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)

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
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PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

Ethylbenzene was administered to groups of male and female Wistar rats by gavage for 4 (n = 5/dose/sex) and 13 weeks (n = 10/dose/sex) (OECD 408) at doses of 0 (vehicle control), 75, 250, and 750 mg/kg bodyweight/day (mg/kg bw/day), administered am/pm as half doses. In the 4-week study, > or =250 mg/kg increased serum alanine aminotransferase, total bilirubin and cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and kidney weights; males also had post-dose salivation, increased urinary epithelial cell casts and cells, and hyaline droplet nephropathy. In the 13-week study, > or =250 mg/kg increased water consumption and produced post-dose salivation. Liver-related effects: increased serum alanine aminotransferase, gamma-glutamyltransferase, bilirubin, total protein, albumin and globulins, cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and reduced prothrombin times. Kidney-related effects: increased serum potassium, calcium, magnesium, kidney weights, and (males only) urea and hyaline droplets in renal tubular epithelium, and reduced sodium (females only); creatinine was reduced in 750 mg/kg males. The NOAEL of ethylbenzene in these studies, based on hepatocyte hypertrophy and liver- and kidney-related clinical chemistry changes, was 75 mg/kg bw/day.
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PMID:Ethylbenzene: 4- and 13-week rat oral toxicity. 1705 4

The subchronic toxicity of 1,3-dichloro-2-propanol (1,3-DCP) was investigated in Fischer 344 rats after 13 weeks of repeated, whole-body inhalation exposure. Groups of 10 rats of each sex were exposed to 1,3-DCP vapor by whole-body inhalation exposure at concentrations of 0, 5, 20 or 80 ppm for 6 h/day, 5 days/week for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were assessed. At 80 ppm, a decrease in the body weight gain, an increase in the urine protein and leukocyte counts and an increase in the liver and kidney weights were observed in both genders. Hematological and serum biochemical investigations revealed decreases in hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular HB, as well as increases in the platelet (PLT) count, serum aspartate aminotransferase and alanine aminotransferase. The number of white blood cells was significantly lower in males than in controls, but this was not the case in females. Histopathological alterations included an increase in the incidence of multifocal necrosis, inflammation, pigmentation, biliary hyperplasia and the foci of cellular alteration of the liver and chronic nephropathy and protein cast of the kidney. At 20 ppm, decreases in HCT and MCV and increases in the liver and kidney weights were observed in both genders. A decrease in the HB of females and an increase in the PLT count of females were also observed. Histopathological alterations included slight increases in the incidences of hepatic necrosis, hepatic inflammation and chronic nephropathy. At 5 ppm, we found decreases in the MCV of males and the HB of females, as well as an increase in the liver weight of both genders. In the present experimental conditions, the target organs were determined to be the liver, kidney and blood cells in rats. The no-observed-adverse-effect level was considered to be <5 ppm/6 h/day and the low-observed-adverse-effect level was believed to be 5 ppm/6 h/day in rats.
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PMID:subchronic inhalation toxicity study of 1,3-dichloro-2-propanol in rats. 1792 Dec 39

Hepatitis C virus (HCV) infection is often associated with kidney diseases such as membranoproliferative glomerulonephritis (MPGN), with and without cryoglobulinemia, membranous glomerulonephritis (MGN) or glomerulosclerosis (FSGN). The aim of our study was to determine the frequency of HCV with or without hypertransaminasemia in patients with chronic nephropathy in the predialytic phase. We tested 340 subjects with chronic renal insufficiency (CRI) from our hospital's nephrology outpatient clinic for anti-HCV antibodies. In positive subjects we tested for HCV RNA by PCR method, monitoring, for at least 4 months, common biohumoral parameters including transaminases (AST, ALT). Of the 340 subjects, 46 (13.5%) were positive for HCV RNA, and 8 of these (17%) showed constant alteration of transaminases. HBsAg was found in 8 of the total study population (2.3%), and none of these showed altered transaminases. Type II diabetes mellitus was found in 26% (12/46) of the HCV-RNA positive patients, and in only 12.5% (37/294) of the negative ones. The kidney diseases we found in the 46 HCV-RNA positive patients were: diabetic nephropathy in 11 (23.9%), MPGN in 7 (15.2%), MPGN + cryoglobulinemia in 2 (4.3%), interstitial nephropathy in 4 (8.7%), IgA mesangial GN in 3 (6.5%), hypertensive nephropathy in 2 (4.3%), focal and segmental GN in 1 (2.2%), urologic disease in 4 (8.7%), other (hematological, genetic, iatrogenic) in 3 (6.6%), unknown in 9 (19.6%). Our data show that the most frequent kidney diseases associated with HCV infection were diabetic related nephropathy and MPGN with and without cryoglobulinemia. HCV infection had a positive association with diabetes. It is interesting to note that in this study population the hepatitis C concomitant to kidney disease was unusually mild: only 4 of the 46 subjects (9%) showed clinical, biohumoral and ultrasound evidence of cirrhosis.
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PMID:Hepatitis C and kidney disease. 1793 31

