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Crosby, M. B., Svenson, J. L., Zhang, J., Nicol, C. J., Gonzalez, F. J., & Gilkeson, G. S. (2005). Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide. J Pharmacol Exp Ther, 312(1), 69–76.
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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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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Hubbell, J. A. E., & Muir, W. W. (2006). Antagonism of detomidine sedation in the horse using intravenous tolazoline or atipamezole. Equine Vet J, 38(3), 238–241.
Abstract: REASONS FOR PERFORMING STUDY: The ability to shorten the duration of sedation would potentially improve safety and utility of detomidine. OBJECTIVES: To determine the effects of tolazoline and atipamezole after detomidine sedation. HYPOTHESIS: Administration of tolazoline or atipamezole would not affect detomidine sedation. METHODS: In a randomised, placebo-controlled, double-blind, descriptive study, detomidine (0.02 mg/kg bwt i.v.) was administered to 6 mature horses on 4 separate occasions. Twenty-five mins later, each horse received one of 4 treatments: Group 1 saline (0.9% i.v.) as a placebo control; Group 2 atipamezole (0.05 mg/kg bwt i.v.); Group 3 atipamezole (0.1 mg/kg bwt i.v.); and Group 4 tolazoline (4.0 mg/kg bwt i.v.). Sedation, muscle relaxation and ataxia were scored by 3 independent observers at 9 time points. Horses were led through an obstacle course at 7 time points. Course completion time was recorded and the ability of the horse to traverse the course was scored by 3 independent observers. Horses were videotaped before, during and after each trip through the obstacle course. RESULTS: Atipamezole and tolazoline administration incompletely antagonised the effects of detomidine, but the time course to recovery was shortened. CONCLUSIONS AND POTENTIAL RELEVANCE: Single bolus administration of atipamezole or tolazoline produced partial reversal of detomidine sedation and may be useful for minimising detomidine sedation.
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Hada, T., Ohmura, H., Mukai, K., Eto, D., Takahashi, T., & Hiraga, A. (2006). Utilisation of the time constant calculated from heart rate recovery after exercise for evaluation of autonomic activity in horses. Equine Vet J Suppl, (36), 141–145.
Abstract: REASONS FOR PERFORMING STUDY: Heart rate (HR) recovery immediately after exercise is controlled by autonomic functions and the time constant (T) calculated from HR recovery is thought to be an index of parasympathetic activity in man. OBJECTIVES: To investigate whether it is possible to evaluate autonomic function using the time constant in horses. METHODS: Five Thoroughbred horses were subjected to a standard exercise test. Following pre-medication with saline, atropine and/or propranolol, the horses ran for 2.5 min at a speed of 8 m/sec at a 10% incline and T was calculated from HR after the exercise. Secondly, 7 Thoroughbred horses were then trained for 11 weeks and T and maximal oxygen uptake (VO2max) measured at intervals of 1 or 2 weeks. In 6 horses, T with atropine pre-medication was also measured before and after the whole training period. Furthermore, the HR variability at rest was evaluated by power spectral analysis at intervals of 3 or 4 weeks. RESULTS: Time constant was increased by atropine and/or propranolol pre-medication, decreased with the progress of training and inversely correlated with VO2max during training (r = 0.43, P<0.005). Parasympathetic blockade significantly decreased T only after and not before, the training; however, T was lower in post training than in pretraining, irrespective of parasympathetic blockade. On the other hand, parasympathetic activity at rest was attenuated and sympathetic activity became predominant following the training. CONCLUSION: Heart rate recovery is affected by sympathetic withdrawal and parasympathetic reactivation in horses and suggests that physical training hastened HR recovery by improving the parasympathetic function after exercise with aerobic capacity. However, the effects of other factors need to be considered because the training effect appeared on T even under parasympathetic blockade. The parasympathetic activity at rest is in contrast to that after exercise, suggesting that T does not reflect parasympathetic activity at rest. POTENTIAL RELEVANCE: If demonstrated how HR recovery is controlled after exercise, its analysis will be important in the evaluation of physical fitness in horses.
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Heistermann, M., Palme, R., & Ganswindt, A. (2006). Comparison of different enzyme-immunoassays for assessment of adrenocortical activity in primates based on fecal analysis. Am. J. Primatol., 68(3), 257–273.
