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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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0008-5472 |
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PMID:15172993 |
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no |
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Call Number |
refbase @ user @ |
Serial |
74 |
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Author |
Dunn, M.F.; Branlant, G. |
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Title |
Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation |
Type |
Journal Article |
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Year |
1975 |
Publication |
Biochemistry |
Abbreviated Journal |
Biochemistry |
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Volume |
14 |
Issue |
14 |
Pages |
3176-3182 |
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Keywords |
*Alcohol Oxidoreductases/metabolism; Aldehydes/*pharmacology; Animals; Binding Sites; Enzyme Activation/drug effects; Horses; Hydrogen-Ion Concentration; Kinetics; Liver/enzymology; *NAD/analogs & derivatives/pharmacology; Oxidation-Reduction; Protein Binding; Spectrophotometry; Spectrophotometry, Ultraviolet; Temperature; *Zinc/pharmacology |
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Abstract |
1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step. |
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0006-2960 |
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PMID:238585 |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3817 |
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Author |
McGreevy, P.D.; Webster, A.J.; Nicol, C.J. |
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Title |
Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses |
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Journal Article |
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Year |
2001 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
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Volume |
148 |
Issue |
19 |
Pages |
592-596 |
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Keywords |
Animals; Behavior, Animal/*physiology; Case-Control Studies; *Digestion; *Gastrointestinal Motility/drug effects; Horse Diseases/*physiopathology; Horses/*physiology/psychology; Male; Stereotyped Behavior/*physiology; Sulfapyridine/blood; Sulfasalazine/diagnostic use/pharmacology |
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Abstract |
The spontaneous behaviour and the apparent digestibility of dry matter and fibre and transit times of digesta were compared in four normal horses and four crib-biters. A technique was developed for measuring total gut transit times (TGTT) by using single-stool analysis of the passage of radio-opaque polyethylene markers. Longer TGTT were recorded in the crib-biters than in the normal horses but the orocaecal transit times did not differ. The crib-biters rested less than the normal horses. |
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Department of Clinical Veterinary Science, University of Bristol, Langford |
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0042-4900 |
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Notes |
PMID:11386445 |
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no |
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Call Number |
refbase @ user @ |
Serial |
86 |
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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 |
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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Notes |
PMID:15456926 |
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no |
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Call Number |
refbase @ user @ |
Serial |
71 |
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Author |
Kirkpatrick, J.F.; Liu, I.M.; Turner, J.W.J.; Naugle, R.; Keiper, R. |
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Title |
Long-term effects of porcine zonae pellucidae immunocontraception on ovarian function in feral horses (Equus caballus) |
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Journal Article |
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Year |
1992 |
Publication |
Journal of reproduction and fertility |
Abbreviated Journal |
J Reprod Fertil |
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Volume |
94 |
Issue |
2 |
Pages |
437-444 |
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Keywords |
Animals; Contraception, Immunologic/*veterinary; *Egg Proteins; Estrogens, Conjugated (USP)/urine; Female; Glycoproteins/*pharmacology; Horses/immunology/*physiology; *Membrane Glycoproteins; Ovary/drug effects/*physiology; Progesterone/metabolism; *Receptors, Cell Surface; Swine/immunology; Time Factors; Zona Pellucida/*immunology |
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Abstract |
Ten feral mares free-roaming in Maryland, USA, were inoculated with porcine zonae pellucidae (PZP) protein before the breeding season for three consecutive years (1988-90). Ovarian function was monitored for 51 days during the peak of the breeding season after the third annual PZP inoculation, in seven of these mares and in four untreated control mares, by means of urinary oestrone conjugates and nonspecific progesterone metabolites. None of the ten inoculated mares became pregnant in 1990, compared with 55% of 20 control mares, which included two of the four monitored for ovarian function. Three of the untreated mares demonstrated apparent normal ovarian activity, characterized by preovulatory oestrogen peaks, concurrent progesterone nadirs at ovulation, breeding activity, and luteal-phase progesterone increases after ovulation. Two of the seven monitored PZP-treated mares demonstrated ovulatory cycles that did not result in conception. One was pregnant as a result of conception in 1989 and demonstrated a normal, late-gestation, endocrine profile. The remaining four PZP-treated mares revealed no evidence of ovulation, and urinary oestrogen concentrations were significantly depressed. The experiments indicated that (i) a third consecutive annual PZP booster inoculation is greater than 90% effective in preventing pregnancies in mares and (ii) three consecutive years of PZP treatment may interfere with normal ovarian function as shown by markedly depressed oestrogen secretion. |
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Address |
Deaconess Research Institute, Billings, MT 59102 |
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0022-4251 |
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Notes |
PMID:1317449 |
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no |
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Call Number |
refbase @ user @ |
Serial |
145 |
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Author |
Tobin, T.; Combie, J.D. |
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Title |
Performance testing in horses: a review of the role of simple behavioral models in the design of performance experiments |
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Journal Article |
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Year |
1982 |
Publication |
