toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author Lyda, R.O.; Hall, J.R.; Kirkpatrick, J.F. openurl 
  Title A comparison of Freund's Complete and Freund's Modified Adjuvants used with a contraceptive vaccine in wild horses (Equus caballus) Type Journal Article
  Year 2005 Publication Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians Abbreviated Journal J Zoo Wildl Med  
  Volume 36 Issue 4 Pages 610-616  
  Keywords Animals; Antibody Formation; Contraception, Immunologic/*veterinary; Estrus/drug effects; Female; Freund's Adjuvant/administration & dosage/adverse effects/*immunology; Horses/immunology/*physiology; *Vaccines, Contraceptive; Zona Pellucida/*immunology  
  Abstract Fifteen captive wild mares (Equus caballus) were treated with porcine zona pellucida contraceptive vaccine and either Freund's Complete Adjuvant (n = 7) or Freund's Modified Adjuvant (n = 8). All mares received a booster inoculation of porcine zona pellucida plus Freund's Incomplete Adjuvant a month later. Anti-porcine zona pellucida antibodies were measured over 10 mo following the initial inoculation. There were no significant differences in antibody titers at any point during the 10 mo, and seven of the eight mares in the Freund's Modified Adjuvant group were above the 60% level at the end of the study, which is considered to be the contraceptive threshold for horses. There were no significant differences in titers between pregnant and nonpregnant horses, nor was there a significant correlation between age and titers. One local injection site reaction occurred after booster treatment with Freund's Incomplete Adjuvant, and 11 healthy foals were born during the course of the study. These data suggest that Freund's Modified Adjuvant is an acceptable substitute for Freund's Complete Adjuvant in certain free-ranging and captive wildlife species.  
  Address Science and Conservation Center, 2100 South Shiloh Road, Billings, Montana 59106, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1042-7260 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:17312717 Approved no  
  Call Number refbase @ user @ Serial 139  
Permanent link to this record
 

 
Author Elhay, M.; Newbold, A.; Britton, A.; Turley, P.; Dowsett, K.; Walker, J. doi  openurl
  Title Suppression of behavioural and physiological oestrus in the mare by vaccination against GnRH Type Journal Article
  Year 2007 Publication Australian Veterinary Journal Abbreviated Journal Aust Vet J  
  Volume 85 Issue 1-2 Pages 39-45  
  Keywords Animals; Antibodies/blood; Estradiol/blood; *Estrus/drug effects/physiology; Female; Gonadotropin-Releasing Hormone/*immunology/*pharmacology; Horses/*physiology; Luteinizing Hormone/blood; Ovulation/*drug effects/physiology; Progesterone/blood; Safety; Sexual Behavior, Animal/drug effects/physiology; Time Factors; Vaccination/veterinary  
  Abstract OBJECTIVE: To examine the immunogenicity of an equine immunocontraceptive vaccine and its efficacy in controlling hormone-related behaviour. DESIGN: A total of 24 mares at two sites in Australia were vaccinated with an immunocontraceptive vaccine comprising gonadotrophin releasing hormone (GnRH) conjugated to a carrier protein in immunostimulating complex as an adjuvant. Twelve animals at each site received a placebo of adjuvant alone and served as controls for seasonal oestrus, hormonal and behaviour patterns. Animals were observed for injection site reactions, ovarian and follicular activity, and serum levels of antibody, 17beta-oestradiol and progesterone in the weeks following vaccination. Mares were also examined for oestrous behaviour by teasing with a stallion. RESULTS: All mares responded to vaccination. Two weeks following the second vaccination there was a peak in antibody response to GnRH that declined gradually over the following weeks. Commensurate with the elevated anti-GnRH antibody there was a marked effect on ovarian activity with a reduction in 17beta-oestradiol and progesterone levels in the 24 vaccinated mares. There was also a reduction of oestrus-related behaviour as determined by a teaser stallion. This effect lasted a minimum of 3 months and correlated with the initial level of antibody response. CONCLUSION: Following a conventional two-dose immunisation regime this commercially available equine immunocontraceptive vaccine was effective at inhibiting oestrous behaviour for at least 3 months. This vaccine has a high level of safety since there were no significant local reactions nor were there any adverse systemic responses to vaccination.  
  Address Veterinary Medicines Research and Development, Pfizer Animal Health, Parkville, VIC 3052. Martin.Elhay@pfizer.com  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0005-0423 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:17300452 Approved no  
  Call Number Serial 1831  
Permanent link to this record
 

