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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance (IR), glucose intolerance and diabetes mellitus are commonly associated with cirrhosis. The exact pathogenetic mechanisms responsible are still unknown; however, they may be related to both hepatitis C virus itself and to liver injury. IR may be the earliest abnormality, which in the following years may progress to clinical diabetes mellitus. The aim of this study was to investigate the presence of IR by euglycaemic hyperinsulinemic clamp technique, in chronic hepatitis C patients. 15 patients and nine healthy controls without any known condition that may affect IR were enrolled to the study. Chronic hepatitis C was diagnosed by liver biopsy (hepatic activity index was also determined in 10 patients) and appropriate viral and biochemical tests. Eight patients were given interferon therapy, which had been stopped for at least 3 months before the study. Euglycaemic hyperinsulinemic clamp technique was performed as previously described and peripheral glucose utilisation rate, M value, was calculated in mg/kg/min by infusion of 40 IU/m2/min regular insulin. M value of the control group was significantly higher than that of chronic hepatitis C patients (M = 5.1+/-1 vs. 3.7+/-1; p = 0.004), which was consistent with IR in the patient group. There was no significant correlation between the M value and alanine aminotransferase, aspartate aminotransferase and hepatic activity index (p = 0.621, 0.549, 0.479, respectively). Our results suggest that IR is present in chronic hepatitis C patients; it is not directly related to hepatic injury, moreover, it may be associated with some component(s) inherent to hepatitis C virus.
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PMID:Insulin resistance in chronic hepatitis C. 1560 64

Ribavirin has recently been demonstrated to be efficacious in combination with interferon (IFN) alpha-2b for the treatment of relapsed hepatitis C infections. The aim of this study was to evaluate the relationship between the pharmacokinetics and adverse reactions of ribavirin when ribavirin plus IFN alpha-2b were administered to patients affected with chronic hepatitis C. Nineteen patients received intramuscular IFN alpha-2b at a dose of 6 or 10 million units and oral ribavirin at 600 mg or 800 mg daily for 24 weeks. The pharmacokinetic profiles of ribavirin were assessed by the measurement of plasma concentrations. Twelve patients were continuously given both ribavirin and IFN alpha-2b, whereas in 7 patients the therapy was discontinued due to severe adverse drug reactions such as skin eruption, anemia and depression. There were no significant differences in ribavirin dose, Hb, ALT and AST values between the continued and the discontinued therapy groups. In contrast, the pretreatment platelet level and patient age of the discontinued therapy group were significantly different to the continued group. The trough plasma concentration of ribavirin in the discontinued therapy group was significantly higher than that in the continued group at week 1. These results suggest that the monitoring of plasma ribavirin concentrations may be valid for predicting the early phase of adverse drug reactions, thereby providing useful information for the adjustment of the ribavirin dosing for each patient.
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PMID:Assessment of adverse reactions and pharmacokinetics of ribavirin in combination with interferon alpha-2b in patients with chronic hepatitis C. 1568 98

To investigate the effects of silymarin on aminotransferase levels in patients with chronic hepatitis C, a standardized treatment with 420mg, 840mg or 1260mg per day was performed in patients of our clinic, who were not eligible for treatment with pegylated interferon and ribavirin. Aminotransferase levels were determined before, at 3-6 week intervals during and at the end of treatment. Predefined inclusion criteria for the retrospective analysis were persistently elevated alanine aminotransferase (ALT) levels (at least 6 months prior to and at beginning of the treatment) and treatment duration of at least three weeks. Liver cirrhosis CHILD B or C, interferon therapy within the last three months before treatment with silymarin, alcohol use >30 g/d, coinfection with hepatitis B virus or other severe diseases were exclusion criteria. According to these criteria 40 patients (13 with 420mg, 20 with 840mg and 7 with 1260mg silymarin per day) were eligible for the analysis. The mean treatment period was 125 +/- 78 days. ALT, aspartate aminotransferase and gamma glutamyltransferase levels did not change significantly from baseline in any group and there were no differences between the treatment groups. Bilirubin and prothrombine time were normal in all but one patient and remained unchanged. Silymarin therapy had no side effects. Silymarin at the doses used, does not improve elevated aminotransferases in patients with chronic hepatitis C.
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PMID:Oral silymarin for chronic hepatitis C - a retrospective analysis comparing three dose regimens. 1581 25