Journal of Veterinary Pharmacology and Therapeutics |
Abbreviated Journal |
J Vet Pharmacol Ther |
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Volume |
5 |
Issue |
2 |
Pages |
105-118 |
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Keywords |
Analgesics, Opioid/pharmacology; Animals; Apomorphine/pharmacology; Behavior, Animal/*drug effects; Dose-Response Relationship, Drug; Fentanyl/pharmacology; Horses/*physiology; Methylphenidate/pharmacology; *Models, Biological; Motor Activity/drug effects |
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English |
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0140-7783 |
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Notes |
PMID:6125601 |
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no |
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Call Number |
refbase @ user @ |
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1957 |
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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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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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Notes |
PMID:15069613 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2527 |
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Author |
Yang, S. |
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Title |
Melioidosis research in China |
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Journal Article |
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Year |
2000 |
Publication |
Acta Tropica |
Abbreviated Journal |
Acta Trop |
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Volume |
77 |
Issue |
2 |
Pages |
157-165 |
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Keywords |
Animals; Anti-Bacterial Agents/pharmacology; Burkholderia pseudomallei/drug effects/immunology/*pathogenicity; China/epidemiology; Cross Reactions; Glanders/immunology/microbiology; Horses; Humans; *Melioidosis/epidemiology/immunology/microbiology/veterinary; Seroepidemiologic Studies; Virulence |
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Abstract |
Research on melioidosis and its pathogen has been ongoing in China for more than two decades. It has been demonstrated that the natural foci are located predominantly in Hainan, Guangdong and Guangxi province, where there is a good correlation between soil isolation and the serum prevalence of antibodies to Burkholderia pseudomallei. The cases of melioidosis reported up to now are concentrated in the Hainan and Zhanjiang peninsula. Investigations on serotype, virulence, ecology, antibiotic susceptibility, whole cell analysis by gas chromatography, and genetics have led to a new understanding of the pathology of the disease. Immunological cross reactions between Burkholderia mallei and B. pseudomallei and the difference between melioidosis and glanders in horses is discussed. |
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Address |
Medical Research Institute, Yan-Ling (510507), Dongguanzhuang Road 91, Guangzhou, People's Republic of China. songyangch@hotmail.com |
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0001-706X |
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Notes |
PMID:11080506 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2649 |
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Author |
Kristiansen, K.K.; Kold, S.E. |
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Title |
Multivariable analysis of factors influencing outcome of 2 treatment protocols in 128 cases of horses responding positively to intra-articular analgesia of the distal interphalangeal joint |
Type |
Journal Article |
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Year |
2007 |
Publication |
Equine Veterinary Journal |
Abbreviated Journal |
Equine Vet J |
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Volume |
39 |
Issue |
2 |
Pages |
150-156 |
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Keywords |
Analgesia/methods/*veterinary; Anesthesia, Local/methods/veterinary; Animals; Anti-Inflammatory Agents/therapeutic use; Female; Foot Diseases/drug therapy/prevention & control/*veterinary; Glycosaminoglycans/therapeutic use; Horse Diseases/*drug therapy/prevention & control; Horses; Injections, Intra-Articular/*veterinary; Joint Diseases/drug therapy/prevention & control/veterinary; Lameness, Animal/drug therapy/prevention & control; Male; Methylprednisolone/analogs & derivatives/therapeutic use; Multivariate Analysis; Pain/prevention & control/veterinary; Retrospective Studies; Time Factors; *Toe Joint/drug effects/pathology; Treatment Outcome |
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Abstract |
REASONS FOR PERFORMING STUDY: There is limited knowledge available of factors influencing response to treatments of the DIP-joint in horses with lameness responding to diagnostic analgesia of the DIP-joint. For this reason a multivariable statistical analysis was performed. HYPOTHESIS: Horses with lameness reduced by > or = 75% 10 min after intra-articular analgesia of the DIP-joint, can be treated successfully by intra-articular medication of the joint. Multiple factors influence the response to treatment. METHODS: The study was performed retrospectively based on clinical records of horses treated with either polysulphated glycosaminoglycan (PSGAG) or methylprednisolone acetate (MPA) in the DIP-joint between January 1996 and January 2003. Information was collected from clinical records and from the owners of the horses via a detailed questionnaire, in which they described their perception of the outcome a minimum of one year after treatment. Allocation of the horses to the 2 treatment groups was done mainly because of a change in treatment policy. In Regime A all horses received 3 intra-articular injections of PSGAG approximately 8 days apart, whereas in Regime B all horses received a single intra-articular injection of MPA as a first treatment. If the horse did not improve sufficiently to return to work by 4 weeks, a series of 3 intra-articular PSGAG injections was administered. RESULTS: Of the horses receiving Regime A, 67% had a successful outcome, compared with 46% of the group receiving Regime B. A significantly better result was obtained in dressage horses than in jumping horses (eventing and showjumping). Other variables such as age, duration of lameness, distribution of lameness, degree of lameness, response to DIP-joint analgesia and radiographic observations were also associated with success of treatment. CONCLUSIONS AND POTENTIAL RELEVANCE: There is a rationale for using either PSGAG or MPA intra-articularly in the treatment of lameness, reduced > or = 75% within 10 min of analgesia of the DIP-joint. |
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Address |
Willesley Equine Clinic Ltd., Tetbury, Gloucestershire, GL8 8QU UK |
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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 |
0425-1644 |
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Conference |
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Notes |
PMID:17378444 |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3707 |
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