Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence-based management guidelines for non-alcoholic fatty liver disease (NAFLD) are lacking in the Asia-Pacific region or elsewhere. This review reports the results of a systematic literature search and expert opinions. The Asia-Pacific Working Party on NAFLD (APWP-NAFLD) has generated practical recommendations on management of NAFLD in this region. NAFLD should be suspected when there are metabolic risk factors and/or characteristic changes on hepatic ultrasonography. Diagnosis by ultrasonography, assessment of liver function and complications, exclusion of other liver diseases and screening for metabolic syndrome comprise initial assessment. Liver biopsy should be considered when there is diagnostic uncertainty, for patients at risk of advanced fibrosis, for those enrolled in clinical trials and at laparoscopy for another purpose. Lifestyle measures such as dietary restrictions and increased physical activity (aerobic exercise) should be encouraged, although the best management strategy to achieve this has yet to be defined. Complications of metabolic syndrome should be screened for regularly. Use of statins to treat hypercholesterolemia is safe and recommended; frequent alanine aminotransferase (ALT) monitoring is not required. Obese patients who do not respond to lifestyle measures should be referred to centers specializing in obesity management; consideration should be given to bariatric surgery or gastric ballooning. The role of pharmacotherapy remains investigational and is not recommended for routine clinical practice. Non-alcoholic fatty liver disease should be recognized as part of the metabolic syndrome and managed in a multidisciplinary approach that addresses liver disease in the context of risk factors for diabetes and premature cardiovascular disease. Lifestyle changes are the first line and mainstay of management.
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PMID:How should we manage patients with non-alcoholic fatty liver disease in 2007? 1756 32

Studies aimed at collecting reference parameters for haematochemical analysis in the elderly are scarce and for the oldest old subjects even more rare. In order to establish the reference values for the most common laboratory text in long living individuals, we measured haematochemical parameters in >100 years old subjects and in aged subjects as control. Six hundred and two centenarians accepted to be enrolled in the study. A case history containing the complete anamnesis, clinical examinations, evaluation of the clinical cognitive and functional tests, was prepared for each centenarian. Blood samples from 120>100 years old subjects free of chronic or acute Illness (i.e. Alzheimer's disease, metabolic diseases, cardiovascular disease, stroke, neoplastic and infectious diseases) were analysed. A population of 381 healthy old subjects (age range 65-85 years old), recruited in the same geographic areas and with the same clinical characteristic of the health centenarians, was utilized as control. Significant differences were observed for blood glucose, ALT, cholesterol and platelet levels, reduced in centenarians respect to the old subjects, whereas blood urea nitrogen levels were found significantly increased in centenarians. In conclusion, reference values of the healthy adults can generally been utilized also for the healthy oldest old group, with the notable exception of the above mentioned laboratory parameters that appear to be modified in long living subjects.
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PMID:Laboratory parameters in centenarians of Italian ancestry. 1768 33

Biochemical traits such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and uric acid are associated with obesity, and with risk of cardiovascular disease, metabolic syndrome and diabetes. Each is subject to genetic influences, but little is known about changes in genetic and environmental influences on these traits over time. We investigated the contribution of genetic and environmental influences to variation in these biochemical traits in adolescent twins and their nontwin siblings from 965 twin families. Twins were studied at ages 12, 14 and 16 years. Multivariate genetic models that included effects of age and sex were fitted to determine whether the same or different genetic or environmental factors influence each trait at different ages. Results showed that the genetic factors influencing AST, ALT, GGT and uric acid change over time during adolescence, and that the magnitude of these effects differs between males and females. The nonshared environment effects were generally time specific. There are developmental changes in genes affecting these traits during adolescence.
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PMID:A longitudinal genetic study of uric acid and liver enzymes in adolescent twins. 1790 17

