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Author |
Dyson, S.; Murray, R. |
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Title |
Pain associated with the sacroiliac joint region: a clinical study of 74 horses |
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Journal Article |
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Year  |
2003 |
Publication |
Equine Veterinary Journal |
Abbreviated Journal |
Equine Vet J |
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Volume |
35 |
Issue |
3 |
Pages |
240-245 |
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Keywords |
Age Factors; Analgesia/veterinary; Anesthetics, Local/pharmacology; Animals; Body Height; Body Weight; Breeding; Female; Forelimb; Gait; Hindlimb; Horse Diseases/*diagnosis/radionuclide imaging; Horses; Lameness, Animal/*physiopathology; Lumbar Vertebrae/physiopathology; Male; Pain/diagnosis/drug therapy/radionuclide imaging/*veterinary; Sacroiliac Joint/*physiopathology; Sacrum/physiopathology |
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Abstract |
REASONS FOR PERFORMING STUDY: There has been no large study of horses with suspected sacroiliac (SI) joint region pain in which the clinical diagnosis has been supported by either abnormal radiopharmaceutical activity in the SI joint region or by periarticular infiltration of local anaesthetic solution. OBJECTIVES: To describe the clinical features of horses with SI joint region pain, to document the age, breed, sex, discipline, size and conformation of affected horses and to compare these with the author's (SD) normal case population and to document the results of infiltration of local anaesthetic solution around the SI joint region. METHODS: Horses were selected for inclusion in the study based upon the exclusion of other causes of lameness or poor performance, together with clinical signs suggestive of SI joint pain and abnormal radiopharmaceutical activity in the SI joint region and/or a positive response to periarticular infiltration of local anaesthetic solution. RESULTS: Sacroiliac joint region disease was identified in 74 horses between November 1997 and March 2002. Dressage and showjumping horses appeared to be at particular risk (P < 0.001). Affected horses were generally slightly older than the normal clinic population (P < 0.0001), taller at the withers (P < 0.0001) and of greater bodyweight (P < 0.01). There was a significant effect of breed (P < 0.001), with a substantially higher proportion of Warmblood horses (51%) in the SI pain group compared to the normal clinic population (29%). There was no correlation between conformation and the presence of SI joint region pain. The tubera sacrale appeared grossly symmetrical in most (95%) horses. Poor development of the epaxial muscles in the thoracolumbar region and asymmetry of the hindquarter musculature were common. Twenty-six horses (35%) showed restricted flexibility of the thoracolumbar region and 10 (16%) had an exaggerated response to pressure applied over the tubera sacrale. Fourteen horses (19%) were reluctant to stand on one hindlimb for prolonged periods. The majority of horses (75%) had a straight hindlimb flight and only 18% moved closely behind or plaited. In all horses restricted hindlimb impulsion was the predominant feature; invariably this was most obvious when the horse was ridden. Stiffness, unwillingness to work on the bit and poor quality canter were common. Sacroiliac joint region pain was seen alone (47%), or in conjunction with thoracolumbar pain (16%), hindlimb lameness (20%), forelimb lameness (7%) or a combination of problems (10%). Seventy-three horses (99%) had abnormalities of the SI joint region identified using nuclear scintigraphy. Infiltration of local anaesthetic solution around the SI joint region produced profound improvement in gait in all 34 horses in which it was performed. CONCLUSIONS AND POTENTIAL RELEVANCE: Careful clinical examination combined with scintigraphic evaluation of the SI joint region and local analgesia can enable a more definitive diagnosis of SI joint region pain than has previously been possible. |
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Centre for Equine Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK |
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0425-1644 |
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Notes |
PMID:12755425 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3723 |
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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. |
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Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
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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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 |
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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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ISSN |
1096-6080 |
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PMID:15456926 |
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no |
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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. |
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Title |
Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice |
Type |
Journal Article |
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Year |
2004 |
Publication |
Metabolism: clinical and experimental |
Abbreviated Journal |
Metabolism |
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Volume |
53 |
Issue |
10 |
Pages |
1284-1289 |
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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 |
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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. |
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Department of Life Sciences, Mokwon University, Taejon, Korea |
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English |
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0026-0495 |
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Notes |
PMID:15375783 |
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no |
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Call Number |
refbase @ user @ |
Serial |
72 |
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Author |
Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. |
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Title |
Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha |
Type |
Journal Article |
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Year |
2004 |
Publication |
Cancer research |
Abbreviated Journal |
Cancer Res |
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Volume |
64 |
Issue |
11 |
Pages |
3849-3854 |
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Keywords |
Animals; Anticholesteremic Agents/pharmacology; Carcinogens/pharmacology; Cell Division; DNA Replication/drug effects; Fatty Acids/metabolism; Hepatocytes/cytology/drug effects/metabolism/*physiology; Humans; Mice; Mice, Transgenic; Oxidation-Reduction; Peroxisome Proliferators/pharmacology; Pyrimidines/pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Species Specificity; Transcription Factors/genetics/*physiology |
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Abstract |
Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators. |
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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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English |
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0008-5472 |
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Notes |
PMID:15172993 |
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no |
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Call Number |
refbase @ user @ |
Serial |
74 |
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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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Abstract |
