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)

Thioredoxin (TRX) is induced by many oxidative stresses. Serum TRX levels were significantly elevated in nonalcoholic steatohepatitis (NASH) patients, as compared to simple fatty liver (FL) patients or healthy controls. Serum TRX levels in NASH patients were significantly correlated with serum ferritin levels, but not with other variables. Removal of hepatic excess iron by phlebotomy significantly decreased the serum levels of TRX and ALT in NASH patient. Therefore, the pathogenesis of NASH may be associated with iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from FL.
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PMID:Elevation of serum thioredoxin levels in patients with nonalcoholic steatohepatitis. 1625 59

A study was conducted to determine the relationship between ferritin and glycosylated isoforms of ferritin and insulin resistance in 69 HIV-infected men receiving HAART. Ferritin levels were significantly correlated with aspartate aminotransferase, alanine aminotransferase, bilirubin and with insulin resistance. The ferritin isoelectric focusing patterns of five insulin-resistant HIV-infected patients under HAART showed large amounts of hyperglycosylated isoforms, which was not found in 56 control subjects and 46 untreated HIV-1-infected patients.
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PMID:Hyperglycosylated ferritin in sera of HIV-1-infected patients treated with highly active antiretroviral therapy. 1643 82

Adult thalassemic patients have reduced bone mass due to disturbances in several different mechanisms affecting bone turnover. To determine if vitamin D deficiency contributes to the low bone mass of adult thalassemic subjects, we studied serum 25-OH-vitamin D levels in 90 patients (age ranging between 21 and 48 years) affected with thalassemia major (TM) and 35 (age 21-56 years) with thalassemia intermedia (TI). TM patients had been receiving regular transfusions from the age of 2 years and had increased serum ferritin, glutamic oxalacetic transaminase, glutamic piruvic transaminase as well as low bone density (L1-L4 Z score -2.07 +/- 0.2). TI patients did not receive transfusions, but their ferritin levels were increased as well (520.3 +/- 138,1). 8 TM patients (10.1%) and 4 TI (11.4%) had serum 25-OH-vitamin D less than 10.4 ng/ml and were considered presenting an absolute deficiency of vitamin D. Mean 25-OH-vitamin D was significantly (P < 0.01) lower in both TM and TI patients (20.3 +/- 0.7 ng/ml and 20.9 +/- 2.3 ng/ml, respectively) than in 100 healthy control subjects of similar age (25.2 +/- 1 ng/ml). 1,25-OH-vitamin D levels were in the normal-lower levels (45.15 +/- 1.5 mg/dl), while 24 H urinary calcium was below the normal range (15.75 mg/dl). In TM patients, the 25-OH-vitamin D levels correlated negatively with age (P < 0.05) and with serum ferritin (P < 0.05). TM and TI patients with low 25-OH-vitamin D levels (<17.8 ng/ml) presented higher serum ferritin levels (P < 0.01) and higher PTH (P < 0.05) compared to those with normal vitamin D. Moreover, TM patients with low 25-OH-vitamin D levels were significantly older (P < 0.05) and had higher GPT (P < 0.05) than patients with normal vitamin D. In conclusion, calcium metabolism is frequently impaired in adult thalassemic patients. An early and effective medical treatment should be taken in consideration by the clinician in order to improve the bone health in these patients.
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PMID:Low serum levels of 25-hydroxy vitamin D in adults affected by thalassemia major or intermedia. 1646 53

Deferiprone (L1) has been recommended as an effective oral chelation therapy for patients with beta-thalassemia major (TM). From 1999 to 2004, 114 patients with TM from five treatment centers were enrolled in this program: iron (Fe) was chelated with L1 in 57 patients, deferoxamine (DFO) in 26, and combined L1/DFO therapy in 31. We found that serum ferritin (SF) was significantly lower in nine patients receiving L1 for more than 5 years (p = 0.04), 22 patients receiving L1 for 1-2 years (p < 0.01) and 31 receiving the combined therapy (p = 0.01), yet significantly higher in those receiving DFO only (p < 0.01). One patient showed transient neutropenia; arthropathy in one patient and gastrointestinal upset in two were noted, with no significant change in alanine aminotransferase (ALT) level. Of 17 patients who were submitted to a liver biopsy, 15 showed no significant change in hepatic fibrosis scores after therapy with L1. None of the 88 patients, including 31 who received the combined therapy, have abandoned oral L1 treatment due to adverse effects. Results of this study proved that L1 or combined therapy with L1 and DFO is effective in reducing SP; incidence of adverse events was low in patients with TM.
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PMID:Deferiprone or deferoxamine vs. combination therapy in patients with beta-thalassemia major: a case study in Taiwan. 1654 Apr 25

