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)

To evaluate the effect of a second cycle of alpha-IFN treatment on patients who have not responded to a first cycle or responded and relapsed, 37 patients, 25 men and 12 women, mean age 41 yr, were retreated with alpha-interferon (IFN). Seven patients responded to the first cycle of treatment, and 30 did not. Five patients who had not responded to the second cycle received a third one. All patients received twice the dose of the first cycle unless they experienced side effects during the first cycle. Thus, nine patients received 9 mU/w, nine received 15 mU/w, and 19 received 30 mU/w for 6 months. Complete response was defined as nondetectable hepatic hepatitis C virus (HCV)-RNA at the end of therapy; sustained response was defined as normal ALT levels with negative serum HCV-RNA at > 6 months after cessation of therapy. Of the 30 nonresponders to the first cycle, eight responded to the second, but only four (13%) had a sustained response. Six of the seven responders to the first cycle responded to the second cycle, but only three had a sustained response (3/7, 43%) (p = NS). Although 33 and 21% (p = NS) of those who were treated with 15 mU/w and 30 mU/w, respectively, showed a sustained response, none of those treated with 9 mU/w had a sustained response (p = NS). Although age or sex of the patients studied had no effect on the response rate, liver histology was an important factor because only noncirrhotics showed a long term response (47 vs 0%; p < 0.02). There was no difference in response rate between patients with chronic active hepatitis and chronic persistent hepatitis. In conclusion, noncirrhotic patients who have not responded or responded and relapsed to a 6-month course of alpha-INF (3-5 mU three times per week) should try a second course at a dose of 15 mU/w. Retreatment may induce complete and long lasting response in 13% of the initial nonresponders and 43% of the initial responders. A second course of alpha-IFN in nonresponding cirrhotics appears ineffective in clearing the virus at the doses used.
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PMID:alpha-Interferon retreatment of patients with chronic hepatitis C. 875 54

To assess the effectiveness and side effects of sequential interferon (IFN)-alpha and beta treatment for patients with chronic hepatitis C, 25 patients were enrolled in a trial of this regimen. The patients were given 6 million units (MU) of natural human INF-beta daily for 2 weeks followed by 6 MU of natural human IFN-alpha three times a week for 10 to 22 weeks. Serum alanine aminotransferase (ALT) levels normalized for at least 24 weeks in 10 patients (40%), of whom 4 (40%) had no detectable serum hepatitis C virus (HCV) RNA. Three variables were significant in predicting a sustained response: a low serum HCV RNA level, a low Knodell's fibrosis score, and a low indocyanine green retention rate at 15 minutes. Elevated serum ALT and proteinurea were observed with IFN-beta treatment but these side effects were mild and disappeared when INF-beta treatment ended. While all patients completed the entire regimen, we concluded that sequential IFN-alpha and beta treatment provides no additional antiviral effects in chronic hepatitis C.
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PMID:Sequential interferon-alpha and beta treatment in patients with chronic hepatitis C. 879 3