The aim of the study was to evaluate the efficacy of interferon alpha (IFNalpha)-2b in combination with oral ribavirin for treatment of chronic hepatitis C in relation to age, sex, liver enzymes activity as well as to grading and staging of liver disease in histologic examination. There were 154 adult patients assigned for the retrospective analysis including 69 females and 85 males of 16 to 70 years of age (mean age 43.3 +/- 12 years) treated with IFNalpha and ribavirin for 24 or 48 weeks. Sustained virological response was achieved in 66 patients (42.9%) and sustained biochemical response rate was 44%. Sustained response correlated with younger age, lower baseline AST, GT and ALP activities as well as with lower staging of liver disease. Combination treatment with interferon and ribavirin was significantly more effective in patient under 40 years of age and in patients without cirrhosis. Sex, baseline ALT activity and histological grading of liver disease did not differ between sustained responders and non-responders. Sustained virological response on combination therapy was achieved in 5 out of 7 previous monotherapy relapsers (71.4%) whereas only 5 patients out of 22 monotherapy non-responders benefited from combination therapy (22.7%). In conclusion, efficacy of combination therapy with IFNalpha and ribavirin in patients with liver cirrhosis is less effective and should be considered in chosen situations, especially in younger patients. Normal ALT activity should not be an exclusion criterion to therapy. Combination retherapy in previous monotherapy non-responders seems to be ineffective whereas in monotherapy relapsers good sustained response can be achieved.
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PMID:[Efficacy of combination therapy with interferon-alpha and ribavirin for chronic hepatitis C in relation to liver fibrosis and serum aminotransferase activity]. 1659 70

The genotype of hepatitis C virus (HCV) and the amount of HCV RNA are often used to predict the efficacy of interferon (IFN) therapy on chronic hepatitis C. In addition to these factors, there may be several factors related to the host. Therefore, the authors undertook a retrospective study in which physical findings and laboratory data before therapy were evaluated by multiple logistic analysis. Two-hundred and five cases with chronic hepatitis C treated with interferon were analyzed in this study. Sustained virological response was observed with 68 cases. Multiple logistic analysis was performed with 29 explanatory variables including HCV genotype, HCV RNA, IFN types, and total dose, along with gender, age, alcohol consumption, body mass index (BMI), histological findings of liver biopsy, platelet counts, and laboratory data of serum enzymes. Analysis on the factors that correlated well with therapeutic efficacy revealed that genotype 2a, 2b showed higher therapeutic responses than genotype 1b with reference to HCV genotypes, and higher IFN dose or lower HCV RNA levels gave better results. With reference to host factors, higher total protein level, lower levels of BMI, total bilirubin, and aspartate aminotransferase were highly correlated with therapeutic efficacy. HCV genotypes and HCV RNA levels have been already identified as prognostic factors. However, the high correlation values of BMI and the total protein level are new findings. It is suggested that probability estimation of therapeutic effects using the logistic regression equation may be a good tool for predicting therapeutic efficacy of IFN therapy on individual cases.
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PMID:Analysis of prognostic factors in therapeutic responses to interferon in patients with chronic hepatitis C. 1689 Jan 48

Changes in hepatic fibrosis after interferon-based therapy may be important in determining the long-term outcome of chronic hepatitis C (CHC). The use of liver biopsy for posttreatment assessment is not a viable option as a routine follow-up procedure. This study evaluated the predictive value of a simple noninvasive index, the aspartate aminotransferase (AST)-to-platelet ratio index assessed 6 months after end of treatment (APRI-M6). We evaluated APRI-M6, platelet-M6, AST-M6, and alpha-fetoprotein-M6 of 776 CHC patients with interferon-based therapy as well as the parameters at baseline of 562 untreated patients who were evaluated to predict the risk of hepatocellular carcinoma (HCC) and mortality, during a mean follow-up period of 4.75 (1.0-12.2) and 5.15 (1.0-16) years, respectively. Based on analysis of receiver operating characteristics (ROC) and using optimized cutoff point, the APRI-M6 and platelet-M6 had superior prediction models for long-term outcome with area under the curve of 0.870-0.875 and 0.824-0.847, respectively, and accuracy of 78%-81% and 76%-78%, respectively, for interferon-based-treated patients. The predictive values of all 4 parameters were poor in untreated patients. In subgroup analysis, the APRI-M6 provided a more consistent prediction ratio than platelet-M6 for sustained responders and cirrhosis-free subgroups; both parameters had similar prediction power for nonresponders and were unsatisfactory in patients with cirrhosis. According to Cox proportional hazards analysis, cirrhosis and APRI-M6 were the 2 most important factors for predicting HCC. In conclusion, APRI-M6 can accurately predict the long-term outcome of patients subjected to interferon-based treatment. Nevertheless, the data needs further validation, particularly since the predictive accuracy for patients with cirrhosis is low.
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PMID:A simple noninvasive index for predicting long-term outcome of chronic hepatitis C after interferon-based therapy. 1753 39

