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Author |
Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. |
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Title |
PPARgamma in endothelial cells influences high fat diet-induced hypertension |
Type |
Journal Article |
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Year |
2005 |
Publication |
American journal of hypertension : journal of the American Society of Hypertension |
Abbreviated Journal |
Am J Hypertens |
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Volume |
18 |
Issue |
4 Pt 1 |
Pages |
549-556 |
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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 |
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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. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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0895-7061 |
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PMID:15831367 |
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Call Number |
refbase @ user @ |
Serial |
69 |
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Author |
Rietmann, T.R.; Stauffacher, M.; Bernasconi, P.; Auer, J.A.; Weishaupt, M.A. |
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Title |
The association between heart rate, heart rate variability, endocrine and behavioural pain measures in horses suffering from laminitis |
Type |
Journal Article |
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Year |
2004 |
Publication |
Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine |
Abbreviated Journal |
J Vet Med A Physiol Pathol Clin Med |
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Volume |
51 |
Issue |
5 |
Pages |
218-225 |
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Keywords |
Animals; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage; Autonomic Nervous System; Behavior, Animal; Electrophysiology/*methods; Endocrine System; Female; Heart Rate; Horse Diseases/blood/drug therapy/*physiopathology; Horses; Joint Diseases/physiopathology/*veterinary; Male; Pain/physiopathology/*veterinary; Pain Measurement/*veterinary; Predictive Value of Tests |
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The objective of this study was to compare the stress response of horses suffering from laminitis after short- and long-term treatment with the intent to evaluate power spectral analysis of heart rate variability (HRV) for pain monitoring. Data were collected from 19 horses with acute or chronic exacerbating laminitis without known primary disease before and after treatment with non-steroidal anti-inflammatory drugs (NSAID). Recordings were carried out the day after admission to the equine hospital. Measurements were repeated on day 7 of the treatment. The recorded parameters included a clinical orthopaedic index (OLPI: Obel-grade plus hoof tester score), frequency of weight-shifting between contralateral limbs, mean beat-to-beat interval (R-R) duration, standard deviation of continuous R-R intervals, low- (LF) and high-frequency (HF) components of HRV, sympatho-vagal balance (LF/HF), and plasma concentration of cortisol, adrenalin and noradrenalin. The LF represents mainly sympathetic influences on the heart whereas HF is mediated by the parasympathetic tone. Weight-shifting and OLPI decreased significantly with treatment. The LF normalized units (n.u.) decreased after NSAID from 60.41 +/- 21.42 to 51.12 +/- 19.81 and was 49.33 +/- 22.64 on day 7, whereas HF n.u. increased from 35.07 +/- 20.02 to 43.14 +/- 18.30 and was 45.98 +/- 23.00 on day 7. Hormone levels showed no tendency to change with treatment. The OLPI was only correlated with LF/HF, LF and HF (R = 0.57, 0.55 and -0.54 respectively). Significant negative correlations existed between HFn.u. and weight-shifting frequency (R = -0.37), HFn.u. and adrenalin (R = -0.47), and HFn.u. and noradrenalin (R = 0.33). The LFn.u. only correlated positively with adrenalin. Cortisol levels were poorly associated with the other parameters. Determination of the sympatho-vagal influences on cardiac function may offer complementary information for reliable assessment of pain and may represent a valuable alternative method to catecholamine measurements. |
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Equine Hospital, Faculty of Veterinary Medicine, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland |
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0931-184X |
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PMID:15315700 |
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Serial |
1899 |
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Author |
Turner, K.K.; Nielsen, B.D.; O'Connor, C.I.; Burton, J.L. |
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Title |
Bee pollen product supplementation to horses in training seems to improve feed intake: A pilot study |
Type |
Journal Article |
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Year |
2006 |
Publication |
Journal of Animal Physiology and Animal Nutrition |
Abbreviated Journal |
J Anim Physiol Anim Nutr (Berl) |
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Volume |
90 |
Issue |
9-10 |
Pages |
414-420 |
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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 |
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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. |
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Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA. kturner@uga.edu |
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0931-2439 |
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PMID:16958799 |
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Call Number |
Equine Behaviour @ team @ |
Serial |
4237 |
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Author |
Lyda, R.O.; Hall, J.R.; Kirkpatrick, J.F. |
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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 |
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Year |
2005 |
Publication |
Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians |
Abbreviated Journal |
J Zoo Wildl Med |
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Volume |
36 |
Issue |
4 |
Pages |
610-616 |
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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 |
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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. |
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Science and Conservation Center, 2100 South Shiloh Road, Billings, Montana 59106, USA |
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1042-7260 |
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PMID:17312717 |
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refbase @ user @ |
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139 |
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Author |
Zehnder, A.M.; Ramer, J.C.; Proudfoot, J.S. |
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Title |
The use of altrenogest to control aggression in a male Grant's Zebra (Equus burchelli boehmi) |
Type |
Journal Article |
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Year |
2006 |
Publication |
Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians |
Abbreviated Journal |
J Zoo Wildl Med |
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Volume |
37 |
Issue |
1 |
Pages |
61-63 |
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Keywords |
Aggression/*drug effects; Animals; Animals, Zoo; Behavior, Animal/*drug effects; Dose-Response Relationship, Drug; Equidae/*physiology; Female; Horses; Male; Treatment Outcome; Trenbolone/*analogs & derivatives/therapeutic use |
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Abstract |
A male Grant's Zebra (Equus burchelli boehmi) housed with two mares at the Indianapolis Zoo had a 9-yr history of intermittent aggressive behavior toward mares and other animals. Periods of separation allowed the mares time to heal after sustaining superficial bite wounds. On 26 March 2003, the male (890293) was started on altrenogest at a dosage of 19.8 mg orally once daily to allow reintroduction. The dosage was doubled (40 mg once a day) because of a perceived lack of response. Reintroduction to the mares occurred on 17 May 2003 with no signs of aggression noted. Treatment was reduced to 19.8 mg orally once a day and then discontinued. Altrenogest was restarted at 39.5 mg orally once a day because of the planned introduction of a new mare. There have been no major aggressive displays at this dosage of altrenogest and the dosage has recently been reduced following successful introduction of a new mare. |
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University of Florida, 2015 SW 16th Street, Gainesville, Florida 32610, USA |
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1042-7260 |
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PMID:17312816 |
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1772 |
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Author |
Hodgson, D.; Howe, S.; Jeffcott, L.; Reid, S.; Mellor, D.; Higgins, A. |
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Title |
Effect of prolonged use of altrenogest on behaviour in mares |
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2005 |
Publication |
Veterinary journal (London, England : 1997) |
Abbreviated Journal |
Vet J |
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169 |
Issue |
1 |
Pages |
113-115 |
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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 |
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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. |
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Faculty of Veterinary Science, University of Sydney, Private Mailbag 4, Narellan Delivery Centre, Narellan, NSW 2567, Australia. davidh@camden.usyd.edu.au |
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ISSN |
1090-0233 |
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PMID:15683772 |
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Call Number |
refbase @ user @ |
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671 |
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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. |
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Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
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Journal Article |
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Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
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Volume |
82 |
Issue |
2 |
Pages |
374-380 |
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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 |
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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. |
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Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA |
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1096-6080 |
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PMID:15456926 |
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Call Number |
refbase @ user @ |
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71 |
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Yamazaki, Y.; Shinohara, N.; Watanabe, S. |
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Visual discrimination of normal and drug induced behavior in quails (Coturnix coturnix japonica) |
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Journal Article |
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2004 |
Publication |
Animal Cognition |
Abbreviated Journal |
Anim. Cogn. |
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7 |
Issue |
2 |
Pages |
128-132 |
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Animals; Behavior, Animal/*drug effects; Classification; Coturnix/*physiology; *Discrimination Learning; *Generalization (Psychology); Ketamine/pharmacology; Male; Methamphetamine/pharmacology; *Pattern Recognition, Visual; Video Recording; Visual Perception |