The health care burden caused by hepatitis C is projected to increase significantly in the next 20 years, on the basis of modeling estimates of cirrhosis, hepatic decompensation, and HCC likely to be seen in this population in the future. The number of cases of HCV-induced liver decompensation and mortality in the United States is projected to be approximately 4 times higher by the year 2018 than is currently seen, because of the aging of those presently infected. HCV also poses a significant quality-of-life decrement in the majority of individuals with chronic infection. Quality-of-life assessment in these patients has shown substantial reductions in both somatic and physical functioning compared with the general population, regardless of disease severity. The impact of chronic HCV on quality-of-life issues has been equated to that of non-insulin-dependent diabetes. Thus, HCV imparts a considerable toll on individual level of functioning and on overall health care resources. Hepatitis C evolves into a chronic infection in approximately 85% of individuals exposed to the virus, and progression to cirrhosis occurs in 20% to 30% of patients, with a disease duration up to 20 years. Hepatic decompensation will occur in approximately 20% and HCC in about 10% of those with HCV-related cirrhosis within 5 years of the determination of cirrhosis. End-stage liver disease caused by HCV is now the most common indication for liver transplantation in this country. Patients in whom liver decompensation develops should be considered for liver transplant evaluation, with referral to appropriate centers if these complications arise. Individuals with decompensated disease should not be treated with any of the current regimens available for HCV eradication, because these agents can accelerate hepatic dysfunction and will not mitigate the clinical outcome after the onset of decompensation. Available treatment options for HCV are rapidly changing, with INF as the standard and combination therapy with INF plus ribavirin rising to prominence as the optimal option. The need for abstinence from alcohol cannot be underestimated, given its documented synergistic effects on hepatotoxicity when combined with chronic HCV. Patients must be counseled in this regard and provided with the rationale for this recommendation. The benefits of therapy from a medical resource standpoint have recently been defined through analyses of cost-effectiveness. Bennett et al. used a mathematical model to estimate the cost-effectiveness of INF in the treatment of mild chronic HCV (no bridging fibrosis or cirrhosis). Therapy was found to be cost-saving for patients aged 20 to 35 years and was found to increase life expectancy by 3 and 1.5 years, respectively, at the spectrums of this age range. Kim et al. found the cost-effectiveness of a 12-month course of INF to compare favorably to other accepted medical interventions in the United States in patients younger than 60 years. Similar data for combination therapy has not yet been reported but would be expected to be comparable. Interferon monotherapy for 12 months is the current standard treatment recommendation for individuals with chronic HCV and elevated ALT levels. The explosive expansion of information now available to, and frequently quoted by, HCV patients seeking treatment will increasingly make this option less acceptable to a great many of this group. Combination therapy has emerged as the most efficacious option to date, both as initial treatment and for patients who relapse after standard INF. Unless data appear to the contrary, combination therapy should be considered first-line treatment in these groups. A suggested treatment algorithm for chronic HCV is outlined in Figure 2. Patients intolerant to ribavirin should be considered for continuation of INF to complete a 12-month course, dependent upon the assessment of HCV PCR status at week 12 of therapy. (ABSTRACT TRUNCATED)
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PMID:Advances in the treatment of hepatitis C. 1063 46

The goals of the present study were to provide information into the controversy about nitric oxide (NO) status of the liver during endotoxemia and to assess the role of the phosphatase inhibitor cyclosporin A (CsA) during the insult. Rats were injected with saline, lipopolysaccharide (LPS, 10 mg/kg i.p.) or cyclosporin A (CsA, 5 mg/kg. i.p.) + LPS, S-nitroso-N-acetyl penicillamine (SNAP, 0.1 mMikg) + CsA + LPS or molsidomine (molsid, 0.2 mg/kg) + CsA + LPS. Rat hepatocytes were isolated and tested for metabolic competence by the rate of urea synthesis and for lipid peroxidation. Hepatocytes were cultured under various treatments as LPS or cytokine mixture (CM, TNF-alpha 500 U/ml, INF-gamma 100 U/ml, IL-1beta 200 U/ ml) with or without CsA and iNOS expression was evaluated by NO productivity and by RT-PCR. Twenty-four hours after LPS dosing in vivo, the mortality rate was 15%, while CsA pretreatment increased mortality rate to 30% and reduced hepatocyte viability, increased ALT leakage and reduced urea synthesis. SNAP and Molsid resulted in complete survival of rats, increased urea synthesis, increased cell viability and reduced alanine aminotransferase leakage. LPS or CM increased iNOS expression while CsA pretreatment reduced iNOS expression. There was no correlation between lipid peroxide levels in hepatocytes and functional status of hepatocytes under various treatments. This study demonstrates that NO produced during endotoxemia and under the present conditions is protective to the liver and may function as an adaptive mechanism and that the inhibition of iNOS by compounds like CsA produce unfavorable effects.
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PMID:Inhibition of endotoxemia-induced nitric oxide synthase expression by cyclosporin A enhances hepatocyte injury in rats: amelioration by NO donors. 1178 62

