Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four adult ostriches developed sudden onset paresis and were unable to stand up when disturbed. After treatment with selenium and vitamin E, one of the birds could stand and move normally. The others died and post mortem examination revealed pale patches in the thigh muscles. Histopathological examination showed degeneration of skeletal muscles as seen in nutritional myopathy. Serum selenium and vitamin E levels were low whereas aspartate aminotransferase and creatine kinase levels were very high. All remaining birds on the farm were given multimineral and vitamin E supplement and no more cases were seen.
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PMID:Selenium-vitamin E responsive myopathy in farmed ostriches (Struthio camelus) in Botswana. 1848 8

Muscle injury is common in Florida manatees (Trichechus manatus latirostris). Plasma aspartate aminotransferase (AST) is frequently used to assess muscular damage in capture myopathy and traumatic injury. Therefore, accurate measurement of AST and alanine aminotransferase (ALT) is important in managed, free-ranging animals, as well as in those rehabilitating from injury. Activities of these enzymes, however, are usually not increased in manatees with either acute or chronic muscle damage, despite marked increases in plasma creatine kinase activity. It is hypothesized that this absence of response is due to apoenzymes in the blood not detected by commonly used veterinary assays. Addition of coenzyme pyridoxal-5-phosphate (P5P or vitamin B6) should, therefore, result in higher measured enzyme activities. The objective of this study was to determine the most accurate, precise, and diagnostically useful method for aminotransferase measurement in manatees that can be used in veterinary practices and diagnostic laboratories. Additionally, appropriate collection and storage techniques were assessed. The use of an optimized commercial wet chemical assay with 100 micromol P5P resulted in a positive bias of measured enzyme activities in a healthy population of animals. However, AST and ALT were still much lower than that typically observed in domestic animals and should not be used alone in the assessment of capture myopathy and muscular trauma. Additionally, the dry chemistry analyzer, typically used in clinics, reported significantly higher and less precise AST and ALT activities with poor correlation to those measured with wet chemical methods found in diagnostic laboratories. Therefore, these results cannot be clinically compared. Overall, the optimized wet chemical method was the most precise and diagnostically useful measurement of aminotransferase in samples. Additionally, there was a statistically significant difference between paired serum and plasma measurement, indicating that separate reference intervals should be established for serum and plasma. Finally, storage of these enzymes at -70 degrees C for 1 mo resulted in up to a 25% decrease in enzymatic activity in manatee plasma.
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PMID:Comparison of blood aminotransferase methods for assessment of myopathy and hepatopathy in Florida manatees (Trichechus manatus latirostris). 1863 8

We diagnosed exertional myopathy (EM) in a grizzly bear (Ursus arctos) that died approximately 10 days after capture by leghold snare in west-central Alberta, Canada, in June 2003. The diagnosis was based on history, post-capture movement data, gross necropsy, histopathology, and serum enzyme levels. We were unable to determine whether EM was the primary cause of death because autolysis precluded accurate evaluation of all tissues. Nevertheless, comparison of serum aspartate aminotransferase and creatine kinase concentrations and survival between the affected bear and other grizzly bears captured by leghold snare in the same research project suggests EM also occurred in other bears, but that it is not generally a cause of mortality. We propose, however, occurrence of nonfatal EM in grizzly bears after capture by leghold snare has potential implications for use of this capture method, including negative effects on wildlife welfare and research data.
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PMID:Exertional myopathy in a grizzly bear (Ursus arctos) captured by leghold snare. 1895 53