 
Author Spadavecchia, C.; Arendt-Nielsen, L.; Spadavecchia, L.; Mosing, M.; Auer, U.; van den Hoven, R. doi  openurl
  Title Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses Type Journal Article
  Year 2007 Publication Veterinary anaesthesia and analgesia Abbreviated Journal Vet Anaesth Analg  
  Volume 34 Issue 1 Pages 48-58  
  Keywords Analgesics, Opioid/pharmacology; Animals; Butorphanol/*pharmacology; Consciousness; Electric Stimulation; Electromyography; Female; Forelimb/physiology; Horses/*physiology; Male; Pain/veterinary; Pain Threshold/*drug effects; Reflex/*drug effects  
  Abstract OBJECTIVE: To assess the effects of a single intravenous dose of butorphanol (0.1 mg kg(-1)) on the nociceptive withdrawal reflex (NWR) using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. STUDY DESIGN: 'Unblinded', prospective experimental study. ANIMALS: Ten adult horses, five geldings and five mares, mean body mass 517 kg (range 487-569 kg). METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the palmar digital nerve. Repeated stimulations were applied to evoke temporal summation. Surface electromyography was performed to record and quantify the responses of the common digital extensor muscle to stimulation and behavioural reactions were scored. Before butorphanol administration and at fixed time points up to 2 hours after injection, baseline threshold intensities for NWR and temporal summation were defined and single suprathreshold stimulations applied. Friedman repeated-measures analysis of variance on ranks and Wilcoxon signed-rank test were used with the Student-Newman-Keul's method applied post-hoc. The level of significance (alpha) was set at 0.05. RESULTS: Butorphanol did not modify either the thresholds for NWR and temporal summation or the reaction scores, but the difference between suprathreshold and threshold reflex amplitudes was reduced when single stimulation was applied. Upon repeated stimulation after butorphanol administration, a significant decrease in the relative amplitude was calculated for both the 30-80 and the 80-200 millisecond intervals after each stimulus, and for the whole post-stimulation interval in the right thoracic limb. In the left thoracic limb a decrease in the relative amplitude was found only in the 30-80 millisecond epoch. CONCLUSION: Butorphanol at 0.1 mg kg(-1) has no direct action on spinal Adelta nociceptive activity but may have some supraspinal effects that reduce the gain of the nociceptive system. CLINICAL RELEVANCE: Butorphanol has minimal effect on sharp immediate Adelta-mediated pain but may alter spinal processing and decrease the delayed sensations of pain.  
  Address Anesthesiology Section, Department of Clinical Veterinary Sciences, Vetsuisse Faculty, University of Berne, Berne, Switzerland. claudia.spadavecchia@veths.no  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1467-2987 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:17238962 Approved no  
  Call Number refbase @ user @ Serial 92  
Permanent link to this record
 

