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)

Interferon-alpha-2a, a single interferon-alpha subtype manufactured by use of recombinant DNA technology, has immmunomodulatory, antiviral and antiproliferative properties. It is a beneficial treatment for about 30% of patients with well-compensated chronic hepatitis C. Biochemical responses [defined as normalisation of serum alanine aminotransferase (ALT) levels] are achieved in 37 to 76% of patients at the end of treatment with interferon-alpha-2a at dosages of 3 to 6MU 3 times weekly (given intramuscularly or subcutaneously) for 6 to 12 months. In contrast, evidence of disease remission is seldom observed in untreated patients. Improvements in liver histology in patients receiving interferon-alpha-2a are associated with complete biochemical responses to the drug. Virological responses (defined as an absence of hepatitis C-RNA in the serum) occur in up to 86% of patients after treatment with interferon-alpha-2a 3 to 6MU 3 times weekly for 12 months. After cessation of interferon-alpha-2a therapy, a considerable proportion of treatment responders experience disease reactivation. Rates of sustained biochemical response are generally higher after 12 months' therapy (27 to 57%) than after 6-month courses of treatment (27 to 30%). The long term efficacy of interferon-alpha-2a in patients with chronic hepatitis C is improved by the concomitant administration of ribavirin. Interferon-alpha-2a shows efficacy similar to that of interferon-alpha-2b or interferon-alpha-n1 in patients with chronic hepatitis C. During the first few days of therapy with interferon-alpha-2a (or other forms of interferon-alpha), most patients experience a transient 'influenza-like' reaction, characterised by fatigue, fever, chills and headache. These symptoms are usually alleviated by paracetamol (acetaminophen). Lethargy, mild myelosuppression, alopecia and neuropsychiatric symptoms are dose-limiting adverse effects that may occur during longer term therapy. Severe adverse effects, experienced by <2% of interferon-alpha-2a recipients, include severe depression, seizures and generalised bacterial infections. Autoimmune thyroid dysfunction develops in 3 to 12% of patients during treatment with interferon-alpha-2a. Conclusion. Interferon-alpha-2a produces sustained responses in about 30% of adults with chronic hepatitis C. Its efficacy appears to be similar to that of other interferon-alpha products. Thus, the drug remains a useful first-line treatment option for adults with well-compensated chronic hepatitis C. Further research into the optimal dosage of interferon-alpha-2a and its role in combination with other agents is likely to contribute towards future advances in the management of chronic hepatitis C.
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PMID:Interferon-alpha-2a: a review of its use in chronic hepatitis C. 1802 May 86

R-etodolac is a novel pro-apoptotic agent with potential antitumor activity against B-cell chronic lymphocytic leukemia (B-CLL). This phase I clinical trial was conducted to determine the tolerability, safety, and maximum tolerated dose (MTD) of R-etodolac, administered orally twice a day (BID), in patients with B-CLL. Secondary objectives included evaluating clinical response, pharmacodynamic activity (reduction of lymphocytes), and pharmacokinetic (PK) profile. Forty-three patients were enrolled in the study. The most frequently reported adverse events were diarrhea, rash, pruritus, and headache. Increases in alanine aminotransferase (ALT) were also observed. Adverse events were generally mild and self-limiting, although in an apparent dose-response relationship, grade 2 and 3 gastrointestinal toxicities and grade 3 skin toxicities were reported with the highest dose regimens (1,800 and 2,400 mg BID). Hematologic toxicity was rare. The MTD was determined to be 1,200 mg BID. PK results indicated that oral absorption of R-etodolac was rapid (time to maximum concentration ranged from 2 to 4 h), and the half-life ranged from 5 to 7 h. The increase in maximum concentration, however, was not proportional to the increase in dose. R-etodolac significantly reduced absolute lymphocyte count (ALC) in B-CLL patients in a dose-dependent manner up to 1,800 mg BID and caused partial responses in 2 patients. Further study of R-etodolac as a possible new maintenance therapy or as a part of combination therapy of B-CLL appears warranted.
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PMID:Phase I study of a novel pro-apoptotic drug R-etodolac in patients with B-cell chronic lymphocytic leukemia. 1809 35