Hepatitis C virus (HCV) infection is highly prevalent among end-stage renal disease (ESRD) patients undergoing haemodialysis and it is an important cause of morbidity and mortality in this population. The aim of this study was to evaluate the diagnostic value of YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in 185 ESRD HCV-infected patients. Significant liver fibrosis was defined as METAVIR F2, F3 or F4 stages. Significant fibrosis was observed in 45 patients (24%). By univariate analysis, higher levels of YKL-40, HA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as well as reduced platelet count were associated with fibrosis. However, by multivariate analysis, only AST (P = 0.001), platelet count (P = 0.004) and HA (P = 0.042) were independently associated with significant fibrosis. For the prediction of significant fibrosis, the areas under receiver operating characterictic curve (AUROC) of the regression model (0.798) was significantly higher than the AUROC of YKL-40 (0.607) and HA (0.650). No difference was noted between the AUROC of the regression model and AST to platelet ratio index (APRI) (0.787). Values <8.38 of the regression model showed a negative predictive value of 94% and scores >or=9.6 exhibited a positive predictive value of 65%. If biopsy indication was restricted to scores in the intermediate range of the regression model, it could have been correctly avoided in 61% of the cases. In conclusion, APRI and a model based on AST, platelet count and HA showed better accuracy than YKL-40 and HA (when used solely) for the prediction of significant fibrosis in ESRD HCV-infected patients.
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PMID:Serum levels of YKL-40 and hyaluronic acid as noninvasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection. 1848 83

Oxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/ kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.
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PMID:Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus. 1856 51

The prevalences of chronic infection by hepatitis C virus (HCV) and its genotypes vary among countries and ethnic groups. Among patients with end-stage renal disease (ESRD) and transplant recipients, the evolution of hepatic disease seems atypical and has not been established. In this study we compared the prevalence and HCV genotypic distribution among Brazilian patients with ESRD on dialysis or with transplantations. Moreover, we sought to compare the behavior of biochemical markers of hepatic activity of HCV infection in both groups. We prospectively evaluated 87 ESRD patients on dialysis and 105 transplant patients. Blood samples were obtained to perform qualitative HCV-RNA, genotyping, and, periodically, serum levels of aminotransferases (ALT, AST), gamma-glutamyltransferase (GGT), alpha-fetoprotein (AFT), and albumin. The prevalence of HCV in ESRD patients was similar to recipients (19.5% vs 25.7%; P = NS) and the most frequent genotype was 1a. There was no difference in the mean values of ALT, GGT, AFT, and serum albumin between both groups with HCV infection. The mean values of aminotransferases were slightly elevated and a high frequency of patients evolved with persistently normal parameters. In contrast, the mean values of the GGT were 3 or 4 times above the reference limit and a greater frequency of patients evolved with values persistently elevated in the 2 groups. In conclusion, in the 2 groups the prevalence of HCV infection was elevated; the most frequent genotype was 1a. Among the biochemical parameters, GGT seemed to be useful as an indirect marker of liver disease.
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PMID:Gamma-glutamyltransferase activity in chronic dialysis patients and renal transplant recipients with hepatitis C virus infection. 1858 96

