptor mRNA in the hypothalamus and choroid plexus.ribonucleic acid in rat hypothalamus. Horm Metab Res 1995,

  12. Association of brominated proteins and changes in protein expression in the rat kidney with subcarcinogenic to carcinogenic doses of bromate

    SciTech Connect (OSTI)

    Kolisetty, Narendrababu [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States); Bull, Richard J. [MoBull Consulting, Richland, WA 99352 (United States); Muralidhara, Srinivasa; Costyn, Leah J. [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States); Delker, Don A. [School of Medicine, University of Utah, Salt Lake City, UT 84132 (United States); Guo, Zhongxian [Water Quality Office, Public Utilities Board, 608576 (Singapore); Cotruvo, Joseph A. [Joseph Cotruvo and Associates, LLC, Washington, DC 20016 (United States); Fisher, Jeffrey W. [National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Cummings, Brian S., E-mail: bsc@rx.uga.edu [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States)

    2013-10-15

    The water disinfection byproduct bromate (BrO{sub 3}{sup ?}) produces cytotoxic and carcinogenic effects in rat kidneys. Our previous studies demonstrated that BrO{sub 3}{sup ?} caused sex-dependent differences in renal gene and protein expression in rats and the elimination of brominated organic carbon in their urine. The present study examined changes in renal cell apoptosis and protein expression in male and female F344 rats treated with BrO{sub 3}{sup ?} and associated these changes with accumulation of 3-bromotyrosine (3-BT)-modified proteins. Rats were treated with 0, 11.5, 46 and 308 mg/L BrO{sub 3}{sup ?} in drinking water for 28 days and renal sections were prepared and examined for apoptosis (TUNEL-staining), 8-oxo-deoxyguanosine (8-oxoG), 3-BT, osteopontin, Kim-1, clusterin, and p-21 expression. TUNEL-staining in renal proximal tubules increased in a dose-related manner beginning at 11.5 mg BrO{sub 3}{sup ?}/L in female rats and 46 mg/L in males. Increased 8-oxoG staining was observed at doses as low as 46 mg/L. Osteopontin expression also increased in a dose-related manner after treatment with 46 mg/L, in males only. In contrast, Kim-1 expression increased in a dose-related manner in both sexes, although to a greater extent in females at the highest dose. Clusterin and p21 expression also increased in a dose-related manner in both sexes. The expression of 3-BT-modified proteins only increased in male rats, following a pattern previously reported for accumulation of ?-2{sub u}-globulin. Increases in apoptosis in renal proximal tubules of male and female rats at the lowest doses suggest a common mode of action for renal carcinogenesis for the two sexes that is independent of ?-2{sub u}-globulin nephropathy. - Highlights: • Bromate induced nephrotoxicity in both male and female rats by similar mechanisms. • Apoptosis was seen in both male and female rats at the lowest doses tested. • Bromate-induced apoptosis correlated to 8-oxo-deoxyguanosine formation. • Bromate increased the level of 3-bromotyrosine-modified proteins in male rats only. • These data identify possible novel mechanisms for bromate-induced nephrotoxicity.

  13. Productive Energy of Certain Feeds as Measured by Production of Fat and Flesh by Growing Rats

    E-Print Network [OSTI]

    Fraps, G. S. (George Stronach)

    1943-01-01

    STATION A B. CONNER, DIRECTOR, College Station, Texas BUIJTJETIN NO. ($32 OCTOBER 1943 PRODUCTIVE ENERGY OF CERTAIN FEEDS AS MEASURED BY PRODUCTION OF FAT AND FLESH BY GROWING RATS G. S. FRAPS Division of Chemistry AGRICULTZTRAL AND MECHANICAL... COLLEGE OF TEXAS T. 0. WALTON, President [Blank Page in Original Bulletin] 'revious work with chickens shoxved that the energy values of feeds re very nearly in proportion to the digestible nutrients. Experiments *e made with a different kind...

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

    E-Print Network [OSTI]

    Wall, Florence Elizabeth

    1989-01-01

    of Committee) John E. Martin (Member) J es E. Womack (Member) Gerald R. Bratton (Head of Department) ~ E~ 4o/oL John R. Gold (Chair of Genetics Faculty) May 1989 ABSTRACT The Gestation-Dependent Variation in Aflatoxin Bt Activation by Rat Liver... . . . . . . avg. . . . . . . . BSA . . . . . . . BP , . . . . . BCA . . . . . . . . cm . . . . . . . . Ci oC . . . . . . . DNA . . . . . . . . . DMSO . . . . . . . E R . . . . . G6P . . . . . . . G6PDH . . . . . . . . HBSS . . . . . . . . . hist...

  15. EXCITABILITY OF ENGINEERED MUSCLE CONSTRUCTS, DENERVATED AND STIMULATED-DENERVATED MUSCLES OF RATS, AND CONTROL SKELETAL

    E-Print Network [OSTI]

    Dennis, Robert G.

    , AND CONTROL SKELETAL MUSCLES IN NEONATAL, YOUNG, ADULT AND OLD MICE AND RATS. Robert G. Dennis, Douglas E. Dow for stimulated-denervated muscles or control muscles in young, adult, or old rodents. The R50 and C50 were: (1 of age), 0.45±0.03 & 0.86±0.03; young (1 to 5 months of age) and adult (8 to 14 months of age), 0

  16. Differential rates of loss of chromosome aberrations in rat thyroids after X rays or Neutrons

    SciTech Connect (OSTI)

    Scott, D.; Gellard, P.A.; Hendry, J.H.

    1984-01-01

    Rat thryoid glands were exposed in vivo to 5.5-Gy X rays or 2.75-Gy neutrons (14.7 MeV) and cell proliferation was stimulated by goitrogen treatment at various intervals up to 48 weeks postirradiation. The amount of chromosome damage in stimulated follicular cells declined much more slowly after neutron than X irradiation, suggesting differential repair. This observation may be relevant to the question of residual cellular damage and oncogenesis after X rays and neutrons.

  17. Oncogenic action of beta, proton, alpha and electron radiation on the rat skin

    SciTech Connect (OSTI)

    Burns, F.J.

    1980-01-01

    Rat skin is being utilized as an empirical model for testing dose and time related aspects of the oncogenic action of ionizing radiation, ultraviolet light, and polycyclic aromatic hydrocarbons. Molecular lesions in the skin DNA, including, strand breaks and thymine dimers, are being measured and compared to tumor induction. The induction and repair kinetics of molcular lesions are being compared to split dose repair. Modifiers and radiosensitizers are being utilized to test specific aspects of a chromosome breakage theory of radiation oncogenesis.

  18. Tumorigenic action of beta, proton, alpha and electron radiation on the rat skin

    SciTech Connect (OSTI)

    Burns, F.J.

    1980-01-01

    Rat skin is utilized as a model system for studying dose and time related aspects of the oncogenic action of ionizing radiation, ultraviolet light and polycyclic aromatic hydrocarbons. Molecular lesions in the DNA of the epidermis, including strand breaks and thymine dimers, are measured and compared to the temporal and dose related aspects of tumor induction. The induction and repair kinetics of molecular lesions are compared to split dose recovery as modified by sensitizers and type of radition of oncogenic damage.

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

    E-Print Network [OSTI]

    Farr, Kathryn Louise

    1982-01-01

    . Two consecutive 25 vl blood samples were col- lected through an indwelling juqular cannula every 5 minutes for a period of 4 hours for each treatment group. Control rats were undis- turbed during the sampling period, while the stress groups... underwent their respective stress during the final 2 hours of the 4 hour samp- ling period. Concentrations of whole blood LH were quantitated by a validated radioimmunoassay. Mean whole blood LH concentration, peak frequency and mean pulse height...

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

    E-Print Network [OSTI]

    Becker, Marion Carol

    1991-01-01

    TOXICITY OF CHLORINATED DIPHENYL ETHERS IN HYDRA . . 34 Materials and Methods Results Discussion 36 37 43 IV EXPERIMENTAL ASSESSMENT OF DEVELOPMENTAL TOXICITY OF CHLORINATED DIPHENYL ETHERS IN THE RAT, 46 Materials and Methods Results Discussion... and little is known about their potential for causing developmental defects. Because the PCDEs are closely related to the chlorinated dibenzo-p-dioxins and the PCBs, it is of interest to review studies conducted to determine the developmental toxicity...

  1. Comparative effects of sodium channel blockers in short term rat whole embryo culture

    SciTech Connect (OSTI)

    Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se [Department of Pharmaceutical Biosciences, Uppsala University (Sweden); Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma [AstraZeneca R and D Södertälje (Sweden); Cebers, Gvido [AstraZeneca R and D, iMed, 141 Portland Street, Cambridge, MA 02139 (United States); Hellmold, Heike; Gustafson, Anne-Lee [AstraZeneca R and D Södertälje (Sweden); Webster, William S [Department of Anatomy and Histology, University of Sydney (Australia)

    2013-10-15

    This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.

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

    E-Print Network [OSTI]

    Trott, Daniel Wayne

    2012-02-14

    diabetes, insulin-stimulated vasodilation is impaired as a result of an imbalance in NO and ET-1 production. We tested the hypothesis that chronic voluntary wheel running (RUN) prevents impair- ments in insulin-stimulated vasodilation associated... with obesity and type 2 diabetes independent of the effects of RUN on adiposity by random- izing Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia-induced obesity and type 2 diabetes, to 1) RUN, 2) caloric restriction (CR; diet adjusted...

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

    E-Print Network [OSTI]

    Griffin, Travis Barton

    1961-01-01

    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...

  4. Cortical Plasticity and Behavioral Recovery Following Focal Lesion to Primary Motor Cortex in Adult Rats

    E-Print Network [OSTI]

    Nishibe, Mariko

    2012-05-31

    ………………………………..…………42 Fig 10 Anatomical substrate for cortical motor map competition: convergence of corticospinal projections of M1………………………………………………………………………….……..43 Fig 11 Single-pellet reach and retrieval task………………………………………….………….44 CHAPTER TWO Fig 1... in inhibiting the inaccurate placing response (Barth et al., 1990). The M1/S1 rough mirror-image connectivity particularly plays a crucial role in the movements presumably necessary for single-pellet reach and retrieval task. Rats first locate a singly...

  5. IDENTIFYING MECHANISMS OF INSULIN PRODUCTION AND SECRETION IN SMALL AND LARGE RAT ISLETS

    E-Print Network [OSTI]

    Huang, Han-Hung

    2011-12-31

    . The PP cell produces pancreatic polypeptide, a regulator of pancreatic secreting activities including exocrine and endocrine. The epsilon cell produces ghrelin, which is thought to be important in growth hormone release, metabolic regulation and energy...M glucose) and during high simulation (20mM) glucose perifusion experiments (Lehmann et al., 2007). In addition, transplanting small rat islets into type 1 diabetic animal model surprisingly led to better blood glucose control 60 days after...

  6. Physiological effects following administration of Citrus aurantium for 28 days in rats

    SciTech Connect (OSTI)

    Hansen, Deborah K.; Pellicore, Linda S.

    2012-06-15

    Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

  7. Use of gamma-hexachlorocyclohexane (lindane) to determine the ontogeny of metabolism in the developing rat

    SciTech Connect (OSTI)

    Copeland, M.F.; Chadwick, R.W.; Cooke, N.; Whitehouse, D.A.; Hill, D.M.

    1986-01-01

    The compound lindane (gamma-hexachlorocyclohexane) has been used to study the ontogeny of metabolism in the developing Fischer 344 rat. The distribution and metabolic fate of lindane at 2, 9, 16, and 23 d of age was investigated following subcutaneous administration of lindane at 20 mg/kg containing 0.5 microCi (U-/sup 14/C)lindane in peanut oil. Groups of 10 pups (5 male and 5 female) were sacrificed at 4-h intervals during the 24-h period following dosing. Adrenals, blood, brain, heart, lung, liver, and kidneys were analyzed for radioactivity. Urine samples were analyzed for radioactivity and metabolites of lindane. There was a significant age-dependent increase in the metabolism of lindane in the rat. High levels of radioactivity in the lung and increased reductive dechlorination suggest that the lung may play a greater role in metabolism of lindane by young rats. Oxidative phase I reactions increased significantly, while anaerobic reductive dechlorination of lindane to 4-chlorophenylmercapturic acid decreased significantly with age. Phase II sulfate and glutathione conjugations decreased significantly and glucuronide conjugation increased significantly with age. Metabolism and excretion of lindane appear to parallel development of the hepatic enzymes involved in phase I and phase II reactions.

  8. Use of. gamma. -hexachlorocyclohexane (lindane) to determine the ontogeny of metabolism in the developing rat

    SciTech Connect (OSTI)

    Copeland, M.F.; Chadwick, R.W.; Cooke, N.; Whitehouse, D.A.; Hill, D.M.

    1986-01-01

    The compound lindane (..gamma..-hexachlorocyclohexane) has been used to study the ontogeny of metabolism in the developing Fischer 344 rat. The distribution and metabolic rate of lindane at 2, 9, 16, and 23 d of age was investigated following subcutaneous administration of lindane at 20 mg/kg containing 0.5 ..mu..Ci (U-/sup 14/C)lindane in peanut oil. Groups of 10 pups (5 male and 5 female) were sacrificed at 4-h intervals during the 24-h period following dosing. Adrenals, blood, brain, heart, lung, liver, and kidneys were analyzed for radioactivity. Urine samples were analyzed for radioactivity and metabolites of lindane. There was a significant age-dependent increase in the metabolism of lindane in the rat. High levels of radioactivity in the lung and increased reductive dechlorination suggest that the lung may play a greater role in metabolism of lindane by young rats. Oxidative phase I reactions increased significantly, while anaerobic, reductive dechlorination of lindane to 4-chlorophenylmercapturic acid decreased significantly and glucuronide conjugation increased significantly with age. Metabolism and excretion of lindane appear to parallel development of the hepatic enzymes involved in phase I and phase II reactions.

  9. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

    SciTech Connect (OSTI)

    Chiang, H.-M.; Fang, S.-H.; Wen, K.-C.; Hsiu, S.-L.; Tsai, Shang-Yuan; Hou, Y.-C.; Chi, Y.-C.; Lee Chao, Pei-Dawn . E-mail: pdlee@mail.cmu.edu.tw

    2005-12-15

    Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC{sub 0-t} by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

  10. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

    SciTech Connect (OSTI)

    Constantinou, Maria A.; Theocharis, Stamatios E.; Mikros, Emmanuel . E-mail: mikros@pharm.uoa.gr

    2007-01-01

    Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using {sup 1}H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. {sup 1}H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the {sup 1}H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.

  11. 12/14/14, 1:51 PMI Trained Rats to Trade, and Win, on Wall Street | VICE | United States Page 1 of 5http://www.vice.com/read/rattraders-0000519-v21n12

    E-Print Network [OSTI]

    by machines--or, as was the case here, by rats. Like the work of many in this field, my research indicates became fat very fast); when they were wrong they received a minor electric shock. Soon some rats were

  12. Direct examination of cadmium bonding in rat tissues dosed with mine wastes and cadmium-containing solutions

    SciTech Connect (OSTI)

    Diacomanolis, V.; Ng, J. C. [University of Queensland, National Research Centre for Environmental Toxicology, Coopers Plains, QLD, 4008 (Australia); Sadler, R. [School of Public Health, Griffith University, Brisbane, QLD (Australia); Harris, H. H. [School of Chemistry and Physics, University of Adelaide, Adelaide, SA (Australia); Nomura, M. [Photon Factory, Institute of Material Structure Science, Tsukuba (Japan); Noller, B. N. [University of Queensland, Centre For Mined Land Rehabilitation, St Lucia 4072 QLD (Australia)

    2010-06-23

    Direct examination by XANES and EXAFS of metal bonding in tissue can be demonstrated by examining cadmium uptake and bonding in animal tissue maintained at cryogenic temperatures. XANES at the K-edge of cadmium were collected at the Photon Factory Advanced Ring (PF-AR), NW10A beam line at KEK-Tsukuba-Japan. Rats fed with 1g mine waste containing 8-400 mg/kg cadmium per 200g body weight (b.w.) or dosed by oral gavage with either cadmium chloride solution alone (at 6 mg/kg b.w.) or in combination with other salts (As, Cu or Zn), 5 days/week for 6 weeks, had 0.1-7.5 and 8-86 mg/kg cadmium in the liver or kidney, respectively. Rats given intraperitoneally (ip) or intravenously (iv) 1-4 times with 1 mg/kg b.w. cadmium solution had 30-120 mg/kg cadmium in the liver or kidney. Tissues from rats were kept and transferred at cryogenic temperature and XANES were recorded at 20 K. The spectra for rat liver samples suggested conjugation of cadmium with glutathione or association with the sulfide bond (Cd-S) of proteins and peptides. EXAFS of rat liver fed by Cd and Zn solutions showed that Cd was clearly bound to S ligands with an inter-atomic distance of 2.54 A ring for Cd-S that was similar to cadmium sulfide with an inter-atomic distance of 2.52 A ring for Cd-S. Liver or kidney of rats fed with mine wastes did not give an edge in the XANES spectra indicating little uptake of cadmium by the animals. Longer and higher dosing regimen may be required in order to observe the same Cd-S bond in the rat tissue from mine wastes, including confirmation by EXAFS.

  13. 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

    2003-12-09

    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.

  14. Radiation-Induced Liver Fibrosis Is Mitigated by Gene Therapy Inhibiting Transforming Growth Factor-{beta} Signaling in the Rat

    SciTech Connect (OSTI)

    Du Shisuo; Qiang Ming [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.c [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zhou Jian [Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Tan Yunshan [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zhang Zhengyu [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Zeng Haiying [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Liu Zhongshan [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)

    2010-12-01

    Purpose: We determined whether anti-transforming growth factor-{beta} (TGF-{beta}) intervention could halt the progression of established radiation-induced liver fibrosis (RILF). Methods and Materials: A replication-defective adenoviral vector expressing the extracellular portion of human T{beta}RII and the Fc portion of immunoglobulin G fusion protein (AdT{beta}RIIFc) was produced. The entire rat liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdT{beta}RIIFc (1 x 10{sup 11} plaque-forming units [PFU] of T{beta}RII), control virus (1 x 10{sup 11} PFU of AdGFP), or saline. Delayed radiation liver injury was assessed by histology and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell activation, and hepatocyte regeneration were also analyzed. Results: In rats infected with AdT{beta}RIIFc, fibrosis was significantly improved compared with rats treated with AdGFP or saline, as assessed by histology, hydroxyproline content, and serum level of hyaluronic acid. Compared with AdGFP rats, AdT{beta}RIIFc-treated rats exhibited decreased oxidative stress damage and hepatic stellate cell activation and preserved liver function. Conclusions: Our results demonstrate that TGF-{beta} plays a critical role in the progression of liver fibrosis and suggest that anti-TGF-{beta} intervention is feasible and ameliorates established liver fibrosis. In addition, chronic oxidative stress may be involved in the progression of RILF.

  15. 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

  16. A STUDY OF FISCHER 344 RATS EXPOSED TO SILICA DUST FOR SIX MONTHS AT CONCENTRATIONS OF 0, 2, 10 OR 20 MG / M3.

    SciTech Connect (OSTI)

    KUTZMAN,R.S.

    1984-02-01

    The major objective of this study was to relate the results of a series of functional tests to the compositional and structural alterations in the rat lung induced by subchronic exposure to silica dust. Fischer-344 rats were exposed for 6 hours/day, 5 days/week for 6 months to either 0, 2, 10, or 20 mg SiO{sub 2}/m{sup 3}. The general appearance of the exposed rats was not different from that of the controls. Interestingly, female rats exposed to silica dust, at all tested concentrations, gained more weight than the controls. The lung weight and the lung-to-body weight ratio was greater in the male rats exposed to the highest concentration of silica dust.

  17. 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.

    2010-01-01

    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.

  18. 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

    2012-11-15

    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.

  19. Subacute effects of hexabromocyclododecane (HBCD) on hepatic gene expression profiles in rats

    SciTech Connect (OSTI)

    Canton, Rocio F. [Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht (Netherlands)], E-mail: rfcanton@gmail.com; Peijnenburg, Ad A.C.M.; Hoogenboom, Ron L.A.P. [RIKILT Institute of Food Safety, Wageningen University and Research Center, P.O. Box 230, 6700 AE Wageningen (Netherlands); Piersma, Aldert H.; Ven, Leo T.M. van der [National Institute of Public Health and the Environment (RIVM), Laboratory for Heath Protection Research, P.O. Box 1, 3720 BA Bilthoven (Netherlands); Berg, Martin van den [Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht (Netherlands); Heneweer, Marjoke [RIKILT Institute of Food Safety, Wageningen University and Research Center, P.O. Box 230, 6700 AE Wageningen (Netherlands)

    2008-09-01

    Hexabromoyclododecane (HBCD), used as flame retardant (FR) mainly in textile industry and in polystyrene foam manufacture, has been identified as a contaminant at levels comparable to other brominated FRs (BFRs). HBCD levels in biota are increasing slowly and seem to reflect the local market demand. The toxicological database of HBCD is too limited to perform at present a solid risk assessment, combining data from exposure and effect studies. In order to fill in some gaps, a 28-day HBCD repeated dose study (OECD407) was done in Wistar rats. In the present work liver tissues from these animals were used for gene expression profile analysis. Results show clear gender specificity with females having a higher number of regulated genes and therefore being more sensitive to HBCD than males. Several specific pathways were found to be affected by HBCD exposure, like PPAR-mediated regulation of lipid metabolism, triacylglycerol metabolism, cholesterol biosynthesis, and phase I and II pathways. These results were corroborated with quantitative RT-PCR analysis. Cholesterol biosynthesis and lipid metabolism were especially down-regulated in females. Genes involved in phase I and II metabolism were up-regulated predominantly in males, which could explain the observed lower HBCD hepatic disposition in male rats in this 28-day study. These sex-specific differences in gene expression profiles could also underlie sex-specific differences in toxicity (e.g. decreased thyroid hormone or increased serum cholesterol levels). To our knowledge, this is the fist study that describes the changes in rat hepatic gene profiles caused by this commonly used flame retardant.

