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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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PMID:15356214 |
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Call Number |
refbase @ user @ |
Serial |
73 |
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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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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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PMID:15519820 |
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Equine Behaviour @ team @ |
Serial |
2632 |
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Author |
Dirikolu, L.; Lehner, A.F.; Karpiesiuk, W.; Hughes, C.; Woods, W.E.; Boyles, J.; Harkins, J.D.; Troppmann, A.; Tobin, T. |
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Title |
Detection, quantification, metabolism, and behavioral effects of selegiline in horses |
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Journal Article |
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Year |
2003 |
Publication |
Veterinary Therapeutics : Research in Applied Veterinary Medicine |
Abbreviated Journal |
Vet Ther |
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4 |
Issue |
3 |
Pages |
257-268 |
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Administration, Oral; Animals; Behavior, Animal/drug effects; Female; Horses/*metabolism; Mass Spectrometry/veterinary; Monoamine Oxidase Inhibitors/administration & dosage/blood/*pharmacokinetics/pharmacology/urine; Selegiline/administration & dosage/blood/*pharmacokinetics/pharmacology/urine; Substance Abuse Detection/veterinary |
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Selegiline ([R]-[-]N,alpha-dimethyl-N-2- propynylphenethylamine or l-deprenyl), an irreversible inhibitor of monoamine oxidase, is a classic antidyskinetic and antiparkinsonian agent widely used in human medicine both as monotherapy and as an adjunct to levodopa therapy. Selegiline is classified by the Association of Racing Commissioners International (ARCI) as a class 2 agent, and is considered to have high abuse potential in racing horses. A highly sensitive LC/MS/MS quantitative analytical method has been developed for selegiline and its potential metabolites amphetamine and methamphetamine using commercially available deuterated analogs of these compounds as internal standards. After administering 40 mg of selegiline orally to two horses, relatively low (<60 ng/ml) concentrations of parent selegiline, amphetamine, and methamphetamine were recovered in urine samples. However, relatively high urinary concentrations of another selegiline metabolite were found, tentatively identified as N- desmethylselegiline. This metabolite was synthesized and found to be indistinguishable from the new metabolite recovered from horse urine, thereby confirming the chemical identity of the equine metabolite. Additionally, analysis of urine samples from four horses dosed with 50 mg of selegiline confirmed that N-desmethylselegiline is the major urinary metabolite of selegiline in horses. In related behavior studies, p.o. and i.v. administration of 30 mg of selegiline produced no significant changes in either locomotor activities or heart rates. |
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Department of Biomedical Sciences, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA |
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1528-3593 |
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PMID:15136987 |
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Call Number |
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Serial |
1901 |
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Author |
Doherty, T.J.; Frazier, D.L. |
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Title |
Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies |
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Journal Article |
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Year |
1998 |
Publication |
Equine veterinary journal |
Abbreviated Journal |
Equine Vet J |
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Volume |
30 |
Issue |
4 |
Pages |
300-303 |
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Keywords |
Anesthetics/administration & dosage/blood/*pharmacology; Anesthetics, Inhalation/administration & dosage/*analysis; Animals; Consciousness/drug effects; Dose-Response Relationship, Drug; Halothane/administration & dosage/*analysis; Horses/*physiology; Infusions, Intravenous/veterinary; Lidocaine/administration & dosage/blood/*pharmacology; Male |
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Abstract |
This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively). The halothane MAC was redetermined after a 60 min infusion of lidocaine or saline. The baseline halothane MAC for the control group was mean +/- s.d. 0.94 +/- 0.03%, and no significant decrease occurred following saline infusion. Lidocaine decreased halothane MAC in a dose-dependent fashion (r = 0.86; P < 0.0003). The results indicate that i.v. lidocaine may have a role in equine anaesthesia. |
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Department of Large Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville 37901-1071, USA |
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0425-1644 |
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PMID:9705112 |
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refbase @ user @ |
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95 |
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Author |
Domjan, M. |