 
Author Turner, K.K.; Nielsen, B.D.; O'Connor, C.I.; Burton, J.L. doi  openurl
  Title Bee pollen product supplementation to horses in training seems to improve feed intake: A pilot study Type Journal Article
  Year 2006 Publication Journal of Animal Physiology and Animal Nutrition Abbreviated Journal J Anim Physiol Anim Nutr (Berl)  
  Volume 90 Issue 9-10 Pages 414-420  
  Keywords *Animal Nutrition Physiology; Animals; Antibody Formation; Bees; Detergents; Dietary Fiber/metabolism; Dietary Supplements; *Digestion; Eating/*drug effects; Exercise Test/veterinary; Female; Heart Rate/drug effects/physiology; Horses/blood/immunology/*physiology; Leukocyte Count/*veterinary; Male; Oxygen Consumption/drug effects/physiology; Physical Conditioning, Animal/*physiology; Pilot Projects; *Pollen; Random Allocation  
  Abstract The objective of this study was to determine the efficacy of supplementation of Dynamic Trio 50/50, a bee pollen-based product, to improve physical fitness, blood leukocyte profiles, and nutritional variables in exercised horses. Ten Arabian horses underwent a standardised exercise test (SET), then were pair-matched by sex and fitness and randomly assigned to BP (receiving 118 g of Dynamic Trio 50/50 daily) or CO (receiving 73 g of a placebo) for a period of 42 days. A total collection was conducted from days 18 to 21 on six geldings to determine nutrient retention and neutral detergent fibre (NDF) and acid detergent fibre (ADF) digestibility. Horses were exercise conditioned and completed another SET on day 42. V160 and V200 were calculated from SET heart rates (HR). Lactate, glucose, haematocrit (HT) and haemoglobin (HB) concentrations were determined from SET blood samples. Total leukocyte count, and circulating numbers of various leukocytes and IgG, IgM and IgA concentrations were determined in rest and recovery blood samples from both SETs. Geldings on BP (n = 3) ate more feed than CO. BP had less phosphorus excretion, and tended to retain more nitrogen. BP tended to digest more NDF and ADF while having lower NDF digestibility and tending to have lower ADF digestibility. No treatment differences existed for V160 and V200, HR, lactate, HT and HB. There was a trend for lymphocyte counts to be lower in BP than CO on day 42. Dynamic Trio 50/50 supplementation may have a positive effect on performance by helping horses in training meet their potentially increased nutrient demands by increasing feed intake and thus nutrient retention.  
  Address Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA. kturner@uga.edu  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0931-2439 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:16958799 Approved no  
  Call Number Equine Behaviour @ team @ Serial 4237  
Permanent link to this record
 

 
Author Hubbell, J.A.E.; Muir, W.W. openurl 
  Title Antagonism of detomidine sedation in the horse using intravenous tolazoline or atipamezole Type Journal Article
  Year 2006 Publication Equine Veterinary Journal Abbreviated Journal Equine Vet J  
  Volume 38 Issue 3 Pages 238-241  
  Keywords Animals; Behavior, Animal/drug effects/physiology; Dose-Response Relationship, Drug; Double-Blind Method; Horses/*physiology; Hypnotics and Sedatives/*antagonists & inhibitors; Imidazoles/*antagonists & inhibitors/*pharmacology; Infusions, Intravenous/veterinary; Kinetics; Safety; Tolazoline/*pharmacology; Videotape Recording  
  Abstract REASONS FOR PERFORMING STUDY: The ability to shorten the duration of sedation would potentially improve safety and utility of detomidine. OBJECTIVES: To determine the effects of tolazoline and atipamezole after detomidine sedation. HYPOTHESIS: Administration of tolazoline or atipamezole would not affect detomidine sedation. METHODS: In a randomised, placebo-controlled, double-blind, descriptive study, detomidine (0.02 mg/kg bwt i.v.) was administered to 6 mature horses on 4 separate occasions. Twenty-five mins later, each horse received one of 4 treatments: Group 1 saline (0.9% i.v.) as a placebo control; Group 2 atipamezole (0.05 mg/kg bwt i.v.); Group 3 atipamezole (0.1 mg/kg bwt i.v.); and Group 4 tolazoline (4.0 mg/kg bwt i.v.). Sedation, muscle relaxation and ataxia were scored by 3 independent observers at 9 time points. Horses were led through an obstacle course at 7 time points. Course completion time was recorded and the ability of the horse to traverse the course was scored by 3 independent observers. Horses were videotaped before, during and after each trip through the obstacle course. RESULTS: Atipamezole and tolazoline administration incompletely antagonised the effects of detomidine, but the time course to recovery was shortened. CONCLUSIONS AND POTENTIAL RELEVANCE: Single bolus administration of atipamezole or tolazoline produced partial reversal of detomidine sedation and may be useful for minimising detomidine sedation.  
  Address Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, 601 Tharp Street, Columbus, Ohio 43210, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0425-1644 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:16706278 Approved no  
  Call Number Serial 1869  
Permanent link to this record
 

