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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 |
Type |
Journal Article |
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Year |
2003 |
Publication |
Veterinary Therapeutics : Research in Applied Veterinary Medicine |
Abbreviated Journal |
Vet Ther |
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Volume |
4 |
Issue |
3 |
Pages |
257-268 |
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Keywords |
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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Address |
Department of Biomedical Sciences, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA |
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English |
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ISSN |
1528-3593 |
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Notes |
PMID:15136987 |
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no |
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Call Number |
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Serial |
1901 |
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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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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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0749-0739 |
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Notes |
PMID:15519820 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2632 |
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Author |
Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
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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 |
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Year |
2005 |
Publication |
The Journal of pharmacology and experimental therapeutics |
Abbreviated Journal |
J Pharmacol Exp Ther |
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Volume |
312 |
Issue |
1 |
Pages |
69-76 |
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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 |
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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. |
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Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA |
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0022-3565 |
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Notes |
PMID:15356214 |
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no |
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Call Number |
refbase @ user @ |
Serial |
73 |
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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 @ |
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74 |
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Author |
Carroll, G.L.; Matthews, N.S.; Hartsfield, S.M.; Slater, M.R.; Champney, T.H.; Erickson, S.W. |
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Title |
The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies |
Type |
Journal Article |
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Year |
1997 |
Publication |
Veterinary surgery : VS : the official journal of the American College of Veterinary Surgeons |
Abbreviated Journal |
Vet Surg |
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Volume |
26 |
Issue |
1 |
Pages |
69-77 |
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Keywords |
Adrenergic alpha-Antagonists/administration & dosage/*pharmacology; Animals; Behavior, Animal/drug effects/physiology; Blood Glucose/metabolism; Blood Pressure/drug effects/physiology; Consciousness/physiology; Dose-Response Relationship, Drug; Drug Interactions; Epinephrine/blood; Fatty Acids, Nonesterified/blood; Female; Heart Rate/drug effects/physiology; Horse Diseases/metabolism/physiopathology/psychology; Horses/blood/metabolism/*physiology; Hydrocortisone/blood; Hypnotics and Sedatives/administration & dosage/*pharmacology; Imidazoles/administration & dosage/*pharmacology; Injections, Intravenous; Male; Norepinephrine/blood; Receptors, Adrenergic, alpha/drug effects/*physiology; Stress/metabolism/physiopathology/veterinary; Time Factors; Tolazoline/administration & dosage/*pharmacology |
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Abstract |
Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minutes before detomidine administration which was immediately before the administration of tolazoline or saline (time [T] = 0), and at 5, 30, and 60 minutes after injections of tolazoline or saline (T = 5, 30, and 60 minutes, respectively). Compared with heart rate at T = 0, tolazoline antagonism increased heart rate 45% at 5 minutes. There was no difference in heart rate between treatments at 30 minutes. Blood pressure remained stable after tolazoline, while it decreased over time after saline. Compared with concentrations at T = 0, tolazoline antagonism of detomidine in awake ponies resulted in a 55% increase in cortisol at 30 minutes and a 52% increase in glucose at 5 minutes. The change in free fatty acids was different for tolazoline and saline over time. Free fatty acids decreased after detomidine administration. Free fatty acids did not change after saline administration. After tolazoline administration, free fatty acids increased transiently. Tolazoline tended to decrease sedation and analgesia at 15 and 60 minutes postantagonism. Antagonism of detomidine-induced physiological and behavioral effects with tolazoline in awake ponies that were not experiencing pain appears to precipitate a stress response as measured by cortisol, glucose, and free fatty acids. If antagonism of an alpha-agonist is contemplated, the potential effect on hormones and metabolites should be considered. |
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Department of Small Animal Medicine and Surgery, Texas A&M University, College Station, USA |
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English |
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ISSN |
0161-3499 |
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Notes |
PMID:9123816 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
96 |
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Author |
Brown, R.F.; Houpt, K.A.; Schryver, H.F. |
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Title |
Stimulation of food intake in horses by diazepam and promazine |
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Journal Article |
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Year |
1976 |
Publication |
Pharmacology, biochemistry, and behavior |
Abbreviated Journal |
Pharmacol Biochem Behav |
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Volume |
5 |
Issue |
4 |
Pages |
495-497 |
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Keywords |
Age Factors; Animals; Diazepam/*pharmacology; Diet; Feeding Behavior/*drug effects; Female; Horses/*physiology; Male; Promazine/*pharmacology; Stimulation, Chemical |
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Abstract |
In two adult horses doses of 0.02-0.03 mg/kg diazepam, intravenously, increased 1 hr intake 54-75% above control levels. Intake was stimulated when the diet was a high grain, calorically dense one and also when the diet was a high fiber, calorically dilute one. Two young rapidly growing weanling horses showed an even more pronounced stimulation of intake. Following diazepam 1 hr intake was increased 105-240% above control lelvels. Promazine at a dose of 0.5 mg/kg also stimulated intake in adult horses, but not as markedly as did diazepam. A transquilizer and a neuroleptic appear to have a stimulatory eff upon short-term intake in horses. |
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English |
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ISSN |
0091-3057 |
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Notes |
PMID:1005496 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