Our objective was to assess the iron indexes of patients with one or more mutations of the HFE gene with a specific interest in studying the effect of the H63D/H63D genotype. Eight hundred twenty subjects who underwent HFE mutational testing for C282Y and H63D mutations were retrospectively identified. Data collected included age, gender, HFE genotype, and values for serum ferritin, iron saturation, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Compared to the Wild/Wild genotype (0.34 +/- 0.17), genotypes H63D/C282Y (0.44 +/- 0.14 P < 0.01), H63D/H63D (0.51 +/- 0.21 P < 0.01), and C282Y/C282Y (0.64 +/- 0.20 P < 0.01) had significantly higher transferrin saturation levels and were independent predictors of higher iron saturation in multivariate regression analysis. Compared to the Wild/Wild genotype, no abnormal HFE genotypes had significantly higher ferritin levels, although the genotype H63D/H63D was an independent predictor of higher serum ferritin (P = 0.02) in regression analysis. There was no significant difference in the proportion of patients with abnormally elevated AST (P = 0.64) or ALT (P = 0.80) between groups. H63D homozygotes have elevated transferrin saturation compared to the Wild genotype, comparable to that of C282Y homozygotes and compound heterozygotes. The clinical significance of this finding is unclear but warrants further study.
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PMID:Individuals homozygous for the H63D mutation have significantly elevated iron indexes. 1661 7

The effects of body iron stores on diquat (DQ)-induced toxicity were examined in male Fischer-344 rats, which are sensitive to this herbicide. The rats (5 weeks old) were fed diets containing 40 (lower iron storage [LIS] group) or 320 ppm iron (higher iron storage [HIS] group) for 5 weeks. The concentrations of nonheme iron and ferritin in the liver and kidney were significantly higher in the HIS group than in the LIS group (P<0.0001), although there was no significant differences between the HIS and LIS groups in hematological parameters, including red blood cell count, hemoglobin concentration, and mean corpuscular volume. Three hours after administration of 0.1 mmol DQ/kg, serum alanine aminotransferase and urea nitrogen were significantly higher than in controls (saline injection) for both the LIS and HIS groups (P<0.01), and, after DQ injection, these parameters were significantly higher in the HIS group than in the LIS group (P<0.01). When the rats were injected with 0.075 or 0.1 mmol DQ/kg, the survival time was significantly shorter in the HIS group than in the LIS group (P<0.05). These findings suggest that higher body iron stores result in more severe DQ toxicity in Fischer-344 rats.
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PMID:Relationship between body iron stores and diquat toxicity in male Fischer-344 rats. 1667 Sep 37

From April 1989 to December 2004, we performed liver biopsy on 475 patients and obtained biopsy proven 35 cases of non-alcoholic fatty liver. Among them, 18 cases were diagnosed as non-alcoholic steatohepatitis (NASH). During the last three years, we have tried to detect NASH using ultrasonography and elevated value of serum ferritin (> 300 ng/ml). All of the eligible 7 cases biopsied during the course were diagnosed as NASH. In these 7 cases, ALT levels improved after the body weight loss accompanied by the parallel decrease of serum ferritin levels. Measurement of serum ferritin is useful in the detection of NASH but the normal value of ferritin cannot rule out the possibility of NASH.
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PMID:[Prevalence of non-alcoholic steatohepatitis (NASH) among biopsied cases of a urban hospital in Japan: significance of measurement of serum ferritin in the detection of NASH]. 1673 57