  20. Response of rat brain protein synthesis to ethanol and sodium barbital

    SciTech Connect (OSTI)

    Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

    1987-01-01

    Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of /sup 14/C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the /sup 14/C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of /sup 14/C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units.

  1. 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

    1986-01-01

    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...

  2. 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

    1987-01-01

    TIIE EFFECT 0F A PR0L0NGED MAGNESIUM RESTRI CTI0N ON THE HUMORAL IMMUNE RESPONSE IN HATERHAL RATS AHD THEIR OFFSPRING A Thesis by DIANE T. COHILL Submitted to the Graduate College of Texas ASM University in Partial fulfillment... of the requirements for the degree of MASTER OF SC IENCE May 1987 Major Subject: Nutrition THE EFFECT OF A PROLONGED MAGNESIUM RESTRICTION ON THE HUMORAL IMMUNE RESPONSE IN MATERNAL RATS AND THEIR OFFSPRING A Thesis by DIANE T. COHILL Approved as to sty le...

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

    E-Print Network [OSTI]

    Brotze, Mary Frances

    1968-01-01

    . 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...

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

    E-Print Network [OSTI]

    Holmes, Kathryn Ellen Hughes

    1988-01-01

    those fed the CD diet, but only for one day (day 8). No physical changes were noted during week 1 of lactation. One dam from group CD exhibited bright pink ears and a slightly pink tail during week 2 of lactation, but these signs were not apparent... with deficient males produced smaller litters. Restricted diets during gestation and lactation in rats have also been shown to cause reduced serum and bone magnesium levels in dams and reduced viability and body weights of offspring (2). Ma nesium and Protein...

  5. Digestibility of Human Foods and Animal Feeds as Measured by Experiments with Rats

    E-Print Network [OSTI]

    Fraps, G. S. (George Stronach)

    1945-01-01

    AND MECHANICAL COLLEGE OF TEXAS GIBB GILCHRIST, President [Blank Page in Original Bulletin] As part of the comprehensive investigation of the energy values of animal feeds and human foods, digestion experiments were made with white rats. Results of 508 tests... This publication is part of a comprehensive investigation of the energy values of animal feeds and human foods. Previous work has shown that the 1 differences in energy values of food and feeds as measured by experiments with chickens are due to a large extent...

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

    E-Print Network [OSTI]

    Shepherd, David Preston

    1967-01-01

    . The rats were exposed separately for a period of two minutes. The dose rate measurements were determined prior to this study by using lithium fluoride dosimeter s, and were brought up to date by calculation. Twenty-four hours before irradiation, one ml... carbonate 10 drops Magnesium sulfate 25 mgm Manganese sulfate 7. 5 mgm Iron phosphate 500 gm Sodium fluoride 1 mgm Potassium iodide 25 mcgm Potassium phosphate 1 mgm Potassium chloride 10 mgm 10 mgm Copper Sulfate 40 rngm Aluminum potassium s ul...

  7. Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

    SciTech Connect (OSTI)

    Karanth, Subramanya [Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078 (United States); Liu, Jing [Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078 (United States); Mirajkar, Nikita [Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078 (United States); Pope, Carey [Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078 (United States)]. E-mail: carey.pope@okstate.edu

    2006-10-01

    This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted in any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some compensatory process(es) downstream from synaptic neurotransmitter accumulation limits the expression of toxicity following acute CPF exposure.

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

    E-Print Network [OSTI]

    Hinkle, Donald King

    1966-01-01

    irradiated in a total of six rad groups as follows: Number in Grou dD 10 6 9 6 7 8 ZOO 400 700 1300 2000 2500 All sections of skin and tumor tissues were submitted to the Anatomic Pathology Section, USAF School of Aerospace 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 AErM University in partial fulfillment of the requirements for the degree of MASTER...

  9. A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors

    SciTech Connect (OSTI)

    Zhou, Dan, E-mail: DZhou@syntapharma.com [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States); Liu, Yuan; Ye, Josephine; Ying, Weiwen; Ogawa, Luisa Shin; Inoue, Takayo; Tatsuta, Noriaki; Wada, Yumiko; Koya, Keizo [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States); Huang, Qin [Department of Pathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132 (United States); Bates, Richard C.; Sonderfan, Andrew J. [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States)

    2013-12-01

    In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24 h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6 h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6 h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential. - Highlights: • In human trials some Hsp90 inhibitors cause visual disorders, others do not. • Prolonged inhibition of Hsp90 in the rat eye results in photoreceptor cell death. • Retina/plasma ratio and retinal elimination rate are linked to toxicity potential. • Rat retinotoxic responses to individual Hsp90 inhibitors reflect clinical profiles. • Rodent modeling may be used to assess ocular risks of targeted Hsp90 compounds.

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

    SciTech Connect (OSTI)

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

    1987-11-23

    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.

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

    E-Print Network [OSTI]

    Hull, Elaine

    studies suggest a possible role for 5-HT in the etiology of anorexia nervosa. Recently, we have examined that promote activity-based anorexia (ABA). In this animal model of anorexia nervosa, rats are food restricted symptoms of anorexia nervosa including hypophagia, hyperactivity, progressive weight loss, and disruptions

  12. COMPARATIVE COMPUTATIONAL MODELING OF AIRFLOWS AND VAPOR DOSIMETY IN THE RESPIRATORY TRACTS OF RAT, MONKEY, AND HUMAN

    SciTech Connect (OSTI)

    Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Minard, Kevin R.; Jacob, Rick E.; Timchalk, Charles; Glenny, Robb W.; Pipavath, Sudhaker; Cox, Timothy C.; Wallis, Chris; Larson, Richard; Fanucchi, M.; Postlewait, Ed; Einstein, Daniel R.

    2012-07-01

    Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomic region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.

  13. 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.

    2005-08-15

    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.

  14. 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

  15. 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

  16. Evidence That Androgen Acts Through NMDA Receptors to Affect Motoneurons in the Rat Spinal Nucleus of the Bulbocavernosus

    E-Print Network [OSTI]

    Breedlove, Marc

    . Twenty-five days later, bulbocavernosus muscles were injected with the retrograde tracer cholera toxin of the bulbocavernosus; neural plasticity; NMDA receptor; androgen; motoneurons; MK-801 The rat spinal nucleus and Breedlove, 1995). The NMDA receptor has been implicated in many instances of neural plasticity, including

  17. In vivo chlorine-35, sodium-23 and proton magnetic resonance imaging of the rat brain , M. Augath2

    E-Print Network [OSTI]

    In vivo chlorine-35, sodium-23 and proton magnetic resonance imaging of the rat brain S. Kirsch1 of the cytoplasm and the volume of cells [1]. In order to investigate the feasibility of combined in vivo 35 Cl, 23 Na and 1 H MRI we developed a rf coil setup to measure 35 Cl, 23 Na and 1 H signals in one scanning

  18. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    SciTech Connect (OSTI)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

    2010-10-27

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

  19. Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat

    SciTech Connect (OSTI)

    Kimbell, J.S.; Gross, E.A.; Joyner, D.R.; Godo, M.N.; Morgan, K.T. (Chemical Industry Institute of Toxicology, Research Triangle Park, NC (United States))

    1993-08-01

    For certain inhaled air pollutants, such as reactive, water soluble gases, the distribution of nasal lesions observed in F344 rats may be closely related to regional gas uptake patterns in the nose. These uptake patterns can be influenced by the currents of air flowing through the upper respiratory tract during the breathing cycle. Since data on respiratory tract lesions in F344 rats are extrapolated to humans to make predictions of risk to human health, a better understanding of the factors affecting these responses is needed. To assess potential effects of nasal airflow on lesion location and severity, a methodology was developed for creation of computer simulations of steady-state airflow and gas transport using a three-dimensional finite element grid reconstructed from serial step-sections of the nasal passages of a male F344 rat. Simulations on a supercomputer used the computational fluid dynamics package FIDAP (FDI, Evanston, IL). Distinct streams of bulk flow evident in the simulations matched inspiratory streams reported for the F344 rat. Moreover, simulated regional flow velocities matched measured velocities in concurrent laboratory experiments with a hollow nasal mold. Computer-predicted flows were used in simulations of gas transport to nasal passage walls, with formaldehyde as a test case. Results from the uptake simulations were compared with the reported distribution of formaldehyde-induced nasal lesions observed in the F344 rat, and indicated that airflow-driven uptake patterns probably play an important role in determining the location of certain nasal lesions induced by formaldehyde. This work demonstrated the feasibility of applying computational fluid dynamics to airflow-driven dosimetry of inhaled chemicals in the upper respiratory tract.

  20. 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)

    2012-09-01

    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.

  1. Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

    SciTech Connect (OSTI)

    Zhang, Shun; Jiang, Chunyang; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Zhenglun; Wang, Aiguo

    2013-09-01

    Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-?B (NF-?B)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress. • Endoplasmic reticulum stress is involved in testis disorder and germ cell apoptosis. • Inflammatory response is implicated in impaired spermatogenesis and germ cell loss.

  2. 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

    2011-02-22

    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...

  3. 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-

    2004-01-01

    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 ...

  4. Leptin acts centrally to induce the prepubertal secretion of luteinizing hormone in the female rat: a potential early role in the pubertal process 

    E-Print Network [OSTI]

    Dearth, Robert Keith

    1999-01-01

    Recent data generated from adult male and female rats indicates that lepton is capable of stimulating luteinizing hormone (LH) secretion via a hypothalamic action. Consequently, we hypothesized that this peptide may similarly play a role...

  5. BurrowView Seeing the world through the eyes of rats Jo Agila Bitsch Link, Gregor Fabritius, Muhammad Hamad Alizai, Klaus Wehrle

    E-Print Network [OSTI]

    , extreme terrestrial environments, such as the natural habitat of rats, present specific challenges: (1) The node size is greatly limited due to increasingly narrow pathways in burrows and to allow for natural

  6. Role of Pulse Repetition Frequency and Exposure Duration on the Superthreshold Behavior of Ultrasound-induced Lung Hemorrhage in Adult Mice and Rats

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    of Ultrasound-induced Lung Hemorrhage in Adult Mice and Rats William D. O'Brien Jr.,1 Leon A. Frizzell,1 David J behavior for ultrasound-in- duced lung hemorrhage was investigated in 150 mice and 150 rats at 2.8 MHz-induced lung hemorrhage and on the size of the lesions at superthreshold levels has been exam- ined to a very

  7. 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.

    2013-08-01

    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.

  8. 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

    2012-06-30

    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.

  9. Distribution of phospholipase C isozymes in various rat tissues and cultured cells

    SciTech Connect (OSTI)

    Suh, P.G.; Ryu, S.H.; Choi, W.C.; Lee, K.Y.; Rhee, S.G.

    1987-05-01

    Monoclonal antibodies prepared against PLC-I or PLC-II enzyme did not cross-react with the other. Using a pair of antibodies which recognizes 2 different antigenic sites on the same molecule, radioimmunoassays were developed for the quantitation of PLC-I and PLC-II in homogenates of various tissues and cultured cells, prepared by homogenization in a 2 M KCl buffer. The contents of PLC enzymes were measured in 19 rat tissues, in human platelets and in 17 cultured cells. Results indicate that the concentration of PLC-I and PLC-II is very high in brain, PLC-I is localized mainly in brain and partly in seminal vesicles, PLC-II is found in most tissues and cells. PLC-I is highly localized even in brain: 5 different neuroblastoma did not contain PLC-I while 2 glioma and 1 astrocytoma contained significant amounts.

  10. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

    SciTech Connect (OSTI)

    Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young

    2011-06-17

    Highlights: {yields} Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. {yields} JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. {yields} Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. {yields} CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

  11. Evaluation of the pharmacokinetics and cardiotoxicity of doxorubicin in rat receiving nilotinib

    SciTech Connect (OSTI)

    Zhou, Zhi-yong; Wan, Li-li; Yang, Quan-jun; Han, Yong-long; Li, Yan; Yu, Qi; Guo, Cheng; Li, Xiao

    2013-10-01

    Doxorubicin (DOX) is a potent chemotherapy drug with a narrow therapeutic window. Nilotinib, a small-molecule Bcr-Abl tyrosine kinase inhibitor, was reported to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) transmembrane transporters. The present study aimed to investigate nilotinib's affection on the steady-state pharmacokinetics, disposition and cardiotoxicity of DOX. A total of 24 male Sprague–Dawley rats were randomized into four groups (6 in each) and received the following regimens: saline, intravenous DOX (5 mg/kg) alone, and DOX co-administrated with either 20 or 40 mg/kg nilotinib. Blood was withdrawn at 12 time points till 72 h after DOX injection and the concentrations of DOX and its metabolite doxorubicinol (DOXol) in serum and cardiac tissue were assayed by LC–MS–MS method. To determine the cardiotoxicity, the following parameters were investigated: creatine kinase, lactate dehydrogenase, malondialdehyde, and superoxide dismutase. Histopathological examination of heart section was carried out to evaluate the extent of cardiotoxicity after treatments. The results showed that pretreatment of 40 mg/kg nilotinib increased the AUC{sub 0–t} and C{sub max} of DOX and DOXol. However, their accumulation in cardiac tissue was significantly decreased when compared with the group that received DOX alone. In addition, biochemical and histopathological results showed that 40 mg/kg nilotinib reduced the cardiotoxicity induced by DOX administration. In conclusion, co-administration of nilotinib increased serum exposure, but significantly decreased the accumulation of DOX in cardiac tissue. Consistent with in vitro profile, oral dose of 40 mg/kg nilotinib significantly decreased the cardiotoxicity of DOX in rat by enhancing P-gp activity in the heart.

  12. 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.

    2012-01-01

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

  13. Transgenic rats overexpressing the human MrgX3 gene show cataracts and an abnormal skin phenotype

    SciTech Connect (OSTI)

    Kaisho, Yoshihiko . E-mail: Kaisho_Yoshihiko@takeda.co.jp; Watanabe, Takuya; Nakata, Mitsugu; Yano, Takashi; Yasuhara, Yoshitaka; Shimakawa, Kozo; Mori, Ikuo; Sakura, Yasufumi; Terao, Yasuko; Matsui, Hideki; Taketomi, Shigehisa

    2005-05-13

    The human MrgX3 gene, belonging to the mrgs/SNSRs (mass related genes/sensory neuron specific receptors) family, was overexpressed in transgenic rats using the actin promoter. Two animal lines showed cataracts with liquification/degeneration and swelling of the lens fiber cells. The transient epidermal desquamation was observed in line with higher gene expression. Histopathology of the transgenic rats showed acanthosis and focal parakeratosis. In the epidermis, there was an increase in cellular keratin 14, keratin 10, and loricrin, as well as PGP 9.5 in innervating nerve fibers. These phenotypes accompanied an increase in the number of proliferating cells. These results suggest that overexpression of the human MrgX3 gene causes a disturbance of the normal cell-differentiation process.

  14. 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

    1989-01-01

    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...

  15. Abstract The aim of this study was to characterize functionally the single-channel properties of rat hypotha-

    E-Print Network [OSTI]

    Burnstock, Geoffrey

    records) at 10 µM was 0.030±0.017 and 0.030±0.028 at 1 mM. Keywords Purinoceptor · Hypothalamus/receptors throughout the adult rat CNS includ- ing the hypothalamus in which P2X4 and P2X6 subunits are expressed that closely resemble native currents in dorsal root ganglion cells [21]. For the hypothalamus

  16. Novel function of glutathione transferase in rat liver mitochondrial membrane: Role for cytochrome c release from mitochondria

    SciTech Connect (OSTI)

    Lee, Kang Kwang; Shimoji, Manami; Hossain, Quazi Sohel [Laboratory of Molecular Genetics and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan); Sunakawa, Hajime [Department of Oral and Maxillofacial Functional Rehabilitation, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan); Aniya, Yoko [Laboratory of Molecular Genetics and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan)], E-mail: yaniya@med.u-ryukyu.ac.jp

    2008-10-01

    Microsomal glutathione transferase (MGST1) is activated by oxidative stress. Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no information about the oxidative activation of mtMGST1. In the present study, we aimed to determine whether mtMGST1 also undergoes activation and about its function. When rats were treated with galactosamine/lipopolysaccharide (GalN/LPS), mtMGST1 activity was significantly increased, and the increased activity was reduced by the disulfide reducing agent dithiothreitol. In mitochondria from GalN/LPS-treated rats, disulfide-linked mtMGST1 dimer and mixed protein glutathione disulfides (glutathionylation) were detected. In addition, cytochrome c release from mitochondria isolated from GalN/LPS-treated rats was observed, and the release was inhibited by anti-MGST1 antibodies. Incubation of mitochondria from control rats with diamide and diamide plus GSH in vitro resulted in dimer- and mixed disulfide bond-mediated activation of mtMGST1, respectively. The activation of mtMGST1 by diamide plus GSH caused cytochrome c release from the mitochondria, and the release was prevented by treatment with anti-MGST1 antibodies. In addition, diamide plus GSH treatment caused mitochondrial swelling accompanied by cytochrome c release, which was inhibited by cyclosporin A (CsA) and bongkrekic acid (BKA), inhibitors of the mitochondrial permeability transition (MPT) pore. Furthermore, mtMGST1 activity was also inhibited by CsA and BKA. These results indicate that mtMGST1 is activated through mixed disulfide bond formation that contributes to cytochrome c release from mitochondria through the MPT pore.

  17. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

    SciTech Connect (OSTI)

    Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E. . E-mail: fenton.suzanne@epa.gov

    2007-02-01

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time.

  18. Changes in testicular fluid production and plasma hormones in the adult rat after testicular 60Co irradiation

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    to irradiation by a medical y-ray machine (Cobalt 60 source ; skin source distance : 70 cm). The gonads were subjected to a total dose of 0.8 Gy in one dose over a period of nearly 1 min. When the rats were irradiated irradiation P. LAPORTE Marie-Claude VIGUIER-MARTINEZ D. ZONGO O. LE FLOCH F. LIPINSKI (1) Station de Physio

  19. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    SciTech Connect (OSTI)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)] [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)] [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 ?mol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-? (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ? Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ? Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ? Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ? The actions of diphenyl ditelluride are mediated by MAPK and Akt signaling pathways.

  20. Inter-strain heterogeneity in rat hepatic transcriptomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    SciTech Connect (OSTI)

    Yao, Cindy Q.; Prokopec, Stephenie D.; Watson, John D.; Pang, Renee; P'ng, Christine; Chong, Lauren C.; Harding, Nicholas J. [Informatics and Biocomputing Platform, Ontario Institute for Cancer Research, Toronto (Canada)] [Informatics and Biocomputing Platform, Ontario Institute for Cancer Research, Toronto (Canada); Pohjanvirta, Raimo [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio (Finland) [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio (Finland); Department of Food Hygiene and Environmental Health, University of Helsinki (Finland); Okey, Allan B. [Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada)] [Department of Pharmacology and Toxicology, University of Toronto, Toronto (Canada); Boutros, Paul C., E-mail: Paul.Boutros@oicr.on.ca [Informatics and Biocomputing Platform, Ontario Institute for Cancer Research, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2012-04-15

    The biochemical and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been the subject of intense study for decades. It is now clear that essentially all TCDD-induced toxicities are mediated by DNA–protein interactions involving the Aryl Hydrocarbon Receptor (AHR). Nevertheless, it remains unknown which AHR target genes cause TCDD toxicities. Several groups, including our own, have developed rodent model systems to probe these questions. mRNA expression profiling of these model systems has revealed significant inter-species heterogeneity in rodent hepatic responses to TCDD. It has remained unclear if this variability also exists within a species, amongst rodent strains. To resolve this question, we profiled the hepatic transcriptomic response to TCDD of diverse rat strains (L-E, H/W, F344 and Wistar rats) and two lines derived from L-E × H/W crosses, at consistent age, sex, and dosing (100 ?g/kg TCDD for 19 h). Using this uniquely consistent dataset, we show that the majority of TCDD-induced alterations in mRNA abundance are strain/line-specific: only 11 genes were affected by TCDD across all strains, including well-known dioxin-responsive genes such as Cyp1a1 and Nqo1. Our analysis identified two novel universally dioxin-responsive genes as well as 4 genes induced by TCDD in dioxin-sensitive rats only. These 6 genes are strong candidates to explain TCDD-related toxicities, so we validated them using 152 animals in time-course (0 to 384 h) and dose–response (0 to 3000 ?g/kg) experiments. This study reveals that different rat strains exhibit dramatic transcriptional heterogeneity in their hepatic responses to TCDD and that inter-strain comparisons can help identify candidate toxicity-related genes.

  1. 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.

    2012-03-03

    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.

  2. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    SciTech Connect (OSTI)

    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden) [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden) [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden) [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden)] [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden) [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children's Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  3. In vivo determination of triglyceride (TG) secretion in rats fed different dietary saturated fats using (2- sup 3 H)-glycerol

    SciTech Connect (OSTI)

    Lai, H.C.; Yang, H.; Lasekan, J.; Clayton, M.; Ney, D.M. (Univ. of Wisconsin, Madison (United States))

    1990-02-26

    Male, Sprague-Dawley rats (154{plus minus}1 g) were fed diets containing 2% corn oil (CO) + 14% butterfat (BF), beef tallow (BT), olive oil (OO) or coconut oil (CN) vs a 16% CO control diet for 5 weeks. Changes in plasma TG specific activity (dpm/mg TG) were determined in individual unanesthetized rats after injection of 100 {mu}Ci (2-{sup 3}H)-glycerol via a carotid cannula. Fractional rate constants were obtained using a 2-compartment model and nonlinear regression analysis. Results demonstrated no difference in the fractional rate constants among dietary groups; but, differences in the rates of hepatic TG secretion were noted. Rats fed BT showed a higher rate of hepatic TG secretion than rats fed CO. Rats fed BF, OO or CN showed somewhat higher rates of hepatic TG secretion than CO. VLDL TG, phospholipid, and apolipoprotein B and E levels were higher with saturated fats vs CO. The data suggest that the higher plasma TG levels noted in response to feeding saturated fats vs corn oil can be explained, in part, by an increased flux of hepatic TG secretion.

