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)

A family with a complete deficiency of lactate dehydrogenase M-subunit was investigated. The propositus was an 18-year-old male who complained of exertional pigmenturia and easy fatigue. Marked discrepancy was observed in the ratio between creatine kinase and lactate dehydrogenase (CK/LDH). Electrophoretic analysis of serum LDH isoenzymes of the propositus demonstrated only one activity band of LDH H4. A complete lack of the LDH M-subunit was similarly demonstrated in erythrocytes, leukocytes and in the intermediate vastus muscle. LDH levels in the muscle specimen were markedly decreased in the patient, whereas CK and aspartate aminotransferase were almost the same as in a control subject. LDH isoenzymes of erythrocytes were analyzed in 5 siblings and in the parents. This demonstrated a complete lack of LDH M-subunit in 3 siblings. The ratio between H-subunit and M-subunit (H/M) in erythrocyte LDH suggested a partial absence of the M-subunit in two siblings and in the parents. An abortive increase of blood lactate and a marked increase in blood pyruvate were observed immediately after ischemic work of the forearm, accompanied by an increase in serum creatine kinase and myoglobinuria. The present case represents a newly described form of genetically determined myopathy.
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PMID:Hereditary deficiency of lactate dehydrogenase M-subunit. 744 46

Plasma CK concentrations have been widely used as the primary muscle enzyme marker for diagnosis and progression of myositis. Recently, total CK and CK-MB serum concentrations have been compared to, and used in conjunction with, serum concentrations of aspartate aminotransferase in diagnosis of myositis. The algorithmic use of CK, AST, and aldolase plasma concentrations to diagnose and categorize patients with myopathy may be a useful method of diagnosing specific muscle disease without invasive procedures. CAIII, as a specific marker for skeletal muscle damage, may replace CK as the enzyme of choice in diagnosis and progression of myositis and other muscle disease. Additional studies are required to determine the usefulness of carbonic anhydrase for the diagnosis and assessment of myositis.
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PMID:Evaluation of laboratory tests as a guide to diagnosis and therapy of myositis. 785 25

The use of serum myosin light chain 1 (MLC1) in the diagnosis and treatment response of a patient with biopsy proven inflammatory myopathy is presented. A serum MLC1 level was elevated at presentation despite a normal creatine phosphokinase level. MLC1 levels more closely paralleled the clinical status than the aspartate aminotransferase and lactate dehydrogenase levels. The results suggest that MLC1 levels may facilitate the early diagnosis and management of patients with inflammatory myopathy. Moreover, the excellent response of our patient to low dose prednisone might suggest that the results of treatment could be improved by early detection and institution of therapy.
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PMID:Inflammatory myopathy--early diagnosis and management by serum myosin light chains measurements. 800 80

Seventy-four patients with plasma low-density lipoprotein cholesterol levels > or = 160 mg/dl after an American Heart Association phase 1 diet were randomized to double-blind treatment with fluvastatin, 20 mg/day, or placebo for 6 weeks. Immediate-release niacin was then added to both treatment regimens and titrated to a maximum of 3 g/day for a further 9 weeks. After 6 weeks of fluvastatin monotherapy, low-density lipoprotein cholesterol levels decreased by 21% (p < 0.001 vs placebo), and after the addition of niacin, response was potentiated to 40% compared with 25% for the niacin control group at study end point (p < 0.001). Fluvastatin, alone and in combination with niacin, also significantly improved high-density lipoprotein cholesterol (increases of about 30%) and triglyceride profiles (decreases of approximately 28%) from baseline. Lipoprotein(a) decreased by 37% in those receiving fluvastatin-niacin but was unaltered in those receiving fluvastatin alone. No serious adverse events were ascribed to fluvastatin, and no cases of myositis were observed. Small, transient, asymptomatic increases in aspartate aminotransferase were noted with fluvastatin-niacin treatment but were not considered clinically relevant. Although the fluvastatin-niacin combination in this study was without evidence of significant transaminitis, myopathy, or rhabdomyolysis, it would seem prudent to continue to monitor its safety with longer term use. In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective, safe, and well-tolerated therapeutic alternative for hypercholesterolemia.
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PMID:Fluvastatin with and without niacin for hypercholesterolemia. 802 79

Subclinical nutritional myopathy was induced in 5-month-old sheep by feeding them a diet low in vitamin E and selenium. Subsequently clinical myopathy was induced by dosing with protected polyunsaturated fatty acids. Plasma activities of creatine kinase (CK), pyruvate kinase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase and aldolase, enzymes of muscle origin, all remained above their reference ranges in clinically affected sheep, but fluctuated widely. Similar fluctuations occurred in subclinically affected animals, resulting in some activities being within the reference ranges and some above, at different times. Plasma malondialdehyde, an indicator of lipid peroxidation, proved of no diagnostic value. Terminal plasma CK activities were significantly correlated with microscopic damage in the vastus lateralis (VL), but not the vastus intermedius (VI) or the tensor fascia lata (TFL) muscles. AST was the most highly correlated with damage in VI and VL. In two clinically affected sheep successfully treated with an oral dose of alpha-tocopherol acetate all enzymes decreased steadily to within their reference ranges, at rates probably related to their plasma half-lives. These results suggest that measurement of plasma CK activity would be useful in monitoring recovery of treated sheep.
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PMID:Plasma indicators of muscle damage in a model of nutritional myopathy in weaner sheep. 817 46

