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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 (up)  
  ISSN 0895-7061 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15831367 Approved no  
  Call Number refbase @ user @ Serial 69  
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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 (up)  
  ISSN 1096-6080 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15456926 Approved no  
  Call Number refbase @ user @ Serial 71  
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Author Jeong, S.; Han, M.; Lee, H.; Kim, M.; Kim, J.; Nicol, C.J.; Kim, B.H.; Choi, J.H.; Nam, K.-H.; Oh, G.T.; Yoon, M. openurl 
  Title Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice Type Journal Article
  Year 2004 Publication Metabolism: clinical and experimental Abbreviated Journal Metabolism  
  Volume 53 Issue 10 Pages 1284-1289  
  Keywords Adipose Tissue/*anatomy & histology/drug effects; Animals; Antilipemic Agents/*pharmacology; Body Composition/*drug effects; Body Weight/drug effects; Dietary Fats/*pharmacology; Eating/drug effects; Fatty Acids/metabolism; Female; Gene Expression Regulation/drug effects; Leptin/metabolism; Liver/metabolism; Mice; Mice, Inbred C57BL; Ovariectomy; Procetofen/*pharmacology; RNA, Messenger/biosynthesis/genetics; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism; Transcription Factors/biosynthesis/genetics/metabolism; Weight Gain/*drug effects  
  Abstract Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice.  
  Address Department of Life Sciences, Mokwon University, Taejon, Korea  
  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 (up)  
  ISSN 0026-0495 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15375783 Approved no  
  Call Number refbase @ user @ Serial 72  
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Author Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. doi  openurl
  Title Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide Type Journal Article
  Year 2005 Publication The Journal of pharmacology and experimental therapeutics Abbreviated Journal J Pharmacol Exp Ther  
  Volume 312 Issue 1 Pages 69-76  
  Keywords Animals; Cell Line; Gene Expression/drug effects; Macrophages/drug effects/metabolism; Mice; Mice, Inbred C57BL; Nitric Oxide/*metabolism; Nitric Oxide Synthase/*metabolism; Nitric Oxide Synthase Type II; PPAR delta/metabolism; PPAR gamma/*agonists/deficiency; Thiazolidinediones/pharmacology  
  Abstract Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 microM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 microM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation.  
  Address Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, 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 (up)  
  ISSN 0022-3565 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15356214 Approved no  
  Call Number refbase @ user @ Serial 73  
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Author Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. doi  openurl
  Title PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis Type Journal Article
  Year 2004 Publication Carcinogenesis Abbreviated Journal Carcinogenesis  
  Volume 25 Issue 9 Pages 1747-1755  
  Keywords 9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers  
  Abstract Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis.  
  Address Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 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 (up)  
  ISSN 0143-3334 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15073042 Approved no  
  Call Number refbase @ user @ Serial 76  
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Author Nicol, C.J.; Potzsch, C.; Lewis, K.; Green, L.E. openurl 
  Title Matched concurrent case-control study of risk factors for feather pecking in hens on free-range commercial farms in the UK Type Journal Article
  Year 2003 Publication British poultry science Abbreviated Journal Br Poult Sci  
  Volume 44 Issue 4 Pages 515-523  
  Keywords *Aggression; Analysis of Variance; Animal Husbandry/methods; Animals; Case-Control Studies; Chickens/*physiology; Feathers; Female; Multivariate Analysis; Odds Ratio; Regression Analysis; Species Specificity  
  Abstract 1. The aim of the study was to compare the management and husbandry of free-range flocks in the UK where feather pecking was either present (case) or absent (control). 2. One hundred flocks were enrolled into a concurrent case-control study: 50 where birds had recently started feather pecking, and 50 matched control flocks where birds of the same age had not started feather pecking. 3. Information was obtained from a detailed interview with the flock manager, and by direct inspection of the flock, house and range. 4. Initial univariate analyses revealed that case flocks were more likely to comprise ISA Brown than Lohmann, were more likely to be restricted from litter areas to prevent floor eggs, and were less likely to use the outside range. 5. Cluster analysis indicated that feather pecking was not associated with any particular husbandry system. 6. The only influential risk factor significant in the multivariable conditional logistic regression analysis was use of the outdoor range. The risk of feather pecking was reduced 9-fold in flocks where more than 20% of birds used the range on sunny days (odds ratio = 0.12). Use of the range was positively associated with the presence of trees and/or hedges on the range.  