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Title |
Selective suppression of drinking during a limited period following aversive drug treatment in rats |
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Journal Article |
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1977 |
Publication |
Journal of Experimental Psychology. Animal Behavior Processes |
Abbreviated Journal |
J Exp Psychol Anim Behav Process |
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3 |
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1 |
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66-76 |
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Animals; *Avoidance Learning; Awareness; Conditioning, Operant; Dose-Response Relationship, Drug; Drinking Behavior/*drug effects; Lithium/*poisoning; Male; Osmolar Concentration; Rats; Saccharin/administration & dosage; *Taste; Time Factors |
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Abstract |
Administration of lithium chloride disrupted the intake of flavored solutions but not water in rats. This intake suppression was directly related to the amount of lithium administered (Experiment 1), occurred with both palatable and unpalatable novel saccharin solutions (Experiment 2), but was only observed if subjects were tested starting less than 75 min. after lithium treatment (Experiment 3). Twenty-five daily exposures to saccharin did not attenuate the effect (Experiment 4). However, in saccharin-reared and vinegar-reared rats, lithium did not disrupt consumption of the solutions these subjects had access to throughout life, even though suppressions of intake were observed when these subjects were tested with novel flavors (Experiment 5). The selective disruption of drinking is interpreted as a novelty-dependent sensitization reaction to the discomfort of aversive drug administration. |
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0097-7403 |
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PMID:845544 |
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Equine Behaviour @ team @ |
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2788 |
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Author |
Dunn, M.F.; Branlant, G. |
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Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation |
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Journal Article |
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Year |
1975 |
Publication |
Biochemistry |
Abbreviated Journal |
Biochemistry |
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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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Equine Behaviour @ team @ |
Serial |
3817 |
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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 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3723 |
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Author |
Elhay, M.; Newbold, A.; Britton, A.; Turley, P.; Dowsett, K.; Walker, J. |
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Title |
Suppression of behavioural and physiological oestrus in the mare by vaccination against GnRH |
Type |
Journal Article |
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Year |
2007 |
Publication |
Australian Veterinary Journal |
Abbreviated Journal |
Aust Vet J |
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Volume |
85 |
Issue |
1-2 |
Pages |
39-45 |
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Keywords |
Animals; Antibodies/blood; Estradiol/blood; *Estrus/drug effects/physiology; Female; Gonadotropin-Releasing Hormone/*immunology/*pharmacology; Horses/*physiology; Luteinizing Hormone/blood; Ovulation/*drug effects/physiology; Progesterone/blood; Safety; Sexual Behavior, Animal/drug effects/physiology; Time Factors; Vaccination/veterinary |
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OBJECTIVE: To examine the immunogenicity of an equine immunocontraceptive vaccine and its efficacy in controlling hormone-related behaviour. DESIGN: A total of 24 mares at two sites in Australia were vaccinated with an immunocontraceptive vaccine comprising gonadotrophin releasing hormone (GnRH) conjugated to a carrier protein in immunostimulating complex as an adjuvant. Twelve animals at each site received a placebo of adjuvant alone and served as controls for seasonal oestrus, hormonal and behaviour patterns. Animals were observed for injection site reactions, ovarian and follicular activity, and serum levels of antibody, 17beta-oestradiol and progesterone in the weeks following vaccination. Mares were also examined for oestrous behaviour by teasing with a stallion. RESULTS: All mares responded to vaccination. Two weeks following the second vaccination there was a peak in antibody response to GnRH that declined gradually over the following weeks. Commensurate with the elevated anti-GnRH antibody there was a marked effect on ovarian activity with a reduction in 17beta-oestradiol and progesterone levels in the 24 vaccinated mares. There was also a reduction of oestrus-related behaviour as determined by a teaser stallion. This effect lasted a minimum of 3 months and correlated with the initial level of antibody response. CONCLUSION: Following a conventional two-dose immunisation regime this commercially available equine immunocontraceptive vaccine was effective at inhibiting oestrous behaviour for at least 3 months. This vaccine has a high level of safety since there were no significant local reactions nor were there any adverse systemic responses to vaccination. |