60 |
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Author |
Blokland, A. |
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Title |
Reaction time responding in rats |
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Journal Article |
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Year |
1998 |
Publication |
Neuroscience and Biobehavioral Reviews |
Abbreviated Journal |
Neurosci Biobehav Rev |
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Volume |
22 |
Issue |
6 |
Pages |
847-864 |
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Keywords |
Amphetamine/pharmacology; Animals; Behavior, Animal/drug effects/*physiology; Conditioning, Operant/drug effects/*physiology; Dopamine Uptake Inhibitors/pharmacology; Dose-Response Relationship, Drug; Male; Rats; Rats, Inbred Lew; Reaction Time/drug effects/*physiology |
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Abstract |
The use of reaction time has a great tradition in the field of human information processing research. In animal research the use of reaction time test paradigms is mainly limited to two research fields: the role of the striatum in movement initiation; and aging. It was discussed that reaction time responding can be regarded as “single behavior”, this term was used to indicate that only one behavioral category is measured, allowing a better analysis of brain-behavior relationships. Reaction time studies investigating the role of the striatum in motor functions revealed that the initiation of a behavioral response is dependent on the interaction of different neurotransmitters (viz. dopamine, glutamate, GABA). Studies in which lesions were made in different brain structures suggested that motor initiation is dependent on defined brain structures (e.g. medialldorsal striatum, prefrontal cortex). It was concluded that the use of reaction time measures can indeed be a powerful tool in studying brain-behavior relationships. However, there are some methodological constraints with respect to the assessment of reaction time in rats, as was tried to exemplify by the experiments described in the present paper. On the one hand one should try to control for behavioral characteristics of rats that may affect the validity of the parameter reaction time. On the other hand, the mean value of reaction time should be in the range of what has been reported in man. Although these criteria were not always met in several studies, it was concluded that reaction time can be validly assessed in rats. Finally, it was discussed that the use of reaction time may go beyond studies that investigate the role of the basal ganglia in motor output. Since response latency is a direct measure of information processing this parameter may provide insight into basic elements of cognition. Based on the significance of reaction times in human studies the use of this dependent variable in rats may provide a fruitful approach in studying brain-behavior relationships in cognitive functions. |
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Address |
Department of Psychology, University of Maastricht, The Netherlands |
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English |
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0149-7634 |
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Notes |
PMID:9809315 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2807 |
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Author |
Aviad, A.D.; Houpt, J.B. |
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Title |
The molecular weight of therapeutic hyaluronan (sodium hyaluronate): how significant is it? |
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Journal Article |
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Year |
1994 |
Publication |
The Journal of rheumatology |
Abbreviated Journal |
J Rheumatol |
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Volume |
21 |
Issue |
2 |
Pages |
297-301 |
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Keywords |
Animals; Horse Diseases/drug therapy; Horses; Humans; Hyaluronic Acid/*chemistry/*therapeutic use; Joint Diseases/*drug therapy/veterinary; Molecular Weight; Osteoarthritis/drug therapy/veterinary; Synovial Fluid/drug effects/physiology; Viscosity |
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Abstract |
Various molecular weight hyaluronic acid (HA) preparations have been injected into joints for the treatment of human and equine osteoarthritis. A therapeutic advantage has been claimed for commercial products with a molecular weight in the range found in normal synovial fluid (SF), compared to lower molecular weight products. But a correlation between molecular weight and efficacy is not borne out by an analysis of the available literature on clinical results. SF viscosity, HA concentration, HA molecular weight and rate of synthesis in joint disease. It is proposed that the beneficial effect of injected HA in joint disease may be due to pharmacological rather than to physical properties. |
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Rheumatic Disease Unit, Mount Sinai Hospital, University of Toronto, ON, Canada |
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ISSN |
0315-162X |
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Notes |
PMID:8182640 |
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no |
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Call Number |
refbase @ user @ |
Serial |
35 |
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Author |
Aronson, L. |
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Title |
Animal behavior case of the month. Aggression directed toward other horses |
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Journal Article |
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Year |
1998 |
Publication |
Journal of the American Veterinary Medical Association |
Abbreviated Journal |
J Am Vet Med Assoc |
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Volume |
213 |
Issue |
3 |
Pages |
358-359 |
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Keywords |
*Aggression; Animals; *Behavior, Animal; Follow-Up Studies; Horse Diseases/*diagnosis/drug therapy/psychology; Horses/*psychology; Housing, Animal; Hypothyroidism/diagnosis/drug therapy/*veterinary; Male; Physical Examination/veterinary; Thyroxine/blood/therapeutic use |
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Address |
Department of Surgery, School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA |
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English |
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0003-1488 |
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Notes |
PMID:9702222 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
1935 |
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Author |
Alexander, F.; Ash, R.W. |
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Title |
The effect of emotion and hormones on the concentration of glucose and eosinophils in horse blood |
Type |
Journal Article |
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Year |
1955 |
Publication |
The Journal of physiology |
Abbreviated Journal |
J Physiol |
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Volume |
130 |
Issue |
3 |
Pages |
703-710 |
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Keywords |
Blood Glucose/*drug effects; Eosinophils/*drug effects; Leukocyte Count/*drug effects; *ACTH/effects; *BLOOD SUGAR/effect of drugs on; *EOSINOPHIL COUNT/effect of drugs on; *EPINEPHRINE/effects; *HISTAMINE/effects; *INSULIN/effects; *STRESS/experimental |
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Publisher |
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Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0022-3751 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
PMID:13278929 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
122 |
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