This paper reports on the effect of GCP-02, a dual activator of the peroxisome proliferator-activated receptors alpha/gamma (PPARalpha/gamma), on glucose and lipid metabolism in insulin-resistant obese mice induced by monosodium glutamate. The mice were divided into four groups on the basis of treatment: control group, rosiglitazone (positive control) (7 micromol/kg), and low- and high-dosage GCP-02 (7 micromol/kg and 3.5 micromol/kg, respectively). Drugs were given orally once a day for 19 days, and mice underwent testing for insulin tolerance, oral glucose tolerance and gluconeogenesis, and plasma cholesterol, triglyceride and free fatty acid levels. Mice were sacrificed, and body length and weight were measured; intraperitoneal adipose, heart and liver weighed; and plasma alanine aminotransferase (ALT) level and aspartate aminotransferase (AST) activity measured. Liver, soleus muscle and myocardium were assayed for glycogen, triglyceride and free fatty acid content and myocardia tested for superoxide dismutase (SOD) activity and malonaldehyde content. RT-PCR revealed expression of insulin receptor substrate 1 and 2 (IRS1, IRS2) and related genes in liver. GCP-02 had a more powerful effect than rosiglitazone on improving insulin sensitivity, ameliorating glucose tolerance, suppressing L-alanine-induced gluconeogenesis, and decreasing plasma levels of cholesterol, triglyceride and free fatty acid. It reduced body weight in control mice, significantly lowered hepatic content of glycogen, triglyceride and free fatty acid and myocardial content of triglyceride, and increased myocardial SOD activity. IRS2 mRNA was down-regulated in control mice but up-regulated by GCP-02. Thus, GCP-02 is a potential candidate for the prevention and therapy of diseases associated with insulin resistance such as type 2 diabetes mellitus and cardiovascular disease.
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PMID:Effect of GCP-02, a PPARalpha/gamma dual activator, on glucose and lipid metabolism in insulin-resistant mice. 1804 28

The aim of the study was to assess gamma-glutamyl transpeptidase (gamma-GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 +/- 12.0 months and 39.8 +/- 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, gamma-GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio [95% confidence interval]: 2.54 [1.26-5.11], P < .05 and 2.21 [0.98-5.43], P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with gamma-GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 [95% confidence interval, 1.5-28.1]), but not diabetes. Elevated gamma-GT or AST is an independent predictor of CVD. An increase of gamma-GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.
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PMID:Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study. 1824 12

Intake of tea flavonoids has been reported to reduce the incidence of cardiovascular disease. The present study was undertaken to investigate the preventive effect of (-)epigallocatechin gallate (EGCG) on heart weight, cardiac marker enzymes, membrane-bound ATPases and electrolytes in isoprenaline (ISO)-induced myocardial infarcted (MI) Wistar rats. Rats subcutaneously administered ISO 100 mgkg(-1) at intervals of 24 h for 2 days resulted in significant increases in heart weight and the activities of cardiac marker enzymes such as creatine kinase, creatine kinase-MB, lactate dehydrogenase (LDH), aspartate transaminase and alanine transaminase in serum, and significant decreases in the activities of these enzymes in the myocardium. ISO injection also increased levels of LDH isoenzymes (LDH 1 and LDH 2). The activity of Na+/K+ ATPase was decreased significantly and the activities of Ca2+ and Mg2+ ATPases were increased significantly in ISO-induced MI rats. Furthermore, the levels of potassium were lowered and the levels of sodium and calcium were increased in ISO-induced MI rats. Prior treatment with EGCG (10, 20 and 30 mgkg(-1)) daily for a period of 21 days reduced the effects of ISO on heart weight, activities of cardiac marker enzymes and membrane bound-ATPases and levels of LDH 1 and LDH 2 and electrolytes. Thus, EGCG exhibits beneficial effects on these enzymes and electrolytes. The observed effects may be due to the antioxidant and membrane-stabilizing effects of EGCG in ISO-induced MI rats.
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PMID:(-)-Epigallocatechin gallate (EGCG) prevents isoprenaline-induced cardiac marker enzymes and membrane-bound ATPases. 1825 Oct 87

Antiretroviral therapy (ART) in HIV-infected patients has been associated with an increased risk of cardiovascular disease. This study evaluates vascular endothelial dysfunction of the peripheral circulation in Brazilian HIV-infected subjects on ART or naive to ART compared to a control group matched for age and body mass index (BMI). We performed a cross-sectional comparative study to measure postischemic peak flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) in HIV-infected patients and healthy controls in Salvador, Bahia, Brazil. Endothelial vasomotor function was evaluated by assessing brachial artery FMD. Forty-four HIV-infected individuals (33 ARV treated and 11 ART naive) were compared to 25 healthy controls matched for age and BMI. FMD % was significantly lower for the ART-experienced patients compared to the ART-naive patients and was also significantly different from controls (ART experienced 8.2 +/- 6.0% vs. 19.3 +/- 4.8% vs. 23.3 +/- 6.1%), respectively (p < 0.0001). The cholesterol, triglyceride, and ALT levels were significantly higher in the ART-experienced group compared to the ART-naive and control subjects (p < 0.028); however, linear regression analysis revealed a statistically significant association of endothelial dysfunction as a dependent variable only with ARV treatment in HIV-infected subjects (p = 0.03). The association of endothelial dysfunction with ARV therapy in HIV-infected patients was independent of protease inhibitor-containing regimens or dyslipidemia. This dysfunction may contribute to the risk for HIV-associated atherosclerosis.
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PMID:Cross-sectional study of endothelial function in HIV-infected patients in Brazil. 1827 45

