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 safety and tolerability of rosuvastatin were assessed (as of August 2003) using data from 12,400 patients who received 5 to 40 mg of rosuvastatin in a multinational phase II/III program, which represented 12,212 patient-years of continuous exposure to rosuvastatin. An integrated database was used to examine adverse events and laboratory data. In placebo-controlled trials, adverse events, irrespective of causality assessment, occurred in 57.4% of patients who received 5 to 40 mg of rosuvastatin (n = 744) and 56.8% of patients who received placebo (n = 382). In fixed-dose trials with comparator statins, 5 to 40 mg of rosuvastatin showed an adverse event profile similar to those for 10 to 80 mg of atorvastatin, 10 to 80 mg of simvastatin, and 10 to 40 mg of pravastatin. Clinically significant elevations in alanine aminotransferase (>3 times the upper limit of normal) and creatine kinase (>10 times the upper limit of normal) were uncommon (<or=0.2%) in the groups that received rosuvastatin and comparator statins. Myopathy (creatine kinase >10 times the upper limit of normal with muscle symptoms) that was possibly related to treatment occurred in <or=0.03% of patients who took rosuvastatin at doses <or=40 mg. A positive finding of proteinuria with dipstick testing at rosuvastatin doses <or=40 mg was comparable to that seen with other statins, and the development of proteinuria was not predictive of acute or progressive renal disease. No deaths in the program were attributed to rosuvastatin, and no rhabdomyolysis occurred in patients who received 5 to 40 mg of rosuvastatin. Rosuvastatin was well tolerated by a broad range of patients who had dyslipidemia, and its safety profile was similar to those of the comparator statins investigated in this extensive clinical program.
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PMID:Safety of rosuvastatin. 1546 70

The side effect of anticancer agents such as nausea and vomiting frequently interrupt chemotherapy. To reduce these side effects, 5-hydroxytryptamine (5-HT3) receptor antagonist or metoclopramide is administered combined with steroid. In this study, we examined the effect of 5-HT3 receptor antagonist on the frequency of nausea and vomiting in a male cancer patient treated with/without steroid. This patient in his sixties had esophageal cancer (stage IV). He was administered nedaplatin 100 mg/day for 1 day and then 5-fluorouracil (5-FU) 750 mg/day for 5 days combined with radiotherapy (60 Gy) as one cycle of this chemotherapy. In the first cycle, 5-HT3 receptor antagonist was administered, and in the second, the antagonist was administered after treatment with steroid. The blood levels of total bilirubin, GOT, GPT, BUN, Cre, Na, K and Cl were stable normally during both cycles of the chemotherapy, indicating that the hepatopathy and nephropathy which cause nausea and vomiting did not occur in these periods. The frequency and period of the nausea and vomiting were one-third decreased, respectively, by the combination of 5-HT3 receptor antagonist and steroid.
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PMID:[Effect of steroid on antiemetic for side effect of anticancer chemotherapy]. 1579 27

Clinical presentations of drug-induced liver injury (DILI) cover essentially the entire spectrum of known liver diseases. However, in the last 8 years the form of liver injury that has most frequently resulted in labeling restrictions is idiosyncratic hepatocellular injury leading to acute liver failure. This rare form of DILI has a characteristic clinical presentation that includes an acute onset after uneventful treatment with drug for weeks to months. Serum alanine aminotransferase rises to very high levels and the appearance of jaundice indicates a high mortality even if the therapy is discontinued. Drugs that can cause this type of injury almost always are associated with frequent (2-15% of all treated patients) and minor serum aminotransferase elevations. These elevations are believed to reflect true liver injury, but often reverse even if drug therapy is continued. The bases for this "adaptation" is not known, as is why some patients do not adapt and develop progressive liver injury. Understanding how drugs cause severe idiosyncratic hepatocellular toxicity has been frustrated by the lack of good preclinical models. Indeed, because these events occur so rarely, the vast majority of humans are not good models. Studies of genomic DNA from affected individuals should provide important insight but not the complete answer because environmental factors almost certainly contribute to individual susceptibility. The most fruitful approach may therefore lie in focused and well-controlled phenotype/genotype studies of the rare patients who have survived this type of injury. The National Institute of Diabetes and Digestive and Kidney Diseases of The National Institutes of Health has recently sponsored a cooperative agreement (UO1) to create a Drug Induced Liver Injury Network (DILIN). DILIN consists of University of Michigan, Indiana University, University of Connecticut, University of California, San Francisco, University of North Carolina, and Duke University. This network should provide heretofore missing resources required to address the problem.
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PMID:Idiosyncratic liver injury: challenges and approaches. 1580 49

