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)

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.
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PMID:A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease. 1253 83

The aim of this study was to evaluate the effect of cariporide, a selective Na(+)/H(+) exchange inhibitor, on isolated and cultured hepatic stellate cells (HSCs) and in 2 in vivo models of rat liver fibrosis. Platelet-derived growth factor (PDGF)-induced HSC proliferation, evaluated by measuring the percentage of bromodeoxyuridine-positive cells, was significantly inhibited by cariporide, with a maximal effect at 10 micromol/L. Incubation with cariporide did not inhibit PDGF-induced extracellular-regulated kinase 1/2 (ERK1/2), Akt (a downstream component of the phosphatidylinositol [PI]-3 kinase pathway), and protein kinase C (PKC) activation but reduced PDGF-induced activation of the Na(+)/H(+) exchanger, with a maximal effect at 10 micromol/L. Rats treated with dimethylnitrosamine (DMN; 10 mg/kg) for 1 and 5 weeks received a diet with or without 6 ppm cariporide. Treatment with cariporide reduced the degree of liver injury, as determined by alanine aminotransferase (ALT) values, also when administered after the induction of hepatic damage. This was associated with reduced HSC activation and proliferation and reduced collagen deposition, as determined by morphometric evaluation of alpha-smooth muscle actin (SMA)/proliferating cell nuclear antigen-positive cells and percentage of Sirius red-positive parenchyma, respectively. Moreover, cariporide was also able to reduce alpha(1)I procollagen messenger RNA (mRNA) expression. Similar effects were observed in bile duct-ligated (BDL) rats. In conclusion, selective inhibition of the Na(+)/H(+) exchanger by cariporide may represent an effective therapeutic strategy in the treatment of hepatic fibrosis.
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PMID:Selective Na+/H+ exchange inhibition by cariporide reduces liver fibrosis in the rat. 1254 Jul 75

Inhibition of Kupffer cells could disrupt the sequence of events leading to organ injury by damping down the fibrogenic stimulus. To elucidate the role of Kupffer cells in liver fibrosis and cirrhosis, rats were treated with gadolinium chloride (GdCl(3)) and cirrhosis was induced by subchronic carbon tetrachoride (CCl(4)) administration. Carbon tetrachloride was administered three times per week for 8 weeks to male Wistar rats treated simultaneously with GdCl(3) (20 mg kg(-1), i.p. daily); appropriate controls were performed. Serum enzyme activities of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) and bilirubin concentration increased significantly by CCl(4), whereas GdCl(3) prevented completely the increase in gamma-GTP and partially prevented the increase in ALP, ALT and bilirubins (P < 0.05). Liver glycogen was depleted by CCl(4), an effect that GdCl(3) was not capable of preventing. Moreover, gadolinium by itself depleted it. Lipid peroxidation increased about 2.5-fold by administration with CCl(4), whereas GdCl(3) preserved lipid peroxidation within normal values. Hepatic collagen increased threefold after subchronic intoxication with CCl(4) (P < 0.05) whereas GdCl(3) prevented partially (P < 0.05) the increase in collagen content, as evidenced by the liver hydroxyproline content and by the histopathological analysis. The present results suggest that Kupffer cells are needed for the production of CCl(4)-induced cirrhosis, because their inactivation with GdCl(3) prevents the disease.
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PMID:Kupffer cells are responsible for liver cirrhosis induced by carbon tetrachloride. 1266 54

Leptin is a 16-kDa hormone with an array of biologic actions. We, and others, have demonstrated that leptin is critical to the development of liver fibrogenesis both in vitro and in the lean littermates of ob/ob mice exposed to carbon tetrachloride (CCl(4)). Controversy exists as to whether leptin can act as a direct cytokine in the development of increased collagen expression, and whether ob/ob mice are resistant to potential injury from CCl(4). Here, we provide evidence that strongly suggests that leptin acts to increase nascent production of mRNA for the alpha2(I) collagen gene based upon ribonuclease protection analysis (RPA). Actinomycin D, but not cyclohexamide, or the pan-neutralizing antibody to transforming growth factor beta one (TGFbeta1), significantly diminished the effect of leptin on total alpha2(I) collagen mRNA levels. Further evidence that leptin acts directly on HSCs to alter gene expression in liver wounding is demonstrated by enhanced binding of phosphorylated signal transduction and activator of transcription factor 3 (pStat3) to a cis-inducible element (SIE) oligonucleotide by electrophoretic mobility shift assay (EMSA). This consensus sequence is responsible for production of a critical collagen transcription factor, AP-1. Finally, we have demonstrated from the ob/ob mouse model that these animals are at least as sensitive to CCl(4) as their respective lean animals as assessed by serum alanine aminotransferase (ALT) measurements. Taken together, the current data provide a continued framework that leptin is a profibrogenic cytokine and plays a key role in liver fibrosis.
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PMID:Leptin induces increased alpha2(I) collagen gene expression in cultured rat hepatic stellate cells. 1270 94