Isopropanol (IPA) is a volatile solvent that is used in many industrial process. The major symptoms of acute isopropanol toxicity include dizziness, incoordination, headache, hypothermia, eye ataxia, irritation of upper respiratory tract and shortness of breath. Vomiting, hematemesis, diarrhoea and hypotension may occur following accidental ingestion of IPA. No data regarding subchronic or chronic toxicity of IPA were identified. The aim of this study was to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and of gamma-glutamyltransferase (gamma-GT) of the last five years in 40 printer workers after the removal of IPA from the industry. The serum levels of ALT, AST and gamma-GT were higher in the exposed workers than in non exposed. In conclusion, the results of this study show that the removal of IPA from the industry had a positive health effect improving the hepatic function of the workers.
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PMID:[Modifications of hepatic transaminases in workers exposed to low doses of isopropanol]. 1840 81

Methoxyisopropanol and Methoxyisopropyl Acetate, commonly known as propylene glycol monomethyl ether (PGME) and propylene glycol monomethyl ether acetate (PGMEA), respectively, have fragrance, solvent, and viscosity-decreasing functions in cosmetics, although only Methoxyisopropanol is in current use at concentrations ranging from 4% to 35%. Methoxyisopropanol is easily absorbed into the bloodstream upon inhalation or ingestion. The acetate ester is readily metabolized to Methoxyisopropanol in the body, which is excreted unchanged in the expired breath or in the urine as free or conjugated Methoxyisopropanol, or as the primary metabolite propylene glycol. In acute oral toxicity studies, the LD(50) values of Methoxyisopropanol were 4.6 to 9.2 g/kg in rats, with similar low acute toxicity in other animal species. Inhalation exposures of rats, mice, and rabbits to 3000 ppm Methoxyisopropanol for 6 h per day for 9 days to 13 weeks produced increased relative liver weights, signs of central nervous system (CNS) depression, and in some cases, elevated serum alkaline phosphatase, alanine aminotransferase, or hepatocellular hypertrophy, but the kidneys were unaffected. The no observed adverse effect level (NOAEL) for 13-week inhalation exposures to Methoxyisopropanol was 1000 ppm in rats and rabbits. In a 90-day dermal exposure study using rabbits, 10 ml/kg undiluted Methoxyisopropanol produced narcosis and increased kidney weights and the NOAEL was 7.0 ml/kg. Chronic (2-year) daily inhalation exposures of rats and mice to 3000 ppm Methoxyisopropanol produced signs of liver toxicity (rats and mice) and some evidence of renal toxicity in rats. The only observation at 1000 ppm was dark foci of the liver in male rats. For female rats and male and female mice, the NOAEL of this chronic inhalation study was 1000 ppm Methoxyisopropanol. Methoxyisopropanol and Methoxyisopropyl Acetate were found to be nonirritating to slightly irritating and non-sensitizing in rabbit and guinea pig skin. Repeated applications of undiluted Methoxyisopropanol to the eyes of rabbits produced transient slight to moderate irritation. Pregnant rats exposed to 200 or 600 ppm Methoxyisopropanol by inhalation on gestation days 6 to 17 had no effects on maternal health or normal fetal development. Adult male rats exposed to these concentrations had no effects on the reproductive organs. Pregnant rats and rabbits exposed to 500 to 3000 ppm Methoxyisopropanol by inhalation during gestation had no significant embryotoxic or fetotoxic effects, althougth CNS depression and reduced body weight gain were observed in the 3000 ppm group. In a two-generation inhalation study using rats, continuous inhalation of 3000 ppm Methoxyisopropanol produced CNS depression, prolonged estrous cycles, reduced fertility indices, reduced pup weights and pup survival, and delayed sexual development, with a NOAEL for reproductive and developmental effects of 1000 ppm. In a continuous breeding protocol using mice, 2.0% Methoxyisopropanol in drinking water produced reduced growth, reduced relative epididymis weight, reduced relative prostate weight, and increased liver weight (females only) in offspring, with a NOAEL at a 1% concentration. Exposure of mice or rats to 300 ppm to 3000 ppm Methoxyisopropanol by inhalation produced no signs of carcinogenicity. Methoxyisopropanol was negative for mutagenicity or genetic toxicity in the bacterial reverse mutation assay (<or= 5000 microg/plate), the unscheduled DNA synthesis (UDS) assay (<or= 0.1 M), V79 Chinese hamster lung assay (>100 mM), and in the Siberian hamster embryo assay (concentrations not reported). In other assays, 100 mM Methoxyisopropanol increased sister chromatid exchanges in V79 cells. In human inhalation exposure studies of 1 to 7 h duration, 50 to 75 ppm Methoxyisopropanol vapor had an objectionable odor; 150 ppm was slightly irritating to the eyes and throat; 250 ppm produced eye irritation, lacrimation, blinking, rhinorrhea, and headache; 300 ppm was mildly irritating to the eyes, nose, and throat; 750 ppm was extremely irritating; and 2050 ppm produced extreme discomfort with severe lacrimation, blepharospasm, and painful breathing. None of the concentrations tested impaired motor coordination or performance on neurological tests. The irritating effects subsided within 15 min to 24 h of removal from the inhalation chamber. The National Institute of Occupational Safety and Health (NIOSH) recommended an 8-h time-weighted average for occupational exposure of 100 ppm. A margin of safety of 500 was determined, based on a calculated exposure from the normal use of nail polish remover products (100% absorption) and the NOAEL for reproductive toxicity. The absorption of Methoxyisopropanol through the nail is likely to be low, suggesting this margin of safety is conservative. Because Methoxyisopropanol is volatile, exposure by inhalation is possible, but the odor becomes objectionable at 50 to 75 ppm in air. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that Methoxyisopropanol and Methoxyisopropyl Acetate are safe for use in nail care products in the practices of use and concentration as described in this safety assessment.
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PMID:Final report on the safety assessment of methoxyisopropanol and methoxyisopropyl acetate as used in cosmetics. 1883 Aug 62