We examined whether treatment with amodiaquine, a potent inhibitor of histamine N-methyltransferase protects mice from Propionibacterium acnes (P. acnes)-primed and lipopolysaccharide (LPS)-induced hepatitis. The subcutaneous injection of amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice, and this improvement was partially associated with the decrease in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Amodiaquine partially suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver, whereas the expression of interleukin (IL)-18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine treatment. In conclusion, the present findings suggested that the elevation of endogenous histamine by amodiaquine may thus play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice.
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PMID:Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. 1722 19

Patients with human granulocytic anaplasmosis present with fever, thrombocytopenia, leukopenia, and an elevated aspartate transaminase level. Clinical and histopathologic features of severe disease suggest macrophage activation. Twenty-nine patients with human granulocytic anaplasmosis had higher ferritin, interleukin-10, interleukin-12 p70, and interferon- gamma levels than did control subjects matched for age and sex; severity correlated with triglyceride, ferritin, and interleukin-12 p70 levels. Several severely affected patients had cases that fulfilled macrophage activation syndrome diagnostic criteria. Macrophage activation and excessive cytokine production may belie tissue injury associated with Ananplasma phagocytophilum infection.
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PMID:Human granulocytic anaplasmosis and macrophage activation. 1757 79

The alcoholic liver disease usually causes overall immunological alterations which might be attributed to hepatic disease, to ethanol action, and/or to malnourishment. In the present study, efficacy of lecithin with vitamin-B complex to treat ethanol induced immunomodulatory activity was compared with the effect of lecithin alone and tocopheryl acetate (vitamin E). Ethanol (1.6 g/kg body wt/day for 12 weeks) exposure increased thiobarbituric acid reactive substance (TBARS) level, while decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) content in whole blood hemolysate of 8-10 week-old male BALB/c mice (weighing 20-30 g). The activities of transaminase (AST and ALT) enzymes, interleukin (IL)-10 and gamma interferon (IFN-gamma) elevated, while IL-2 and IL-4 reduced in mice serum due to ethanol exposure. These suggested that oxidative stress and immunomodulatory activities were interdependent and associated with ethanol induced liver damage. Lecithin treatment significantly reduced AST (32.44%), ALT (32.09%), IL-10 (25.63%) activities and TBARS content (12.76%) compared to ethanol treated group. However, lecithin with vitamin-B complex treatment, significantly reduced AST (62.83%); ALT (61.96%); IL-10 (35.88%); IFN-gamma (22.55%) activities and TBARS content (31.58%), while significantly elevated GSH content (36.49%) and SOD activity (61.21%). Tocopheryl acetate treatment significantly reduced AST (62.83%); ALT (61.54%); IL-10 (36.35%): IFN-gamma (23.28%) activities and TBARS content (35.84%). while significantly elevated GSH content (28.76%) and SOD activity (62.42%) compared to ethanol treated group. These findings persuasively argued that lecithin with vitamin-B complex was a new promising therapeutic approach in controlling ethanol induced immunomodulatory activities involving liver damage processes. Prevention of oxidative stress with correction of nutritional deficiency caused alteration in the ethanol-induced immunomodulatory activities and associated liver diseases.
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PMID:Effect of lecithin with vitamin-B complex and tocopheryl acetate on long-term effect of ethanol induced immunomodulatory activities. 1787 44

To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-gamma) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-gamma and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.
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PMID:Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi. 1796 57


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