  4. Ethanol-induced cell damage in cultured rat antral mucosa assessed by chromium-51 release

    SciTech Connect (OSTI)

    Sewell, R.B.; Ling, T.S.; Yeomans, N.D.

    1986-08-01

    We have developed an in vitro method for studying ethanol-induced injury to gastric mucosa using organ culture of rat antrum. Cell damage was assessed by measurement of the release of (/sup 51/Cr)sodium chromate from preloaded cells, a method adapted from a standard immunologic technique. This system provided rapid and highly reproducible quantitation of tissue injury as assessed by /sup 51/Cr release into the culture medium. The threshold concentration for ethanol-induced damage was between 10 and 15% v/v, similar to in vivo thresholds observed by others. /sup 51/Cr release could also be induced by very short exposure to ethanol (5-15 min), and then continued despite ethanol removal. Interestingly, after continuous ethanol exposure, a plateau of maximum /sup 51/Cr release was reached 60 min after exposure to ethanol over the concentration range 20-50%, suggesting tissue adaptation to ethanol damage. This organ culture system, which allows precise control of experimental conditions, may be useful for studying mechanisms of gastric mucosal injury and protection.

  5. 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

    2013-01-15

    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.

  6. Influence of copper and iron on subacute cadmium intoxication in protein-malnourished rats

    SciTech Connect (OSTI)

    Tewari, P.C.; Kachru, D.N.; Tandon, S.K.

    1986-10-01

    Male albino rats maintained on low-protein (9%) diets were dosed intraperitoneally with 0.75 mg Cd/kg, as cadmium chloride, for 20 days. Groups of these animals were provided with diets supplemented with 40 ppm Cu, 400 ppm Fe or a combination of both during the exposure period. Hepatic and renal distribution of Cd, Zn, Cu, and Fe along with activity of acid and alkaline phosphatases and ribonuclease and glutathione content were studied. Uptake of Cd both in liver and in kidney was significant and was accompanied by increased Zn and depletion of Fe concentration. The Cu level remained unaltered. Dietary supplementation of Cu or Fe interacted effectively and influenced the metal distribution. Acid and alkaline phosphatases in both liver and kidney were inhibited by Cd exposure. However, Cu and/or Fe supplements could to a varying degree offset the Cd-induced inhibition. Cadmium exposure did not, however, elicit any effect on hepatic and renal ribonuclease activity of low-protein-fed animals. The glutathione concentration registered profound increase on Cd exposure, possibly to act as a defense mechanism.

  7. 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

    2011-09-01

    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.

  8. Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet

    E-Print Network [OSTI]

    Cedernaes, Jonathan; Alsiö, Johan; Västermark, Åke; Risérus, Ulf; Schiöth, Helgi B

    2013-01-08

    were 8 weeks old and weighed 352 ± 12 g (mean ± SD). The rats were housed one per cage, in standard macrolon cages (type IV), which had a wood chip bedding and a wooden house as enrichment. All rats had free access to water. Ambient temperature (21-22°C... storage and oxidation [20,21]. Certain FAs and their ratios can also be utilized as important risk markers for various diseases and desaturase indices have been closely linked to several obesity-related conditions [22-26]. Especially, SCD-16 and D6D have...

  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

    1991-01-01

    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. 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)

    2013-11-01

    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.

  11. Hippocampal proteomic and metabonomic abnormalities in neurotransmission, oxidative stress and apoptotic pathways in a chronic phencyclidine rat model

    E-Print Network [OSTI]

    Wesseling, Hendrik; Want, Elizabeth J.; Guest, Paul C.; Rahmoune, Hassan; Holmes, Elaine; Bahn, Sabine

    2015-06-04

    Sprague–Dawley rats (Charles River, Margate, UK) were housed in groups of four under standard laboratory conditions with food (Harlan UK, Bicester, UK) and water available ad libitum. All experiments were conducted during the light cycle and were in full... homogenisation and cooling on dry ice. The mixtures were then centrifuged at 10,000g for 10min at 4oC. Supernatants (aqueous extracts) were collected and transferred to clean Eppendorf tubes. Aqueous extracts were dried in a vacuum concentrator (Savant...

  12. Effects of dietary fat and fiber on the oxidative status of the small intestine and colon of rats 

    E-Print Network [OSTI]

    Sanders, Lisa Merle

    2006-08-16

    stream_source_info etd-tamu-2005A-NUTR-Sanders.pdf.txt stream_content_type text/plain stream_size 222131 Content-Encoding ISO-8859-1 stream_name etd-tamu-2005A-NUTR-Sanders.pdf.txt Content-Type text/plain; charset=ISO-8859-1... and Fiber on the Oxidative Status of the Small Intestine and Colon of Rats. (May 2005) Lisa Merle Sanders, B.S., Texas A&M University Chair of Advisory Committee: Dr. Joanne R. Lupton Colon cancer is one of the most commonly diagnosed cancers...

  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.

    1989-05-01

    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. Interdisciplinary neurotoxicity inhalation studies: Carbon disulfide and carbonyl sulfide research in F344 rats

    SciTech Connect (OSTI)

    Sills, Robert C. [Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, 111 Alexander Drive, South Campus, MD B3-08, PO Box 12233, Research Triangle Park, NC 27709 (United States)]. E-mail: sills@niehs.nih.gov; Harry, G. Jean [Laboratory of Neurobiology, National Institute of Environmental Health Sciences, 111 Alexander Drive, South Campus, PO Box 12233, Research Triangle Park, NC 27709 (United States); Valentine, William M. [Department of Pathology and Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Morgan, Daniel L. [Laboratory of Molecular Toxicology, NIEHS, Research Triangle Park, NC 27709 (United States)

    2005-09-01

    Inhalation studies were conducted on the hazardous air pollutants, carbon disulfide, which targets the central nervous system (spinal cord) and peripheral nervous system (distal portions of long myelinated axons), and carbonyl sulfide, which targets the central nervous system (brain). The objectives were to investigate the neurotoxicity of these compounds by a comprehensive evaluation of function, structure, and mechanisms of disease. Through interdisciplinary research, the major finding in the carbon disulfide inhalation studies was that carbon disulfide produced intra- and intermolecular protein cross-linking in vivo. The observation of dose-dependent covalent cross-linking in neurofilament proteins prior to the onset of lesions is consistent with this process contributing to the development of the neurofilamentous axonal swellings characteristic of carbon disulfide neurotoxicity. Of significance is that valine-lysine thiourea cross-linking on rat globin and lysine-lysine thiourea cross-linking on erythrocyte spectrin reflect cross-linking events occurring within the axon and could potentially serve as biomarkers of carbon disulfide exposure and effect. In the carbonyl sulfide studies, using magnetic resonance microscopy (MRM), we determined that carbonyl sulfide targets the auditory pathway in the brain. MRM allowed the examination of 200 brain slices and made it possible to identify the most vulnerable sites of neurotoxicity, which would have been missed in our traditional neuropathology evaluations. Electrophysiological studies were focused on the auditory system and demonstrated decreases in auditory brain stem evoked responses. Similarly, mechanistic studies focused on evaluating cytochrome oxidase activity in the posterior colliculus and parietal cortex. A decrease in cytochrome oxidase activity was considered to be a contributing factor to the pathogenesis of carbonyl sulfide neurotoxicity.

  15. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF ? mediators

    SciTech Connect (OSTI)

    Orona, N.S.; Tasat, D.R.

    2012-06-15

    Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 ?M). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO{sub 3} 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO{sub 3}. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O{sub 2}{sup ?}). At high doses it provokes the secretion of TNF? and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O{sub 2}{sup ?} may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O{sub 2}{sup ?} may be blocked, prevailing damage to DNA by the TNF? route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium?related diseases. -- Highlights: ? Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ? At low doses uranyl nitrate induces generation of superoxide anion. ? At high doses uranyl nitrate provokes secretion of TNF?. ? Uranyl nitrate induces apoptosis through all the range of doses tested.

  16. Functional and inflammatory alterations in the lung following exposure of rats to nitrogen mustard

    SciTech Connect (OSTI)

    Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Patel, Kinal J., E-mail: kinalv5@gmail.com [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Shen, Jianliang, E-mail: jianliangs@gmail.com [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Reimer, David, E-mail: reimerd@las.rutgers.edu [Laboratory Animal Services, Rutgers University, Piscataway, NJ (United States); Gow, Andrew J., E-mail: gow@rci.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

    2011-01-01

    Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of the lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.

  17. Initiation, promotion, initiation experiments with radon and cigarette smoke: Lung tumors in rats

    SciTech Connect (OSTI)

    Moolgavkar, S.H.

    1990-02-01

    Much recent attention has focused on the recessive oncogenesis model according to which inactivation of both alleles of a tumor suppressor gene (anti-oncogene) leads to cancer. Over the past decade Dr. Moolgavkar has been involved in the development and testing of a two-mutation model for carcinogenesis, which may be viewed as a mathematical generalization of the recessive oncogenesis model. In a series of papers this model has been shown to be consistent with a large body of epidemiologic and experimental data. Thus, the current project funded under the auspices of DOE, is part of a much larger program. The goals of this larger program are: the mathematical development of the two-mutation model for application to various epidemiologic and experimental data sets; investigation of the statistical properties of the model and development of software for fitting the model to various data sets, including cohort and case-control data in epidemiology. Directly relevant to the radon program, we have completed an analysis of radon-induced lung tumors in rats within the context of the two-mutation model. We found that the model described the data well. The results indicate that fractionation of exposure increased the lifetime probability of tumor. Examination of the parameters of the model suggests that the effect of fractionation can be explained by the relative effects of radon daughters on the mutation rates and on the kinetics of growth of initiated cells. The first mutation rate is very strongly dependent upon the rate of exposure to radon daughters, the second mutation rate much less so, suggesting that the nature of the two mutational events is different.

  18. Covalent modification of hepatic microsomal lipids of rats by carbon tetrachloride

    SciTech Connect (OSTI)

    Kaphalia, B.S.; Ansari, G.A. (Univ. of Texas Medical Branch, Galveston (USA))

    1989-07-01

    The present study was undertaken to isolate and identify various lipids bound to 14C label during hepatic microsomal metabolism of 14CCl4 in vitro under anaerobic conditions and in vivo in rats. The two major radioactive fractions identified by thin-layer chromatography each for neutral lipids and phospholipids from in vitro and in vivo experiments corresponded to fatty acids and triglycerides and to phosphatidylcholine (PC) and phosphatidylethanolamine (PE), respectively. Approximately 89% of the radioactivity associated with phospholipids was found in PC and PE fractions. Hydrolysis of PC and PE with phospholipase A2 released about 50% of the total radioactivity as lipid moieties corresponding to fatty acids. The radioactive neutral lipids and the lipid moieties hydrolyzed from PC and PE were methylated with boron trifluoride in methanol. These methylated lipids were separated by reversed-phase high-performance liquid chromatography (HPLC), and the elution profiles of 14C label found for the lipids obtained from in vitro experiments were similar to those from in vivo. The major radioactive fractions eluted immediately after methyl oleate were identified as trichloromethyloctadecenoic and trichloromethyleicosatrienoic acid methyl esters by chemical ionization mass spectrometry. The mass spectral analysis of these fractions also indicated the formation of dichlorocarbene adduct of oleic acid. However, similar mass spectrometric detection of trichloromethylated lipids was not evident in neutral lipids and phospholipids isolated from in vivo studies. The 14C-labeled lipids eluted as a nonpolar fraction exhibited a high molecular weight containing more than three chlorines. Dimerization and cross-linking of trichloromethylated lipids based on HPLC and mass spectral analysis are also discussed in this paper.

  19. Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat

    SciTech Connect (OSTI)

    Vikram, A.; Tripathi, D.N.; Ramarao, P. [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062 (India); Jena, G.B. [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062 (India)], E-mail: gbjena@gmail.com

    2008-01-01

    Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic {beta}-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the {beta}-cells. The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level.

  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)

    2011-03-01

    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. Toxicokinetics of ?-thujone following intravenous and gavage administration of ?-thujone or ?- and ?-thujone mixture in male and female F344/N rats and B6C3F1 mice

    SciTech Connect (OSTI)

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. ?-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of ?-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of ?-thujone or a mixture of ?- and ?-thujone (which will be referred to as ?,?-thujone). Absorption of ?-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of ?-thujone following administration of ?-thujone or ?,?-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ?} increased greater than proportional to the dose in female rats following administration of ?-thujone and in male and female mice following administration of ?,?-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ?} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of ?-thujone and ?,?-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, ?-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of ?-thujone and ?,?-thujone where females were more sensitive than males of both species to ?-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to ?-thujone concentration. - Highlights: • Absorption of ?-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to ?-thujone than mice. • ?-Thujone brain:plasma ratios were greater than 1 in both rats and mice. • Brain:plasma ratio in females was higher than in males. • These data are in support of the observed neurotoxicity of ?-thujone.

  2. 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

    2014-11-26

    of images, use heuristics that are time consuming to develop, or do not generalize well to three dimensional data. In this thesis, I propose two methods based on random forests for detecting neuron bodies in the rat and mouse brain KESM data. The proposed...

  3. 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

    2006-08-16

    weeks earlier and at the end of the study had morbidity/mortality rate 14.2% higher (P=0.0005) than non-irradiated rats. There was no significant effect of HZE radiation on colon cancer incidence. The effects of dietary fibers and oils on health state...

  4. 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

    2005-11-01

    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. ...

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

    E-Print Network [OSTI]

    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

  6. Differential Effects of HIF-1 Inhibition by YC-1 on the Overall Outcome and Blood-Brain Barrier Damage in a Rat Model of Ischemic Stroke

    E-Print Network [OSTI]

    Yan, Jingqi; Zhou, Bo; Taheri, Saeid; Shi, Honglian

    2011-11-16

    Hypoxia-inducible factor 1 (HIF-1) is a master regulator of cellular adaptation to hypoxia and has been suggested as a potent therapeutic target in cerebral ischemia. Here we show in an ischemic stroke model of rats that inhibiting HIF-1 and its...

  7. The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury

    E-Print Network [OSTI]

    Burnstock, Geoffrey

    The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers the effect BRX-220, a co-inducer of heat shock proteins, in injury-induced peripheral neuropathy. Following sciatic nerve injury in adult rats and treatment with BRX-220, the following features of the sensory

  8. Strain-guided mineralization in the bone–PDL–cementum complex of a rat periodontium

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Grandfield, Kathryn; Herber, Ralf -Peter; Chen, Ling; Djomehri, Sabra; Tam, Caleb; Lee, Ji -Hyun; Brown, Evan; Woolwine III, Wood R.; Curtis, Don; Ryder, Mark; et al

    2015-04-18

    Objective: The objective of this study was to investigate the effect of mechanical strain by mapping physicochemical properties at periodontal ligament (PDL)–bone and PDL–cementum attachment sites and within the tissues per se. Design: Accentuated mechanical strain was induced by applying a unidirectional force of 0.06 N for 14 days on molars in a rat model. The associated changes in functional space between the tooth and bone, mineral forming and resorbing events at the PDL–bone and PDL–cementum attachment sites were identified by using micro-X-ray computed tomography (micro-XCT), atomic force microscopy (AFM), dynamic histomorphometry, Raman microspectroscopy, and AFM-based nanoindentation technique. Results frommore »these analytical techniques were correlated with histochemical strains specific to low and high molecular weight GAGs, including biglycan, and osteoclast distribution through tartrate resistant acid phosphatase (TRAP) staining. Results: Unique chemical and mechanical qualities including heterogeneous bony fingers with hygroscopic Sharpey's fibers contributing to a higher organic (amide III — 1240 cm?¹) to inorganic (phosphate — 960 cm?¹) ratio, with lower average elastic modulus of 8 GPa versus 12 GPa in unadapted regions were identified. Furthermore, an increased presence of elemental Zn in cement lines and mineralizing fronts of PDL–bone was observed. Adapted regions containing bony fingers exhibited woven bone-like architecture and these regions rich in biglycan (BGN) and bone sialoprotein (BSP) also contained high-molecular weight polysaccharides predominantly at the site of polarized bone growth. Conclusions: From a fundamental science perspective the shift in local properties due to strain amplification at the soft–hard tissue attachment sites is governed by semiautonomous cellular events at the PDL–bone and PDL–cementum sites. Over time, these strain-mediated events can alter the physicochemical properties of tissues per se, and consequently the overall biomechanics of the bone–PDL–tooth complex. From a clinical perspective, the shifts in magnitude and duration of forces on the periodontal ligament can prompt a shift in physiologic mineral apposition in cementum and alveolar bone albeit of an adapted quality owing to the rapid mechanical translation of the tooth.« less

  9. Long-term effects on reproductive parameters in female rats after translactational exposure to PCBs

    SciTech Connect (OSTI)

    Sager, D.B.; Girard, D.M. (Univ. of Wisconsin, Green Bay, WI (United States))

    1994-07-01

    In an integrated series of experiments, we assessed effects of translactational exposure to Aroclor 1254 at three different ages: As young adults (2-4.5 months), as mature adults (5-8 months), and as older adults (8.5-13 months). Developing female rats were exposed postnatally to polychlorinated biphenyls (PCBs) via oral treatment of the dams on Days 1, 3, 5, 7, and 9 of lactation at the following doses: 8 [mu]g/g (PCBI), 32 [mu]g/g (PCBII), and 64 [mu]g/g (PCBIII) in peanut oil. Puberty, both vaginal opening and first estrus, was delayed in PCBII and PCBIII offspring. PCB exposure at all doses had a pronounced and consistent effect on uterine response. In mature PCBII and PCBIII adults, uterine wet weights were reduced at all stages of the estrous cycle and in light-induced persistent vaginal estrus (PVE). PCBI offspring exhibited a decreased uterine weight in proestrus and in light-induced PVE. Analysis of estrous cycles for 40 days at all ages indicated increases in diestrus. Fertility in young adults and mature adults was affected, with PCBIII young adults exhibiting less success with preimplantation stages, and PCBII and PCBIII mature adults showing an effect at pre- and/or postimplantation stages. As determined by patterns in estrous cycling and rate of development of PVE in 64 days of constant light, exposure to PCBs did not hasten reproductive aging at any of the ages examined. Instead, PCBIII young adults and PCBII and PCBIII older adults exhibited a delay in onset of light-induced PVE. This study demonstrates that translactational exposure to a PCB mixture that has little notable effect on the dams, not only delays puberty in the female offspring, but also several months later results in decreased uterine response, impairment of fertility, and irregular cycle patterns. Reproductive aging, however, is not hastened, and even may be delayed. Many of these effects could be explained, in part, by interference with estrogen. 67 refs., 10 figs., 7 tabs.

  10. Urine acidification has no effect on peroxisome proliferator-activated receptor (PPAR) signaling or epidermal growth factor (EGF) expression in rat urinary bladder urothelium

    SciTech Connect (OSTI)

    Achanzar, William E. Moyer, Carolyn F.; Marthaler, Laura T.; Gullo, Russell; Chen, Shen-Jue; French, Michele H.; Watson, Linda M.; Rhodes, James W.; Kozlosky, John C.; White, Melvin R.; Foster, William R.; Burgun, James J.; Car, Bruce D.; Cosma, Gregory N.; Dominick, Mark A.

    2007-09-15

    We previously reported prevention of urolithiasis and associated rat urinary bladder tumors by urine acidification (via diet acidification) in male rats treated with the dual peroxisome proliferator-activated receptor (PPAR){alpha}/{gamma} agonist muraglitazar. Because urine acidification could potentially alter PPAR signaling and/or cellular proliferation in urothelium, we evaluated urothelial cell PPAR{alpha}, PPAR{delta}, PPAR{gamma}, and epidermal growth factor receptor (EGFR) expression, PPAR signaling, and urothelial cell proliferation in rats fed either a normal or an acidified diet for 5, 18, or 33 days. A subset of rats in the 18-day study also received 63 mg/kg of the PPAR{gamma} agonist pioglitazone daily for the final 3 days to directly assess the effects of diet acidification on responsiveness to PPAR{gamma} agonism. Urothelial cell PPAR{alpha} and {gamma} expression and signaling were evaluated in the 18- and 33-day studies by immunohistochemical assessment of PPAR protein (33-day study only) and quantitative real-time polymerase chain reaction (qRT-PCR) measurement of PPAR-regulated gene expression. In the 5-day study, EGFR expression and phosphorylation status were evaluated by immunohistochemical staining and egfr and akt2 mRNA levels were assessed by qRT-PCR. Diet acidification did not alter PPAR{alpha}, {delta}, or {gamma} mRNA or protein expression, PPAR{alpha}- or {gamma}-regulated gene expression, total or phosphorylated EGFR protein, egfr or akt2 gene expression, or proliferation in urothelium. Moreover, diet acidification had no effect on pioglitazone-induced changes in urothelial PPAR{gamma}-regulated gene expression. These results support the contention that urine acidification does not prevent PPAR{gamma} agonist-induced bladder tumors by altering PPAR{alpha}, {gamma}, or EGFR expression or PPAR signaling in rat bladder urothelium.