Subchronic inhalation toxicity of p-dichlorobenzene (p-DCB) was examined by exposing BDF1 mice and F344 rats of both sexes (6 h/d and 5 d/wk) to inhalation of 25, 55, 120, 270 or 600 ppm (v/v) p-DCB vapor for 13 wk. The exposure to p-DCB vapor retarded the growth rate in the male mice, and induced hepatotoxicity in the mice and rats of both sexes and renal and hematological toxicity in the male rats. Hepatotoxicity was characterized by increased liver weight, hepatocellular hypertrophy, and increased serum levels of total cholesterol. Liver necrosis and increased serum levels of AST and ALT were observed in the exposed mice, whereas these changes, which indicate hepatocellular death, did not occur in any of the exposed rats. p-DCB-induced renal lesions occurred only in the male rats. Hyaline droplets were observed in the proximal tubular epithelial cells, and were stained positively with anti-alpha2u-globulin, suggesting excessive accumulation of alpha2u-globulin in the epithelial cells. Granular casts were formed in the tubular lumen, resulting from the necrotic desquamation of the renal tubular epithelium. Papillary mineralization in the renal pelvis and increased serum levels of BUN and creatinine were noted. These renal changes indicated alpha2u-globulin nephropathy. Decreases in red blood cell counts, hemoglobin concentration, hematocrit and mean corpuscular volume and increased spleen weight occurred in the exposed male rats. The NOAEL was 120 ppm for the hepatic endpoint in mice and for the renal endpoint in rats. The maximum tolerated dose for a 2-yr bioassay inhalation study of rodent carcinogenicity was estimated to be 300 ppm, based on the present results.
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PMID:Thirteen-week inhalation toxicity of p-dichlorobenzene in mice and rats. 1595 47

There is increasing evidence that advanced glycation end products (AGEs) and their interactions with various receptors (in particular, the receptor RAGE) play a pivotal role in the development and progression of diabetic macro- and microvascular complications. Several approaches have been used to inhibit tissue accumulation of AGEs in diabetes, including inhibitors of AGE formation such as aminoguanidine, ALT 946, and pyridoxamine-or putative cross-link breakers such as ALT 711. Alternative interventions have also included the administration of a soluble receptor for RAGE, sRAGE, thus capturing circulating AGEs and preventing them from binding to the cell-bound full-length receptor RAGE, thereby inhibiting the proinflammatory and profibrotic response following AGE-RAGE binding. In this review we summarize the evidence for such antiglycation therapies in retarding or delaying the development and progression of diabetes-associated atherosclerosis and renal disease while focusing on interventional strategies inhibiting AGE accumulation. In summary, all approaches have been shown to confer some degree of antiatherosclerotic and renoprotective effects, albeit to different degrees and by different mechanisms.
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PMID:Advanced glycation end products in diabetes-associated atherosclerosis and renal disease: interventional studies. 1603 3

Subchronic toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) was examined by feeding F344 rats and BDF mice of both sexes a diet containing 1,481, 2,222, 3,333, 5,000 or 7,500 ppm DCNB (w/w) for 13 wk. Oral administration of DCNB in feed to rats and mice retarded growth rates and induced subchronic toxicity affecting the liver, kidney, testes and blood. Liver and kidney were most responsive to DCNB. BMDL10 values for relative liver weight were 12.0 and 22.6 mg/kg/d for male and female rats, respectively, and 88.7 and 94.4 mg/kg/d for male and female mice, respectively. Increased liver weights and centrilobular hypertrophy of hepatocytes were observed in the DCNB-fed rats and mice of both sexes. Both increased serum activities of AST and ALT and liver necrosis occurred in the DCNB-fed mice. Increased incidences of hyaline droplets and granular casts in the proximal renal tubules were observed only in the DCNB-fed male rats, indicating alpha2v-globulin nephropathy. Eosinophilic droplets in the renal tubular cells and increased BUN concentrations occurred in the DCNB-fed female rats. DCNB-induced testicular and hematologic changes were noted in rats and mice. On the basis of these results, the highest dose level for the 2-yr bioassay study of rodent carcinogenicity was determined to be 2,000 ppm.
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PMID:Thirteen-week oral toxicity study of 1,4-dichloro-2-nitrobenzene in rats and mice. 1610 Sep 38

