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Cho, K. C., & Chan, K. K. (1984). Kinetics of cold-induced denaturation of metmyoglobin. Biochimica et Biophysica Acta (BBA) – Protein Structure and Molecular Enzymology, 786(1-2), 103–108.
Abstract: Using a slow temperature-jump spectrophotometer, we have studied the kinetics of cold-induced denaturation of metmyoglobin between 0[degree sign]C and 20[degree sign]C at acidic pH. The time-scale of the transition is slow and is of the order of minutes. The results are consistent with the transition's involving a total of three states, native (N), transient intermediate (I) and denatured (D), which are converted from one to the other in that order.
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Geutjens, C. A., Clayton, H. M., & Kaiser, L. J. (2008). Forces and pressures beneath the saddle during mounting from the ground and from a raised mounting platform. The Veterinary Journal, 175(3), 332–337.
Abstract: The objective was to use an electronic pressure mat to measure and compare forces and pressures of the saddle on a horse's back when riders mounted from the ground and with the aid of a mounting platform. Ten riders mounted a horse three times each from the ground and from a 35 cm high mounting platform in random order. Total force (summation of forces over all 256 sensors) was measured and compared at specific points on the force-time curve. Total force was usually highest as the rider's right leg was swinging upwards and was correlated with rider mass. When normalized to rider mass, total force and peak pressure were significantly higher when mounting from the ground than from a raised platform (P < 0.05). The area of highest pressure was on the right side of the withers in 97% of mounting efforts, confirming the importance of the withers in stabilizing the saddle during mounting.
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Meschan, E. M., Peham, C., Schobesberger, H., & Licka, T. F. (2007). The influence of the width of the saddle tree on the forces and the pressure distribution under the saddle. The Veterinary Journal, 173(3), 578–584.
Abstract: As there is no statistical evidence that saddle fit influences the load exerted on a horse's back this study was performed to assess the hypothesis that the width of the tree significantly alters the pressure distribution on the back beneath the saddle. Nineteen sound horses were ridden at walk and trot on a treadmill with three saddles differing only in tree width. Kinetic data were recorded by a sensor mat. A minimum of 14 motion cycles were used in each trial. The saddles were classified into four groups depending on fit. For each horse, the saddle with the lowest overall force (LOF) was determined. Saddles were classified as “too-narrow” if they were one size (2 cm) narrower than the LOF saddle, and “too-wide” if they were one size (2 cm) wider than the LOF saddle. Saddles two sizes wider than LOF saddles were classified as “very-wide”. In the group of narrow saddles, the pressure in the caudal third (walk 0.63 N/cm2 +/- 0.10; trot 1.08 N/cm2 +/- 0.26) was significantly higher compared to the LOF saddles (walk 0.50 N/cm2 +/- 0.09; trot 0.86 N/cm2 +/- 0.28). In the middle transversal third, the pressure of the wide saddles (walk 0.73 N/cm2 +/- 0.06; trot 1.52 N/cm2 +/- 0.19) and very-wide saddles (walk 0.77 N/cm2 +/- 0.06; trot 1.57 N/cm2 +/- 0.19) was significantly higher compared to LOF saddles (walk 0.65 N/cm2 +/- 0.10/ 0.63 N/cm2 +/- 0.11; trot 1.33 N/cm2 +/- 0.22/1.27 N/cm2 +/- 0.20). This study demonstrates that the load under poorly fitting saddles is distributed over a smaller area than under properly fitting saddles, leading to potentially harmful pressures peaks.
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Jallon, J. M., Risler, Y., & Iwatsubo, M. (1975). Beef liver L-Glutamate dehydrogenase mechanism: presteady state study of the catalytic reduction of 2.oxoglutarate by NADPH. Biochem Biophys Res Commun, 67(4), 1527–1536.
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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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Alexander, F., & Collett, R. A. (1974). Proceedings: Some observations on the pharmacokinetics of trimethoprim in the horse. Br J Pharmacol, 52(1), 142p.