  11. In Vitro and In Vivo Evaluation of a Novel Ferrocyanide Functionalized Nanopourous Silica Decorporation Agent for Cesium in Rats

    SciTech Connect (OSTI)

    Timchalk, Charles; Creim, Jeffrey A.; Sukwarotwat, Vichaya; Wiacek, Robert J.; Addleman, Raymond S.; Fryxell, Glen E.; Yantasee, Wassana

    2010-09-01

    Novel decorporation agents are being developed to protect against radiological terrorist attacks. These sorbents, known as the self-assembled monolayer on mesoporous supports (SAMMS™), are hybrid materials where differing organic moieties are grafted onto mesoporous silica (SiO2). In vitro experiments focused on the evaluation, and optimization of SAMMS for capturing radiocesium (137Cs); based on these studies, a ferrocyanide copper (FC-Cu-EDA)-SAMMS was advanced for in vivo evaluation. In vivo experiments were conducted comparing the performance of the SAMMS vs. insoluble Prussian blue. Groups of jugular cannulated rats (4/treatment) were evaluated. Group I was administered 137Cs (~40 ?geq/kg) by intravenous (iv) injection and oral gavage; Group II was administered pre-bound 137Cs-SAMMS and sequential 137Cs + SAMMS (~61 ngeq/kg) by oral gavage; and Group III evaluated orally administered 137Cs (~0.06 ?geq/kg) followed by 0.1 g of either SAMMS or Prussian blue. Following dosing the rats were maintained in metabolism cages for 72 hour and blood, urine and fecal samples were collected for 137Cs analysis (gamma counting). Rats were then humanely euthanized, and selected tissues analyzed. Orally administered 137Cs was rapidly and well absorbed (~100% relative to iv dose), and the pharmacokinetics (blood, urine, feces & tissues) were very comparable to the iv dose group. For both exposures the urine and feces accounted for 20 and 3% of the dose, respectively. The prebound 137Cs-SAMMS was retained primarily within the feces (72% of the dose), with ~1.4% detected in the urine, suggesting that the 137Cs remained tightly bound to SAMMS. SAMMS & Prussian blue both effectively captured available 137Cs in the gut with feces accounting for 80-88% of the administered dose, while less than 2% was detected in the urine. This study suggests that the functionalized SAMMS out performs Prussian blue in vitro at low pH, but demonstrates comparable in vivo sequestration efficacy at low exposure concentrations. The comparable response may be the result of the low 137Cs dose and high sorbent dosage that was utilized. Future studies are planned to optimize SAMMS in vivo performance over a broader range of doses and conditions.

  12. 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; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-12-01

    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.

  13. Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

    SciTech Connect (OSTI)

    Gilat, E. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel)]. E-mail: gilat@iibr.gov.il; Kadar, T. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Levy, A. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Rabinovitz, I. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Cohen, G. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Kapon, Y. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Sahar, R. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Brandeis, R. [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel)

    2005-11-15

    Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.

  14. 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.?

    1991-01-01

    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...

  15. On-off intermittency of thalamo-cortical oscillations in the electroencephalogram of rats with genetic predisposition to absence epilepsy

    E-Print Network [OSTI]

    Evgenia Sitnikova; Alexander E. Hramov; Alexey A. Ovchinnikov; Alexey A. Koronovskii

    2013-02-17

    Spike-wave discharges (SWD) are electroencephalographic hallmarks of absence epilepsy. SWD are known to originate from thalamo-cortical neuronal network that normally produce sleep spindle oscillations. Although both sleep spindles and SWD are considered as thalamo-cortical oscillations, functional relationship between them is still uncertain. The present study describes temporal dynamics of SWD and sleep spindles as determined in long-term EEG recordings in WAG/Rij rat model of absence epilepsy. It was found that non-linear dynamics of SWD fits well to the law of 'on-off intermittency'. Typical sleep spindles that occur during slow-wave sleep (SWS) also demonstrated 'on-off intermittency' behavior, in contrast to high-voltage spindles during intermediate sleep stage, whose dynamics was uncertain. This implies that both SWS sleep spindles and SWD are controlled by a system-level mechanism that is responsible for regulating circadian activity and/or sleep-wake transitions.

  16. Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.; Paturi, Satyanarayana; Arvapalli, Ravikumar; Blough, Eric

    2015-03-28

    Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore »(F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of ?-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

  17. 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)

    2013-11-08

    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.

  18. 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; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    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.

  19. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

    SciTech Connect (OSTI)

    Jin Haiyan [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505 (Japan); Department of Gastroenterology and Hepatology, Yanbian University Hospital, Yanji, Jilin (China); Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505 (Japan); Sakaida, Isao [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505 (Japan)], E-mail: sakaida@yamaguchi-u.ac.jp

    2007-12-28

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

  20. Site-directed mutagenesis and molecular modelling studies show the role of Asp82 and cysteines in rat acylase 1, a member of the M20 family

    SciTech Connect (OSTI)

    Herga, Sameh; Brutus, Alexandre; Vitale, Rosa Maria; Miche, Helene; Perrier, Josette; Puigserver, Antoine; Scaloni, Andrea; Giardina, Thierry . E-mail: thierry.giardina@univ.u-3mrs.fr

    2005-05-06

    Acylase 1 from rat kidney catalyzes the hydrolysis of acyl-amino acids. Sequence alignment has shown that this enzyme belongs to the metalloprotein family M20. Site-directed mutagenesis experiments led to the identification of one functionally important amino acid residue located near one of the zinc coordinating residues, which play a critical role in the enzymatic activity. The D82N- and D82E-substituted forms showed no significant activity and very low activity, respectively, along with a loss of zinc coordination. Molecular modelling investigations indicated a putative role of D82 in ensuring a proper protonation of catalytic histidine. In addition, none of the five cysteine residues present in the rat kidney acylase 1 sequence seemed involved in the catalytic process: the loss of activity induced by the C294A substitution was probably due to a conformational change in the 3D structure.

  1. Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

    SciTech Connect (OSTI)

    Sharkey, Leslie C.; Radin, M. Judith; Heller, Lois; Rogers, Lynette K.; Tobias, Anthony; Matise, Ilze; Wang, Qi; Apple, Fred S.; McCune, Sylvia A.

    2013-11-15

    Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids increased in response to doxorubicin in SHR and SHHF. • Altered leukotriene metabolism may contribute greater toxicity in SHR vs. SHHF rats.

  2. Perinatal lead exposure sensitizes rats to the rewarding effects of cocaine, but not cocaine/3,4-methylenedioxymethamphetamine(MDMA) combinations 

    E-Print Network [OSTI]

    Cardon, Aaron Lynn

    2013-02-22

    . , & Bratton, G. R. (1993). Chronic exposure to lead attenuates cocaine- induced behavioral activation. Pharmacolo Biochemist and Behavior 44, 221-225. Guilaite, T. R. (1 997). Pb inhibits NMDA function at high and low affinity sites: Developmental d gt Ih I...'" Edition. Prentice Hall, NJ; 1997. Miller, D. K. , Nation, J. R. , Jost, T. E. , Schell, J. B. , & Bratton, G. R. (2000). Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats. Pharmacolo Biochemist...

  3. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

    SciTech Connect (OSTI)

    Liu, Tao, E-mail: liutaomedical@qq.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China)] [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China) [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China) [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China) [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Guo, Xinjin, E-mail: guo.xinjin@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China)] [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China) [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China) [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); and others

    2012-11-01

    The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ? Cisplatin induces acute renal failure (ARF). ? The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ? The regulated expression of Oat1, Oat3 and Mrp2 is an adaptive protected response. ? JBP485 could facilitate the adaptive protective action.

  4. JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

    SciTech Connect (OSTI)

    Guo, Xinjin [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Meng, Qiang; Liu, Qi; Wang, Changyuan; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China); Kaku, Taiichi [Japan Bioproducts Industry Co. Ltd., Tomigaya, Shibuya-ku, Tokyo (Japan); Liu, Kexin, E-mail: kexinliu@dlmedu.edu.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China)

    2013-09-01

    We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.

  5. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    SciTech Connect (OSTI)

    Fonsart, Julien [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France); Menet, Marie-Claude [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[Universite Paris Descartes, Faculte de Pharmacie, Plateau Spectrometrie de Masse (IFR 71), Service de Chimie Analytique, Paris F-75006 (France); Decleves, Xavier [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France); Galons, Herve [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[INSERM, U648, Paris F-75006 (France); Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France); Noble, Florence [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France)]|[CNRS, UMR 7157, Paris F-75006 (France)]|[INSERM, U705, Paris F-75006 (France)], E-mail: florence.noble@univ-paris5.fr

    2008-07-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg{sup -1} sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences.

  6. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    SciTech Connect (OSTI)

    Stanko, Jason; Enoch, Rolondo; Rayner, Jennifer L; Davis, Christine; Wolf, Douglas; Malarkey, David; Fenton, Suzanne

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  7. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    SciTech Connect (OSTI)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (?) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (?), myo-Inositol (mIns) and Asp (?), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (?). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of repeated intermittent ethanol intoxication in the frontal cortex.

  8. Phase-Contrast MRI and CFD Modeling of Apparent 3He Gas Flow in Rat Pulmonary Airways

    SciTech Connect (OSTI)

    Minard, Kevin R.; Kuprat, Andrew P.; Kabilan, Senthil; Jacob, Rick E.; Einstein, Daniel R.; Carson, James P.; Corley, Richard A.

    2012-08-01

    Phase-contrast (PC) magnetic resonance imaging (MRI) with hyperpolarized 3He is potentially useful for developing and testing patient-specific models of pulmonary airflow. One challenge, however, is that PC-MRI provides apparent values of local 3He velocity that not only depend on actual airflow but also on gas diffusion. This not only blurs laminar flow patterns in narrow airways but also introduces anomalous airflow structure that reflects gas-wall interactions. Here, both effects are predicted in a live rat using computational fluid dynamics (CFD), and for the first time, simulated patterns of apparent 3He gas velocity are compared with in-vivo PC-MRI. Results show (1) that correlations (R2) between measured and simulated airflow patterns increase from 0.23 to 0.79 simply by accounting for apparent 3He transport, and that (2) remaining differences are mainly due to uncertain airway segmentation and partial volume effects stemming from relatively coarse MRI resolution. Higher-fidelity testing of pulmonary airflow predictions should therefore be possible with future imaging improvements.

  9. 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)

    2006-06-02

    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.

  10. Toxicity of polychlorinated diphenyl ethers in hydra attenuata and in rat whole-embryo culture. Master's thesis

    SciTech Connect (OSTI)

    Becker, M.C.

    1991-05-01

    Polychlorinated diphenyl ethers (PCDEs) are a class of biaryl compounds that have little commercial application, but appear to be widespread in the environment. They have been found in wood preservative waste dumpsites and in fly ash from municipal waste incinerators. They have been detected in bird eggs and tissues, fish, and other edible marine organisms in the United States, Canada, and Europe. There are limited reports in the extant literature on the toxicity of PCDEs. This study was designed to evaluate the toxicity of selected PCDEs in cultures of Hydra attenuata and post-implantation rat whole embryos. The toxicity of several closely related polychlorinated biphenyls (PCBs) was evaluated in both cultures and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was evaluated in whole embryo culture. Embryonic growth and development parameters (yolk sac diameter, crown-rump length, somite count, and DNA and protein content) and gross morphology were determined. Findings indicated that these chemicals were neither embryotoxic nor teratogenic. Thus, the PCDEs, which elicit other diverse toxic and biochemical responses in rodents, are relatively inactive in these bioassays for developmental toxicity.

  11. Metabolomic changes in follicular fluid induced by soy isoflavones administered to rats from weaning until sexual maturity

    SciTech Connect (OSTI)

    Wang, Wenxiang; Zhang, Wenchang; Liu, Jin; Sun, Yan; Li, Yuchen; Li, Hong; Xiao, Shihua; Shen, Xiaohua

    2013-06-15

    Female Wistar rats at 21 days of age were treated with one of three concentrations of soy isoflavones (SIF) (50, 100 or 200 mg/kg body weight, orally, once per day) from weaning until sexual maturity (3 months) in order to evaluate the influence of SIF on ovarian follicle development. After treatment, the serum sex hormone levels and enumeration of ovarian follicles of the ovary were measured. The metabolic profile of follicular fluid was determined using HPLC-MS. Principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was used to identify differences in metabolites and reveal useful toxic biomarkers. The results indicated that modest doses of SIF affect ovarian follicle development, as demonstrated by decreased serum estradiol levels and increases in both ovarian follicle atresia and corpora lutea number in the ovary. SIF treatment-related metabolic alterations in follicular fluid were also found in the PCA and PLS-DA models. The 24 most significantly altered metabolites were identified, including primary sex hormones, amino acids, fatty acids and metabolites involved in energy metabolism. These findings may indicate that soy isoflavones affect ovarian follicle development by inducing metabolomic variations in the follicular fluid. - Highlights: ? Modest doses of soy isoflavones (SIF) do affect ovarian follicle development. ? SIF treatment-related metabolic alterations in follicular fluid were found. ? The 24 most significantly altered metabolites were identified.

  12. 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.; Williams, Kurt J.; Zacharewski, Timothy R.

    2013-12-15

    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.

  13. 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

    2013-11-15

    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.

  14. Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

    SciTech Connect (OSTI)

    Fonsart, Julien, E-mail: julien.fonsart@lrb.aphp.f [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France); CNRS, UMR 7157, Paris F-75006 (France); INSERM, U705, Paris F-75006 (France); Assistance Publique-Hopitaux de Paris, Laboratoire de Toxicologie Biologique, Hopital Lariboisiere, Paris F-75010 (France); Menet, Marie-Claude [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France); Universite Paris Descartes, Faculte de Pharmacie, Plateau Spectrometrie de Masse (IFR 71), Service de Chimie Analytique, Paris F-75006 (France); Debray, Marcel; Hirt, Deborah; Noble, Florence; Scherrmann, Jean-Michel; Decleves, Xavier [Universite Paris Descartes, Faculte de Pharmacie, Paris F-75006 (France); CNRS, UMR 7157, Paris F-75006 (France); INSERM, U705, Paris F-75006 (France)

    2009-12-15

    The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC{sub last} and C{sub max} were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C{sub max} and AUC{sub last} were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC{sub last} and t{sub 1/2} were 50% higher in females given MDMA (1 mg/kg iv). MDA C{sub max} and AUC{sub last} were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC{sub last} of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

  15. 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

    1966-01-01

    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...

  16. Relative Biological Effectiveness of Carbon Ions in a Rat Prostate Carcinoma In Vivo: Comparison of 1, 2, and 6 Fractions

    SciTech Connect (OSTI)

    Karger, Christian P., E-mail: c.karger@dkfz.de [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Peschke, Peter [Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)] [Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Scholz, Michael [Department of Biophysics, Helmholtz Center for Heavy Ion Research (GSI), Darmstadt (Germany)] [Department of Biophysics, Helmholtz Center for Heavy Ion Research (GSI), Darmstadt (Germany); Huber, Peter E. [Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany) [Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Department of Radiation Oncology, University Hospital of Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, University Hospital of Heidelberg (Germany)] [Department of Radiation Oncology, University Hospital of Heidelberg (Germany)

    2013-07-01

    Purpose: To determine the relative biological effectiveness (RBE) and the effective ?/? ratio for local tumor control of a radioresistant rat prostate tumor (Dunning subline R3327-AT1) after 6 fractions of carbon ions and photons. Methods and Materials: A total of 82 animals with tumors in the distal thigh were treated with 6 fractions of either photons or carbon ions, by use of increasing dose levels and a 2-cm spread-out Bragg peak. Endpoints of the study were local control (no tumor recurrence within 300 days) and volumetric changes after irradiation. The resulting values for dose at 50% tumor control probability were used to determine RBE values. Including data for 1 and 2 fractions from a previous study, we estimated ?/? ratios. Results: For 6 fractions, the values for dose at 50% tumor control probability were 116.6 ± 3.0 Gy for photons and 43.7 ± 2.3 Gy for carbon ions and the resulting RBE was 2.67 ± 0.15. The ?/? ratio was 84.7 ± 13.8 Gy for photons and 66.0 ± 21.0 Gy for carbon ions. Using these data together with the linear-quadratic model, we estimated the maximum RBE to be 2.88 ± 0.27. Conclusions: The study confirmed the increased effectiveness of carbon ions relative to photons over the whole dose range for a highly radioresistant tumor. The maximum RBE below 3 is in line with other published in vivo data. The RBE values may be used to benchmark RBE models. Hypoxia seems to have a major impact on the radiation response, although this still has to be confirmed by dedicated experiments.

  17. 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)

    2011-07-15

    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.

  18. Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: Developmental exposure of rats to 4-methylbenzylidene camphor

    SciTech Connect (OSTI)

    Maerkel, Kirsten [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Durrer, Stefan [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Henseler, Manuel [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Schlumpf, Margret [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland); Lichtensteiger, Walter [Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, CH-8057 Zurich (Switzerland)]. E-mail: Walter.Lichtensteiger@access.unizh.ch

    2007-01-15

    The developing neuroendocrine brain represents a potential target for endocrine active chemicals. The UV filter 4-methylbenzylidene camphor (4-MBC) exhibits estrogenic activity, but also interferes with the thyroid axis. We investigated effects of pre- and postnatal exposure to 4-MBC in the same rat offspring at brain and reproductive organ levels. 4-MBC (7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to the offspring until adulthood. mRNA of estrogen target genes involved in control of sexual behavior and gonadal functions was measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area (MPO) of adult offspring. 4-MBC exposure affected mRNA levels of ER alpha, progesterone receptor (PR), preproenkephalin (PPE) and insulin-like growth factor-I (IGF-I) in a sex- and region-specific manner. In order to assess possible changes in sensitivity of target genes to estrogens, offspring were gonadectomized on day 70, injected with estradiol (E2, 10 or 50 {mu}g/kg s.c.) or vehicle on day 84, and sacrificed 6 h later. The acute induction of PR mRNA, and repression (at 6 h) of PPE mRNA by E2 was enhanced by 4-MBC in male and female VMH and female MPO, whereas male MPO exhibited reduced responsiveness of both genes. Steroid receptor coactivator SRC-1 mRNA levels were increased in female VMH and MPO. The data indicate profound sex- and region-specific alterations in the regulation of estrogen target genes at brain level. Effect patterns in baseline and E2-induced gene expression differ from those in uterus and prostate.

  19. 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

    2008-11-07

    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.

  20. 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

  1. 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

    2014-01-15

    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.

  2. 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)

    2012-06-01

    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.

  3. Phosphorus-31 NMR magnetization-transfer measurements of ATP turnover during steady-state isometric muscle contraction in the rat hind limb in vivo

    SciTech Connect (OSTI)

    Brindle, K.M.; Blackledge, M.J.; Challiss, R.A.J.; Radda, G.K. )

    1989-05-30

    Phosphorus-31 NMR magnetization-transfer measurement have been used to measure the flux between ATP and inorganic phosphate during steady-state isometric muscle contraction in the rat hind limb in vivo. Steady-state contraction was obtained by supramaximal sciatic nerve stimulation. Increasing the stimulation pulse width from 10 to 90 ms, at a pulse frequency of 1 Hz, or increasing the frequency of a 10-ms pulse from 0.5 to 2 Hz resulted in an increase in the flux which was an approximately linear function of the increase in the tension-time integral. The flux showed an approximately linear dependence on the calculated free cytosolic ADP concentration up to an ADP concentration of about 90 {mu}M. The data are consistent with control of mitochondrial ATP synthesis by the cytosolic ADP concentration and indicate that the apparent K{sub m} of the mitochondria for ADP is at least 30 {mu}M.

  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

    2015-01-01

    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. 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.; Mecawi, André S.; Batalhão, Marcelo E.; Carnio, Evelin C.; Antunes-Rodrigues, José; Queiroz, Regina H.; Touyz, Rhian M.; Tirapelli, Carlos R.

    2012-11-01

    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.

  6. 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)

    2013-10-15

    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.

  7. 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

    2013-08-15

    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.

  8. 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

    1995-03-20

    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.

  9. Sex ratio of the offspring of Sprague-Dawley rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero and lactationally in a three-generation study

    SciTech Connect (OSTI)

    Rowlands, J.C. [Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI 48674 (United States); Budinsky, R.A. [Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI 48674 (United States)]. E-mail: RABudinsky@dow.com; Aylward, L.L. [Summit Toxicology, L.L.P., 6343 Carolyn Drive, Falls Church, VA 22044 (United States); Faqi, A.S. [MPI Research, Department of Developmental and Reproductive Toxicology, 54943 N. Main Street, Mattawan, MI 49071 (United States); Carney, E.W. [Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI 48674 (United States)

    2006-10-01

    Reports of a decreased male/female sex ratio in children born to males exposed to TCDD in Seveso, Italy, at a young age have sparked examinations of this endpoint in other populations exposed to TCDD or related compounds. Overall, the male/female sex ratio results reported in these studies, with slightly different age-exposed male populations, have shown mixed results. Experimental studies of the effects of in utero exposure to TCDD in laboratory animals have reported no effect on the f{sub 1} sex ratio and mixed results for the sex ratio of the f{sub 2} generation. In order to better understand the potential effects of TCDD on second generation sex ratio, we retrieved archived data from a comprehensive three-generation feeding study of TCDD in rats that was conducted and published in the 1970s, but which did not publish data on sex ratio of the offspring [Murray, F.J., Smith, F.A., Nitschke, K.D., Humiston, C.G., Kociba, R.J., Schwetz, B.A., 1979. Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. Toxicol. Appl. Pharmacol. 50, 241-252]. A re-examination of the original Murray et al. data found no statistically significant treatment-related changes in postnatal day 1 sex ratio in any generation of treated animals, consistent with one other relatively large study reporting on this endpoint. We discuss mechanistic data underlying a potential effect of TCDD on this endpoint. We conclude that the inconsistency in findings on sex ratio of the offspring of male rats exposed to TCDD in utero is likely due to random variation associated with a relatively small sample size, although differences between studies in strain of rat, dose regimen, and day of ascertainment of sex ratio cannot be ruled out.

