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)

Biliary atresia (BA) is a neonatal obliterative cholangiopathy of unknown etiology. Despite the Kasai procedure, hepatic fibrosis and portal hypertension (PH) still occur. Interleukin-8 (IL-8) is an important mediator of inflammation and immune response in human disease. The objective of this study was to investigate the potential role of IL-8 in the pathogenesis of the progressive, sclerosing, inflammatory process and fibrosis in BA. A total of 60 pediatric patients with BA and 15 healthy children were evaluated. The mean ages of BA patients and controls were 6.3 +/- 0.6 and 6.7 +/- 1.1 years, respectively. The patients were classified into two groups according to their clinical outcomes: patients with jaundice (total bilirubin +/- 25.5 micromol/l) and patients without jaundice (total bilirubin < 25.5 micromol/l). The IL-8 levels in serum samples were determined by commercially available enzyme-linked immunosorbent assay. Serum IL-8 levels were higher in the BA patients than in healthy children (236.2 +/- 60.1 vs. 34.5 +/- 12.1 pg/ml, P < 0.001). Patients with jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Serum IL-8 levels in the jaundice group were significantly higher than in those without jaundice (516.5 +/- 130.0 vs. 49.3 +/- 10.4 pg/ml, P < 0.0005). Furthermore, patients with PH had higher IL-8 levels than those without PH (378.1 +/- 102.2 vs. 106.6 +/- 48.4 pg/ml, P < 0.005). In the jaundice-free group, IL-8 levels were elevated in patients with PH compared with those without PH (79.0 +/- 17.4 vs. 19.7 +/- 5.8 pg/ml, P < 0.005). The present study demonstrated elevation of serum IL-8 levels in children with BA. Serum IL-8 levels were also higher in patients with jaundice compared with patients without jaundice. These findings suggest that IL-8 may play a significant role in the pathogenesis of BA.
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PMID:Serum interleukin-8 in children with biliary atresia: relationship with disease stage and biochemical parameters. 1561 91

To increase our understanding of the effect of thiazolidinediones, a new class of antidiabetic drugs, on liver function as well as glycemic control, we investigated liver function before, during, and after treatment with troglitazone and pioglitazone. A total of 32 patients with type 2 diabetes were studied. Glycemic control and liver function were measured before, during, and after 4 to 12 weeks of treatment with troglitazone or pioglitazone. Glycemic control was assessed by fasting levels of plasma glucose, hemoglobin A 1c , and serum insulin, and liver function was assessed by asparatate aminotransferase (AST), alanine aminotransferase (ALT), and gamma -glutamyl transpeptidase ( gamma-GTP). Homeostasis model assessment for insulin resistance was used as an index of insulin resistance. During treatment with troglitazone, fasting plasma glucose and hemoglobin A 1c levels and homeostasis model assessment for insulin resistance were significantly decreased. Serum AST, ALT, and gamma-GTP levels were significantly decreased during treatment (AST, -17.4%; ALT, -27.2%; gamma-GTP, -47.9%) and returned to pretreatment levels after 4 weeks of withdrawal of the drug. A similar tendency was observed during treatment with pioglitazone (AST, -4.7%; ALT, -16.4%; gamma-GTP, -30.8%). These data suggest that, in contrast to the deterioration of liver function reported in a small subset of patients treated with troglitazone, treatment with thiazolidinediones was associated with a decrease in serum transaminases in most patients. The improvement in liver function parameters known to be associated with fatty liver in the present study, together with an improvement in fatty liver reported for another class of insulin sensitizers, biguanides, suggests that thiazolidinediones may have a beneficial effect on fatty liver.
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PMID:Improvement of liver function parameters in patients with type 2 diabetes treated with thiazolidinediones. 1579 62

