69 research outputs found
The impact of MK-467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal
The effect of MKâ467, a peripheral α2âadrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2âweek washout periods. Medetomidine (MED) 30 Όg/kg alone or combined in the same syringe with MKâ467 300 Όg/kg (MMK) was injected intramuscular, followed by ATI 150 Όg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. With MKâ467, medetomidine plasma concentrations were threefold higher prior to ATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidineârelated cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly when MKâ467 was included. In this study, MKâ467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement. </p
Effects of dexmedetomidine and MK-467 on plasma glucose, insulin and glucagon in a glibenclamide-induced canine hypoglycaemia model
The commonly used sedative α2-adrenoceptor agonist
dexmedetomidine has adverse cardiovascular effects in dogs that can be
prevented by concomitant administration of the peripherally acting α2-adrenoceptor
antagonist MK-467. An ancillary effect of dexmedetomidine is to
decrease insulin release from the pancreas, whereas MK-467 stimulates
insulin release. This study assessed the effects of co-administered
dexmedetomidine and MK-467 in a canine glibenclamide-induced
hypoglycaemia model. In a randomised, cross-over experiment, eight
beagle dogs received five intravenous treatments, comprising two
administrations of saline, with dexmedetomidine or dexmedetomidine and
MK-467, and three administrations of glibenclamide, with saline,
dexmedetomidine or dexmedetomidine and MK-467. Plasma concentrations of
glucose, lactate, insulin, glucagon and the test drugs were monitored.
Administration of glibenclamide significantly increased insulin
secretion and decreased blood glucose concentrations. Dexmedetomidine
counteracted glibenclamide-evoked hypoglycaemia. This was opposed by the
α2-adrenoceptor antagonist MK-467, but the
glibenclamide-evoked hypoglycaemia was not potentiated by
co-administration of dexmedetomidine and MK-467. None of the dogs
developed uncontrolled hypoglycaemia. Thus, the combination of
dexmedetomidine and MK-467 appeared to be safe in this canine
hypoglycaemia model. Nevertheless, when MK-467 is used to alleviate the
undesired cardiovascular effects of α2-adrenoceptor agonists
in dogs, it should be used with caution in animals at risk for
hypoglycaemia because of its insulin-releasing and hypoglycaemic
effects.</p
Genetic diversity in the modern horse illustrated from genome-wide SNP data
Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection
Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data
Horses were domesticated from the Eurasian steppes 5,000â6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection
Detecting early kidney damage in horses with colic by measuring matrix metalloproteinase -9 and -2, other enzymes, urinary glucose and total proteins
BACKGROUND: The aim of the study was to investigate urine matrix metalloproteinase (MMP-2 and -9) activity, alkaline phosphatase/creatinine (U-AP/Cr) and gamma-glutamyl-transpeptidase/creatinine (U-GGT/Cr) ratios, glucose concentration, and urine protein/creatinine (U-Prot/Cr) ratio and to compare data with plasma MMP-2 and -9 activity, cystatin-C and creatinine concentrations in colic horses and healthy controls. Horses with surgical colic (n = 5) were compared to healthy stallions (n = 7) that came for castration. Blood and urine samples were collected. MMP gelatinolytic activity was measured by zymography. RESULTS: We found out that horses with colic had significantly higher urinary MMP-9 complex and proMMP-9 activities than horses in the control group. Colic horses also had higher plasma MMP-2 activity than the control horses. Serum creatinine, although within reference range, was significantly higher in the colic horses than in the control group. There was no significant increase in urinary alkaline phosphatase, gamma-glutamyltranspeptidase or total proteins in the colic horses compared to the control group. A human cystatin-C test (Dako Cytomation latex immunoassay(Âź )based on turbidimetry) did not cross react with equine cystatin-C. CONCLUSION: The results indicate that plasma MMP-2 may play a role in the pathogenesis of equine colic and urinary MMP-9 in equine kidney damage
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