In the present study we used patient data to calculate laboratory-specific indirect reference intervals. These values were compared with reference intervals obtained for a healthy group according to recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine and manufacturer suggestions. Laboratory results (422,919 records) from all subjects of 18-45 years of age over a 1-year period were retrieved from our laboratory information system and indirect reference intervals for 40 common analytes were estimated using a modified Bhattacharya procedure. Indirect reference intervals for most of the biochemical analytes were comparable, with small differences in lower [alkaline phosphatase (ALP) (male), alanine aminotransferase (ALT), creatine kinase, iron (male), total iron-binding capacity, folic acid, calcium (female), lactate dehydrogenase (LDH), lipoprotein (a) [Lp(a)], thyroid-stimulating hormone (TSH), total triiodothyronine (T(3)), direct bilirubin, apolipoprotein A-I (apoA-I), glucose, homocysteine, total cholesterol, ferritin, total protein, ceruloplasmin, sodium, blood urea nitrogen (BUN) and uric acid (female)] and/or upper limits [albumin, ALP (male), amylase, apoA-I, creatine kinase-MB (CK-MB), total iron-binding capacity, phosphorus, glucose, total cholesterol, gamma-glutamyltransferase (gamma-GT), magnesium, total protein, high-density lipoprotein cholesterol (HDL-C), total T(3), ALP (male), ALT, aspartate aminotransferase (AST) (male), direct bilirubin (male), creatine kinase, iron, folic acid (female), Lp(a), uric acid and triglycerides], to the reference intervals determined for healthy subjects in our laboratory. The indirect reference intervals, with the exception of a few parameters (creatinine, direct total bilirubin, calcium, BUN and potassium), were not similar to the reference intervals suggested by the manufacturers. We conclude that laboratory-specific reference intervals can be determined from stored data with a relatively easy and inexpensive method. Indirect reference intervals derived from stored data may be particularly suitable for the evaluation of results for the presenting population.
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PMID:Use of total patient data for indirect estimation of reference intervals for 40 clinical chemical analytes in Turkey. 1677 35

To assess the effects of liver iron overload and fibrosis after treatment with a chelating agent in hepatitis C virus (HCV)-infected thalassemia, from April 1999 to July 2004, 45 patients with thalassemia major (age range 9-33 years, mean 19.3) received daily deferiprone (L1) for 23-60 months (75 mg/kg). The patients were divided into two groups on the basis of their hepatitis status (27 with, 18 without). Their serum was analyzed for alanine aminotransferase (GPT), aspartate aminotransferase (GOT), bilirubin (total/direct), r-glutamyl transpeptidase (r-GT), alkaline phosphatase (Alk-P), and ferritin. Liver iron overload and fibrosis were defined by a senior pathologist. No significant differences were demonstrated in serum levels of GPT, GOT, bilirubin, r-GT, Alk-P or ferritin; comparison was made for each group before and after L1 treatment. Iron scores were 2.3 +/- 0.9 and 2.8 +/- 0.9 for the hepatitis C negative and positive groups, respectively (p = 0.07), with liver fibrosis scores of 1.0 +/- 0.5 and 0.4 +/- 0.52 (p = 0.56). The two scores were not higher for the positive group. There was no evidence of: 1) greater iron overload and fibrosis in the HCV-infected thalassemic patients; 2) L1 inducing progressive hepatic fibrosis or worsening iron overload in HCV-infected thalassemic patients after long-term therapy; 3) further damage to liver cells associated with L1 treatment.
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PMID:Effect of deferiprone on liver iron overload and fibrosis in hepatitis-C-virus-infected thalassemia. 1679 45

Increased hepatic iron deposition may play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to test whether iron removal by phlebotomy improves serum transaminase activities in patients with NASH. Eleven patients (six males and five females) with biopsy-proven NASH underwent phlebotomy biweekly until they reached near-iron deficiency (NID) (serum ferritin concentration lower than or equal to 30ng/ml). Nine patients completed this study. Serum ferritin levels in these patients fell from 563+/-322 to 18+/-9ng/ml (p=0.001). The treatment reduced mean serum alanine aminotransferase (ALT) activity from 126+/-47 to 56+/-17IU/l (p=0.002). Their weight did not change significantly throughout the study period. Although two patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required discontinuing the treatment. In conclusion, this pilot study suggests that iron reduction therapy by phlebotomy will be one of the promising therapies for NASH.
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PMID:Effect of iron reduction by phlebotomy in Japanese patients with nonalcoholic steatohepatitis: A pilot study. 1697 Nov 74


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