Trichloroethylene-induced hypersensitivity dermatitis is one of the serious occupational health events in China, however, little is known about the clinical features and possible mechanism of this disorder. The objective of the present study was to report some typical trichloroethylene-induced dermatitis patients and investigate their occupational exposure as well as the clinical features. We sampled and tested some cleaning agents from the companies where TCE-induced skin disorder occurred, the trichloroethylene concentrations were also monitored in the workplace air. Additionally, the symptoms, signs and laboratory test results of patients were collected. TCE concentrations varied from 10.2% to 91.4% in the cleaning agent by gas chromatography-mass chromatography analysis, and TCE levels in the workplace air ranged between 18 mg/m(3) and 683 mg/m(3), at most sampled sites TCE levels were higher than China national health standard for TCE. The trichloroethylene exposure time of the patients was 5-90 days (average 38.2 d), the patients with headache, dizziness, skin itch, fever were 90.5%, 100%, 100%, and 61.9%, respectively. 85.7% patients had skin erythema, 90.5% with rashes, and 38.1% with blisters. In addition, liver enlargement occurred in 3 patients, the abnormal rate of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-Bil) were 90.5%, 85.7% and 76.2%, respectively. 6 out of 15 patients were with abnormal electrocardiogram, and trichloroacetic acid (TCA) elevated in 14 patients (66.7%). Taken together, the major detrimental effect of trichloroethylene was to induce hypersensitivity dermatitis and liver dysfunction, the occurrence of this disorder is likely related to the individual hypersensitivity to trichloroethylene exposure.
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PMID:Severe hypersensitivity dermatitis and liver dysfunction induced by occupational exposure to trichloroethylene. 1936 38