1. The worldwide epidemic of obesity in adults has been mirrored in children in developed and developing countries. 2. Central obesity appears to be driving a cluster of abnormalities often referred to as the metabolic syndrome. 3. The definition of the metabolic syndrome in children is not suited to arbitrary cut-offs and a definition using the significant clustering of risk factors that is already evident in childhood and adolescent populations may be preferable. 4. An Australian population study showed that 25% of 8-year-olds and 29% of 14-year-olds could be described by the high risk cluster with features similar to adult metabolic syndrome. 5. The high risk cluster was significantly linked to high and low birthweight, shorter duration of breast-feeding, larger postnatal weight gains after 12 months of age and raised C-reactive protein, gamma glutamyl transferase and alanine transaminase levels. At-risk young adults have also been shown to have macroscopic atherosclerosis in post-mortem studies. 6. Identification of at-risk children has obvious benefits for the individual and as well, for prevention of a future cohort with raised cardiovascular morbidity and mortality; however, complexities and controversies exist in doing so. Familial, genetic and lifestyle risk factors aggregate and labelling children with predisease may be problematic. Committed political and societal changes are necessary to reduce childhood obesity and subsequent adult cardiovascular disease.
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PMID:Childhood obesity, hypertension, the metabolic syndrome and adult cardiovascular disease. 1830 30

Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups. We examined cardiovascular disease risk factors and iron and liver biomarkers, as well as morbidity and mortality associated with the C282Y and H63D variants of HFE in the Atherosclerosis Risk in Communities (ARIC) study, which is a population-based cohort of nearly 16,000 U.S. white and black men and women who were 45-64 years old at baseline. Subjects were followed for an average of 15 years for death, incident coronary heart disease, stroke, and heart failure, and an average of 8 years for incident diabetes. The prevalence of C282Y homozygosity was 0.42% (45/10,800) in whites, which is similar to other North American population-based studies. C282Y homozygotes had significantly lower mean low-density lipoprotein (LDL) cholesterol and fibrinogen as well as higher mean levels of iron (ferritin, transferrin saturation) and liver biomarkers (alanine aminotransferase, Hepascore) compared with HFE wild-type subjects. Rates of all-cause mortality, cardiovascular disease, and diabetes were similar across HFE genotypes. These prospective, population-based data indicate higher serum iron indices and possible mild liver dysfunction or disease in some C282Y homozygotes, but they provide little evidence that HFE C282Y or H63D mutations are related to all-cause mortality, cardiovascular disease, or diabetes. Reduced LDL in C282Y homozygotes may be because of effects of excess iron on cholesterol metabolism and lipoprotein formation in the liver.
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PMID:HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study. 1859 31

Blood lipids and high-sensitivity C-reactive protein (hsCRP) are used to assess cardiovascular disease (CVD) risk. We evaluated in a cross-sectional design the relationship of hsCRP to markers of liver function (aspartate and alanine transaminases [AST and ALT, respectively]), CVD risk factors and HIV-disease progression markers in 226 HIV-1 sero-positive drug users. hsCRP showed a significant inverse relationship with ALT and high-density lipoprotein, independent of age, gender, viral load, CD4 cell-count and antiretroviral (ARV) use, and was not significantly associated with HIV-disease progression markers. Serum markers of liver damage, AST and ALT, were associated with lower hsCRP, total cholesterol, low-density lipoproteins and triglycerides. Elevated liver enzymes (> or =40 IU/L) were predictive of hsCRP levels that are considered a low risk for CVD. In conclusion, hsCRP may not be a reliable marker of CVD risk in populations with HIV at-risk for elevated liver enzymes due to high hepatitis B virus/hepatitis C virus prevalence and ARV use.
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PMID:C-reactive protein: a poor marker of cardiovascular disease risk in HIV+ populations with a high prevalence of elevated serum transaminases. 1859 80


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