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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English |
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ISSN |
0931-184X |
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Notes |
PMID:15315700 |
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no |
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Call Number |
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Serial |
1899 |
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Author |
Yamazaki, Y.; Shinohara, N.; Watanabe, S. |
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Title |
Visual discrimination of normal and drug induced behavior in quails (Coturnix coturnix japonica) |
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Journal Article |
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Year |
2004 |
Publication |
Animal Cognition |
Abbreviated Journal |
Anim. Cogn. |
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Volume |
7 |
Issue |
2 |
Pages |
128-132 |
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Keywords |
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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Abstract |
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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Address |
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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English |
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ISSN |
1435-9448 |
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Notes |
PMID:15069613 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2527 |
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Author |
Dargatz, D.A.; Traub-Dargatz, J.L. |
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Title |
Multidrug-resistant Salmonella and nosocomial infections |
Type |
Journal Article |
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Year |
2004 |
Publication |
The Veterinary Clinics of North America. Equine Practice |
Abbreviated Journal |
Vet Clin North Am Equine Pract |
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Volume |
20 |
Issue |
3 |
Pages |
587-600 |
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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 |
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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. |
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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 |
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ISSN |
0749-0739 |
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Notes |
PMID:15519820 |
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Call Number |
Equine Behaviour @ team @ |
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2632 |
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Author |
Touma, C.; Palme, R.; Sachser, N. |
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Analyzing corticosterone metabolites in fecal samples of mice: a noninvasive technique to monitor stress hormones |
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Journal Article |
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Year |
2004 |
Publication |
Hormones and Behavior |
Abbreviated Journal |
Horm Behav |
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Volume |
45 |
Issue |
1 |
Pages |
10-22 |
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Keywords |
Adrenal Cortex/drug effects; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone/pharmacology; Analysis of Variance; Animals; Circadian Rhythm; Corticosterone/*analysis/metabolism; Dexamethasone/pharmacology; Feces/*chemistry; Female; Immunoenzyme Techniques/*methods; Male; Mice; Mice, Inbred C57BL; Models, Animal; Reproducibility of Results; Stress, Psychological/*metabolism |
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Abstract |
In small animals like mice, the monitoring of endocrine functions over time is constrained seriously by the adverse effects of blood sampling. Therefore, noninvasive techniques to monitor, for example, stress hormones in these animals are highly demanded in laboratory as well as in field research. The aim of our study was to evaluate the biological relevance of a recently developed technique to monitor stress hormone metabolites in fecal samples of laboratory mice. In total, six experiments were performed using six male and six female mice each. Two adrenocorticotropic hormone (ACTH) challenge tests, two dexamethasone (Dex) suppression tests and two control experiments [investigating effects of the injection procedure itself and the diurnal variation (DV) of glucocorticoids (GCs), respectively] were conducted. The experiments clearly demonstrated that pharmacological stimulation and suppression of adrenocortical activity was reflected accurately by means of corticosterone metabolite (CM) measurements in the feces of males and females. Furthermore, the technique proved sensitive enough to detect dosage-dependent effects of the ACTH/Dex treatment and facilitated to reveal profound effects of the injection procedure itself. Even the naturally occurring DV of GCs could be monitored reliably. Thus, our results confirm that measurement of fecal CM with the recently established 5alpha-pregnane-3beta,11beta,21-triol-20-one enzyme immunoassay is a very powerful tool to monitor adrenocortical activity in laboratory mice. Since mice represent the vast majority of all rodents used for research worldwide and the number of transgenic and knockout mice utilized as animal models is still increasing, this noninvasive technique can open new perspectives in biomedical and behavioral science. |
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Department of Behavioural Biology, University of Muenster, D-48149 Muenster, Germany. touma@uni-muenster.de |
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English |
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0018-506X |
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Notes |
PMID:14733887 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
4084 |
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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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Year |
2005 |
Publication |
Veterinary journal (London, England : 1997) |
Abbreviated Journal |
Vet J |
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Volume |
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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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. |
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Address |
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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English |
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1090-0233 |
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PMID:15683772 |
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refbase @ user @ |
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671 |
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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 |
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Journal Article |
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2005 |
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American journal of hypertension : journal of the American Society of Hypertension |
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Am J Hypertens |
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18 |
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4 Pt 1 |
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549-556 |
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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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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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refbase @ user @ |
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69 |
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