  Address Department of Clinical Veterinary Science, University of Bristol, England. c.j.nicol@bris.ac.uk  
  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 (up)  
  ISSN 0007-1668 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:14584840 Approved no  
  Call Number refbase @ user @ Serial 79  
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Author Albentosa, M.J.; Kjaer, J.B.; Nicol, C.J. openurl 
  Title Strain and age differences in behaviour, fear response and pecking tendency in laying hens Type Journal Article
  Year 2003 Publication British poultry science Abbreviated Journal Br Poult Sci  
  Volume 44 Issue 3 Pages 333-344  
  Keywords Age Factors; Aggression/*physiology; Animal Husbandry; Animals; *Behavior, Animal; Breeding; Chickens/genetics/*physiology; Fear/*physiology; Feathers/*injuries; Female; Housing, Animal; Population Density; Social Behavior  
  Abstract 1. Behaviours associated with a high or low tendency to feather peck could be used as predictors of feather pecking behaviour in selective breeding programmes. This study investigated how strain and age at testing influenced responses in behavioural tests. 2. Four layer-type strains (ISA Brown, Columbian Blacktail, Ixworth and a high feather pecking (HP) and a low feather pecking (LP) line of White Leghorn) were reared in 6 same-strain/line pens of 8 birds from one day old. Birds in half the pens were given an open field test, a novel object test and a test with loose feather bundles between 4 and 12 weeks of age and a tonic immobility (TI) test at 13 weeks of age. All pens were tested with fixed feather bundles at 26 weeks, and undisturbed behaviour in the home pens was videoed at 1 and 27 weeks of age. Daily records of plumage damage were used as an indicator of feather pecking activity in the home pens. 3. Strain did not influence novel object test, open field test or loose feather test behaviour, although age effects in all three tests indicated a reduction in fearfulness and/or an increase in exploratory behaviour with increasing age. 4. White Leghorns showed longer TI durations than the other strains but less pecking at fixed feather bundles than ISA Browns and Columbian Blacktails. 5. There were few associations between behaviour in the 5 different tests, indicating that birds did not have overall behavioural traits that were consistent across different contexts. This suggests hens cannot easily be categorised into different behavioural 'types', based on their test responses and casts doubt on the usefulness of tests as predictors of feather pecking.  
  Address Centre for Behavioural Biology, Division of Farm Animal Science, University of Bristol, Langford, Bristol, England. MAlbentosa@lincoln.ac.uk  
  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 (up)  
  ISSN 0007-1668 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:13677322 Approved no  
  Call Number refbase @ user @ Serial 80  
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Author Abeyesinghe, S.M.; Nicol, C.J.; Wathes. C.M.; Randall, J.M. doi  openurl
  Title Development of a raceway method to assess aversion of domestic fowl to concurrent stressors Type Journal Article
  Year 2001 Publication Behavioural Processes Abbreviated Journal Behav. Process.  