 
Author Heistermann, M.; Palme, R.; Ganswindt, A. doi  openurl
  Title Comparison of different enzyme-immunoassays for assessment of adrenocortical activity in primates based on fecal analysis Type Journal Article
  Year 2006 Publication American journal of primatology Abbreviated Journal Am. J. Primatol.  
  Volume 68 Issue 3 Pages 257-273  
  Keywords 11-Hydroxycorticosteroids/*analysis; Adrenocorticotropic Hormone/pharmacology; Anesthesia; Animals; Corticosterone/analysis; Feces/*chemistry; Glucocorticoids/*analysis; Haplorhini/*metabolism; Hydrocortisone/analysis; Hypothalamo-Hypophyseal System/drug effects/physiology; Immunoenzyme Techniques/*methods; Pituitary-Adrenal System/drug effects/physiology; Species Specificity  
  Abstract Most studies published to date that used fecal glucocorticoid measurements to assess adrenocortical activity in primate (and many nonprimate) species applied a specific cortisol or corticosterone assay. However, since these native glucocorticoids are virtually absent in the feces of most vertebrates, including primates, the validity of this approach has recently been questioned. Therefore, the overall aim of the present study was to assess the validity of four enzyme-immunoassays (EIAs) using antibodies raised against cortisol, corticosterone, and reduced cortisol metabolites (two group-specific antibodies) for assessing adrenocortical activity using fecal glucocorticoid metabolite (GCM) measurements in selected primate species (marmoset, long-tailed macaque, Barbary macaque, chimpanzee, and gorilla). Using physiological stimulation of the hypothalamo-pituitary-adrenocortical (HPA) axis by administering exogenous ACTH or anesthesia, we demonstrated that at least two assays detected the predicted increase in fecal GCM levels in response to treatment in each species. However, the magnitude of response varied between assays and species, and no one assay was applicable to all species. While the corticosterone assay generally was of only limited suitability for assessing glucocorticoid output, the specific cortisol assay was valuable for those species that (according to high-performance liquid chromatography (HPLC) analysis data) excreted clearly detectable amounts of authentic cortisol into the feces. In contrast, in species in which cortisol was virtually absent in the feces, group-specific assays provided a much stronger signal, and these assays also performed well in the other primate species tested (except the marmoset). Collectively, the data suggest that the reliability of a given fecal glucocorticoid assay in reflecting activity of the HPA axis in primates clearly depends on the species in question. Although to date there is no single assay system that can be used successfully across species, our data suggest that group-specific assays have a high potential for cross-species application. Nevertheless, regardless of which GC antibody is chosen, our study clearly reinforces the necessity of appropriately validating the respective assay system before it is used.  
  Address Department of Reproductive Biology, German Primate Center, Gottingen, Germany. mheiste@gwdg.de  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0275-2565 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:16477600 Approved no  
  Call Number Equine Behaviour @ team @ Serial 4078  
Permanent link to this record
 

 
Author Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. doi  openurl
  Title PPARgamma in endothelial cells influences high fat diet-induced hypertension Type Journal Article
  Year 2005 Publication American journal of hypertension : journal of the American Society of Hypertension Abbreviated Journal Am J Hypertens  
  Volume 18 Issue 4 Pt 1 Pages 549-556  
  Keywords Administration, Oral; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Diabetes Mellitus, Type 2/physiopathology; Dietary Fats/*administration & dosage/pharmacology; Dose-Response Relationship, Drug; Endothelial Cells/*metabolism; Female; Heart Rate/drug effects; Hypertension/*etiology; Ligands; Male; Mice; Mice, Knockout; PPAR gamma/*metabolism; Sodium Chloride/administration & dosage/pharmacology; Thiazolidinediones/pharmacology  
  Abstract BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.  
  Address Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0895-7061 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:15831367 Approved no  
  Call Number refbase @ user @ Serial 69  
Permanent link to this record
 

 
Author Hodgson, D.; Howe, S.; Jeffcott, L.; Reid, S.; Mellor, D.; Higgins, A. doi  openurl
  Title Effect of prolonged use of altrenogest on behaviour in mares Type
  Year 2005 Publication Veterinary journal (London, England : 1997) Abbreviated Journal Vet J  
  Volume 169 Issue 1 Pages 113-115  
  Keywords Administration, Oral; Anabolic Agents/adverse effects/*pharmacology; Animals; Behavior, Animal/*drug effects; Body Constitution/drug effects; Body Weight/drug effects; *Doping in Sports; Female; Horses/*physiology; Social Behavior; Social Dominance; Time Factors; Trenbolone/adverse effects/*analogs & derivatives/*pharmacology  
  Abstract Erratum in:

Vet J. 2005 May;169(3):321.