Treatment of chronic hepatitis C in renal-transplant (RT) recipients with alpha-interferon is associated with a high rate of acute rejection. We therefore evaluated the biochemical, virological, histological efficacies, as well as the safety of one year ribavirin monotherapy in 16 HCV-(+) RNA (+) RT patients (group A) matched to 32 HCV-(+) RNA (+) RT patients (group B) who did not receive ribavirin. Ribavirin was initially started at a daily dose of 1000 mg and then adapted to hemoglobin level. Ribavirin monotherapy was associated with a significant decrease in AST, ALT and gamma glutamyl transpeptidase levels. Serum creatinine decreased as well. When proteinuria was present (n = 5), this decreased or disappeared. There was no significant changes in HCV viremia. The histological analysis of liver biopsies revealed a significant progression in liver fibrosis with no improvement in inflammation scores. There was a significant decrease in hemoglobin levels, despite an important support by recombinant erythropoeitin. However, in three cases, ribavirin therapy had to be stopped. In group B, after 1 year of follow up, there was a significant increase in serum ALT and creatinine values. Proteinuria decreased in only 2 of 12 patients. In conclusion, one year ribavirin therapy in HCV-(+) RNA (+)ve RT has no impact upon liver histology, although it improves liver enzyme levels. It impact upon renal function remains unknown. Nevertheless when proteinuria is present it disappears.
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PMID:[Is there a place for ribavirin in the treatment for renal transplant patients infected by hepatitis C virus?]. 1272 14

Purpose - To evaluate whether Doppler sonography measurement of portal flow velocity (PFV) after glucagon injection can be useful in assessing the severity of liver damage in chronic HCV infection. Methods - Forty-five patients (32 males and 13 females; mean age 54.1 14.8 years) with biochemical (raised serum ALT levels), virological (positive serum HCV RNA test) and histological (liver biopsy) evidence of chronic HCV infection were included in the study. According to hepatitis staging (degree of liver fibrosis), as assessed by Knodell histological activity index, patients were divided into three groups: group 1 (n.=17), with no or mild fibrosis (fibrosis score: 0-1); group 2 (n.=11), with severe fibrosis (score: 3); and group 3 (n.=17), with liver cirrhosis (score: 4). For sonographic measurements of PFV, a Doppler ultrasound multi-purpose equipment and a convex 3.5 MHz probe were used. All patients were examined after an 8-hour fast, in supine position, 10 min before (baseline), as well as 5 and 10 min after, intravenous administration of 1 mg of glucagon chloride (Novo Nordisk). Statistical analysis was performed by ANOVA test, Bonferroni t test and Spearman rank correlation test. Results - No significant differences were found in mean basal PFV of group 1 (19.4 2.4 cm/sec), group 2 (20.1 3.6 cm/sec) and group 3 (17.5 3.7 cm/sec) (p > 0.05). Five minutes after glucagon injection, all the three groups showed a significant increase in PFV (25.6 4.8,23.7 4.0 and 19.5 5.0 cm/sec, respectively; p < 0.05 vs baseline). The peak increase in PFV after glucagon injection was significantly higher in group 1 (7.9 3.7 cm/sec; 40.7% of basal value) than in group 2 (4.5 3.9 cm/sec; 22.4%) (p < 0.05) and in group 3 (2.7+2.3 cm/sec; 15.4%) (p < 0.05). A significant (p< 0.001) inverse correlation was also found between the patients fibrosis scores and peak increments of PFV induced by glucagon. Conclusions - In some patients with chronic HCV infection, Doppler sonography measurement of PFV after glucagon injection can be useful, in combination with other non invasive ultrasound investigations, both in staging of liver disease and in monitoring the progression of liver histological damage.
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PMID:[Glucagon test for Doppler sonography measurement of portal flow in chronic HCV infections] 1273 Jun 45