  Volume 56 Issue 3 Pages 175-194  
  Keywords previous termConcurrent stressors; Aversion; Domestic fowlnext term; Transport; Vibration; Hyperthermia  
  Abstract The requirement for assessing the effects of stressor combinations in improving the welfare of animals has not been widely recognised. Knowledge of the effects of concurrent stressors is needed to improve environments such as transport, where animals are presented with many simultaneous challenges. However, no method for measuring the effects of different stressors with a common unit is currently available. A locomotor passive avoidance method was developed as a common currency measure of the aversion of domestic fowl to concurrent stressors, using vibrational and thermal stressors as an exemplar. Juvenile fowl, fasted overnight, were trained to run a raceway into a goal-box for small food rewards (FR1). When running consistently, the reinforcement schedule was superimposed with a FR5 treatment schedule (60 min confinement in the goal-box with either a control of no other stressors [N] or concurrent vibration and thermal stressors [VT]). Subsequent latency to return to the goal-box was recorded as a measure of aversion. The factors affecting bird response were addressed in a series of experiments to optimise the method and clarify interpretation of results. Pre-feeding (20% ration 2 h prior to testing) did not affect response, but increasing the number of treatment presentations facilitated learning and increased method sensitivity. Treatment responses were consistent across experiments; overall VT was avoided (P<0.001), but N was not. However, there was large individual variation in response to VT. A final experiment indicated that, given a visual discriminatory cue, birds were capable of learning the required association between entering the goal-box and receiving the treatment, suggesting that the delay responses were due to aversion rather than the immediate impact of treatment on ability to respond. Further work is required to test the singular stressors, but the method retains common currency potential for assessing aversion to multiple stressors.  
  Address Bio-Engineering Division, Silsoe Research Institute, Wrest Park, Silsoe, MK45 4HS, Bedford, UK  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN 0376-6357 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:11738510 Approved no  
  Call Number refbase @ user @ Serial 85  
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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  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition (up)  
  ISSN 1467-2987 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:17238962 Approved no  
  Call Number refbase @ user @ Serial 92  
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Author Spadavecchia, C.; Arendt-Nielsen, L.; Andersen, O.K.; Spadavecchia, L.; Doherr, M.; Schatzmann, U. openurl 
  Title Comparison of nociceptive withdrawal reflexes and recruitment curves between the forelimbs and hind limbs in conscious horses Type Journal Article
  Year 2003 Publication American journal of veterinary research Abbreviated Journal Am J Vet Res  
  Volume 64 Issue 6 Pages 700-707  
  Keywords Animals; Consciousness; Female; Forelimb/*physiology; Hindlimb/*physiology; Horses/*physiology; Male; Nociceptors/physiology; Pain/*physiopathology/*veterinary; Pain Threshold/physiology; Recruitment, Neurophysiological/physiology; Reflex/*physiology  
  Abstract OBJECTIVE: To compare nociceptive withdrawal reflexes (NWRs) evoked from the distal aspect of the left forelimb and hind limb in conscious standing horses and to investigate NWR recruitment for graded electrical stimulation intensities. ANIMALS: 20 adult horses. PROCEDURE: Surface electromyographic (EMG) activity evoked by transcutaneous electrical stimulation of the digital palmar (or plantar) nerve was recorded from the common digital extensor and cranial tibial muscles. Stimuli consisted of 25-millisecond train-of-5 constant current pulses. Current intensity was gradually increased until NWR threshold intensity was reached. The EMG signal was analyzed for quantification of the NWR. Behavioral responses accompanying the reflex were scored (scale, 0 to 5). The NWR recruitment curves were determined at 0.9, 1.1, 1.2, and 1.3 times the NWR threshold intensity. RESULTS: The NWR threshold was significantly higher for the hind limb (median value, 6.6 mA; range, 3 to 10 mA) than the forelimb (median, 3 mA; range, 1.7 to 5.5 mA). The NWR of the hind limb had a significantly longer latency (median, 122.8 milliseconds; range, 106 to 172 milliseconds), compared with the forelimb (median, 98 milliseconds; range, 86 to 137 milliseconds), and it was associated with significantly stronger behavioral reactions. Gradual increase of NWR amplitude was evident at increasing stimulation intensities and supported by the behavioral observations. CONCLUSIONS AND CLINICAL RELEVANCE: We documented NWRs evoked from the forelimb and hind limb and their recruitment with stimuli of increasing intensity in horses. These results provide a basis for use of NWRs in studies on nociceptive modulation in horses.  
  Address Department of Clinical Veterinary Sciences, University of Berne, Switzerland  
  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 (up)  
  ISSN 0002-9645 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:12828255 Approved no  
  Call Number refbase @ user @ Serial 93  
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