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Hodgson, D., Howe, S., Jeffcott, L., Reid, S., Mellor, D., & Higgins, A. (2005). Effect of prolonged use of altrenogest on behaviour in mares (Vol. 169).
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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Guo, G. L., Moffit, J. S., Nicol, C. J., Ward, J. M., Aleksunes, L. A., Slitt, A. L., et al. (2004). Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci, 82(2), 374–380.
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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Nicol, C. J., Adachi, M., Akiyama, T. E., & Gonzalez, F. J. (2005). PPARgamma in endothelial cells influences high fat diet-induced hypertension. Am J Hypertens, 18(4 Pt 1), 549–556.
Abstract: BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.
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Cheung, C., Akiyama, T. E., Ward, J. M., Nicol, C. J., Feigenbaum, L., Vinson, C., et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res, 64(11), 3849–3854.
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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Milgram, N. W., Head, E., Muggenburg, B., Holowachuk, D., Murphey, H., Estrada, J., et al. (2002). Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy. Neurosci Biobehav Rev, 26(6), 679–695.
Abstract: The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition.
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Yang, S. (2000). Melioidosis research in China. Acta Trop, 77(2), 157–165.
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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Forbes, A. B. (1993). A review of regional and temporal use of avermectins in cattle and horses worldwide. Vet Parasitol, 48(1-4), 19–28.
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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Aviad, A. D., & Houpt, J. B. (1994). The molecular weight of therapeutic hyaluronan (sodium hyaluronate): how significant is it? J Rheumatol, 21(2), 297–301.
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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Lyda, R. O., Hall, J. R., & Kirkpatrick, J. F. (2005). A comparison of Freund's Complete and Freund's Modified Adjuvants used with a contraceptive vaccine in wild horses (Equus caballus). J Zoo Wildl Med, 36(4), 610–616.
Abstract: Fifteen captive wild mares (Equus caballus) were treated with porcine zona pellucida contraceptive vaccine and either Freund's Complete Adjuvant (n = 7) or Freund's Modified Adjuvant (n = 8). All mares received a booster inoculation of porcine zona pellucida plus Freund's Incomplete Adjuvant a month later. Anti-porcine zona pellucida antibodies were measured over 10 mo following the initial inoculation. There were no significant differences in antibody titers at any point during the 10 mo, and seven of the eight mares in the Freund's Modified Adjuvant group were above the 60% level at the end of the study, which is considered to be the contraceptive threshold for horses. There were no significant differences in titers between pregnant and nonpregnant horses, nor was there a significant correlation between age and titers. One local injection site reaction occurred after booster treatment with Freund's Incomplete Adjuvant, and 11 healthy foals were born during the course of the study. These data suggest that Freund's Modified Adjuvant is an acceptable substitute for Freund's Complete Adjuvant in certain free-ranging and captive wildlife species.
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Zehnder, A. M., Ramer, J. C., & Proudfoot, J. S. (2006). The use of altrenogest to control aggression in a male Grant's Zebra (Equus burchelli boehmi). J Zoo Wildl Med, 37(1), 61–63.
Abstract: A male Grant's Zebra (Equus burchelli boehmi) housed with two mares at the Indianapolis Zoo had a 9-yr history of intermittent aggressive behavior toward mares and other animals. Periods of separation allowed the mares time to heal after sustaining superficial bite wounds. On 26 March 2003, the male (890293) was started on altrenogest at a dosage of 19.8 mg orally once daily to allow reintroduction. The dosage was doubled (40 mg once a day) because of a perceived lack of response. Reintroduction to the mares occurred on 17 May 2003 with no signs of aggression noted. Treatment was reduced to 19.8 mg orally once a day and then discontinued. Altrenogest was restarted at 39.5 mg orally once a day because of the planned introduction of a new mare. There have been no major aggressive displays at this dosage of altrenogest and the dosage has recently been reduced following successful introduction of a new mare.
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