OBJECTIVE: This study was designed to investigate the pharmacokinetic effects of coadministration of saquinavir/ritonavir with efavirenz at steady state. METHODS: Healthy volunteers in this open-label, two-arm, one-sequence, two-period crossover study (planned enrollment of 40 participants) were randomized to one of two treatment arms: those in Arm 1 were scheduled to receive saquinavir/ritonavir 1,000/100 mg orally twice daily for 29 days and efavirenz 600 mg orally once daily starting on day 15 and continuing through day 29; participants randomized to Arm 2 were to receive efavirenz once daily for 29 days and saquinavir/ritonavir 1,000/100 mg twice daily starting on day 15 through day 29. Assessments included vital signs, laboratory analyses, electrocardiography, and blood levels of total saquinavir, ritonavir, and efavirenz. Pharmacokinetic parameters included C(max) (maximum observed plasma concentration), t(max) (time to reach the maximum observed plasma concentration), (apparent elimination half-life), and AUC(0-tau) (area-under-the-plasma-concentration-time curve over one dosing interval). RESULTS: Eight participants (four in each arm) were enrolled; only two (one from each treatment arm) reached day 15 of the study and received the concurrent initial doses of saquinavir/ritonavir and efavirenz. The study was terminated prematurely after these two participants experienced nonserious adverse events. The participant in Arm 1 experienced mild abdominal discomfort, diarrhea, sleep disorder, and headache and the participant in Arm 2 experienced moderate-intensity abdominal pain and mild vomiting with leukocytosis accompanied by elevated pancreatic and hepatic enzymes (aspartate aminotransferase and alanine aminotransferase values of 2-fold and 3.5-fold the upper limit of normal, respectively). Both participants recovered completely following treatment discontinuation. Only limited pharmacokinetic data were generated on these two participants. CONCLUSIONS: The early termination of this study precluded drawing any definitive conclusions regarding the pharmacokinetics at steady state of coadministered saquinavir/ritonavir and efavirenz.
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PMID:Potential Hepatotoxicity of Efavirenz and Saquinavir/Ritonavir Coadministration in Healthy Volunteers. 1938 37

Scrub typhus is a zoonotic disease that is caused by Orientia tsutsugamushi. Although hepatic dysfunction occurred in 77-96.7% of the scrub typhus patients, its mechanism is unknown. IL-17 is a potent proinflammatory cytokine known for its role in several chronic disease conditions. Abundant IL-17 was found in conditions affected by microbial pathogens, including the synovial fluid of patients with Lyme arthritis or Chlamydia-induced reactive arthritis, Helicobacter pylori-infected gastric mucosa, and listeria infection. It is also suggested as a marker of acute hepatic injury. In our study, we postulated that IL-17 might be a cytokine with a role in hepatic dysfunction in scrub typhus. In September-November 2006, our study involved 43 patients with Boryong-type scrub typhus patients and 40 age- and sex-matched control healthy people. Scrub typhus was confirmed on the basis of immunofluorescence and a nested polymerase chain reaction assay. IL-17 was measured using human IL-17 immunoassay. We gathered the clinical and laboratory data by chart reviews. We used an independent t-test, Kolmogorov-Smirnov test, and correlation analysis. The IL-17 levels were significantly higher in scrub typhus patients than in the healthy group. Also, the patients with scrub typhus showed significantly higher aspartate aminotransferase and alanine aminotransferase levels, and lower hemoglobin levels than the healthy group. However, in our correlation analysis, we did not find any correlation between IL-17 and hepatic, kidney, and hemogram panels. The IL-17 level in patients with headaches was higher than in patients without headaches, showing a borderline significance. This suggests that IL-17 level might be a cause of a vasculitis-associated headache. More prospective, large-scale studies are needed about the mechanism of hepatic dysfunction and headaches in scrub typhus patients.
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PMID:Does IL-17 play a role in hepatic dysfunction of scrub typhus patients? 1948 73