A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.
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PMID:Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. 819 20

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. Drug-related 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 not significantly distinguishable from the rate associated with placebo.
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PMID:Safety profile of fluvastatin. 1948 70

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. 1949 70

The ultrasonographic appearance of the equine triceps muscle of clinically normal horses, before and after general anaesthesia, was investigated and compared with 5 cases of post anaesthetic myopathy. The triceps muscle areas were examined bilaterally using a 7.5 MHz linear array probe in 2 different planes, with each limb both weightbearing and nonweightbearing. The triceps muscles of 4 unanaesthetised horses were scanned twice, 24 h apart. Six horses underwent general anaesthesia and were scanned pre-anaesthesia and at 1 and 24 h intervals after recovery. Blood samples were obtained in the unanaesthetised group at each scan time and, in the anaesthetised group, pre-anaesthesia and at 10 min, 5 and 24 h after recovery. Creatine kinase (CK) and aspartate aminotransferase (AST) concentrations were measured. Anaesthetic details and recovery were related to the ultrasonographic and muscle enzyme findings. Five horses with post anaesthetic myopathy were scanned at intervals after the onset of clinical signs. In normal horses, the triceps muscle appeared ultrasonographically as echoic striations separated by anechoic areas. The fascia dividing muscle bellies was visible as an echoic line. Ultrasonographs obtained with the limb nonweightbearing had no change or a slight overall increase in echogenicity. The scans of control unanaesthetised horses were unchanged on successive days. All anaesthetised horses had uncomplicated anaesthesia and recoveries and did not exhibit any clinical signs of post anaesthetic myopathy. Elevated CK and AST values were found up to 342 and 195%, respectively, of the pre-anaesthetic values but no significant alterations in the ultrasonographic appearance of the muscles were detected. Clinical cases of post anaesthetic myopathy had disruption of the normal ultrasonographic pattern. There was an overall increase in echogenicity with a loss of the normal striated pattern. In 3 cases, there was localised increased echogenicity within the muscle. One of these horses was humanely destroyed for other reasons and histological examination of the affected muscle revealed a necrotic area correlating with the hyperechoic region. Two horses had bilateral involvement of the triceps musculature. Four horses recovered clinically from the myopathy and the ultrasonographic appearance returned to normal except in 1 horse where focal hyperechoic regions remained 10 weeks after the onset of the clinical signs.
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PMID:Ultrasonography of the equine triceps muscle before and after general anaesthesia and in post anaesthetic myopathy. 881 97

Because of the very low concentrations of selenium in the dry matter of grass, grass silage, hay and maize silage Slovenian dairy herds need to be supplemented with selenium. Selenium in the form of mineral and feed mixtures maintained adequate mean (sd) blood serum selenium concentrations of 43.9 (27.6) to 65.3 (18.5) micrograms/litre in lactating cows, but in late lactation and in the dry period when only mineral mixtures were used, about 60 per cent of the cows had marginal serum selenium concentrations, mainly because of the low intake of the mineral supplement. In 18 herds which were either unsupplemented or irregularly supplemented with selenium, the mean (sd) concentrations in blood serum were 13.7 (5.5) micrograms/litre and 17.4 (9.2) micrograms/litre, respectively, for selenium and 2.98 (2.72) mg/litre and 1.62 (1.73) mg/litre for vitamin E, indicating that under extensive farming conditions in Slovenia the lack of both micronutrients may be responsible for nutritional muscular dystrophy in calves. Among 37 clinical cases, cardiorespiratory signs predominated in 25 of the calves and skeletal myopathy was dominant in 12. A very low mean serum selenium concentration [9.7 (7.2) micrograms/litre] and typically high activities of aspartate aminotransferase (AST) [1125 (373) U/litre] and creatine kinase (CK) [9169 (3681) U/litre) were observed for the myocardial form of the disease, and 2797 (550) U/litre and 22,650 (13,500) U/litre were observed for the skeletal form of the disease. A highly significant (P < 0.0001) difference in the selenium concentration of liver dry matter between the regularly supplemented [402 (207) micrograms/kg] and irregularly supplemented [173 (69) micrograms/kg] herds was observed. If a minimum value of 300 micrograms/kg of liver dry matter is accepted as the criterion for the determination of adequate selenium status, 93 per cent of the samples from the irregularly supplemented herds were selenium deficient. A similar proportion was estimated to be selenium deficient when the criterion was taken to be 30 micrograms selenium/litre of blood serum.
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PMID:Assessment of selenium and vitamin E deficiencies in dairy herds and clinical disease in calves. 891 12


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