  10. 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)

    2010-05-28

    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.

  11. 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)

    2007-10-15

    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.

  12. 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)

    2012-06-27

    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.

  13. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    SciTech Connect (OSTI)

    Kalayarasan, Srinivasan, E-mail: kalaivasanbio@gmail.com; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail: sudhandiran@yahoo.com

    2013-09-01

    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, ?-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

  14. 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; Bragin, Anatol; Brain Research Institute, University of California at Los Angeles, CA 90095 ; Faull, Kym; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095; Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 ; Cascio, Duilio; Damoiseaux, Robert; Schibler, Matthew J.; Pushkin, Alexander

    2012-09-15

    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.

  15. 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; Breljak, Davorka; Ljubojevic, Marija; Flajs, Dubravka; Balen, Daniela; Brzica, Hrvoje; Domijan, Ana-Marija; Peraica, Maja; Fuchs, Radovan; Anzai, Naohiko; Sabolic, Ivan

    2009-09-15

    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.

  16. 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

  17. 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)

    2013-09-20

    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.

  18. 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; Andersson, Patrik L.; Schrenk, Dieter

    2013-10-01

    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.

  19. 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)

    2013-05-01

    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.

  20. S O long as thE dewpoint raiairis low, thErc is no fog, and tSe co&lingof t b E t h E ratE of mElting; t h E r E i s 1atEn.t k a t from condEnsation of noisturE on t h E

    E-Print Network [OSTI]

    S O long as thE dewpoint raiairis low, thErc is no fog, and tSe co&lingof t b E t h E ratE of m, and h m t is 2ouring into thc stow dW m d night by radiation and conduction fron t l i E tvarmr fog. ing, t h E r E is so rmch moisturE t o bE condEnsEd. A i r IiEarly calm ovEr EL snov SUr=- TI`LE fog d

  1. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan

    2008-01-01

    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

  2. Sequential Causal Learning in Humans and Rats

    E-Print Network [OSTI]

    Hongjing Lu; Randall R. Rojas; Tom Beckers; Alan Yuille

    2011-01-01

    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

  3. Rat Trachea Dose Distribution Model Using MCNPTM 

    E-Print Network [OSTI]

    Almanza, Christian

    2010-01-15

    , ?, by ionizing radiation within a specific volume, V, of mass m (2), i.e., dm d D ? = . This quantity has units of gray, Gy, where 1 Gy = 1 J/kg. Monte Carlo N-Particle (MCNP TM ) code is based on the Monte Carlo method and is frequently used to model....0035 73562 g tally for photons electrons cell 201 cell 201 28 1.83858E-11 0...

  4. Ultrastructural development of the rat corpus luteum 

    E-Print Network [OSTI]

    Bailey, John Franklin

    1971-01-01

    ' -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...

  5. The Metabolism of Curium in the RAT

    E-Print Network [OSTI]

    Hamilton, J.

    2010-01-01

    alpha particle transmutation of plutonium by the follow- ingan alpha. particle to form plutonium 238 which, in turn, isits radioactive daughter, plutonium 238, has a half-life of

  6. Sampling Blood from the Lateral Tail Vein of the Rat

    E-Print Network [OSTI]

    Lee, Graham

    Blood samples are commonly obtained in many experimental contexts to measure targets of interest, including hormones, immune factors, growth factors, proteins, and glucose, yet the composition of the blood is dynamically ...

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

    E-Print Network [OSTI]

    Nall, Jennifer L.

    2010-10-12

    = iv 0.09) palmitic acid incorporation into total lipids in epididymal adipose tissue. CLA plus arginine supplementation also reduced glucose incorporation into total lipid (P = 0.20). Arginine stimulated lipid synthesis from glucose in the absence... in the liver and decreases PPAR?2 expression in adipose tissue (18,19,20). PPAR?2 is a master gene that is found in brown and white adipose tissue. It acts to increase SCD expression and increase fatty acid synthesis (18,19,20). By decreasing PPAR...

  8. Huddling and Independent Feeding of Neonatal Rats Can be

    E-Print Network [OSTI]

    Sullivan, Regina M.

    : various tactile stimuli (e.g., stroking a pup's back or pinching its tail; Pedersen, Williams, & Blass) in the presence of a novel odor, attach to the cleansednipples of a dam only when that odor is present. These data

  9. The influence of biotin on reproduction in the white rat 

    E-Print Network [OSTI]

    Cooper, William Anderson

    1957-01-01

    ??G?????G? ??G?? ???i?????i G? 6i??G?? 0??? ??ifi?G? r?A?? ?i?A???1G?? ?i?A?? 0???G? 3???GfGA???f ??? 3???G??i????f ???????G?? ?? 4??i???i???f ??? 9G???Gf 0??? 3i??? ????i? 7??i? ?5?98??5r6 ?6? 9r6978?5r6? ?8???0? ?7?Y4? 75Y40?Y804 95Y4? ???46?5? 5 9... ????? ??? ?? ?? ?G??G? ??? ??? ?? 3? 3G????? G? ??i 1?GfGA? ?i?????i??? ??? ?? 0? 9G??? ??? ??? ?? ?? ??i??G?? G? ??i ?i?????i?? G? 1?G??i?????? ??? 6??????G?? ??? ??? ?? 7? ???G? G? ??i ??f?f??i ????Ai?i?? ?i?????i??? ?ff G? ??i ?A????f????f ??? ?i???????f 9Gffi...

  10. Methamphetamine self-administration in rats developmentally exposed to lead 

    E-Print Network [OSTI]

    Rocha, Angelica

    2009-05-15

    with automatic, non-directed, sensory-driven behaviors, such as is seen in drug addiction. Hypodopaminergic effects impair functioning of the orbitofrontal cortex (OFC) and anterior cingulate gyrus (CG) contributing to impulsive behavior and impaired..., preservation of incorrect responses, poor judgment, impulse control (Bellinger et al, 1994; Brockel and Cory-Slechta, 1997; Canfield et al, 2003; Hubbs-Tait et al, 2005), and delinquent behavior (Needleman et al, 1996). Glutamatergic Systems. Lead is a...

  11. Distribution of ochratoxin A in the pregnant rat 

    E-Print Network [OSTI]

    Ballinger, Michael Brent

    1983-01-01

    in the Laboratory Animal Resources and Research Facility (LARR), Gloves and lab coat were worn at all times when handling the toxin or contaminated materials. Radioactive waste was disposed of by the Radiological Sa ety Office, and animal carcasses were disposed...-derived radioactivity fr om plasma was bi phasic. The distribution (alpha) half life was 3, 09 hr. The overall elimination (beta) half life was 55. 88 hr. Fecal elimination of radioactivity accounted for 29. 1% of the total radioactivity in the first 24 hours and 44...

  12. 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

  13. Neuropeptidomics of the Supraoptic Rat Nucleus Adriana Bora,

    E-Print Network [OSTI]

    Gillette, Martha U.

    , and Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 Received May 29-translational modifications (PTMs) such as amidation, acetylation, pyroglutamination, and disulfide bond formation.2

  14. 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

    2010-01-01

    Rodgers CD, Locke M. Altered heat stress response followingHSP70 activation by heat stress, 23 although subsequentrats following heat stress. 24 Further interventional

  15. EFFECT OF DIETARY CHOLESTEROL ON BRAIN CHOLESTEROL IN DEVELOPING RATS

    E-Print Network [OSTI]

    Gottipati, Bhavana Sindhu

    2008-04-29

    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...

  16. The role of spatial context in rat vision

    E-Print Network [OSTI]

    Meier, Philip Martin

    2011-01-01

    training system, and Balaji Sriram for his enthusiasm in theNeuroscience (Cosyne), 2011, Sriram B.S. , Meier, P. M. ,collaboratively with Balaji Sriram. Thalamic neurons are

  17. Meeting the oxygen requirements of an isolated perfused rat liver

    E-Print Network [OSTI]

    Izamis, Maria-Louisa, 1979-

    2006-01-01

    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 ...

  18. Population dynamics of the cotton rat (genus Sigmodon 

    E-Print Network [OSTI]

    Inglis, Jack Morton

    1955-01-01

    Laiepoadecoe to eggcceaA the etedp oa ~ ?ea toreeg Tbe Tacae Cooper?ties gildlLA Bait ie dae thaehe Ar Lte pert ia asbiag the stadt possible, I m obliged te Qr ~ Biehecil Beattea Doris Ar bio ewieteaee ia deeigaieg tho ebi~ tost of habitat who?45?a shish... ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~3 Planta Aaeoeiateh eith tho Silver Son~rane Typo on tho Cnograt ~ ~ ~ o ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 11 ?%ante laeooiatog eith the Tleesaen Tpyo oa tho III ~ ~ ~ ~ 1 ~ ~ ~ ~ 1 ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ Roiative UtDiaation of yoo4 Tyyoe...

  19. Of pungency, pain, and naked mole rats: chili peppers revisited

    E-Print Network [OSTI]

    Borges, Renee M

    that produce powerful alkaloids such as nicotine (tobacco) and atropine (Atropa). This is the same family. The centre of origin of pungent chili peppers is now believed to be the desert chaco of Bolivia and Peru

  20. THE METABOLSIM AND TOXICITY OF RADIUM-223 IN RATS

    E-Print Network [OSTI]

    Durbin, Patricia W.

    2008-01-01

    Z W w 30 Ra 223 DOSE, J1. Gig MU-14632 Fig. 11. The effecta:: w Ra 223 DOSE, j.t Gig MU-14636 Fig. 12. The percentagew 30 a::: w Ra 223 DOSE, jJ. Gig MU-14633 Fig. 8. The effect

  1. Radiobiology of normal rat lung in Boron Neutron Capture Therapy

    E-Print Network [OSTI]

    Kiger, Jingli Liu

    2006-01-01

    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 ...

  2. Brainstem cholinergic modulation of muscle tone in infant rats

    E-Print Network [OSTI]

    between these two regions. First, in unanesthetized pups, we found that chemical infusion the cholinergic antagonist scopolamine (10 mm, 0.1 lL) was infused into the DLPT. Scopolamine effectively muscle tone, infusion of the sodium channel blocker lidocaine (2%) into the PnO of unanesthetized pups

  3. Melatonin modulates intercellular communication among immortalized rat suprachiasmatic nucleus cells 

    E-Print Network [OSTI]

    Cox, Kimberly Yvonne

    2009-05-15

    . Melatonin caused a significant reduction in the spread of calcium waves in cycling SCN2.2 cultures as determined by ratiometric calcium imaging with Fura-2 AM, a calcium sensitive indicator dye. This reduction was greatest when an endogenous circadian rhythm...

  4. Mini Implant Facilitated Accelerated Tooth Movement in Rats

    E-Print Network [OSTI]

    Cheung, Tracy Li

    2014-01-01

    initiates the process of demineralization (38). This processtheoretically there is demineralization, rather than loss ofthe interplay of demineralization and remineralization found

  5. Quantifying non-axial deformations in rat myocardium 

    E-Print Network [OSTI]

    Aghassibake, Kristina Diane

    2005-02-17

    Nearly forty years after the introduction of the sliding filament theory, Zahalak expanded Huxley?s cross-bridge model from a uniaxial description of length changes in the fiber direction to a three-dimensional model that accounts for non-axial active..., and is therefore a viscoelastic material. However, in the case of cyclic loading, myocardium behaves elastically when the loading and unloading phases are considered independently; hence, 16 many investigators choose to treat myocardium as a pseudoelastic...

  6. TWO NEW SPECIES OF HYMENOLEPIS (CESTODA: HYMENOLEPIDIDAE) FROM MURID RODENTS (RODENTIA: MURIDAE) IN THE PHILIPPINES

    E-Print Network [OSTI]

    Clayton, Dale H.

    ) IN THE PHILIPPINES Arseny A. Makarikov, Vasyl V. Tkach*, and Sarah E. Bush Institute of Systematics and Ecology, Apomys microdon, and Rattus everetti collected on Luzon Island, Philippines. Hymenolepis bicauda n. sp Hymenolepis diminuta was the only member of the genus previously reported from the Philippines. The genus

  7. Hippocampalcortical interaction in decision making , Loren M. Frank

    E-Print Network [OSTI]

    Frank, Loren

    . Deliberation in the rat Behavioral observations in naturalistic settings demonstrated that the brown rat

  8. Supplement 17, Part 5, Parasite-Subject Catalogue, Parasites: Arthropoda And Miscellaneous 

    E-Print Network [OSTI]

    Segal, Dorothy B.; Humphrey, Judith M.; Edwards, Shirley J.; Kirby, Margie D.

    1969-01-01

    bubalis bubalis Capra hircus Bos taurus Sus verrucosus Bos sondaicus sondaicus Sus barbatus Amblyomma testudinarum buffle Amblyomma testudinarium (Koch) man Tupaia glis Rattus bowersi Amblyomma testudinarium Koch, 1844 Sumatra and Java... Sumatra Sumatra and Flores Java I! Celebes Bergeon, P., 1965 a, 78 Cambodia Domrow, R.; and Nadchatram, M., 1963 a all from Gunong Jerai, Malaya Houdesmer, F. E., 1938 a, 158 Indochina Amblyomma testudinarum Koch, I844 key buffalo, water...

  9. Protocol: Rat Cardiac CINE with Tagging, Page 1 of 4 Author: rgb 3/16/2012 Protocol: Rat Cardiac CINE with Tagging

    E-Print Network [OSTI]

    California at San Diego, University of

    the heart at isocenter. Water Phantom Place a 15 mL tube containing water and sealed with a screw top.5 mm 5cmx5cm 15 min Protocol Steps 1. Set up the physio equipment. Follow the instructions below. See the "Positioning" section below. 4. Protocol directory. The protocols can be loaded from

  10. Computational molecular phenotyping of retinal sheet transplants to rats with retinal degeneration

    E-Print Network [OSTI]

    Seiler, MJ; Jones, BW; Aramant, RB; Yang, PB; Keirstead, HS; Marc, RE

    2012-01-01

    nuclei; 10 seconds of uranyl acetate stain. (B) Enlargementto ribbon synapse. Ten seconds of uranyl acetate stain. (E)adjacent section. Ten seconds of uranyl acetate stain. (G)

  11. Statistical Approaches to Analyzing Energy Expenditure Data Among Zucker Diabetic Fatty Rats

    E-Print Network [OSTI]

    Kim, Hyunkyoung

    2014-01-07

    mixed effects models with smoothing splines. We find that in our current analyses, the use of the mixed effects models with a quadratic term for the time of observation following a summary of the data from minutes to hours and a log transformation...

  12. Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model

    E-Print Network [OSTI]

    Dede, Ozgur; Akel, Ibrahim; Demirkiran, Gokhan; Yalcin, Nadir; Marcucio, Ralph; Acaroglu, Emre

    2011-01-01

    more time standing erect. Dual energy X-ray absorbtiometry (acid; DEXA: Dual energy X-ray absorptiometry; BMD: Bone

  13. Effects of Age on Pavlovian Autoshaping of Ethanol Drinking in Non-Deprived Rats

    E-Print Network [OSTI]

    Tomie, Arthur; Mohamed, Walaa M.; Pohorecky, Larissa A.

    2005-01-01

    Differential effects of ethanol on motor coordination into the motor-impairing effects of ethanol (Silveri & Spear,the present study. Ethanol’s effects on motor impairment are

  14. PLASTICITY IN THE AUDITORY CORTEX AND CHANGES IN PERCEPTUAL DISCRIMINATION AFTER NUCLEUS BASALIS STIMULATION IN RATS

    E-Print Network [OSTI]

    Kilgard, Michael P.

    PLASTICITY IN THE AUDITORY CORTEX AND CHANGES IN PERCEPTUAL DISCRIMINATION AFTER NUCLEUS BASALIS 2008 Amanda Christine Reed All Rights Reserved #12;PLASTICITY IN THE AUDITORY CORTEX AND CHANGES to thank Crystal Engineer for being such a wonderful friend and behavior training partner throughout

  15. Orthotopic ovarian allografts in rats with respect to endocrinologic and gametogenic function 

    E-Print Network [OSTI]

    Turner, Sandra Scarborough

    1968-01-01

    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...

  16. Development of imaging methods to quantify the laminar microstructure in rat hearts 

    E-Print Network [OSTI]

    Hudson, Kristen Kay

    2004-11-15

    can be investigated and its laminar structure can be quantified. Many of the techniques that have been used to view the microstructure of the heart require the use of toxic or caustic chemicals for fixation or staining. An efficient imaging method...

  17. The Effects of Multiple Unloading Exposures on Bone Properties in the Femur of Adult Male Rats 

    E-Print Network [OSTI]

    Morgan, Derrick Scott

    2012-07-16

    (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...

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

    E-Print Network [OSTI]

    Shirazi-Fard, Yasaman

    2013-04-29

    or crewmembers who make repeated missions. Exercise offers a way to reduce or reverse these effects. Dual-energy X-ray absorptiometry (DXA) densitometry and bone mineral density (BMD) alone are generally insufficient for capturing the complex changes in bone...

  19. Acquisition of cocaine and heroin self-administration in rats developmentally exposed to lead 

    E-Print Network [OSTI]

    Rocha, Angelica

    2005-08-29

    with dopamine neuromechanisms greatly implicated in drug-taking behavior. 12 Cocaine exerts its neurophysiological effects by blocking the dopamine transporter and to a lesser extent norepinephrine and serotonin transporters (Rocha et al., 1998a... in human studies (Schlaepfer, 1997). Serotonergic Systems Dopaminergic systems have been of primary focus in the study of drug-induced reward potency and dependence for many years. However, other transmitter systems, such as serotonin (5-HT), also...

  20. Characterizing strain in the proximal rat tibia during electrical muscle stimulation 

    E-Print Network [OSTI]

    Vyvial, Brent Aron

    2007-09-17

    Hindlimb unloading is a widely used model for studying the effects of microgravity on a skeleton. Hindlimb unloading produces a marked loss in bone due to increased osteoclast activity. Electrical muscle stimulation is being investigated as a...

  1. Injectable chemokine-releasing gelatin matrices for enhancing endogenous regenerative responses in the injured rat brain

    E-Print Network [OSTI]

    Lim, Teck Chuan

    2014-01-01

    Brain injuries acquired from hemorrhage, ischemic strokes and trauma affect millions worldwide each year and often cause irreversible loss of neural tissue that disrupts vital neurological functions. Cell transplantation ...

  2. 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 ...

  3. RAT 6932 Seminar in Medical Physics Fall 2014, Thursday @ 4 pm, SE 101

    E-Print Network [OSTI]

    Fernandez, Eduardo

    Treatment Plans in HDR (High Dose Rate) Brachytherapy of Skin Lesions Using Freiburg Flap Applicator Therapy September 18 Mikko Hyvarinen Investigation of Dose Variation in HDR Brachytherapy due to Small-therapeutic management of skin cancer, including teletherapy, isotopic, and electronic brachytherapy October 16 Andreea

  4. Effects of dietary fat, fiber and carcinogen on fecal diacylglcyerols in the rat 

    E-Print Network [OSTI]

    Pickering, Jennifer Sharon

    1996-01-01

    Fecal diacylglycerols (DAG) are known activators of protein kinase C (PKC), which in turn modulate colonic epithelial cell growth programs and, therefore, could play a role in the malignant transformation process. However, the effects...

  5. Optical Coherence Tomography Elastography Technique for the Early Detections of Osteoarthritis in Rat Articular Cartilage

    E-Print Network [OSTI]

    Ma, Jonathan Keewon

    2013-01-01

    preparation embedding in gelatin with coverslip placed onA coverslip embedded in gelatin was imaged as the ultrasoundpreparation embedding in gelatin with coverslip placed on

  6. Serotonin 5HT-1A receptor density in the brain of the spontaneously hypertensive rats

    E-Print Network [OSTI]

    Valdez, Shakti Regmi

    2010-01-01

    doxycycline treatment by gelatin gel zymography. Chapter 2:5HT-1A receptor………………………..18 2.7 Gelatin gel zymographytreatment determined by gelatin gel zymography…………………………

  7. Blood proteolytic activity elevation and plasma protein degradation in spontaneously hypertensive rat models

    E-Print Network [OSTI]

    Chow, Jason C.

    2011-01-01

    Urine Protease Activity: Gelatin Zymography………………………. 31Plasma Protease Activity: Gelatin Zymography……..………. 19Plasma Protease Activity: Gelatin Zymography (Low M.W. )….

  8. Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodelling

    E-Print Network [OSTI]

    Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido; Pluchino, Stefano; Marzola, Pasquina

    2015-01-01

    Cortical reorganization occurring in Multiple Sclerosis (MS) patients is thought to play a key role in limiting the impact of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates...

  9. Fields of Expertise RECtoRatEUniv.-CoUnCil SEnatE

    E-Print Network [OSTI]

    Ganster, Maximilian

    R academic affairs Bernhard Hofmann-Wellenhof BIOTECHMED Graz l F F P F il Sustainable Systems Mobility Lifelong Learningl International Relations and Mobility Programmes l Information Technology Services

  10. Macrophage Polarization And Nitric Oxide Mechanisms In Lymphatic Dysfunction In A Rat Model Of Metabolic Syndrome 

    E-Print Network [OSTI]

    Zawieja, Scott D

    2014-12-10

    ). The reactive oxygen species scavenging agent 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) did not restore flow sensitivity, however control vessels treated with the nitric oxide synthase inhibitor L-NG-nitro arginine methyl ester (LNAME) had...