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1-2 days, and fibrosis developed 2-3 wk after bile duct ligation. Additionally, procollagen-alpha1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of alpha-smooth muscle actin and transforming growth factor-beta and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45-73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.
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PMID:Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats. 1279 96

The prevalence of hepatitis C is 7-10-fold higher in alcoholics than it is in the general population. Among alcoholics, the prevalence of hepatitis C is higher in alcoholics with advanced liver disease. Serum ALT and hepatitis C viral load may improve if alcoholic patients with hepatitis C stop drinking for more than 4 months.Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks per day increases the rate of liver fibrosis. Hepatitis C patients who ingest more than 5 alcoholic drinks per day are at increased risk for cirrhosis, hepatocellular carcinoma and, possibly, death from liver disease. Recent alcohol use decreases the response rate to interferon treatment. The detrimental effects of small amounts (3 or fewer drinks per day) of alcohol consumption in patients with hepatitis C are not known.
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PMID:Liver disease in alcohol and hepatitis C. 1282 60

Holotrichia diomphalia larvae, one of the most widely used Korean folk medicinal preparations, have long been used for the treatment of chronic liver cirrhosis. The present study was undertaken to clarify whether extract of Holotrichia diomphalia larvae could prevent acute liver damage and liver fibrosis in rats. A single administration of Holotrichia diomphalia protected rats from acute liver damage induced by carbon tetrachloride (200 micro l/kg, i.p.) and beta-D-galactosamine (600mg/kg, i.p.). This was evidenced by the lowered serum aminotransferase (ALT, AST) activities in rats treated with Holotrichia diomphalia. The hepatic cirrhosis was induced by 28 days of bile duct ligation/scission in rats. The four-week treatment with Holotrichia diomphalia reduced the serum ALT, AST, alkaline phosphatase activities, and hydroxyproline content in the liver and improved the histological appearance of the liver sections. The present results led us to conclude that Holotrichia diomphalia larvae can reduce the degree of hepatocellular damage and may become a promising antifibrotic agent for liver fibrosis/cirrhosis.
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PMID:Effect of Holotrichia diomphalia larvae on liver fibrosis and hepatotoxicity in rats. 1286 Mar 4

The effects of glucan and liposomized glucan, alone or co-administered with vitamin C, and empty liposomes on hepatic fibrosis in mice infected with Mesocestoides corti (M. vogae) tetrathyridia were studied. Preparations were administered every third day from day 7 to day 31 post-infection (p.i.), nine doses in total. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cholesterol levels were measured in sera collected on days 11, 15, 21, 28, 32, 42, 50 and 65 p.i. Liver fibrosis was studied on the same days by measuring hydroxyproline concentration, which is considered a marker for collagen content. Larvicidal effects of the glucan and liposome preparations were estimated on day 65 p.i. in the liver and peritoneal cavity. Glucan formulations significantly enhanced collagen content, most prominently after administration of liposomized glucan in combination with vitamin C. Activities of both enzymes and cholesterol levels were slightly modified after administration of glucan alone. Liposomized glucan with vitamin C significantly increased ALT and AST activity and cholesterol levels up to days 28-32 p.i., after which they plateaued or declined. The most pronounced decrease was after administration of liposomized glucan and vitamin C. The same pattern of biochemical parameters in serum was observed after administration of empty liposomes, however, collagen content was not modified significantly. Larval counts in the liver and the peritoneal cavity were significantly reduced after treatment with either glucan formulation, but were unaffected following treatment with empty liposomes. In summary, intense fibrosis in the liver of mice treated with liposomized glucan and vitamin C did not result in the most extensive parenchymal cell injury but, rather in the highest efficacy of treatment. Liposomal lipids were probably utilized in the reparation of the damaged parenchymal cells, while glucan stimulated phagocytic cells.
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PMID:Modulation of liver fibrosis and pathophysiological changes in mice infected with Mesocestoides corti (M. vogae) after administration of glucan and liposomized glucan in combination with vitamin C. 1289 80


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