Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the potential dose effect of rosuvastatin on triglyceride (TG) levels in Japanese hypertriglyceridemic patients, we randomized 154 patients with TG levels of >or=200 and <800 mg/dL to 8 weeks of treatment with rosuvastatin 5, 10 or 20mg once daily; bezafibrate 200mg twice daily; or placebo. Compared with placebo, TG was reduced by 30.1% with rosuvastatin 5mg, 30.1% with 10mg and 32.3% with 20mg (all p<or=0.0001), with no evidence of a dose effect. Changes in TG were evident after 2 weeks of treatment and maintained thereafter. In a benchmark comparison, rosuvastatin across its dose range reduced TG by 29.1-31.1% from baseline versus 45.4% for bezafibrate. Compared with bezafibrate, rosuvastatin was superior with respect to changes in non-high-density lipoprotein cholesterol (non-HDL-C, -36.8 to -44.3% for rosuvastatin versus -2.0% for bezafibrate), low-density lipoprotein cholesterol (-31.9 to -41.0% versus +29.3%), total cholesterol (-27.1 to -33.3% versus +2.1%), although smaller improvements in HDL-C (12.4-16.7% versus 19.6%) were observed. Rosuvastatin also produced superior dose-related decreases in median high-sensitivity C-reactive protein (22.9-38.5%). Treatment was well tolerated in both rosuvastatin and bezafibrate patients, with clinically important increases in alanine aminotransferase being rare, no adverse effect on renal function being observed and no cases of myopathy or rhabdomyolysis being reported. The current study does not suggest a dose-related effect of rosuvastatin in lowering TG in hypertriglyceridemic Japanese patients, although dose-related improvements in other elements of the atherogenic lipid profile were observed.
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PMID:Effect of rosuvastatin 5-20mg on triglycerides and other lipid parameters in Japanese patients with hypertriglyceridemia. 1722 12

Exertional myopathy developed in three whooping cranes (Grus americana) secondary to routine capture, handling, and trauma. Presumptive diagnosis of exertional myopathy was based on history of recent capture or trauma, clinical signs, and elevation of aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, and serum potassium. Treatments were attempted in each case, but ultimately were not successful. Gross and microscopic lesions at necropsy confirmed the diagnosis in each case, with the leg musculature most severely affected. Guidelines for determining prognosis of exertional myopathy in cranes have been included based on the analysis of these cases and others in the literature. As treatment is largely unrewarding, prevention remains the key in controlling exertional myopathy. Identification of predisposing factors and proper handling, immobilization, and transportation techniques can help prevent development of exertional myopathy in cranes.
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PMID:Exertional myopathy in whooping cranes (Grus americana) with prognostic guidelines. 1731 70

3-Hydroxy-3-methyl-glytaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") have been proved to be extremely useful in the management of hypercholesterolemia, as well as in prevention of primary and secondary coronary heart disease. However, they may produce rare but severe muscle-related symptoms such as myopathy and rhabdomyolysis. Recent findings in vitro have shown that statins can reduce cardiomyocyte viability. The exact mechanism of statin myotoxicity still remains unclear. Diltiazem as CYP3A4 inhibitor, is a well recognized risk factor of skeletal muscles myopathy, if co-administered with simvastatin. It is not known whether such interaction affects myocardial efficiency causing biochemical changes. The experiments were performed on thirty six New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% MC (control group): diltiazem (5 mg/kg); simvastatin (50 mg/kg) or diltiazem + simvastatin, daily for 14 days (po). The following biochemical parameters were estimated: creatine kinase (CK), serum transaminases (ALT and AST), as well as myocardial injury markers: troponin I (Tnl) and creatine kinase MB (CK-MB). Simultaneous administration of simvastatin and diltiazem caused 23-fold increase (p < 0.01), in rabbit serum CK levels and 20-fold increase (p = 0.056) in TnI levels, as compared to the initial values. Also in these rabbits significant increase in CK (12411,60 vs 839.87 IU/L) and TnI (0,26 vs 0,014 ng/mL), as compared to control group were observed. Significant increase in CK (12411,60 vs 1100,92 IU/L) and TnI (0,26 vs 0,012 ng/mL), as compared to diltiazem alone were noted, too. This may suggest another mechanism of drug-drug interaction than the one based on CYP3A4 inhibition if the impact on cardiac or skeletal muscle is considered.
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PMID:The influence of simvastatin at high dose and diltiazem on myocardium in rabbits, the biochemical study. 1735 90

Hyper-transaminasemia (HT) is a well-known laboratory sign of celiac disease (CD); however, hyper-creatine phosphokinase (CK)-emia (HCK) is not so familiar. As there are reported cases of myopathy associated CD in the literature, we aimed to investigate serum CK levels of children with CD. Newly diagnosed 126 children were included. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and CK levels were determined. Mean age was 8.7+/-4.4 years (11 mo to 18 y). Of patients, 77 (61.1%) had classic form, 49 (38.9%) had atypical form. Elevated levels of AST, ALT, and CK, respectively, were found in 65 (51.6%), 45 (35.7%), and 50 (39.7%) patients. Isolated HCK was detected in 9 (7.1%) patients. AST, ALT, and CK were all elevated in 29 (23.0%) children. Mean serum AST, ALT, and CK levels were found as 56.1+/-53.7 U/L (11 to 403), 44.7+/-44.0 U/L (7 to 290), and 258.0+/-686.5 U/L (36 to 5956), respectively. In 95 (75.4%) children, AST/ALT value was greater than 1, and in 19 (15.1%) it was greater than 2. We found positive correlations with the level of CK and AST, and ALT (P=0.01). CK level was inversely correlated with hemoglobin and cholesterol levels (P=0.013 and 0.007). In conclusion, this is the first study, which determined elevated serum levels of CK in CD and demonstrated that HCK is as common as HT in children with CD. We emphasize that HT seen in CD is not necessarily a sign of liver injury, but may also be due to myopathy.
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PMID:Hyper-CK-emia in pediatric celiac disease: prevalence and clinical importance. 1766 50

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

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 new antivirals clevudine, telbivudine and emtricitabine may be potent agents for the treatment of hepatitis B virus (HBV). However, there have been no reports on serious adverse events associated with the use of clevudine. A son and his mother both had HBV infection (ages: 27 and 47 years, respectively), and they had received antivirus treatment with clevudine (30 mg daily). They developed progressive weakness of the lower extremities and difficulty arising from the ground. Both the patients had symptoms for the previous 3 approximately 4 months in process of 14 approximately 17 months of clevudine therapy. The physical examinations showed positive Gower's sign, a decreased gait velocity and symmetrical proximal weakness (MRC grade 4/5). Their blood tests at admission revealed elevated or positive HBs Ag, HBV DNA, AST, ALT, creatine kinase, LDH, myoglobin and CK-MB. For both patients, the electrodiagnostic studies indicated myopathy and the pathologic findings of biopsied muscles revealed myositis. Drug-induced polymyositis was suspected and the clevudine was finally withdrawn. The muscle weakness and laboratory findings were improved for both patients after conservative care. We report here on the first cases of polymyositis that may have been caused by administering the new nucleoside analog clevudine for treating HBV infection.
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PMID:Polymyositis in patients taking antiviral clevudine therapy: a report of two cases. 2020 82

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

Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid-alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile-onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile-onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow-up is still limited. We report the results of a long-term follow-up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0-295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m(2) (Z-score = 4.3) and decreased to normal values since the 3-month follow-up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow-up in a symptomatic neonatal patient with Pompe disease.
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PMID:Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report. 2083 May 24


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