  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. Chronic administration of corticosterone impairs spatial reference memory before spatial working memory in rats

    E-Print Network [OSTI]

    Anderson, Brenda

    of glucocorticoids occur in numerous disorders, such as anorexia nervosa (Seed, Dixon, McCluskey, & Young, 2000) and CushingÕs syndrome (Starkman et al., 1992, 1999), as well as memory deficits in anorexia nervosa (Seed et

  13. Temporal Organization of Eating in Low- and High- Saccharin-Consuming Rats

    E-Print Network [OSTI]

    Dess, Nancy K; Richard, Jocelyn M; Severe, Susan Fletcher; Chapman, Clinton D

    2007-01-01

    in restrictive anorexia nervosa: A consequence of the logicperspective on anorexia nervosa. Psychological Review, 110(

  14. Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

    E-Print Network [OSTI]

    Palanker, Daniel

    photovoltaic arrays Jacob G. Light a, b , James W. Fransen c , Adewumi N. Adekunle a , Alice Adkins b , Gobinda: Retina Prosthetic Bipolar cells Amacrine cells Müller glial cells a b s t r a c t Photovoltaic arrays

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

    E-Print Network [OSTI]

    Gallagher, Sharon Lee

    1997-01-01

    pair-fed group. Ethanol animals were intubated with 1. 14 g/kg of 5% ethanol two consecutive days per week for five weeks. Pair-fed animals received an isocaloric maltose/dextrin solution in place of the alcohol. Tetracycline hydrochloride and calcein...

  16. The effects of bicuculline on cocaine self-administration in male rats developmentally exposed to lead 

    E-Print Network [OSTI]

    Valles, Rodrigo, Jr.

    2004-09-30

    calcium, particularly at the C2 binding site located on calcium mediated proteins (Markovac and Goldstein, 1988). Lead is believed to affect calcium-dependent activation of protein kinase C (PKC). This could potentially impact numerous endpoints from...). Lead effects on the GABAergic system are similar to those of the glutamatergic system, acting primarily on voltage-dependent calcium channels. Decreases in the amounts of evoked GABA release seem to occur in the brains of animals exposed to chronic...

  17. Increased AMPA Receptor GluR1 Subunit Incorporation in Rat

    E-Print Network [OSTI]

    Abraham, Nader G.

    Benzodiazepine Withdrawal PAROMITA DAS,1 SCOTT M. LILLY,1,2 RICARDO ZERDA,3 WILLIAM T. GUNNING III,4 FRANCISCO J the risk of dependence. Flurazepam (FZP) withdrawal is associated with increased anxiety correlated synapses during benzodiazepine withdrawal is mediated by increased incorporation of GluR1-containing AM

  18. THE DYNAMIC RELATIONSHIP BETWEEN LANGERHANS CELLS AND INTRAEPIDERMAL NERVE FIBERS IN THE MOUSE AND RAT FOOTPAD

    E-Print Network [OSTI]

    Doss, Argenia Lanisha Necole

    2011-12-31

    Skin disorders are often associated with immune and nervous system dysfunction. Intraepidermal nerve fibers (IENFs) detect mechanical, thermal, and noxious stimuli. Although immune cells such as mast and T cells can alter ...

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

    E-Print Network [OSTI]

    Bennett, Edward L.

    2010-01-01

    Piscataway, NJ. Anisomycin (ANI) was purchased from Pfizerbehavioral studies (6), ANI was administered subcutaneouslyml of 0.9% NaCl. ments, ANI was not administered; results

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

    E-Print Network [OSTI]

    Groves, Jennifer Ann

    1998-01-01

    were tested in cantilever bending using a notched hole in a plate to support the femur. Slices of the distal femur were tested in a reduced-platen compression test to measure the mechanical properties of the cancellous core. The composite beam model...

  1. Rat colonic reactive oxygen species production and DNA damage are mediated by diet and age 

    E-Print Network [OSTI]

    Henderson, Cara Aletha Everett

    2001-01-01

    increase with age, and it is possible that ROS and/or DNA damage accumulate in aged animals and lead to carcinogenic mutations. Dietary factors, particularly fat and fiber, are important risk modifiers of colon cancer. Differences in the production of ROS...

  2. The light-activated signaling pathway in SCN-projecting rat retinal ganglion cells

    E-Print Network [OSTI]

    Newman, Eric A.

    candidate channels, cyclic nucleotide-gated (CNG) channels and transient receptor potential (TRP) channels nucleotides modulate the signaling pathway, CNG channels do not appear to conduct the light-activated current the light response, (ii) CNG channel blockers fail to inhibit the light response, (iii) the effects

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

    E-Print Network [OSTI]

    Simpson, Ashley

    2009-09-30

    normal inflammatory response [19]. However, contrary to what was observed in the study by Blanco et.al. (2004, 2005) and Davis & Syapin (2004), ethanol alone had no affect on nitric oxide...NOS activity. Further, Blanco et al. (2005) reported that an ethanol concentration of 10-50 mM was sufficient to stimulate the signaling response. The concentration of ethanol in our study was comparable to the lower concentration of ethanol (approximately...

  4. Fear extinction in rats: Implications for human brain imaging and anxiety disorders

    E-Print Network [OSTI]

    Quirk, Gregory J.

    ). For example, a soldier in combat may associate the sound of a helicopter with a severe traumatic event. Years after the war, the sound of the helicopter will continue to induce conditioned fear responses in those

  5. Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats

    E-Print Network [OSTI]

    Breedlove, Marc

    Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH; accepted 3 October 2006 Available online 21 November 2006 Abstract The ventromedial hypothalamus (VMH Introduction The ventromedial hypothalamus (VMH) is one of several sexually differentiated nuclei

  6. Serotonin 5HT-1A receptor density in the brain of the spontaneously hypertensive rats

    E-Print Network [OSTI]

    Valdez, Shakti Regmi

    2010-01-01

    domain receptor density in hypothalamus in WKY andtreatment in hypothalamus in WKY and SHR………………………………26by immunofluorescence in the hypothalamus. 2. Determine the

  7. Elevation of Plasma Tryptophan by Insulin in Rat By J. D. Fernstrom and R. J. Wurtman

    E-Print Network [OSTI]

    Wurtman, Richard

    is available on the effects of insulin on plasma tryptophan. A few reports have appeared showing that plasma per cage and exposed to light (40-60 Rw/s cm; Vita- Lite, Duro-Test Corp., North Bergen, N.J.) between

  8. Personality composition in a translocated population of the endangered species of kangaroo rat, Dipodomys stephensi

    E-Print Network [OSTI]

    Farrell, Anthony P.

    for Social Sciences (SPSS): · Intraclass correlations were used to assess reliability of ratings across two raters: 11 of 21 descriptive adjectives remained (Table 1) Introduction Translocations, movement of wild an animal uses to survive in the wild (Texeira et al. 2007). Current theory suggests that these stressors

  9. Swamp rats, fat cats and soggy suburbs : planners and engineers in south east Florida

    E-Print Network [OSTI]

    Phelan, Katherine A., 1971-

    2004-01-01

    U.S. cities continue to physically expand, supported by and creating demand for water supply, road, sewerage, electricity networks. But the relationship between the professional values, education and practices of city or ...

  10. An analytical method for simultaneously assessing biological and physical barriers of the rat intestinal mucosa

    E-Print Network [OSTI]

    Mudra, D. R.; Borchardt, Ronald T.

    2006-10-25

    strength(?) on the retention time of four analytes: atenolol (maroon), metoprolol (black), norverapamil (purple) and verapamil (green). 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 A V N Gut Buffer + eq vol NaOH Plasma + eq vol NaOH tBME t... STANDARDS Nominal Calc. Accuracy CV Nominal Calc. Accuracy CV Nominal Calc. Accuracy CV 50 46 91.6% 10.3% 5 5 100.5% 8.2% 5 6 111.1% 23.1% 100 94 94.0% 25.6% 25 24 96.3% 9.0% 25 29 114.9% 10.5% 500 477 95.4% 7.7% 50 47 93.1% 1.5% 50 51 102.9% 7.3% 1000 1022...

  11. Demo Abstract: RatMote A Sensor Platform for Animal Habitat Monitoring

    E-Print Network [OSTI]

    . It also allows us to maintain a stable supply voltage over the whole battery life time of a Lithium-Ion battery without using a switch- ing voltage regulator. This is particularly important for the precise

  12. Immunocytochemical analysis of cyclic AMP receptor proteins in the developing rat parotid gland

    E-Print Network [OSTI]

    Terasaki, Mark

    of RII in secretory granules is similar to the pattern of the major salivary proteins, amylase and PSP

  13. Synaptic response patterns of neurons in the cortex of rat inferior , M. Steven Evans b

    E-Print Network [OSTI]

    Li, Yang V.

    al., 1991; Saldan¬a and Mercha¨n, 1992; Covey et al., 1996; Kuwada et al., 1997). The IC arise from cells in the ICc and the contralateral IC (Coleman and Clerici, 1987; Saldan¬a and Mercha

  14. The effects of dietary phenylalanine supplementation on ochratoxicosis in normal and partially nephrectomized rats 

    E-Print Network [OSTI]

    Parker, Roger William

    1983-01-01

    -Chai rmen of Advisory Committee: Dr. Leon H. Russell Dr. Timothy D. Ph11 lips Ochratoxin A (OA), a naturally occurring nephrotoxic mycotoxin, is an inhibitor of protein synthesis, competing with L-beta-phe- nylalanine at the enzyme phenylalanine...-tRNA synthetase. Previous investigators have reported decreasing OA toxicity in bacteria, yeast. cultured cells, and mice by administering phenylalanine simultane- ously; thus, they have hypothes1zed that an1mals may be protected from OA poisoning through...

  15. Local functional input to neurons in deep layers of rat visual cortex

    E-Print Network [OSTI]

    Zarrinpar, Amir

    2006-01-01

    et al. , 1988; Koester and O'Leary, 1992; Kasper et al. ,54:205-218. Koester SE, O'Leary DD (1992) Functional classesregions) (Koester and O'Leary, 1992; Kasper et al. , 1994).

  16. 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

    2012-10-01

    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.

  17. Sexually Dimorphic Effects of Ancestral Exposure to Vinclozolin on Stress Reactivity in Rats

    E-Print Network [OSTI]

    Crews, David

    ­12), bisphenol A (BPA; 13, 14), and tributyltin (15). Such transgenera- tional modifications affect all levels. Abbreviations: BLA, basolateral amygdaloid nucleus; BnST, bed nucleus of the stria ter- minalis; BPA, bisphenol

  18. Natural ozone scavenger prevents asthma in sensitized rats Ehud Keinan,a,*,

    E-Print Network [OSTI]

    Keinan, Ehud

    , breathlessness, chest tightness, and cough associated with evidence of reversible airway obstruction

  19. Discovery of small molecules that enhance astrocyte differentiation in rat fetal neural stem cells

    E-Print Network [OSTI]

    Suh, Young-Ger

    -Jung Kim b, , Kyung Hoon Min c, a College of Pharmacy, Seoul National University, Seoul 151-741, Republic to understand how the cell fate of NSCs is regulated. In addition, much attention has been paid to the role of astrocytes in neuro- pathological conditions.12 An in-house chemical library was there- fore screened to see

  20. Biomechanics and cortical representation of whisking in the rat vibrissa system

    E-Print Network [OSTI]

    Hill, Daniel Nicholas

    2009-01-01

    Zeigler HP, Kleinfeld D. Biomechanics of the vibrissa motorJH, Hartmann MJ (2006) Biomechanics: Robotic whiskers usedOF CALIFORNIA, SAN DIEGO Biomechanics and Cortical

  1. Chronic Pain, Memory, and Injury: Evolutionary Clues from Snail and Rat Nociceptors

    E-Print Network [OSTI]

    Walters, Edgar T.

    2009-01-01

    neurons innervating siphon skin and mantle shelf in Aplysia.innervate the animal’s siphon (Byrne, Castellucci, & Kandel,

  2. Microbead-based biomimetic synthetic neighbors enhance survival and function of rat pancreatic ?-cells

    E-Print Network [OSTI]

    Li, Wei

    Diabetes is caused by the loss or dysfunction of insulin-secreting ?-cells in the pancreas. ?-cells reduce their mass and lose insulin-producing ability in vitro, likely due to insufficient cell-cell and cell-extracellular ...

  3. 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-

    2004-01-01

    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 ...

  4. Carbon Monoxide Pollution Promotes Cardiac Remodeling and Ventricular Arrhythmia in Healthy Rats

    E-Print Network [OSTI]

    Boyer, Edmond

    worldwide by outdoor air pollution caused by vehicles and industrial emissions (http://www.who.int; http:// www.infoforhealth.org). Notably, air pollution increases the risk of mortality from cardiovascular investigating the effects of urban air pollution in humans are mainly restricted to epide- miological studies

  5. Correlating mechanical properties of cancellous bone in the rat with various density measures 

    E-Print Network [OSTI]

    Ramaswamy, Ramya

    2004-09-30

    . Recommendations for future study include advanced technology like finite element analysis and custom shaped platens to enhance RPC testing....

  6. 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)

    1931-01-01

    KNOX M S. AnzmalNusbandry L. MACKEY, M. S., Anzmal Husbandry A. L: DARN~LL, M: A., Dairy Husbandry - Dean School of Veterinary Medicine. ?As of January 1. 1932. :In cooperation with U. S. Department of Agriculture. The importance of a sufficient...

  7. Chondroitin sulfates in the developing rat hindbrain confine commissural projections of vestibular nuclear neurons

    E-Print Network [OSTI]

    Kwok, Jessica C. F.; Yuen, Ying Lai; Lau, Wai Kit; Zhang, Fu Xing; Fawcett, James W.; Chan, Ying Shing; Shum, Daisy K. Y.

    2012-02-03

    showed that treatment of the fil- ter with ChABC resulted in cultures bearing longer neur- ites [19]. Treatment of chiasmatic brain slice cultures (E13 to E15, mouse) with ChABC resulted in misrouting of retinal ganglion cell projections at the optic...

  8. Temporal Organization of Eating in Low- and High- Saccharin-Consuming Rats

    E-Print Network [OSTI]

    Dess, Nancy K; Richard, Jocelyn M; Severe, Susan Fletcher; Chapman, Clinton D

    2007-01-01

    shock: Modulation by quinine adulteration, stressorsolution adulterated with quinine, but not with citric acid,

  9. Three-Dimensional Left and Right Ventricular Strain Distributions in The Rat Heart /

    E-Print Network [OSTI]

    Barrio, Martin J.

    2013-01-01

    Ventricular Function." Heart 94.7 (2008): 855-59. Print. 35)our control and hypertensive heart results to publishedhuman control and hypertensive hearts. Peak systolic !! ,

  10. Exercise training regulation of extracellular matrix and remodeling in the aging rat heart 

    E-Print Network [OSTI]

    Kwak, Hyo Bum

    2009-05-15

    in the aging heart. In contrast, exercise training not only improves cardiac function, but also reduces the risk of heart disease. However, the ability of exercise training to modulate ECM and remodeling in the aging heart remains unknown. Therefore...

  11. Collagen implants to promote regeneration of the adult rat spinal cord

    E-Print Network [OSTI]

    Cholas, Rahmatullah H. (Rahmatullah Hujjat)

    2006-01-01

    Over 250,000 people in the United States currently live with a spinal cord injury and approximately 11,000 new cases occur every year. People with spinal cord injuries experience a significant reduction in quality of life ...

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

    E-Print Network [OSTI]

    Baumgardner, George D

    1979-01-01

    62 14 r 17 16 o. -: w, 15) ! c X t J . r I e 1 1 19 ~ Ie 20 ~ 21 63 / ) / ! 22 i e i ~ 24 e, e e 26 ~, I ~ !') '! ), 11 2'g 2. og pt' 1 1't' of D~. d y t?do. d' f tf . Dq d t* 11 t' g 't f D. ~t; o'*t, D. ordi; and triangles, both... ~ so ~ 22 ~ 34 ~ 39 37 39 ~ 4o ~ 41 e42 g 43 ~ 4 e 45 5 ~ ~ 5 ~ 51 55 ~ 2 ~ 53 5 ~ 57 8 ~ ~ ~ se ~ 55 ~ ea 0 10203040 0 kilomeie ra 0 15 20 30 40 50 mI les (26) Aguascalientes and S Zacatecus; (27) S San Luis Potosi; (63...

  13. Effects of Supplemental Food on Population Dynamics of Cotton Rats, Sigmodon Hispidus

    E-Print Network [OSTI]

    Doonan, Terry J.; Slade, Norman A.

    1995-04-01

    Variation in resource abundance affects population dynamics by altering demographic processes and interactions among individuals in the population. For small mammals, food is likely to be a critical resource. Population ...

  14. The effect of food restriction and simulated microgravity on the rat skeleton 

    E-Print Network [OSTI]

    Currado, Alicia Anne

    2002-01-01

    Bone loss commonly occurs during space flight, creating an increased risk for fractures. It is also known that undereating commonly occurs on space flight missions, and ingesting insufficient calories has been shown to ...

  15. The development of processing methods for a quantitative histological investigation of rat hearts 

    E-Print Network [OSTI]

    Jetton, Emily Hope

    2004-11-15

    In order to understand the mechanical functions of the cardiac muscle it is important to first understand the microstructure of the tissue. Young et al. (1998) realized that quantitative three-dimensional information about the ventricular...

  16. Level of osteopenia and bone recovery in alcohol-fed adolescent rats 

    E-Print Network [OSTI]

    Spears, Heather Lynae

    1999-01-01

    Adolescence is a period in human growth and development that is a time of rapid and drastic change. It is also known to be an age of widespread alcohol abuse. Studies addressing the reversibility of the deleterious effects ...

  17. Effects of spinal TLR3 activation in non-neuronal cells of rats on pain processing

    E-Print Network [OSTI]

    Ehsani-Nia, Hamid

    2011-01-01

    Biology by Hamid Ehsani-Nia Committee in charge: ProfessorTour Copyright Hamid Ehsani-Nia, 2011 All rights reservedThesis of Hamid Ehsani-Nia is approved and it is acceptable

  18. Amygdala norepinephrine levels after training predict inhibitory avoidance retention performance in rats

    E-Print Network [OSTI]

    O'Toole, Alice J.

    ) reported that b-adrenoceptor antagonists infused into the amygdala immediately after inhibitory avoidance-training infusions of the b-adrenoceptor antagonist propranolol into the amygdala also block the memory enhancement). Moreover, post-training, intra-amygdala infusions of NE produce dose-dependent enhancement of memory (Liang

  19. Four-Dimensional Elastic Light-Scattering Fingerprints as Preneoplastic Markers in the Rat Model

    E-Print Network [OSTI]

    Bustamante, Fabián E.

    of these microarchitectural changes. Colorectal neoplasms are the second-leading cause of cancer deaths in the United States- tal cancer, which is in marked contrast to screening rates for other common malignancies (e.g., breast

  20. EFFECT OF ELEVATED TEMPERATURES ON CELL CYCLE KINETICS OF RAT GLIOSARCOMA CELLS

    E-Print Network [OSTI]

    Ross-Riveros, Pepi

    2011-01-01

    effect in incrensod reaction velocities which have anas much as the velocity constant the reactions that depletethe reaction(s) that build for be intact but the velocity

  1. Impact of Ghrelin and Cocaine on Intracranial Self-Stimulation in Rats 

    E-Print Network [OSTI]

    Kniffin, Tracey C

    2012-07-11

    the differences between the effects of GHR administration on acute versus chronic psychostimulant administration (both acquisition of SA and sensitization to the drug). 29 REFERENCES Abizaid A. Department of Neuroscience; Carleton University. Personal...

  2. Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia

    E-Print Network [OSTI]

    2009-01-01

    from the fact that direct injection into the ganglion makescolleagues [3] showed that direct injection of a GABA A Pagesite of action. Direct gan- glion injection of CGP46381, a

  3. Aerosol Deposition in Healthy and Emphysematous Rat Lungs : : Insights From MRI Measurements and Computational Simulations

    E-Print Network [OSTI]

    Oakes, Jessica M.

    53] Schroeter, J. D. , Kimbell, J. S. , Gross, E. a. ,307. [58] Schroeter, J. D. , Kimbell, J. S. , Gross, E. a. ,

  4. Dietary L-arginine supplementation reduces fat mass in diet-induced obese rats 

    E-Print Network [OSTI]

    Jobgen, Wenjuan Shi

    2009-06-02

    Diabetes Research Foundation, National Institutes of Health, United States Department of Agriculture, and Texas A&M University for support of this research. I deeply thank my parents for providing me with a nurturing and loving environment. I truly... and almost tripled in men between 1989 and 1997 (Bell et al. 2001). Worldwide, more than 300 million adults are obese and over one billion are overweight (Hill et al. 2003). Obesity is a major risk factor for insulin resistance, type II diabetes...

  5. Sex Differences in Long Bone Fatigue Using a Rat Model Luisa D. Moreno,1

    E-Print Network [OSTI]

    Waldman, Stephen D.

    response to fatigue, we also determined the creep that occurred during the fatigue test. From the creep progress (Fig. 1). Caler and Carter32 studied cortical bone creep behavior during fatigue testing. When adaptation. From these results, we hypothesized that creep was the underlying mechanism that accounted

  6. Reaction to heat stress in the albino rat maintained on a vitamin B complex deficient diet 

    E-Print Network [OSTI]

    Baban, Riadh M. Ali

    1965-01-01

    was made to be equal to that consumed by the 5 per- cent level group ir order to obtain equality in caloric intake among these groups. The control group was the one with 100%%u, B-complex level and full fed. CHAPTER II REVIEW OF LITERATURE Diet ard B... concerning the requirement for thiamine in high environmental temperatures are conflicting. Kline (65) reported a requirement for less thiamine which approximates the reduced caloric intake, while Mills (75) reported its requirements to be higher...