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Machnik, M., Hegger, I., Kietzmann, M., Thevis, M., Guddat, S., & Schanzer, W. (2007). Pharmacokinetics of altrenogest in horses. J Vet Pharmacol Ther, 30(1), 86–90.
Abstract: The Federation Equestre Internationale has permitted the use of altrenogest in mares for the control of oestrus. However, altrenogest is also suspicious to misuse in competition horses for its potential anabolic effects and suppression of typical male behaviour, and thus is a controlled drug. To investigate the pharmacokinetics of altrenogest in horses we conducted an elimination study. Five oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose interval of 24 h. Following administration blood and urine samples were collected at appropriate intervals. Altrenogest concentrations were measured by liquid chromatography-tandem mass spectrometry. The plasma levels of altrenogest reached maximal concentrations of 23-75 ng/mL. Baseline values were achieved within 3 days after the final administration. Urine peak concentrations of total altrenogest ranged from 823 to 3895 ng/mL. Twelve days after the final administration concentrations were below the limit of detection (ca 2 ng/mL).
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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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Dirikolu, L., Lehner, A. F., Karpiesiuk, W., Hughes, C., Woods, W. E., Boyles, J., et al. (2003). Detection, quantification, metabolism, and behavioral effects of selegiline in horses. Vet Ther, 4(3), 257–268.
Abstract: Selegiline ([R]-[-]N,alpha-dimethyl-N-2- propynylphenethylamine or l-deprenyl), an irreversible inhibitor of monoamine oxidase, is a classic antidyskinetic and antiparkinsonian agent widely used in human medicine both as monotherapy and as an adjunct to levodopa therapy. Selegiline is classified by the Association of Racing Commissioners International (ARCI) as a class 2 agent, and is considered to have high abuse potential in racing horses. A highly sensitive LC/MS/MS quantitative analytical method has been developed for selegiline and its potential metabolites amphetamine and methamphetamine using commercially available deuterated analogs of these compounds as internal standards. After administering 40 mg of selegiline orally to two horses, relatively low (<60 ng/ml) concentrations of parent selegiline, amphetamine, and methamphetamine were recovered in urine samples. However, relatively high urinary concentrations of another selegiline metabolite were found, tentatively identified as N- desmethylselegiline. This metabolite was synthesized and found to be indistinguishable from the new metabolite recovered from horse urine, thereby confirming the chemical identity of the equine metabolite. Additionally, analysis of urine samples from four horses dosed with 50 mg of selegiline confirmed that N-desmethylselegiline is the major urinary metabolite of selegiline in horses. In related behavior studies, p.o. and i.v. administration of 30 mg of selegiline produced no significant changes in either locomotor activities or heart rates.
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Bykov, S., Lednev, I., Ianoul, A., Mikhonin, A., Munro, C., & Asher, S. A. (2005). Steady-state and transient ultraviolet resonance Raman spectrometer for the 193-270 nm spectral region. Appl Spectrosc, 59(12), 1541–1552.
Abstract: We describe a state-of-the-art tunable ultraviolet (UV) Raman spectrometer for the 193-270 nm spectral region. This instrument allows for steady-state and transient UV Raman measurements. We utilize a 5 kHz Ti-sapphire continuously tunable laser (approximately 20 ns pulse width) between 193 nm and 240 nm for steady-state measurements. For transient Raman measurements we utilize one Coherent Infinity YAG laser to generate nanosecond infrared (IR) pump laser pulses to generate a temperature jump (T-jump) and a second Coherent Infinity YAG laser that is frequency tripled and Raman shifted into the deep UV (204 nm) for transient UV Raman excitation. Numerous other UV excitation frequencies can be utilized for selective excitation of chromophoric groups for transient Raman measurements. We constructed a subtractive dispersion double monochromator to minimize stray light. We utilize a new charge-coupled device (CCD) camera that responds efficiently to UV light, as opposed to the previous CCD and photodiode detectors, which required intensifiers for detecting UV light. For the T-jump measurements we use a second camera to simultaneously acquire the Raman spectra of the water stretching bands (2500-4000 cm(-1)) whose band-shape and frequency report the sample temperature.
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