Corrected and republished in:

Vet J. 2005 May;169(3):322-5.

Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. We concluded that prolonged oral administration of altrenogest at recommended dose rates to sedentary mares resulted in no effect on dominance hierarchies, body mass or condition score.
 
  Address Faculty of Veterinary Science, University of Sydney, Private Mailbag 4, Narellan Delivery Centre, Narellan, NSW 2567, Australia. davidh@camden.usyd.edu.au  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1090-0233 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:15683772 Approved no  
  Call Number refbase @ user @ Serial 671  
Permanent link to this record
 

 
Author Dargatz, D.A.; Traub-Dargatz, J.L. doi  openurl
  Title Multidrug-resistant Salmonella and nosocomial infections Type Journal Article
  Year 2004 Publication The Veterinary Clinics of North America. Equine Practice Abbreviated Journal Vet Clin North Am Equine Pract  
  Volume 20 Issue 3 Pages 587-600  
  Keywords Animals; Anti-Bacterial Agents/*pharmacology; Cross Infection/prevention & control/*veterinary; Disease Outbreaks/prevention & control/veterinary; Drug Resistance, Bacterial; *Drug Resistance, Multiple, Bacterial; Horse Diseases/*drug therapy/transmission; Horses; Infection Control/methods; Microbial Sensitivity Tests/veterinary; Salmonella/*drug effects; Salmonella Infections, Animal/*drug therapy/transmission  
  Abstract Nosocomial infections are a serious threat to optimum patient care. In addition, nosocomial infections can have far-reaching consequences for the hospital personnel and the financial aspects of the hospital. Nosocomial infections with Salmonella spp have been described among hospitalized equine populations more frequently than any other agent. Salmonella spp associated with hospitalized equids often possess more antimicrobial resistance determinants than do Salmonella spp isolated from healthy horses in the general population. There is little evidence to suggest that resistant salmonellae are more virulent than nonresistant forms. MDR forms of Salmonella complicate the selection of appropriate antimicrobials when they are indicated, however. Furthermore, the use of some antimicrobials may apply selection pressure toward enhanced ability of MDR Salmonella to colonize equine patients. Further research should help to elucidate the risky uses of antimicrobials in the hospital setting and define the role of disinfectants and treatments such as NSAIDs in the ecology of MDR forms of nosocomial infections, including Salmonella. In the meantime, thoughtful selection of when and how to use antimicrobials in equine patients, together with deliberate selection of which antimicrobials to use based on monitoring data and other factors, such as safety and spectrum, is advised.  
  Address Animal and Plant Health Inspection Service, Veterinary Services, Centers for Epidemiology and Animal Health, United States Department of Agriculture, 2150 Centre Avenue, Building MS 2E7, Fort Collins, CO 80521, USA. david.a.dargatz@aphis.usda.gov  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0749-0739 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:15519820 Approved no  
  Call Number Equine Behaviour @ team @ Serial 2632  
Permanent link to this record
 

 
Author Guo, G.L.; Moffit, J.S.; Nicol, C.J.; Ward, J.M.; Aleksunes, L.A.; Slitt, A.L.; Kliewer, S.A.; Manautou, J.E.; Gonzalez, F.J. doi  openurl
  Title Enhanced acetaminophen toxicity by activation of the pregnane X receptor Type Journal Article
  Year 2004 Publication Toxicological sciences : an official journal of the Society of Toxicology Abbreviated Journal Toxicol Sci  
  Volume 82 Issue 2 Pages 374-380  
  Keywords Acetaminophen/pharmacokinetics/*toxicity; Analgesics, Non-Narcotic/pharmacokinetics/*toxicity; Animals; Aryl Hydrocarbon Hydroxylases/biosynthesis; Biotransformation; Blotting, Northern; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Membrane Proteins; Mice; Mice, Knockout; Oxidoreductases, N-Demethylating/biosynthesis; Pregnenolone Carbonitrile/pharmacology; Receptors, Cytoplasmic and Nuclear/*drug effects; Receptors, Steroid/*drug effects; Sulfhydryl Compounds/metabolism  
  Abstract The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation.  
  Address Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1096-6080 ISBN Medium  
  Area Expedition Conference  
  Notes (down) PMID:15456926 Approved no  
  Call Number refbase @ user @ Serial 71  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print