  7. Warfarin Causes Rapid Calcification of the Elastic Lamellae in Rat Arteries and Heart Valves

    E-Print Network [OSTI]

    Price, Paul A.

    was originally discovered in demineralization extracts of bone but is now known to be expressed by a wide variety

  8. In vivo ultrasonic attenuation slope estimates for detecting cervical ripening in rats: Preliminary results

    E-Print Network [OSTI]

    Illinois at Urbana-Champaign, University of

    tissue properties collagen and extracellular matrix remodeling House and Socrate, 2006 . The loading forces are: 1 passive, the enlarged size and weight of the uterus; and 2 active, the forces of the uterine contractions House and Socrate, 2006 . Parturition involves orderly and biologically timed events

  9. Establishing a rodent (Fischer 344 rat) model of mild cognitive impairment in aging 

    E-Print Network [OSTI]

    LaSarge, Candi Lynn

    2009-05-15

    Mild Cognitive Impairment is characterized by age-related decline in a variety of cognitive domains, including reference and working memory and olfactory function. Importantly, declining age-related mnemonic abilities is not inevitable; learning...

  10. Substructure within the dorsal lateral geniculate nucleus of the pigmented rat

    E-Print Network [OSTI]

    Discenza, Claire B.

    2011-01-01

    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. Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats

    E-Print Network [OSTI]

    Javkhedkar, AA; Quiroz, Y; Rodriguez-Iturbe, B; Vaziri, ND; Lokhandwala, MF; Banday, AA

    2015-01-01

    doi:10.1152/ajpregu.00308.2014. Resveratrol restored Nrf2Lokhandwala MF, Banday AA. Resveratrol restored Nrf2 func-in blood pressure, the resveratrol-treated group showed no

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

    E-Print Network [OSTI]

    Reynoso, Jose T.

    2000-01-01

    Previous demonstrations of associative tolerance to the analgesic effects of nicotine have been confounded by either (1) novelty-induced stress in the tolerance test-session, or (2) instrumental learning of the test response ...

  13. Temporal Organization of Eating in Low- and High- Saccharin-Consuming Rats

    E-Print Network [OSTI]

    Dess, Nancy K; Richard, Jocelyn M; Severe, Susan Fletcher; Chapman, Clinton D

    2007-01-01

    Risk Food Availability Toxins & Nutrients Palatability Foraging Eating and Absorption Energy Storage

  14. LANL12-RS-107J PYTHON Radiography Analysis Tool (PyRAT). Mid-Year

    Office of Scientific and Technical Information (OSTI)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity of NaturalDukeWakefieldSulfate Reducing(Journalspectroscopy of aerosols in(JournalTechnicalConnectArticle)!LANL

  15. LANL12-RS-107J PYTHON Radiography Analysis Tool (PyRAT). Mid-Year

    Office of Scientific and Technical Information (OSTI)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity of NaturalDukeWakefieldSulfate Reducing(Journalspectroscopy of aerosols in(JournalTechnicalConnectArticle)!LANLDeliverable

  16. sequential ultracentrifugation. ApoHDLs were identified after migration in area-gel

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    . Twenty-eight male Zucker rats were divided into four groups: seven lean rats fed ad libitum (group A), seven obese rats fed ad libitum (group B), seven obese rats fed a 25% energy-restricted diet, which provided 10% of total energy from fat (group C) and seven obese rats fed a 25% energy-restricted diet

  17. The Role of CA1 in the Acquisition of an ObjectTraceOdor Paired Associate Task

    E-Print Network [OSTI]

    Wagner, Anthony

    , rats were to dig in the odor cup for a reward. If unpaired, rats were to refrain from digging. Rats as well as controls. These results support the idea that the hippocampus is involved in forming arbitrary

  18. 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

    2009-04-29

    Background: Sialic acid and cholesterol are present in human milk and accumulate rapidly in the brain during development. Infant formulas contain little sialic acid or cholesterol. Sialic acid and cholesterol supplementation ...

  19. Response of the Femur to Exercise During Recovery Between Two Bouts of Hindlimb Unloading in Adult Male Rats 

    E-Print Network [OSTI]

    Gonzalez, Estela

    2012-10-19

    of BMC increased following exercise recovery above AC at the FN and DFM. Ambulatory recovery values revealed incomplete recovery in total and cortical BMC at the DFM and full recovery in other parameters. DFM and FD vBMD data indicated there were further...

  20. Abstract Using immunocytochemistry, we have investi-gated the localization of CD15 in the rat retina. In the

    E-Print Network [OSTI]

    Grzywacz, Norberto

    of the inner plexiform layer (IPL). Type 2 cells have a smaller soma and processes branching in stra- tum 1 of the IPL. A third population showing CD15 im- munoreactivity was a class of displaced amacrine cells-N-acetyl-lactosamine, is a glycoconjugate. The epitope has been reported to be in- volved in cellular adhesion by homophilic reactions (Bird

  1. Adaptation to elastic loads and BMI robot controls during rat locomotion examined with point-process GLMs

    E-Print Network [OSTI]

    Song, Weiguo

    Currently little is known about how a mechanically coupled BMI system's actions are integrated into ongoing body dynamics. We tested a locomotor task augmented with a BMI system driving a robot mechanically interacting ...

  2. 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

    1985-01-01

    fed the magnesium- deficient diet. Magnesium deficiency did not lower femur calcium content, but it significantly decreased femur magnesium. Studies of the human situation would be of interest. ACKNOWLEDGEMENTS The author wishes to express thanks... of dietary magnesium and protein source on tissue 42 Table 11 Effects of dietary treatment on serum magnesium and femur magnesium and calcium 44 LIST OF FIGURES page Figure 1 Weights of dams fed control diet, low magnesium casein diet, soy diet...

  3. HumanWildlife Interactions 5(1):100105, Spring 2011 A rat-resistant artificial nest box for

    E-Print Network [OSTI]

    to the island of Kauai, Hawaii. The sole population of about 500 birds is currently restricted to remote, higher, Hawaii Field Station, P.O. Box 10880, Hilo, HI 96721, USA will.pitt@aphis.usda.gov LAURA C. DRISCOLL, USDA/APHIS/Wildlife Services' National Wildlife Research Center, Hawaii Field Station, P.O. Box 10880

  4. Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma docosahexaenoic acid concentration in rats

    E-Print Network [OSTI]

    van Wijk, Nick

    Background: Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation ...

  5. Exploring Adaptations to Famine: Rats Selectively Bred for Differential Intake of Saccharin Differ on Deprivation-Induced Hyperactivity and Emotionality

    E-Print Network [OSTI]

    Dess, Nancy K.; Arnal, Jill; Chapman, Clinton D.; Siebel, Sara; VanderWeele, Dennis A.; Green, Kenneth F.

    2000-01-01

    diagnoses in anorexia nervosa. Archives of Generalin adolescent anorexia nervosa. International Journal ofand physical activity in anorexia nervosa and high-level

  6. 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

    1997-01-01

    2, 4, 6 and 8 weeks after the feeding began. I-Estomorphometric analyses were performed using a BioQuant Morphometric system on 5um undecalcified longitudinal sections of the proximal tibia. A decrease in the amount of trabecular bone was found...

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

    E-Print Network [OSTI]

    Huebel, Leon William

    1934-01-01

    SOuree Of fzeeyharuo and yetaoeiunx but it is loxx in oaloinm, 'Ixe oozxootion. for this defioieoor in oaloium xxxdx be bro~t aleut by the addition of ground marble oz ground oyster shell, yrerisue Studieo Xzith regard tO mineral any xlemsnt hmes... oontaining oea1 ~akisod with ths sons n4norol salt, Gros?sr ~ was exhibited le Qrwuy 12, ?he anine1s roooivtng tho ration sop'lecwented with X, PO ysr oont oyster shell, than ?hat exhib itsd 'hy Crony Q the ~ vihioh roooivod, the meal nineralised with l...

  8. Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model

    E-Print Network [OSTI]

    Hammock, Bruce D.

    stimuli, leading to heightened pain transmission. Local, systemic, or neurogenic release of inflammatory, peripheral sensitization of nociceptors can, in turn, lead to central sen- sitization in the spinal cord receptors, nitric oxide production, as well as spinal upregulation of COX and resulting prostaglandin

  9. 17?-Estradiol and Progesterone Regulate Expression of ?-Amyloid Clearance Factors in Primary Neuron Cultures and Female Rat Brain

    E-Print Network [OSTI]

    Jayaraman, Anusha; Carroll, Jenna C.; Morgan, Todd E.; Lin, Sharon W.; Zhao, Liqin; Arimoto, Jason M.; Murphy, M. Paul; Beckett, Tina L.; Finch, Caleb E.; Brinton, Roberta Diaz; Pike, Christian J.

    2012-01-01

    The accumulation of ?-amyloid protein (A?) is a key risk factor in the development of Alzheimer's disease. The ovarian sex steroid hormones 17?-estradiol (E2) and progesterone (P4) have been shown to regulate A? accumulation, although the underlying...

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

    E-Print Network [OSTI]

    Meacher, Mary Melanie

    1986-01-01

    of digesta through the gastrointestinal tract. . . . . . . CHAPTER V. DISCUSSION. 31 31 35 35 39 . 61 TABLE OF CONTENTS (continued) CONCLUSION. REFERENCES, . 68 . 69 VITA LIST OF TABLES TABLE Page 1 Composition of basal fiber free control diet.... . . . . 20 2 Percentage composition of the experimental diets. . . . 22 3 Percentage composition of wheat bran and oat bran. . . . . . . , 22 4 Transit time measurements. 30 5 Effect of dietary fiber on food and energy intake. . . . . . . . 32 6 Effect...

  11. 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

    1989-01-01

    Committee: Dr. Joanne R. Lupton The short chain fatty acid (SCFA) production from the fermentation of dietary fiber may have important physiological effects on human health and disease, indicating the importance of selecting the appropriate animal model... DETERMINATION OF pH DETERMINATION OF PERCENT RECOVERY OF FIBERS 16 18 20 20 CHAPTER PAGE SHORT CHAIN FATTY ACID ANALYSIS 23 STATISTICAL ANALYSIS 24 IV. RESULTS 25 INTERSPECIES DIFFERENCE OF SHORT CHAIN FATTY PRODUCTION PROFILE OF SCFA PRODUCTION...

  12. Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique

    E-Print Network [OSTI]

    Lin, Jian

    We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for ...

  13. Microvessel structure formation in a 3D perfused co-culture of rat hepatocytes and liver endothelial cells

    E-Print Network [OSTI]

    Hwa, Albert J

    2006-01-01

    Many liver physiological and pathophysiological behaviors are not adequately captured by current in vitro hepatocyte culture methods. A 3D perfused microreactor previously demonstrated superior hepatic functional maintenance ...

  14. Fetal germ cell development in the rat testis and the impact of di (n-Butyl) phthalate exposure 

    E-Print Network [OSTI]

    Jobling, Matthew S.

    2010-01-01

    During gonad development and fetal life, the germ cells (GC) undergo a range of different developmental processes necessary for correct postnatal gametogenesis and the production of the next generation. If these fetal ...

  15. Oestradiol Increases Phosphorylation of a Dopamine-and Cyclic AMP-Regulated Phosphoprotein (DARPP-32) in Female Rat Brain

    E-Print Network [OSTI]

    . Key words: oestrogen, steroids, dopamine, hypothalamus, brain. Abstract Recent studies suggest, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and the ventromedial nucleus of the hypothalamus, 48 h after treatment. These data suggest that oestradiol increases

  16. 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

    1973-01-01

    accidents as an epidemic or a pandemic or a great accumulation of endemics, estimates that at any given time patients injured in accidents occupy 65, 000 American hospital beds. According to the National Health Survey, if injuries of a lesser severity... Alcoholism like accidents is considered by several authors to be a disease (4, 7 &12). The dictionary defines chronic alcoholism as a, "pathological condition& affect- ing chiefly the nervous and gastro-enteric systems, caused by the habitual use...

  17. Pyramidal neurons in the superficial layers of rat retrosplenial cortex exhibit a late-spiking firing property

    E-Print Network [OSTI]

    Kurotani, Tohru

    The rodent granular retrosplenial cortex (GRS) is reciprocally connected with the hippocampus. It is part of several networks implicated in spatial learning and memory, and is known to contain head-direction cells. There ...

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

    E-Print Network [OSTI]

    Graham, Zachary Aaron

    2010-07-28

    Abstract Introduction: Integrins (IN) are heterodimers made up of an alpha subunit and a beta subunit. They are transmembrane proteins that are capable of detecting and relaying signals from the extracellular matrix to the ...

  19. The role of nitric oxide in testosterone-induced vasodilation in pig coronary arteries and rat thoracic aorta 

    E-Print Network [OSTI]

    Piefer, Jason William

    2013-02-22

    arteries from exercised and sedentary, female Yucatan Mini-Swine were treated with N[]-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase (NOS). Following blockade of NOS, seven cumulative doses (5 []M to 300 []M) of testosterone...

  20. The hematological response and survival of acutley irradiated rats previously exposed to continuous and fractionated, low intensity gamma irradiation 

    E-Print Network [OSTI]

    Hooper, John Anderson

    1964-01-01

    72 ro sixteen dnyS sfcoE' tliQ lane Gmnkk dosog chc animals were exposed to BOO I. The average Gnrrivnl tRee was 8. 8 days es cemiierod to 4. 2 days fer controls. There was no nnrtnkkty esseckeced viCh, Che coitilitkoaing dose Encronsecll...- inclusions (nuclear satellites) W-tha. peripheral Head ?8 Cpl Silas female mice after- total bad~ axpesnra- :- to X=Mys ~ . The incidaaca ef these inclusioas rangsd gemM~ par cant, ', :-. w' -". a "v:d to, l. l6 per cont for acute doses of l00 to 000 r...

  1. Quantifying the strain response in the rat tibia during simulated resistance training used as a disuse countermeasure 

    E-Print Network [OSTI]

    Jeffery, Jay Melvin

    2009-05-15

    the protocol affects the strain environment, but the number of animals in each group was too low to permit statistically significant comparisons. The current study paralleled a study by Lindsay Sumner 2 , who extended the work of Justin Alcorn (2006) 3... is the relationship between strain on the tibia and torque at the ankle? Further, does this relationship change from the very beginning of the study (i.e., before hindlimb unloading plus exercise (HU+Ex) starts, and also after 3 weeks of HU+Ex? 3. What can...

  2. Organ-Specific Alterations in Fatty Acid De Novo Synthesis and Desaturation in a Rat Model of Programmed Obesity

    E-Print Network [OSTI]

    Yee, Jennifer K; Lee, Wai-Nang P; Han, Guang; Ross, Michael G; Desai, Mina

    2011-01-01

    end of the nursing period, then develop adult obesity. Thethe end of the nursing period, and become obese adults. The

  3. Artificial Rearing of Rat Pups Reveals the Beneficial Effects of Mother Care on Neonatal Inflammation and Adult

    E-Print Network [OSTI]

    Sokolowski, Marla

    Inflammation and Adult Sensitivity to Pain CYNTHIA B. DE MEDEIROS, ALISON S. FLEMING, CELESTE C. JOHNSTON, Mississauga, Ontario L5L 1C6, Canada; School of Nursing [C.C.J., C.-D.W.], McGill University, Montreal H3A 2A7 previously showed that maternal care provided to pups experiencing pain re- duced adult pain sensitivity

  4. The effects of forced nest-site feeding on the food preferences of wild rat pups at weaning*

    E-Print Network [OSTI]

    Galef Jr., Bennett G.

    and of the role of neophobia in maintaining adult-initiated food preferences. Observation of the behavior by interaction with adult conspecifics. Examination of the literature suggests that adult feeding patterns can female's milk can reflect the flavor of the diet she eats during the nursing period, and her young may

  5. The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and

    E-Print Network [OSTI]

    Ritchie, Robert

    The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged greater than can be explained by an increase in bone mineral density. In this study, 18-month Fischer 344 to measure lumbar vertebral bone microarchitecture, the degree of bone mineralization (DBM

  6. Effects of Hemorrhagic Shock and Fraction of Inspired Oxygen on Hydrogen Peroxide and Apoptosis in Rat Lung and Diaphragm

    E-Print Network [OSTI]

    Mach, William J.

    2010-04-07

    Abstract Hemorrhagic shock (HS) is the single most common cause of death in civilian and military personnel experiencing trauma (Alam & Rhee, 2007). Immediate resuscitation for HS can involve the administration of supplemental ...

  7. In Vivo Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized 13C-Pyruvate

    E-Print Network [OSTI]

    2009-01-01

    JR et al (1986) Hepatic gluconeogenesis from alanine: 13 Cutilized during gluconeogenesis, e.g. , due to fasting [28].to the degree of gluconeogenesis, specifically showing more

  8. Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

    E-Print Network [OSTI]

    Binsalamah, Ziyad Mohammed; Paul, Arghya; Khan, Afshan Afsar; Prakash, Satya; Shum-Tim, Dominique

    2011-10-31

    Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, ...

  9. EVALUATION OF COMPRESSION TESTING METHODS FOR THE CORTICAL RING IN THE DISTAL FEMUR METAPHYSIS OF ADULT MALE RATS 

    E-Print Network [OSTI]

    Bishop, Ryan

    2012-04-26

    . Finkelstein JS, Butler JP, Cleary RL, Neer RM 1994 Compar- ison of four methods for cross-calibrating dual-energy X-ray absorptiometers to eliminate systematic errors when upgrading equipment. J Bone Miner Res 9:1945?1952. 3. Peel NFA, Eastell R 1995...

  10. Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats

    E-Print Network [OSTI]

    Burnstock, Geoffrey

    ) and PPADS (17 mmol kgÀ1 ) each caused maintained bladder contractions to occur during the infusion of saline into the bladder. PPADS (17 mmol kgÀ1 minÀ1 ) had a similar effect when infused intravesicularly. Regular bladder contractions were not observed until the infusion of saline was halted. For IP5I, TNP-ATP, MRS 2179 and PPADS

  11. Parental responses of hispid cotton rats (Sigmodon hispidus) to intrusion by red imported fire ants (Solenopsis invicta) into simulated nests 

    E-Print Network [OSTI]

    Ferris, Kathleen Patricia

    1994-01-01

    modon hispidus were observed in simulated nests at 24, 72, and 120 hours of offspring age in the presence (5 different litters observed at each age, n = 15) and absence (6 unique litters observed at each age, n = 6) of fire ants (Solenopsis Lnvicta...

  12. Biosynthesis of ascites sialoglycoprotein-1, the major O-linked glycoprotein of 13762 rat mammary adenocarcinoma ascites cells

    SciTech Connect (OSTI)

    Spielman, J.

    1987-01-01

    The present studies were undertaken to determine the timing of the major events in biosynthesis, and to characterize the contributions of chain initiation and elongation in maturation of the glycoprotein. Initiation of the earliest O-linked chains was detected by analysis of conversion of {sup 3}H-thr to {sup 3}H 2-aminobutyrate following mild alkaline borohydride elimination of O-linked sugars from peanut lectin-precipitated ASGP-1. Initiation was detected within 5 min of translation; amino sugar analysis of GlcNH{sub 2}-labeled, trypsinized cells also showed that GalNAc was added as late as 5 min prior to arrival of ASGP-1 at the cell surface. Thus initiation occurs throughout biosynthesis. Maturation of the glycoprotein from a lightly-glycosylated immature form to the heavily-glycosylated mature from involved both continued initiation of new chains and chain elongation, and occurred with a half-time of about 30 min. Analysis of labeled ASGP-1 released from the cell surface by trypsinization showed that although some newly-synthesized ASGP-1 reached the cell surface within 70-80 min of protein synthesis, the half-time for appearance of mature glycoprotein was in excess of 4 hr, indicating that most molecules reside in an intracellular compartment(s) for a considerable time.

  13. Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

    SciTech Connect (OSTI)

    Roos, Daniel Henrique [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 (Brazil); Puntel, Robson Luiz [Departamento de Ciencias Naturais, Universidade Federal do Pampa, Uruguaiana, CEP 97087-600 (Brazil); Farina, Marcelo [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Neuroscience Graduate Program, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Bohrer, Denise [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 (Brazil); Rocha, Joao Batista T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 (Brazil); Vargas Barbosa, Nilda B. de, E-mail: nvbarbosa@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 (Brazil)

    2011-04-01

    Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg-Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this study was performed to evaluate the effects of methionine (Met) on Hg uptake, reactive species (RS) formation, oxygen consumption and mitochondrial function/cellular viability in both liver slices and mitochondria isolated from these slices, after exposure to MeHg or the MeHg-Cys complex. The liver slices were pre-treated with Met (250 {mu}M) 15 min before being exposed to MeHg (25 {mu}M) or MeHg-Cys (25 {mu}M each) for 30 min at 37 {sup o}C. The treatment with MeHg caused a significant increase in the Hg concentration in both liver slices and mitochondria isolated from liver slices. Moreover, the Hg uptake was higher in the group exposed to the MeHg-Cys complex. In the DCF (dichlorofluorescein) assay, the exposure to MeHg and MeHg-Cys produced a significant increase in DFC reactive species (DFC-RS) formation only in the mitochondria isolated from liver slices. As observed with Hg uptake, DFC-RS levels were significantly higher in the mitochondria treated with the MeHg-Cys complex compared to MeHg alone. MeHg exposure also caused a marked decrease in the oxygen consumption of liver slices when compared to the control group, and this effect was more pronounced in the liver slices treated with the MeHg-Cys complex. Similarly, the loss of mitochondrial activity/cell viability was greater in liver slices exposed to the MeHg-Cys complex when compared to slices treated only with MeHg. In all studied parameters, Met pre-treatment was effective in preventing the MeHg- and/or MeHg-Cys-induced toxicity in both liver slices and mitochondria. Part of the protection afforded by Met against MeHg may be related to a direct interaction with MeHg or to the competition of Met with the complex formed between MeHg and endogenous cysteine. In summary, our results show that Met pre-treatment produces pronounced protection against the toxic effects induced by MeHg and/or the MeHg-Cys complex on mitochondrial function and cell viability. Consequently, this amino acid offers considerable promise as a potential agent for treating acute MeHg exposure.