CASE DESCRIPTION - A 6-year-old castrated male Llewelyn Setter was evaluated because of an acute onset of myalgia and respiratory distress. CLINICAL FINDINGS - Physical examination revealed a stiff stilted gait, swollen muscles that appeared to cause signs of pain, panting, and ptyalism. The dog had a decrease in palpebral reflexes bilaterally and a decrease in myotatic reflexes in all 4 limbs. The panniculus reflex was considered normal, and all other cranial nerve reflexes were intact. Serum biochemical analysis revealed markedly high cardiac troponin-I concentration and creatine kinase and aspartate aminotransferase activities. Urinalysis revealed myoglobinuria. Results for thoracic and abdominal radiography, blood pressure measurement, and an ECG were within anticipated limits. Echocardiographic findings were consistent with secondary systolic myocardial failure. Arterial blood gas analysis confirmed hypoxemia and hypoventilation. The dog had negative results when tested for infectious diseases. Examination of skeletal muscle biopsy specimens identified necrotizing myopathy. TREATMENT AND OUTCOME - Treatment included ventilatory support; IV administration of an electrolyte solution supplemented with potassium chloride; administration of dantrolene; vasopressor administration; parenteral administration of nutrients; use of multimodal analgesics; administration of clindamycin, furosemide, mannitol, and enrofloxacin; and dietary supplementation with L-carnitine and coenzyme Q(10). Other medical interventions were not required, and the dog made a rapid and complete recovery. CLINICAL RELEVANCE - Necrotizing myopathy resulting in rhabdomyolysis and myoglobinuria can lead to life-threatening physical and biochemical abnormalities. Making a correct diagnosis is essential, and patients require intensive supportive care. The prognosis can be excellent for recovery, provided there is no secondary organ dysfunction.
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PMID:Successful management of a dog that had severe rhabdomyolysis with myocardial and respiratory failure. 1936 38

Statins are regarded as a well-tolerated class of drugs, particularly when compared with some of the older lipid-modifying agents, which have poor rates of compliance. Despite some early concern, the incidence of lens opacities observed in clinical studies involving statin use is no different from that in a normal ageing population. Similarly, the occurrence of insomnia with lipophilic agents appears to have been overemphasised and is not a clinically significant problem, irrespective of the statin under study. Fluvastatin is the newest representative of this class of agents; it has already been evaluated in thousands of patients who have hyperlipidaemia with and without additional risk factors. In controlled clinical studies, the incidence of the majority of adverse events observed with fluvastatin therapy is no higher than that seen with placebo, with the exception of gastrointestinal disturbances (known to be common to all stains). Nonetheless, the incidence of these effects seen with fluvastatin treatment is noted to be lower than that associated with cholestyramine or fibrate use. Elevations in levels of liver transaminases (aspartate aminotransferase and alanine aminotransferase) have been reported with fluvastatin therapy but have led to discontinuation of treatment with the same frequency as with placebo. Elevations in creatine kinase levels as a cause of discontinuing fluvastatin are not more frequent than with placebo. Myopathy and rhabdomyolysis have not been reported with fluvastatin therapy, and myalgia does not occur more frequently than with placebo. In terms of drug interactions, fluvastatin does not interfere with the efficacy of antihypertensive agents. In controlled clinical trials, the overall reported discontinuation rate due to adverse events noted with fluvastatin therapy is 3.3%, which is not significantly distingushable from the rate associated with placebo (3.5%)2.
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PMID:Safety profile of fluvastatin. 872 86

Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been studied in several models to examine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (cholestyramine), and niacin. The combination of fluvastatin with bezafibrate has been studied in a double-blind trial involving patients with well-documented familial hypercholesterolaemia. Fluvastatin 40 mg/day, combined with either bezafibrate 400 mg/day or cholestyramine 8 g/day, resulted in reductions in levels of low-density lipoprotein cholesterol (LDL-C), these being indistinguishable between the groups; however, significantly greater increases in levels of high-density lipoprotein cholesterol (21.3%) and reductions in levels of triglycerides (25.1%) were seen with the fluvastatin-bezafibrate combination. No notable increases were seen in levels of serum creatine kinase, aspartate aminotransferase, or alanine aminotransferase, and no cases of myopathy were observed. In a study model that examined low-dose combinations of fluvastatin with cholestyramine, reductions in levels of LDL-C of 15.8% and 19.3% were seen with fluvastatin 10 mg and 20 mg, respectively. After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26.3% in the 10 mg fluvastatin-cholestyramine group and 31.2% in the 20 mg fluvastatin-cholestyramine group were observed, whereas the placebo-cholestyramine group displayed a reduction of 14.9%. Doubling the resin dosage to 16 g/day for the final 8 weeks of the study provided little additional benefit. Myotoxicity has been observed when lovastatin is coadministered with niacin, and so the combination of niacin with fluvastatin has also been studied to examine the possibility of this effect occurring. Patients were randomised to either fluvastatin 20 mg or placebo for 6 weeks, after which time open-label niacin was administered to all patients and titrated to a final dosage of 3 g/day. After 6 weeks, fluvastatin produced a 20.8% reduction in LDL-C levels from baseline. When combined with niacin, a 43.7% reduction was noted at the week 15 endpoint, against the 26.5% reduction seen with niacin monotherapy. The combination was well tolerated, with no reports of myopathy or of significant elevations in creatine kinase or liver transaminase levels. Combinations of fluvastatin with a variety of other agents have been shown to have significant effects on lipid profiles, with no evidence to date of clinically remarkable safety findings. Thus, the use of combination therapies may result in optimal management of patients with moderately severe hypercholesterolaemia and mixed dyslipidaemic profiles.
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PMID:Fluvastatin in combination with other lipid-lowering agents. 872 88

The purpose of this investigation was to determine the utility of fast-twitch skeletal muscle troponin I (fsTnI) and urinary myoglobin (uMB) as biomarkers of skeletal muscle injury in 8-week-old Sprague-Dawley rats. fsTnI and uMB were quantified by enzyme-linked immunosorbent assay and compared with standard clinical assays including creatine kinase, aldolase, aspartate aminotransferase, and histopathological assessments. Detectable levels of uMB were normalized to urinary creatinine to control for differences in renal function. Seven compounds, including those with toxic effects on skeletal muscle, cardiac muscle, or liver, were evaluated. fsTnI was typically nondetectable (< 5.9 ng/ml serum) in vehicle-treated female and male rats but increased in a dose-dependent manner to at least 300 ng/ml in cerivastatin-induced severe fast-twitch specific myotoxicity. Minimal myopathy induced by investigational compounds BMS-600149 and BMS-687453 increased serum fsTnI to about 30-50 ng/ml, suggesting a reasonable dynamic range for detecting mild to severe skeletal muscle toxicity. In direct contrast, fsTnI was only marginally increased relative to population control values in rats treated with triamcinolone acetonide, which produces muscle atrophy or the cardiotoxins isoproterenol and CoCl2. uMB was typically nondetectable (< 1.6 ng/ml urine) in vehicle-treated female and male rats but increased to approximately 140, 300, and 30 ng/mg creatinine in rats treated with cerivastatin, BMS-687453, and triamcinolone acetonide, respectively. Cardiotoxicity also increased uMB in rats treated with isoproterenol and CoCl2 with urine concentrations ranging from 20 to 30 ng/mg creatinine. Severe hepatotoxicity (coumarin) did not significantly affect serum fsTnI or uMB levels. Collectively, these data suggest that fsTnI is specific for skeletal muscle toxicity, whereas uMB is nonspecific, increasing with skeletal muscle and cardiac toxicity. Accordingly, the complement of fsTnI and uMB, in conjunction with standard clinical assays may comprise a useful diagnostic panel for assessing drug-induced myopathy in rats.
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PMID:Biomarkers of drug-induced skeletal muscle injury in the rat: troponin I and myoglobin. 1962 85