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The ability to discriminate the physical states of others could be an adaptive behavior, especially for social animals. For example, the ability to discriminate illness behavior would be helpful for avoiding spoiled foods. We report on an experiment with Japanese quails testing whether these birds can discriminate the physical states of conspecifics. The quails were trained to discriminate between moving video images of quails injected with psychoactive drugs and those in a normal (not injected) condition. Methamphetamine (stimulant) or ketamine (anesthetic) were used to produce drug-induced behaviors in conspecifics. The former induced hyperactive behavior and the latter hypoactive behavior. The subject quails could learn the discrimination and showed generalization to novel images of the drug-induced behaviors. They did not, however, show discriminative behavior according to the type and dosage of the drugs. Thus, they categorized the behavior not on the basis of degree of activity, but on the basis of abnormality. |
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Biopsychologie, Institut fur Kognitive Neurowissenschaft, Fakultat fur Psychologie, Ruhr-Universitat Bochum, 44780 Bochum, Germany. yumyam@bio.psy.ruhr-uni-bochum.de |
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1435-9448 |
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PMID:15069613 |
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Equine Behaviour @ team @ |
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2527 |
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Author |
Spadavecchia, C.; Arendt-Nielsen, L.; Spadavecchia, L.; Mosing, M.; Auer, U.; van den Hoven, R. |
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Title |
Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses |
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Journal Article |
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Year |
2007 |
Publication |
Veterinary anaesthesia and analgesia |
Abbreviated Journal |
Vet Anaesth Analg |
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34 |
Issue |
1 |
Pages |
48-58 |
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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 |
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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. |
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Anesthesiology Section, Department of Clinical Veterinary Sciences, Vetsuisse Faculty, University of Berne, Berne, Switzerland. claudia.spadavecchia@veths.no |
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1467-2987 |
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PMID:17238962 |
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refbase @ user @ |
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92 |
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Author |
Dirikolu, L.; Lehner, A.F.; Karpiesiuk, W.; Hughes, C.; Woods, W.E.; Boyles, J.; Harkins, J.D.; Troppmann, A.; Tobin, T. |
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Title |
Detection, quantification, metabolism, and behavioral effects of selegiline in horses |
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Journal Article |
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2003 |
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Veterinary Therapeutics : Research in Applied Veterinary Medicine |
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Vet Ther |
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4 |
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3 |
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257-268 |
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Administration, Oral; Animals; Behavior, Animal/drug effects; Female; Horses/*metabolism; Mass Spectrometry/veterinary; Monoamine Oxidase Inhibitors/administration & dosage/blood/*pharmacokinetics/pharmacology/urine; Selegiline/administration & dosage/blood/*pharmacokinetics/pharmacology/urine; Substance Abuse Detection/veterinary |
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Abstract |
Selegiline ([R]-[-]N,alpha-dimethyl-N-2- propynylphenethylamine or l-deprenyl), an irreversible inhibitor of monoamine oxidase, is a classic antidyskinetic and antiparkinsonian agent widely used in human medicine both as monotherapy and as an adjunct to levodopa therapy. Selegiline is classified by the Association of Racing Commissioners International (ARCI) as a class 2 agent, and is considered to have high abuse potential in racing horses. A highly sensitive LC/MS/MS quantitative analytical method has been developed for selegiline and its potential metabolites amphetamine and methamphetamine using commercially available deuterated analogs of these compounds as internal standards. After administering 40 mg of selegiline orally to two horses, relatively low (<60 ng/ml) concentrations of parent selegiline, amphetamine, and methamphetamine were recovered in urine samples. However, relatively high urinary concentrations of another selegiline metabolite were found, tentatively identified as N- desmethylselegiline. This metabolite was synthesized and found to be indistinguishable from the new metabolite recovered from horse urine, thereby confirming the chemical identity of the equine metabolite. Additionally, analysis of urine samples from four horses dosed with 50 mg of selegiline confirmed that N-desmethylselegiline is the major urinary metabolite of selegiline in horses. In related behavior studies, p.o. and i.v. administration of 30 mg of selegiline produced no significant changes in either locomotor activities or heart rates. |
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Department of Biomedical Sciences, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA |
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1528-3593 |
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PMID:15136987 |
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1901 |
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