  14. BrainResearch, 376(1986)71-77 71 Phenytoin Increases the Severity of Cortical Hemiplegia in Rats

    E-Print Network [OSTI]

    Knight, Robert T.

    1986-01-01

    cannula through which saline or GABA were infused chronicallyvia an osmotic minipump. Phenytoin (50 mg in those animals also receivingintracorticalGABA infusions. The anticonvulsant at the dose used had GABA infusion. Thus, intracortical GABA infusion increases the functional deficit with- * On leave

  15. NO and NO-independent mechanisms mediate ETB receptor buffering of ET-1-induced renal vasoconstriction in the rat

    E-Print Network [OSTI]

    Just, Armin

    elicited by ET-1 injected into the renal artery from 15 to 30%. Additional infusion of the NO donor%) and were unaffected by subsequent NP infusion ( 21%). These results indicate that the responsiveness to ET. Infusion of the ETB receptor antag- onist BQ-788 into the renal artery further enhanced the ET-1 con

  16. Preparation of Pulmonary SMC Pulmonary smooth muscle cells are isolated from ten 6-day neonatal rat lungs.

    E-Print Network [OSTI]

    Mecham, Robert

    lungs. The lungs are dissected with the trachea still attached and placed in Puck's saline A solution

  17. Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex

    E-Print Network [OSTI]

    Fiala, Jeannette Louise Allen

    Aflatoxin B1 (AFB1) is a DNA-binding toxin that contributes to the burden of liver cancer in tropical areas. AFB1-DNA adducts are powerful biomarkers that discern individual and population risk from exposure to this ...

  18. IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 50, NO. 5, MAY 2003 559 Manipulating Epileptiform Bursting in the Rat

    E-Print Network [OSTI]

    Cvitanovc', Predrag

    IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 50, NO. 5, MAY 2003 559 Manipulating Epileptiform Foundation. Asterisk indi- cates corresponding author. M. W. Slutzky is with the Department of Biomedical of Biomedical Engineering, Pritzker In- stitute of Biomedical Science and Engineering, Illinois Institute

  19. Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone 

    E-Print Network [OSTI]

    Russell J.A.; McKay A.J.; Brunton P.J.; Ochedalski T.; Piastowska A.; Rebas E.; Lachowicz A.

    2009-05-01

    The hypothalamus-pituitary-adrenal (HPA) axis is the major neuroendocrine stress response system. Corticotropin-releasing hormone (CRH) neurons in the parvocellular paraventricular nucleus (pPVN) play a key role in ...

  20. Effect of the NMDA receptor antagonist MK-801 on recovery from spinal cord injury in rats given uncontrollable stimulation 

    E-Print Network [OSTI]

    Petrich, Christine

    2006-08-16

    in the absence of blinking. A 7.0-cm incision was made over the vertebral column, and an incision was made on each side of the vertebral column, extending approximately 3.0 cm rostral and caudal to the T10?T11 (thoracic vertebrae 10?11) segment. Next... the vertebrae dorsal and medial to T10?T11 were cleared to expose the spinal tissue. The vertebral column was secured with the MASCIS device, and the 10-g impactor with 3-mm tip was dropped 12.5 mm to produce a moderate injury. The subject was then removed from...

  1. Alterations in skeletal muscle arteriolar vasoreactivity during the progression of type 2 diabetes in the Zucker Diabetic Fatty rat 

    E-Print Network [OSTI]

    Lesniewski, Lisa AnnMarie

    2004-09-30

    Altered vasoreactivity and mechanical properties of skeletal muscle arterioles could impact peripheral insulin resistance and hypertension observed in type 2 diabetes. The purpose was to determine if increased vasoconstrictor reactivity, decreased...

  2. Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver Rola Barhoumi a,

    E-Print Network [OSTI]

    Hammock, Bruce D.

    combustion of fossil fuels. These compounds have been identified in ground and rain water, tap water, waste water, sewage sludge and foodstuffs (Ramesh et al., 2004b; Samanta et al., 2002). Due

  3. Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction

    E-Print Network [OSTI]

    Paul, Arghya; Nayan, Madhur; Khan, Afshan Afsar; Shum-Tim, Dominique; Prakash, Satya

    2011-10-06

    The objective of this study was to develop angiopoietin-1 (Ang1)-expressing genetically modified human adipose tissue derived stem cells (hASCs) for myocardial therapy. For this, an efficient gene delivery system using recombinant baculovirus...

  4. A study of the effect of pantothenic acid deficiency on the reproductive organs of the male albino rat 

    E-Print Network [OSTI]

    Lorenzen, Gerald Andrew

    1958-01-01

    " Creme of vitamin free casein wns used in 'ta pince. 0 Q0 M O A, -Q P, I 0)03 0) M I I I C CJ IO). 0 H A CO Vl M GJ O O GJ M O 1:I C) ? CO c0 O I I I I I H ACG MOJ O I Gl O 0 )GMO - O(4 MO I I M LG QG'c0 M 1 I ( O O )4 ~td 0 IQ 0 4 CQ 0 0...

  5. RESPONSE OF MARSH RICE RAT (ORYZOMYS PALUSTRIS) T O INUNDATION Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409

    E-Print Network [OSTI]

    Strauss, Richard E.

    cambio completo de la poblaci6n, estimamos una densidad poblacional de aproximadamente 29 individuos por

  6. The Roles of Introduced Rats and Commercial Fishing in the Decline of Ancient Murrelets on Langara Island,,

    E-Print Network [OSTI]

    , un indice potencial dei tama~o poblacional, declin6 de 101 ha. en 1981 a 48 ha. en 1988. Sin embargo, la densidad de cuevas se increment6 durante el mismo perfodo, lo que sugiere que la colonia se ha consolidado. En 1988, la esti- maci6n poblacional fue de 24,200 +__4000 (S.E.) pares de reproductores en

  7. 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

    2006-04-12

    Many senescent individuals demonstrate an inability to regulate mean arterial pressure (MAP) in response to standing or head-up tilt; however, whether this aging effect is the result of depressed cardiac function or an inability to reduce peripheral...

  8. Effects of aging and exercise training on the mechanisms of Angiotensin II-induced vasoconstriction in rat skeletal muscle arterioles 

    E-Print Network [OSTI]

    Park, Yoonjung

    2009-05-15

    Aging is associated with increases in regional and systemic vascular resistance and impaired ability to increase blood flow to active muscles during exercise. Aging enhances vasoconstrictor responsiveness in both humans and animals, and an increase...

  9. The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    . MONTERO-MENEI1* 1 Inserm, U646, Angers, F49100 France Univ Angers, UMR-S646, Angers, F49100 France 2 GRECC *Corresponding author: Claudia N. Montero-Menei Inserm U646, 10 rue André Boquel, Angers, France Phone : +33(0)2.41.73.58.94 Fax : +33(0)2.41.73.58.53 E-mail : claudia.montero-menei@univ-angers.fr Grant information: this work

  10. Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: in vitro characterization & migration potential in rat brain

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    LEMAIRE1, 2 , Laurence SINDJI1, 2 , Florence FRANCONI3 , Jean-Jacques LE JEUNE1, 2 , Claudia N. MONTERO: Claudia N. Montero-Menei Inserm U646, 10 rue André Boquel, Angers, France Phone : +33(0)2.41.73.58.94 Fax : +33(0)2.41.73.58.53 E-mail : claudia.montero-menei@univ-angers.fr inserm-00354437,version1-19Jan2009

  11. Calcium Signaling Mechanisms Mediate Clock-Controlled ATP Gliotransmission among Immortalized Rat SCN2.2 Cell Cultures 

    E-Print Network [OSTI]

    Burkeen, Jeffrey Franklin

    2010-10-12

    The hypothalamus is an integral part of the brain's regulation of mammalian physiology and behavior. Among many functions, this regulatory center activates the sympathetic nervous system, maintains appropriate body ...

  12. Central, peripheral, and contextual regulation of food intake

    E-Print Network [OSTI]

    Parylak, Sarah Lynne; Parylak, Sarah Lynne

    2012-01-01

    leptin action in rat hypothalamus. J Clin Invest. 1996,98:stimulation of lateral hypothalamus. Nature. [59] Margules,systems in the lateral hypothalamus of rats. Science.

  13. Analysis of Ipsilateral Functional and Anatomical Associations Between the Nucleus Accumbens Shell and the Lateral Hypothalamus: Relations With Feeding Behaviors

    E-Print Network [OSTI]

    Urstadt, Kevin

    2014-01-01

    1998). The hypocretins: hypothalamus- specific peptides withof the rat lateral hypothalamus after insulin treatment.rat preoptic area and hypothalamus in response to physical

  14. CHEMICAL BIODYNAMICS DIVISION ANNUAL REPORT 1978

    E-Print Network [OSTI]

    Authors, Various

    2011-01-01

    TX) for telemetering biopotentials in rats and other smallrecording of a variety of biopotentials from unanesthetized

  15. INTRODUCTION Gap junctions are intercellular protein channels formed by

    E-Print Network [OSTI]

    Snyder, Scott A.

    expressed in both HeLa transfectants (rat Cx26, rat Cx32 and mouse Cx45) and Xenopus oocytes (rat Cx26 and rat Cx32). In HeLa cells, we examined permeability to two fluorescent molecules: Lucifer Yellow (LY of the kinetics of fluorescent dye transfer showed Cx32, Cx26 and Cx45 to have progressively decreasing

  16. Short-and Long-Term Effects of Various Milk-Delivery

    E-Print Network [OSTI]

    Sullivan, Regina M.

    contingencies differentially affect sucking in rat pups as measured by jaw-muscle electromyographic activity

  17. MECHANISMS OF MICROVASCULAR INFLAMMATION INDUCED BY ALVEOLAR HYPOXIA

    E-Print Network [OSTI]

    Chao, Jie

    2010-08-23

    hypoxia produced a rapid increase in plasma MCP-1 concentration of conscious intact rats, but not of AMØ-depleted rats. 2) Degranulation occurred when mast cells were immersed in the plasma of hypoxic intact rats, but not of AMØ-depleted rats. 3) MCP-1...

  18. Biochemical Pharmacology, Vol. 37, No. 7, pp. 1331-1341, 1988. 0006-2952/88 $3.00 + 0.00 Printed in Great Britain. ~ 1988. Pergamon Press plc

    E-Print Network [OSTI]

    Hammock, Bruce D.

    in Great Britain. ~ 1988. Pergamon Press plc SODIUM CHOLATE EXTRACTION OF RAT LIVER NUCLEAR XENOBIOTIC

  19. Effects of Resistance Trainging and -hydroxy--methylbutyrate (HMB) on Muscle Fiber CSA and Lean Body Mass in Aged Rats: A DTI and DEXA Study

    E-Print Network [OSTI]

    McQuade, D. Tyler

    and volumetric measurements. In vivo and prior to sacrifice, pre- and post-RT LBM was assessed by dual energy X

  20. Neither in vivo MRI nor behavioural assessment indicate a therapeutic efficacy for a novel 5HT1A agonist in rat models of ischaemic stroke

    E-Print Network [OSTI]

    Ashioti, Maria; Beech, John S.; Lowe, Andrew S.; Bernanos, Michel; McCreary, Andrew; Modo, Michel M.; Williams, Steve C. R.

    2009-07-16

    Abstract Background 5HT1A agonists have previously been shown to promote recovery in animal models of stroke using ex vivo outcome measures which have raised the hopes for a potential clinical implementation. The purpose of this study...

  1. A set of genes previously implicated in the hypoxia response might be an important modulator in the rat ear tissue response to mechanical stretch

    E-Print Network [OSTI]

    Saxena, Vishal

    Background: Wounds are increasingly important in our aging societies. Pathologies such as diabetes predispose patients to chronic wounds that can cause pain, infection, and amputation. The vacuum assisted closure device ...

  2. A novel bioengineering platform using functionalized self-assembly peptides to enhance CYP3A2 activity in modified rat hepatocyte sandwich cultures

    E-Print Network [OSTI]

    Wu, Jonathan (Jonathan G.)

    2007-01-01

    Isolated hepatocytes removed from their microenvironment soon lose their hepatospecific functions when cultured. Highly oxygen-demanding hepatocytes are commonly maintained under oxygen-deficient culture conditions, limited ...

  3. Uncoupling at the GABA(A) receptor with chronic ethanol in the rat medial septum/diagonal band (MS/DB) 

    E-Print Network [OSTI]

    Wallace, Kathleen Allison

    1997-01-01

    allosteric potentiation of GABAAreceptors by a benzodiazepine, a novel anticonvulsant or a neurosteroid is uncoupled by chronic ethanol treatment which may contribute to functional tolerance and physical dependence. Chronic ethanol was not found to induce...

  4. Layer-Specific Manganese-Enhanced MRI of the Diabetic Rat Retina in Light and Dark Adaptation at 11.7 Tesla

    E-Print Network [OSTI]

    Duong, Timothy Q.

    Antonio, TX 78229, USA; duongt@uthscsa.edu. ERM and SBC contributed equally to the work presented here

  5. A study of the effect of feeding Albino rats with cottonseed meal to which various chemicals have been added during the cooking process 

    E-Print Network [OSTI]

    Staffel, Eugene Otto

    1933-01-01

    XCALS SAYS SMf ADDED OURXffff mf COOKXSO HfOCEQB 5%54llO'COLL ~ ~ ~ 0 e e e e e ~ e e e ~ I I e E1$1?tiOC4 ~ ~ e e e ~ e ~ e ~ ~ e e ~ e 4 IIe PSOO4QXO ~ ~ ~ e ~ 1 ~ e e e e e ~ 1 ~ ell IIIe EgIXNLX ~ ~ e e ~ e e e e e e e e o eIS Pe BiNlLSt4L ~ e ~ e e... ?g eoc?a |jase %bat ?f ?oeeaL ~ so%isaac?4 aeal e?a ae?be yc eyav?4 Aee tea oil, ?ale@jag aa4 ?a?xa?4ioa m?bat, jb ejLL tahe a hggQg aai?4- 1 Rimless?esa ??4 Ocean Iabsjijoe Xa?ee?jg??jeae ea CO??ea ~, S~. ot Saal. ~ CC, yy. 4~ tLCLV&. 9 Osborne...

  6. 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

    1985-01-01

    H. Chromium Concentration. IS 19 19 19 25 25 26 TABLE OF CONTENTS DISCUSSION. CONCLUSION. REFERENCES. . Page 32 47 50 LIST OF TABLES Page 1. COMPOSITION OF BASAI FIBER-FREE DIET. . . . 2. COMPOSITION OF THE EXPERIMENTAL DIETS. . . 13 3.... COMPOSITION OF WHEAT BRAN AND OAT BRAN SUPPLEMENTS. . 14 4. EFFECT OF FIBER SUPPLEMENTATION ON FOOD AND ENERGY INTAKE 5. EFFECT OF FIBER SUPPLEMENTATION ON WEIGHT GAIN. . 6. EFFECT OF FIBER ON 24-HOUR FECAL DRY WEIGHT. . . . . 20 21 22 7. EFFECT...

  7. The effect of iron chloride and glutamate on glutamine synthetase activity in primary cultured rat cortical astrocytes: a model for epileptic induction 

    E-Print Network [OSTI]

    Roberts, Julie Ann

    1986-01-01

    Phillips, Department of Veterinary Public Health for their valuable suggestions, advice and criticisms of the thesis manuscript and for serving as member s of the Advisory Committee. The author is grateful to Dr. Gerald Bratton, Head, Department... for depolarization and r epolarization of the membrane. A pertubation that disrupts the intricate balance could result in a hypersensitive neuron and the genera- tion of an epileptic focus. The resting membrane potential of a neuron is about -60 mV, while...

  8. Distinct Roles for Glycine and GABA in Shaping the Response Properties of Neurons in the Superior Paraolivary Nucleus of the Rat

    E-Print Network [OSTI]

    inferior colliculus (Kelly et al. 1998; Kulesza Jr and Berrebi 2000; Saldan~a and Berrebi 2000). Ascending

  9. The Journal of Neuroscience, March 1994, 14(3): 1060-l 078 Mossy Fiber Growth and Synaptogenesis in Rat Hippocampal Slices

    E-Print Network [OSTI]

    Dailey, Michael E.

    - cell recordings of MF-driven excitatory postsynaptic cur- rents (50 pA to 1 nA) in pyramidal cells, hippocampus, brain slice, synapsin I, Oil, confocal microscopy, electron microscopy, whole-cell recording

  10. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats

    E-Print Network [OSTI]

    Jaenisch, Rudolf

    Recent advances in deriving induced pluripotent stem (iPS) cells from patients offer new possibilities for biomedical research and clinical applications, as these cells could be used for autologous transplantation. We ...

  11. Alterations in the vimentin cytoskeleton in response to single impact load in an in vitromodel of cartilage damage in the rat

    E-Print Network [OSTI]

    Henson, Frances M D; Vincent, Thea A

    2008-06-24

    articular cartilage: structure and distribution of actin, tubulin, and vimentin fil- aments. J Histochem Cytochem 2000, 48(10):1307-1320. 13. Lee DA, Knight MM, Bolton JF, Idowu BD, Kayser MV, Bader DL: Chondrocyte deformation within compressed agarose con...

  12. A study of histological and histochemical changes in the reproductive organs of male rats fed on riboflavin deficient diets of known concentration 

    E-Print Network [OSTI]

    Zeilinga de Boer, Jelle

    1956-01-01

    ON RIBQFlkVIN DEFICIENT DIETS OF ENONN CONCENTRATION A Theele Jelle de Boer Ayyroved aa to otyle and coateat bye (Chal rmaa the ceaal thee) ( ead of the departeumt Auguet 19/6 l nish to express sy gratitude to Dr. Sidney 0. green, Professor... eliot and acre ln)ected 'pageategaig ?1th hasen ecsscgto ci' i lheflavin varIlaN froa Q to LB @lcrogreas psr dng, lllatilogica1 etadlee cere sado of tho, gate in the flget too oier~? vhego ths rata oars fed a ccatro1 dicta a restricted diet ead a...

  13. What Shall We Do With Corp'rat Fat Cats? Tune of What Shall We Do With a Drunken Sailor? (A minor; start on E)

    E-Print Network [OSTI]

    Nightingale, Peter

    ! What shall we do with Wall Street gamblers? (! 3) Say: "Your gig is up now!" Way-hay, rise up neighbors

  14. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    SciTech Connect (OSTI)

    Park, Eun-Seok [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kang, Shin-il [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Yoo, Kyu-dong [Hazardous Substances Analysis Division, Gwangju Regional Food and Drug Administration, Gwangju (Korea, Republic of); Lee, Mi-Yea [Department of Nursing Kyungbok University, Pocheon (Korea, Republic of); Yoo, Hwan-Soo; Hong, Jin-Tae [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Shin, Hwa-Sup [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, Bokyung [Department of Physiology, Konkuk Medical School, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Yun, Yeo-Pyo, E-mail: ypyun@chungbuk.ac.kr [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2013-04-15

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 ?M and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 ?M ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-?1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ? CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ? CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ? CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ? LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ? Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway.

  15. 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]

    2013-01-01

    article as: Chan et al. : Combustion-derived flame generatedRESEARCH Open Access Combustion-derived flame generated6]. Vehicle exhaust from combustion of gasoline, diesel and

  16. The role of 5-HT_2C receptors in touchscreen visual reversal learning in the rat: a cross-site study

    E-Print Network [OSTI]

    Alsiö, J.; Nilsson, S. R. O.; Gastambide, F.; Wang, R. A. H.; Dam, S. A.; Mar, A. C.; Tricklebank, M.; Robbins, T. W.

    2015-05-26

    , UK 3 Department of Neuroscience, Unit of Functional Neurobiology, University of Uppsala, Uppsala SE-75124, Sweden 4 Lilly Centre for Cognitive Neuroscience, Eli Lilly & Co. Ltd., Erl Wood Manor, Windlesham GU20 6PH, UK Psychopharmacology DOI 10.1007/s... , Georgia, VT, USA) to receive 45 mg sucrose reward pellets (Sandown Scientific, Middlesex, UK). Full details of the pretraining procedure and of the apparatus are provided in the Supplementary Material. 3-Stimulus discrimination and reversal learning For ex...

  17. Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

    E-Print Network [OSTI]

    2010-01-01

    from NIH NS/AG-91-03 (E.G.S. ), NINDS NS 27601 and NIA AGand manuscript drafting. EGS: Designed human hypothalamus/

  18. Remodeling of fiber and laminar architecture of rat heart septum in a transitional normal state between pressure overload hypertrophy and failure 

    E-Print Network [OSTI]

    Hegde, Bharati Krishna

    2009-06-02

    Congestive Heart Failure (CHF) is a major fatal disease today in the United States. The heart's function is a mechanical one. To diagnose and treat CHF effectively there is a need to understand at the microstructural level, the differences...

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

    E-Print Network [OSTI]

    2012-01-01

    inflammatory ef- fects of probiotics in murine experimentalCH, Yeh TF, Oh W. Oral probiotics reduce the incidence andCaplan M, Hammerman C. Oral probiotics prevent necrotizing

  20. The evolution of nuclear microsatellite DNA markers and their flanking regions using reciprocal comparisons within the African mole-rats (Rodentia: Bathyergidae) 

    E-Print Network [OSTI]

    Ingram, Colleen Marie

    2006-10-30

    and molecular data. Using mitochondrial and nuclear DNA, a robust phylogeny was generated for the Bathyergidae. From my results, I proposed the new genus, Coetomys. I designed species-specific genotyping and microsatellite flanking sequence (MFS) primers...