Hepatitis B virus (HBV) infection remains a major issue among dialysis patients. It is associated with a high risk of hepatic complication. The liver disease runs a unique clinical course in dialysis patients, as it can progress with modest hepatic inflammation and prominent fibrosis. The conventional cut-off level of serum alanine aminotransferase (ALT) for commencing antiviral therapy may prove too high and inappropriate for dialysis patients, and liver biopsy appears to be the only definitive means to establish the activity of liver disease in dialysis patients. Liver biopsy should be considered in patients with a serum ALT level that is persistently greater than 30 IU/L, or 0.75-fold the upper limit of the normal level, and/or other clinical and laboratory findings that suggest active liver disease. For antiviral treatment, preliminary reports have shown that lamivudine is effective and well tolerated in dialysis patients. However, the long-term efficacy of lamivudine and its optimal effective dose in dialysis patients remain unknown. The prevention of nosocomial transmission among dialysis patients is also important. Universal precaution measures should be strictly observed and the segregation of hepatitis B surface antigen-positive hemodialysis patients should be considered. For HBV non-immune patients, the importance of HBV vaccination should not be overemphasized. Until a new generation of highly immunogenic vaccines that are proven to be safe and effective in patients with end-stage renal disease becomes available, early vaccination before the development of end-stage renal failure remains the best way to secure immunological protection against HBV infection in dialysis patients.
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PMID:Hepatitis B virus infection in dialysis patients. 1624 80

We present a case of chronic hepatitis B with membranous nephropathy, that was improved by lamivudine treatment. A 37-year-old man was admitted to our hospital for the evaluation of proteinuria. He was diagnosed as having chronic glomerulonephritis associated with chronic hepatitis B. Histopathological findings of the renal biopsy specimen indicated membranous nephropathy. He suffered from nephrotic syndrome associated with leg edema, which was parallel to the exacerbation of hepatitis. Lamivudine was started for the treatment of hepatitis, which caused the disappearance of serum hepatitis B virus DNA and the normalization of ALT level in 4 weeks. Additionally, proteinuria disappeared 120 weeks after the treatment was started. Lamivudine treatment may remit HBV-associated nephropathy.
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PMID:Successful treatment of hepatitis B virus-associated membranous nephropathy with lamivudine. 1642 43

The objective of this study was to investigate the effects of types of dialysis treatments on hepatitis C virus infection and the epidemiologic properties of hepatitis C virus (HCV) infection at three Baskent University hospitals, in Ankara, Adana, and Izmir, Turkey, in 655, 326, and 118 patients with end-stage renal disease, respectively. One hundred thirty patients with HCV viremia among 271 patients with end-stage renal disease seropositive for HCV were included in this cross-sectional study. HCV RNA-positive patients were classified according to the renal replacement therapies (hemodialysis or continuous ambulatory peritoneal dialysis), and viral load, transaminase levels, and distribution of genotypes were compared between these subgroups. In the continuous ambulatory peritoneal dialysis group, 26 of 165 patients (16%) were serum anti-HCV positive, and 11 of 26 patients (42%) were serum HCV RNA positive. Twenty-six percent of the patients undergoing hemodialysis were anti-HCV positive, and 49% were HCV RNA positive. The prevalence of genotype 1b was 68% and 73% for patients in the continuous ambulatory peritoneal dialysis and hemodialysis groups, respectively. No significant differences were found between the genotype 1b and the non-1b groups or between different dialysis types with regard to age and sex and serum aspartate transaminase, alanine aminotransferase, and HCV RNA levels. We conclude that HCV seropositivity may differ between different types of dialysis treatments, although viral load and genotypes may be similar in persons with end-stage renal disease and those without.
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PMID:Distribution of HCV genotypes in patients with end-stage renal disease according to type of dialysis treatment. 1686 30

Epidemiological studies have implicated hepatitis C virus (HCV) infection in the pathogenesis of diabetes mellitus (DM) both in the population as a whole and after solid organ transplantation. Whether this association exists in patients with end-stage renal disease (ESRD) undergoing dialysis is unclear. The aim of this study is to investigate the relationship between HCV and DM in a large group (n=742) of patients with ESRD from Europe and North America. The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting glucose measurement and medication history. Presence of HCV infection was assessed by serum testing for anti-HCV antibodies. The prevalence of anti-HCV antibody positive patients was 15% (112/742); the frequency of DM was higher among anti-HCV positive than -HCV negative patients but the difference did not approach statistical significance, 32% (36/112) vs 29.5% (186/630). The frequency of patients with diabetic nephropathy was not higher in anti-HCV positive than -negative patients; 21.4% (24/112) vs 23.3% (147/630), NS. Logistic regression model showed an independent and significant link between anti-HCV seropositive status and raised GPT (P=0.032), male gender (P = 0.0462), positive history of prior renal transplant (P=0.0006), and longer time on dialysis (P=0.00001). In summary, no link between anti-HCV antibody and DM occurred in this ESRD population; there was no association between rate of anti-HCV antibody and diabetic nephropathy.
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PMID:Hepatitis C virus infection and diabetes mellitus in end-stage renal disease: evidence of a negative association. 1687 74


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