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Veterinary Medicines Research and Development, Pfizer Animal Health, Parkville, VIC 3052. Martin.Elhay@pfizer.com |
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0005-0423 |
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Notes |
PMID:17300452 |
Approved |
no |
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Call Number |
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Serial |
1831 |
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Author |
Forbes, A.B. |
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Title |
A review of regional and temporal use of avermectins in cattle and horses worldwide |
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Journal Article |
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Year |
1993 |
Publication |
Veterinary Parasitology |
Abbreviated Journal |
Vet Parasitol |
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Volume |
48 |
Issue |
1-4 |
Pages |
19-28 |
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Keywords |
Animals; Anthelmintics/therapeutic use; Arthropods; Cattle; Cattle Diseases/drug therapy/*prevention & control; Ectoparasitic Infestations/drug therapy/prevention & control/veterinary; Horse Diseases/drug therapy/*prevention & control; Horses; Insecticides; Ivermectin/*analogs & derivatives/*therapeutic use; Nematode Infections/drug therapy/prevention & control/veterinary; Parasitic Diseases/drug therapy/prevention & control; *Parasitic Diseases, Animal |
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Abstract |
Ivermectin and abamectin are two members of the group of parasiticides known as the avermectins; ivermectin was first registered as an injectable treatment for cattle in 1981. Since then, abamectin has been registered for cattle and ivermectin for horses. The relative popularity of the avermectins amongst farmers and veterinarians can be attributed to their spectrum of activity, convenience, wide margin of safety and the improved health and performance of stock following their use. Patterns of use in grazing animals apply equally to the avermectins as to other antiparasitics, particularly anthelmintics; these are based on a knowledge of epidemiology integrated with practical management considerations. For cattle, programs are commonly aimed at control of abomasal nematodes of the genera Ostertagia and Haemonchus. Use of avermectins is largely strategic in cattle, treatments being favored at the end of the period of transmission of these parasites; this frequently coincides with housing, entry into a feedlot or movement to another pasture. Simultaneous control of important ectoparasites at this time is an added benefit. Prophylactic use of avermectins at pasture is primarily targeted at the young first season grazing animal. In horses, a bimonthly treatment schedule during the period of risk has proved effective in helping prevent adverse effects of the main target parasites, including large and small strongyles and stomach bots. These patterns of use can be applied to the evaluation of the potential for avermectin residues in feces to have impact on pasture ecology. The evidence presented suggests that any effects are temporally and spatially limited. After more than a decade of practical use, there is no indication that avermectins have had a significant impact on pasture ecology and the environment. |
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MERCK AgVet, Rahway, NJ 07065-0912 |
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0304-4017 |
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PMID:8346632 |
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Equine Behaviour @ team @ |
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2665 |
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Author |
Grubb, T.L.; Foreman, J.H.; Benson, G.J.; Thurmon, J.C.; Tranquilli, W.J.; Constable, P.D.; Olson, W.O.; Davis, L.E. |
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Hemodynamic effects of calcium gluconate administered to conscious horses |
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Journal Article |
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1996 |
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Journal of veterinary internal medicine / American College of Veterinary Internal Medicine |
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J Vet Intern Med |
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10 |
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6 |
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401-404 |
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Animals; Blood Pressure/drug effects/physiology; Calcium/blood; Calcium Gluconate/administration & dosage/*pharmacology; Cardiac Output/drug effects/physiology; Consciousness/*physiology; Dose-Response Relationship, Drug; Female; Heart Rate/drug effects/physiology; Hemodynamic Processes/*drug effects/physiology; Horses/blood/*physiology; Infusions, Intravenous; Male; Myocardial Contraction/drug effects/physiology; Respiration/drug effects/physiology; Stroke Volume/drug effects/physiology; Time Factors |
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Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function. |
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Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, USA |
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0891-6640 |
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PMID:8947873 |
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refbase @ user @ |
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97 |
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