Reports have described a decrease in glomerular filtration rate (eGFR) associated with tenofovir disoproxil fumarate (TDF) use in HIV positive individuals. However, no study has examined renal function over a prolonged period in HIV/hepatitis B virus (HBV) co-infected patients. We assessed the long-term durability and toxicity of TDF in a cohort of 39 e antigen (eAg) positive co-infected patients commenced on TDF 245 mg daily either in addition to or as part of standard antiretroviral therapy. Immunological and virological parameters were followed to 260 weeks, with the median follow-up period being 251 weeks (range 69-290 weeks). eGFR was calculated using the Modification in Diet in Renal Disease equation. On treatment at 260 weeks, 88% (14/16) had HIV viral load <50 copies/mL, median CD4 count rose from 318 to 532 cells/mm(3), median alanine aminotransferase (ALT) fell from 61 IU/L to 42 IU/L, with 35% (7/20) having a normal ALT, median HBV DNA fell from 69 x 10(6) copies/mL to 500 copies/mL, with 75% (12/16) having an undetectable HBV DNA level and 55% (6/11) becoming eAg negative. Of those with detectable HBV DNA, none had TDF resistance mutations. The eGFR declined by 22.19 mL/min/1.73 mm(2) from baseline (P = 0.023) over this period, which was unaffected by protease inhibitor use, baseline CD4 count, ALT or HBV DNA level. Three patients discontinued TDF therapy due to renal dysfunction. In conclusion, TDF has sustained efficacy but is associated with a significant decline in eGFR. Further larger studies are required to clarify this observation.
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PMID:Reduced glomerular filtration rate but sustained virologic response in HIV/hepatitis B co-infected individuals on long-term tenofovir. 1945 40

Lead is known to induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory animals and humans. This includes age-specific variations in absorption, retention, and tissue distribution of lead. This study was carried out to investigate the effects of chronic exposure to lead (50 mg/L) on liver and kidneys of two different age groups of male rats treated with lead from delivery until puberty period (40 days) and postpuberty period (65 days). For this purpose, the concentrations of thiobarbituric acid reactive substance (TBARS), total thiol groups (SH), and superoxide dismutase (SOD) activity were measured in the liver and kidney of rats. Renal function was analyzed by determining creatinine, acid uric, and urea. Plasma activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and albumin were determined spectrophotometrically to evaluate hepatic function. These markers of damage were determined to assess the level of toxicity in these animals. Our results clearly show that the administration of lead produces oxidative damage in liver and kidney, as strongly suggested by the significant increase in TBARS, decrease in total SH, and the alteration of SOD activity. In young lead-exposed animals, lead-induced perturbations on the synthetic function of the liver and the kidney were more pronounced. However, nephropathy is evident for adult lead-exposed animals. It is concluded that lead induces severe hepatic and renal toxicity, which depends on the age of the animals and the target organ.
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PMID:Effect of age-dependent exposure to lead on hepatotoxicity and nephrotoxicity in male rats. 2001 31

The effectiveness of rituximab in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC) has been shown. However, the risk of an increase in viral replication limits its use in cirrhosis, a condition frequently observed in patients with MC. In this prospective study, 19 HCV-positive patients with MC and advanced liver disease, who were excluded from antiviral therapy, were treated with rituximab and followed for 6 months. MC symptoms included purpura, arthralgias, weakness, sensory-motor polyneuropathy, nephropathy, and leg ulcers. Liver cirrhosis was observed in 15 of 19 patients, with ascitic decompensation in 6 cases. A consistent improvement in MC syndrome was evident at the end-of-treatment (EOT) and end-of-follow-up (EOF-U). Variable modifications in both mean viral titers and alanine aminotransferase values were observed at admission, EOT, third month of follow-up, and EOF-U (2.62 x 10(6), 4.28 x 10(6), 4.82 x 10(6), and 2.02 x 10(6) IU/mL and 63.6, 49.1, 56.6, and 51.4 IU/L, respectively). Improvement in liver protidosynthetic activity and ascites degree was observed at EOT and EOF-U, especially in more advanced cases. This study shows the effectiveness and safety of rituximab in MC syndrome with advanced liver disease. Moreover, the depletion of CD20(+) B cells was also followed by cirrhosis syndrome improvement despite the possibility of transient increases of viremia titers.
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PMID:Safety and efficacy of rituximab in patients with hepatitis C virus-related mixed cryoglobulinemia and severe liver disease. 2030 4


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