Rayless goldenrod (Isocoma pluriflora) sporadically poisons livestock in the southwestern United States. Similarities with white snakeroot (Ageratina altissima) poisoning and nearly identical chemical analyses led early researchers to conclude that tremetol, a mixture of benzofuran ketones, is the rayless goldenrod toxin. The toxicity of these ketone toxins have not been fully characterized nor are the pathogenesis and sequelae of poisoning completely understood. The objective of the current study was to characterize and describe the clinical and pathologic changes of rayless goldenrod toxicity in goats. Fifteen goats were gavaged with rayless goldenrod to obtain benzofuran ketone doses of 0, 10, 20, 40, and 60 mg/kg/day. After 7 treatment days, the goats were euthanized, necropsied, and tissues were processed for microscopic studies. After 5 or 6 days of treatment, the 40-mg/kg and 60-mg/kg goats were reluctant to move, stood with an erect stance, and became exercise intolerant. They had increased resting heart rate, prolonged recovery following exercise, and increased serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatinine kinase activities. All treated animals developed skeletal myopathy with dose-related distribution and severity. The goats dosed with 20 mg/kg and higher also developed myocardial degeneration and necrosis. Although skeletal myonecrosis was patchy and widely distributed, the quadriceps femoris was consistently damaged, even in low-dosed animals. Myocardial lesions were most severe in the papillary muscles of 60-mg/kg-dosed animals. This indicates that goats are highly susceptible to rayless goldenrod poisoning, and that the characteristic lesion of poisoning is skeletal and cardiac myonecrosis.
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PMID:Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in goats. 2062 27

The aim of this study was to determine the occurrence and frequency of a mutation in the gene coding for skeletal muscle glycogen synthase type 1 (GYS-1), which is the cause of equine polysaccharide storage myopathy (PSSM) type 1 in a population of 50 Haflingers. GYS-1 genotyping of 50 Haflingers was performed with a validated restriction fragment length polymorphism (RFLP) assay. The second aim was to compare resting and post-exercise muscle enzyme activities as well as parameters of glucose metabolism in blood between horses with and without the mutation. Nine of the 50 Haflingers were identified to be heterozygous for the mutation (HR). None was homozygous (HH). The estimated HR prevalence was 18 per cent in this herd. Mean aspartate aminotransferase (AST) activity at rest and mean creatine kinase and AST activity after exercise were significantly higher in HR compared with RR (homozygote normal) horses. No significant differences could be found in the other parameters.
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PMID:Estimated prevalence of the GYS-1 mutation in healthy Austrian Haflingers. 2194 56

Capture myopathy is a complication of capture and handling in many species of birds and mammals. Muscular necrosis leads to ataxia, paralysis, and pain, whereas metabolic disturbances can result in death. We conducted an opportunistic clinical trial on Bar-tailed Godwits (Limosa lapponica baueri) that developed capture myopathy after a cannon-net capture in New Zealand in October 2008. We assessed the beneficial effects of midazolam, a benzodiazepine with the effects of anxiolysis, muscle relaxation, and sedation, in the adjunctive treatment of capture myopathy. Physical and biochemical parameters were analyzed retrospectively for their potential as indicators for survival until release. Birds (n=16) were treated with subcutaneous fluid therapy, a nonsteroidal anti-inflammatory (meloxicam), gavage feeding, and sling therapy twice daily. The treatment group (n=8) was treated twice daily with intramuscular midazolam injections, 1.5 mg/kg. Surviving godwits were released over 1-9 days, with 6 of 8 treated birds (75%) surviving to release, compared with 3 of 8 controls (38%). Inability to counteract weight loss in captivity was the most significant problem for both groups. Lack of waterproofing and predation were contributing causes of death for at least two godwits after release. Birds treated with midazolam showed subjective benefits including improved tolerance of handling and sling therapy. Clinical parameters (change in body mass, packed cell volume [PCV], plasma creatine kinase [CK], aspartate aminotransferase [AST], total protein, and uric acid [UA] over time) were not statistically different between groups, although peak average values for CK, AST, and UA were lower in the treatment group. Decline in body mass (%), PCV, final plasma UA, and peak plasma CK were the most useful prognostic indicators. Midazolam shows potential as an ancillary treatment for capture myopathy in birds and is worthy of continued study and use.
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PMID:Midazolam as an adjunctive therapy for capture myopathy in Bar-tailed Godwits (Limosa lapponica baueri) with prognostic indicators. 2210 63


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