Abstract: Most studies published to date that used fecal glucocorticoid measurements to assess adrenocortical activity in primate (and many nonprimate) species applied a specific cortisol or corticosterone assay. However, since these native glucocorticoids are virtually absent in the feces of most vertebrates, including primates, the validity of this approach has recently been questioned. Therefore, the overall aim of the present study was to assess the validity of four enzyme-immunoassays (EIAs) using antibodies raised against cortisol, corticosterone, and reduced cortisol metabolites (two group-specific antibodies) for assessing adrenocortical activity using fecal glucocorticoid metabolite (GCM) measurements in selected primate species (marmoset, long-tailed macaque, Barbary macaque, chimpanzee, and gorilla). Using physiological stimulation of the hypothalamo-pituitary-adrenocortical (HPA) axis by administering exogenous ACTH or anesthesia, we demonstrated that at least two assays detected the predicted increase in fecal GCM levels in response to treatment in each species. However, the magnitude of response varied between assays and species, and no one assay was applicable to all species. While the corticosterone assay generally was of only limited suitability for assessing glucocorticoid output, the specific cortisol assay was valuable for those species that (according to high-performance liquid chromatography (HPLC) analysis data) excreted clearly detectable amounts of authentic cortisol into the feces. In contrast, in species in which cortisol was virtually absent in the feces, group-specific assays provided a much stronger signal, and these assays also performed well in the other primate species tested (except the marmoset). Collectively, the data suggest that the reliability of a given fecal glucocorticoid assay in reflecting activity of the HPA axis in primates clearly depends on the species in question. Although to date there is no single assay system that can be used successfully across species, our data suggest that group-specific assays have a high potential for cross-species application. Nevertheless, regardless of which GC antibody is chosen, our study clearly reinforces the necessity of appropriately validating the respective assay system before it is used.
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Turner, K. K., Nielsen, B. D., O'Connor, C. I., & Burton, J. L. (2006). Bee pollen product supplementation to horses in training seems to improve feed intake: A pilot study. J Anim Physiol Anim Nutr (Berl), 90(9-10), 414–420.
Abstract: The objective of this study was to determine the efficacy of supplementation of Dynamic Trio 50/50, a bee pollen-based product, to improve physical fitness, blood leukocyte profiles, and nutritional variables in exercised horses. Ten Arabian horses underwent a standardised exercise test (SET), then were pair-matched by sex and fitness and randomly assigned to BP (receiving 118 g of Dynamic Trio 50/50 daily) or CO (receiving 73 g of a placebo) for a period of 42 days. A total collection was conducted from days 18 to 21 on six geldings to determine nutrient retention and neutral detergent fibre (NDF) and acid detergent fibre (ADF) digestibility. Horses were exercise conditioned and completed another SET on day 42. V160 and V200 were calculated from SET heart rates (HR). Lactate, glucose, haematocrit (HT) and haemoglobin (HB) concentrations were determined from SET blood samples. Total leukocyte count, and circulating numbers of various leukocytes and IgG, IgM and IgA concentrations were determined in rest and recovery blood samples from both SETs. Geldings on BP (n = 3) ate more feed than CO. BP had less phosphorus excretion, and tended to retain more nitrogen. BP tended to digest more NDF and ADF while having lower NDF digestibility and tending to have lower ADF digestibility. No treatment differences existed for V160 and V200, HR, lactate, HT and HB. There was a trend for lymphocyte counts to be lower in BP than CO on day 42. Dynamic Trio 50/50 supplementation may have a positive effect on performance by helping horses in training meet their potentially increased nutrient demands by increasing feed intake and thus nutrient retention.
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Spadavecchia, C., Arendt-Nielsen, L., Spadavecchia, L., Mosing, M., Auer, U., & van den Hoven, R. (2007). Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. Vet Anaesth Analg, 34(1), 48–58.
Abstract: OBJECTIVE: To assess the effects of a single intravenous dose of butorphanol (0.1 mg kg(-1)) on the nociceptive withdrawal reflex (NWR) using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. STUDY DESIGN: 'Unblinded', prospective experimental study. ANIMALS: Ten adult horses, five geldings and five mares, mean body mass 517 kg (range 487-569 kg). METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the palmar digital nerve. Repeated stimulations were applied to evoke temporal summation. Surface electromyography was performed to record and quantify the responses of the common digital extensor muscle to stimulation and behavioural reactions were scored. Before butorphanol administration and at fixed time points up to 2 hours after injection, baseline threshold intensities for NWR and temporal summation were defined and single suprathreshold stimulations applied. Friedman repeated-measures analysis of variance on ranks and Wilcoxon signed-rank test were used with the Student-Newman-Keul's method applied post-hoc. The level of significance (alpha) was set at 0.05. RESULTS: Butorphanol did not modify either the thresholds for NWR and temporal summation or the reaction scores, but the difference between suprathreshold and threshold reflex amplitudes was reduced when single stimulation was applied. Upon repeated stimulation after butorphanol administration, a significant decrease in the relative amplitude was calculated for both the 30-80 and the 80-200 millisecond intervals after each stimulus, and for the whole post-stimulation interval in the right thoracic limb. In the left thoracic limb a decrease in the relative amplitude was found only in the 30-80 millisecond epoch. CONCLUSION: Butorphanol at 0.1 mg kg(-1) has no direct action on spinal Adelta nociceptive activity but may have some supraspinal effects that reduce the gain of the nociceptive system. CLINICAL RELEVANCE: Butorphanol has minimal effect on sharp immediate Adelta-mediated pain but may alter spinal processing and decrease the delayed sensations of pain.
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Elhay, M., Newbold, A., Britton, A., Turley, P., Dowsett, K., & Walker, J. (2007). Suppression of behavioural and physiological oestrus in the mare by vaccination against GnRH. Aust Vet J, 85(1-2), 39–45.
Abstract: 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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Kristiansen, K. K., & Kold, S. E. (2007). 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. Equine Vet J, 39(2), 150–156.
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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