To elucidate the potential factors modulating exposure to aflatoxin B1 (AFB1) in three Chinese populations, an epidemiologic study was conducted in Fusui County and Nanning City of Guangxi Province and Chengdu City of Sichuan Province. The incidence rates of hepatocelluar carcinoma (HCC) for males in these three regions were 92-97 per 100,000, 32-47 per 100,000, and 21 per 100,000, respectively. Eighty-nine residents from Fusui, 196 residents from Nanning, and 118 residents from Chengdu were screened for AFB1-albumin adduct (AAA) levels and hepatitis virus (HBV, HCV, HDV, HEV, and HGV) infections, as well as liver biochemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], y-glutamyl transpeptidase [GGT], 5'-nucleotidase, globulin [GLO], direct bilirubin, indirect bilirubin, and bile acid levels). At least one marker of hepatitis virus (HV) infection was present in 47.2% (42/89) of subjects from Fusui, while in Nanning and Chengdu the values were 15.8% (31/196) and 22.0% (26/118), respectively. In contrast to females, a higher level of AAA was observed in males; the difference was statistically significant in both the Nanning (P = 0.023) and the Chengdu (P = 0.026) subjects. In the Chengdu group, there was a significantly higher level of AAA in cases with HV infection (P = 0.041). There was a close association between AAA level and BMI in the adults without HV infection (r = 0.148, P = 0.044). Also, AAA was closely associated with DBIL and GGT in non-HV-infected minors (P < 0.05), closely associated with ALB, GLO, and GGT in HV-infected minors (P < 0.05), and closely associated with IBIL, GLO, TBA, and AST in non-HV-infected adults (P < 0.01). The co-effect of HV infection and AFB1 exposure may be responsible for the high risk of HCC in the Fusui region, whereas age, gender, BMI, and HV infection may modify individual aflatoxin levels. The relationship between AAA level and liver biochemistry indicates injury induced by aflatoxin to both hepatic parenchyma and biliary tract. But the associations vary with age and HV infection status.
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PMID:Associated factors in modulating aflatoxin B1-albumin adduct level in three Chinese populations. 1581 Jun 36

Mice primed by feeding griseofulvin or diethyl 1,4-dihydro 1,4,6-trimethyl 3,5-pyridine decarboxylate for 5 months followed by drug withdrawal for 1 month (drug-primed mice) were given thioacetamide intraperitoneally, and the livers were subsequently studied at intervals up to 7 days. The hepatocellular proliferative response was measured by immunostaining for proliferative cell nuclear antigen. Necrosis was followed by measuring ALT. Mallory bodies were identified by immunoperoxidase stains for ubiquitin and cytokeratin. Preneoplastic foci were localized using immunofluorescence stain for glutathione S-transferase (GST mu) and histochemical stain for gamma glutamyl transpeptidase (GGT). The results showed that the preneoplastic foci selectively proliferated and expanded and formed nodules as indicated by quantitation of nuclei stained positive for proliferating cell nuclear antigen after thioacetamide treatment. Data support the hypothesis that the preneoplastic foci consisted of clones of hepatocytes which preferentially express GST mu, GGT and Mallory bodies. These preneoplastic cells selectively proliferate in response to the promoter effects of necrosis-induced liver cell regeneration ("chemical partial hepatectomy").
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PMID:Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice. 1672 98

The aim of this study was to investigate the antioxidant effect of acetyl-L-carnitine (ALC) against gamma-irradiation-induced oxidative damage in liver and lung tissue after total body irradiation with a single dose of 6Gy. To achieve the ultimate goal of this study, 40 adult rats were randomly divided into 4 groups of 10 animals each. Group I was injected intraperitoneally with saline solution for 5 consecutive days and served as control group. Group II was irradiated with a single dose of 6Gy. Group III was daily injected with ALC (250 mg kg(-1), i.p.) for 5 consecutive days. Group IV received a daily i.p. injection of ALC (250 mg kg(-1), i.p.) for 5 consecutive days and 1h after the last dose, rats were irradiated with a single dose (6Gy). The animals were sacrified after 24h. Administration of ALC for 5 consecutive days resulted in a significant increase in the activities of both superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) and the level of reduced glutathione (GSH), in lung and liver tissues which were reduced by radiation treatment. Also, ALC resulted in a significant decrease in total nitrate/nitrite (NO(x)) and malondialdehyde (MDA) levels in both lung and liver tissues and a significant decrease in triglycerides, low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL), total cholesterol, Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and Gamma glutamyl transpeptidase (GGTP) compared to irradiated group. In conclusion, data obtained from this study indicate that ALC could increase the endogenous antioxidant defense mechanism in rat and there by protect the animals from radiation-induced organs toxicity.
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PMID:Protective role of carnitine ester against radiation-induced oxidative stress in rats. 1675 76