To compare the clinical and laboratory characteristics and disease severity between adults and children with dengue in Taiwan in 2002, we retrospectively studied 661 serologically confirmed dengue-infected patients (606 adults and 55 children) admitted between June and December 2002 to a single medical centre. The medical charts of the patients were reviewed for demographic, clinical, laboratory and imaging information. Compared with children, adult patients were found to have: higher incidences of arthralgia (P<0.001), myalgia (P=0.002), headache (P=0.028), abdominal pain (P=0.004) and upper gastrointestinal bleeding (P=0.013); lower platelet counts (P<0.001), prothrombin time (P=0.030) and serum albumin levels (P=0.037); a higher incidence of elevated alanine aminotransferase levels (P=0.001); and a higher prevalence of dengue haemorrhagic fever (DHF) (14.4% vs. 3.6%; P=0.026). The current data showed differences in clinical manifestations and laboratory characteristics between children and adults with dengue virus infection. Notably, a higher incidence of DHF was observed in adult patients compared with children in the 2002 dengue epidemic in Taiwan.
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PMID:Differences in clinical and laboratory characteristics and disease severity between children and adults with dengue virus infection in Taiwan, 2002. 1950 Aug 13

The purpose of this report is to describe the overall safety profile of both short- and longer-term duloxetine treatment of fibromyalgia. Data from four double-blind, randomized, placebo-controlled studies (two with 6-month open-label extension phases) and a 1-year, open-label safety study were included. Safety measures included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms. The most common TEAEs for short-term treatment with duloxetine were nausea (29.3%), headache (20.0%), dry mouth (18.2%), insomnia (14.5%), fatigue (13.5%), constipation (14.5%), diarrhea (11.6%), and dizziness (11.0%; all p < 0.05 vs. placebo). Most TEAEs emerged early and were mild to moderate in severity. The profile of adverse events in patients enrolled at least 6 months, and for patients in the 1-year study, was similar to that found in the short-term treatment studies, with no new adverse events emerging at a notable rate. About 20% of patients discontinued due to adverse events in the short-term treatment studies and in the 1-year study. SAEs were uncommon, and none occurred at a significantly higher frequency for duloxetine compared with placebo. Mean changes in vital signs and weight were small. Rates of treatment-emergent potentially clinically significant (PCS) vital sign, laboratory, and electrocardiogram measures were low, with only PCS rates of alanine aminotransferase being significantly higher for duloxetine compared with placebo in the placebo-controlled treatment studies. In the 1-year study, four patients (1.1%) had suicide-related behavior. The data provided here summarize short- and long-term safety from five clinical studies in patients treated with duloxetine for fibromyalgia. In addition, postmarketing surveillance continues for adverse events reported with duloxetine in fibromyalgia, as in other indications.
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PMID:Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials. 1953 10

Pulmonary Hypertension is a serious complication of sickle cell disease (SCD), with high morbidity and mortality. Endothelin (ET)-1, a potent vasoconstrictor elevated in SCD, acts through the ET receptors (ETR), ETR-A and ETR-B. Bosentan and ambrisentan are ETR blockers used in primary pulmonary hypertension. We report on the use of ETR blocking agents in a cohort of 14 high-risk SCD adult patients with pulmonary hypertension. Patients underwent right heart catheterization, 6-min walk test, echocardiogram, physical examination and blood work-up before starting ETR blockers. Eight patients received ETR blockers as initial therapy; six patients were already taking sildenafil. Over more than 6 months of therapy, sequential measurements of 6-min walk distance increased significantly (baseline 357 +/- 22 to 398 +/- 18 m at 5-6 months, P < 0.05). Downward trends were observed for amino-terminal brain natriuretic peptide and tricuspid regurgitant velocity. Pulmonary artery mean pressures decreased in three patients that had repeat right heart catheterization (44-38 mmHg). Adverse events were: increased serum alanine aminotransferase (2), peripheral oedema (4), rash (1), headache (3), decreased haemoglobin (2). Therapy was stopped in two patients who were switched then to the other ETR blocker agent. These data suggest preliminary evidence for the benefit of bosentan and ambrisentan in pulmonary hypertension in SCD.
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PMID:Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease. 1977 99


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