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

The purpose of this study was to determine the possible role of serum levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) in the pathogenesis of the progressive inflammation and fibrosis in biliary atresia (BA). Serum concentrations of TIMP-1 were measured in 57 BA patients and 15 healthy controls using commercially available enzyme-linked immunosorbent assays. The mean ages of the BA patients and the controls were 6.1 +/- 0.6 and 6.7 +/- 1.1 years, respectively. The patients were categorized into two groups according to their clinical outcomes: patients with jaundice (total bilirubin > or = 2 mg/dl) and patients without jaundice (total bilirubin < 2 mg/dl). In our study, serum levels of TIMP-1 were significantly higher in the BA patients than in healthy subjects (4.8 +/- 0.4 vs. 3.5 +/- 0.3 ng/ml, respectively; p < 0.05). Additionally, serum levels of TIMP-1 significantly increased in the BA patients with jaundice in comparison to those without jaundice (6.3 +/- 0.7 vs. 3.1 +/- 0.3 ng/ml, respectively; p = 0.001). Patients with persistent jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Furthermore, patients with portal hypertension (PH) had higher TIMP-1 levels than those without PH (5.3 +/- 0.4 vs. 1.9 +/- 0.3 ng/ml, respectively; p < 0.001). It is concluded that serum levels of TIMP-1 increased in patients with BA. The significant increase in TIMP-1 levels is related to the presence of PH and the severity of jaundice. The elevated TIMP-1 levels may reflect the degree of hepatic fibrosis and development of PH. The data suggest that TIMP-1 may play a role in the pathophysiology of post-Kasai BA.
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PMID:Association of serum levels of tissue inhibitors of metalloproteinase-1 with clinical outcome in children with biliary atresia. 1713 82

We investigated the therapeutic effect of oculo-acupuncture on dogs induced with acute hepatic injury. Hepatic injury was induced by intraperitoneal injection with carbon tetrachloride (CCl(4)) in 8 mongrel dogs (4 females and 4 males, aged 2 to 4 years). The dogs were divided into the control group (4 dogs) and the experimental group (4 dogs). The experimental group was treated with oculo-acupuncture at the liver/gallbladder regions plus the zhong jiao region of the eye after the induction of hepatic injury. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transpeptidase (GGT) activities were measured in both control and experimental groups. The serum AST, ALT, and GGT activities in the experimental group were decreased as compared to those in the control group. The significant differences were detected on the third day (AST, p < 0.05), second day (ALT, p < 0.05) and third day (GGT, p < 0.05) in the experimental group, respectively. Oculo-acupuncture alleviated acute liver damage induced by carbon tetrachloride in dogs was also confirmed by histopathological examination. We concluded that oculo-acupuncture at the liver/gallbladder regions plus the zhong jiao region was effective in the recovery of dogs from hepatic injury in a CCl(4)-induced model.
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PMID:The effect of oculo-acupuncture on acute hepatic injury induced by carbon tetrachloride in dogs. 1726 50

A 37-year-old female subject had been convicted of driving under the influence of alcohol, and 19 months later, claimed abstinence after supervised disulfiram treatment. Our aim was to elucidate the value of direct ethanol metabolites as measures of abstinence. Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) in hair, phosphatidylethanol in whole blood and EtG and ethyl sulphate in urine were measured. The results were compared with self-report of alcohol consumption and traditional blood biomarkers for chronically elevated alcohol consumption as carbohydrate deficient transferrin (CDT), gamma glutamyl transpeptidase, mean corpuscular erythrocyte volume, aspartate aminotransferase and alanine aminotransferase. EtG was found in distal parts of hair only, whereas the proximal parts were negative. Furthermore, FAEE concentrations were found in the typical distribution over the hair length and showed values typical for either moderate social drinking or abstinence. CDT was above cut-off in 9 out of 16 analyses with a decreasing tendency and the lowest values in the last 2 months before the end of sampling. The data suggest that in addition to traditional markers, a combination of direct ethanol metabolites can be useful in the expert assessment of judging driving ability. A careful individual interpretation of the results for the different markers, however, is an absolute necessity.
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PMID:Measurement of direct ethanol metabolites in a case of a former driving under the influence (DUI) of alcohol offender, now claiming abstinence. 1825 45

Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-alpha and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage.
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PMID:Single dose intravenous thioacetamide administration as a model of acute liver damage in rats. 1842 1


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