Background: Rebound hepatitis is a potentially life-threatening complication of withdrawal from immunosuppressive therapy in patients with chronic Hepatitis B viral (HBV) infections. Objectives: To document the incidence of rebound hepatitis and determine whether the hepatitis is associated with serologic evidence of immunological rebound or the appearance of specific mutations in the HBV genome. Methods: Serum cytokines (IL-6, IL-10, TNF-alpha and INF-gamma) were documented by enzyme linked immunoassays and previously described HBV mutants (surface, core, pre-core and basal core promoter) by signal probe hybridization analysis in chronic HBV carriers treated with either 6 weeks of prednisone followed by 6 weeks of acyclovir (PR/AC, n = 20) or placebo/placebo (PL/PL, n = 20). Results: Rebound hepatitis (serum ALT > 2X baseline) occurred in 6/20 (30%) PR/AC patients versus 2/20 (10%) PL/PL recipients (P = 0.24). Serum cytokine levels were similar in those who developed rebound hepatitis compared to those who did not. HBV mutants were absent prior to and during treatment but developed in the follow-up period in three patients. All three patients were PR/AC recipients and in each case, the HBV mutation was in the basal core promoter gene. In two of the three patients, the mutant appeared just prior to the onset of rebound hepatitis while in the third, rebound hepatitis did not occur. Conclusions: The results of this study indicate an association exists between some cases of rebound hepatitis and the development of HBV mutants.
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PMID:Rebound hepatitis following withdrawal of immunosuppressive therapy in patients with chronic Hepatitis B viral infections. 1534 68

In the present study, three materials extracted or isolated from the roots of B. kaoi, an endemic plant to Taiwan, were used to be examined the hepatoprotective effect against dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats, they were water extract (BKW), polysaccharide-enriched fractions (BKP) and saponin-enriched fractions (BKS). After treated with DMN for 4 weeks, the levels of aminotrasferases (GOT, GPT) were significantly elevated in serum, and the levels of total protein (TP) and albumin were significantly decreased in serum and liver homogenates. Furthermore, the collagen contents were significantly elevated in liver homogenates and corresponded to the hepatofibrotic pathological examination. As the results showed, treated with groups of BKW, BKP, BKS markedly reduced GOT, GPT levels in rats serum. In addition, treated with groups of BKW, BKP, BKS markedly raised TP levels in rats serum and liver homogenates. Furthermore, treated with groups of BKW, BKP markedly raised albumin levels in rats serum and liver homogenates. Treated with groups of BKW, BKP, BKS markedly raised interferon-gamma (IFN-gamma) levels in rats serum, where only BKS and silymarin markedly raised interkeukin-10 (IL-10) levels in rats serum compared to that of DMN treated rats. None of test materials of B. kaoi except silymarin reduced the malondialdehyde (MDA) levels, but BKW, BKP markedly raised hepatic glutathione (GSH) levels to reveal the activity of anti-lipid peroxidation. Otherwise, treated with groups of BKW, BKP, BKS significantly reduced collagen contents in rats liver homogenates. In conclusion, B. kaoi demonstrated the anti-inflammatory and anti-fibrotic activities followed by anti-oxidant activity of enhanced GSH production, enhanced the liver cell regeneration and concerned with regulations of INF-gamma and IL-10. The ability of hepatoprotective and anti-fibrotic activities of B. kaoi are higher than B. chinense, a Bupleuri Radix imported from China to Taiwan.
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PMID:The hepatoprotective effect of Bupleurum kaoi, an endemic plant to Taiwan, against dimethylnitrosamine-induced hepatic fibrosis in rats. 1574 66

The aim of the study was comparison of the efficacy of treatment with INF and lamivudine in chronic hepatitis B. 103 patients with chronic hepatitis B were included in this trial and divided into two groups. Group I consisted of 34 patients treated with INF-alpha (5MU 3x per week during 4-6 months), group II included 69 patients treated with lamivudine (100mg per day during 1-4 years). Virologic, serologic and biochemical factors at ETR were analyzed. Costs of these two therapies were estimated too. In group I HBV DNA clearance was observed in 26/34 cases (76%), seroconversion HBeAg/anti-HBe in 5/34 (15%) and normalization of ALT in 22/30 patients (73%). In group II virological response occurred in 37/69 cases (53%), serological in 16/41 (39%) and biochemical in 34/50 (68%). Patients from group I suffered from adverse events typical for INF therapy. No adverse events were observed in group II. Cost of virological response in group I was 4 500 zl, in group II 8 000 zl, biochemical--INF 4 700 zl, lamivudine 5 700 zl and serological--group I 18 600 zl, in group II 18 700 zl.
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PMID:[Treatment of chronic hepatitis B]. 1580 74

Abrogation of Ron receptor tyrosine kinase function results in defects in macrophage activation and dysregulated acute inflammatory responses in vivo. Several naturally occurring constitutively active alternative forms of Ron have been identified, including from primary human tumors and tumor cell lines. One of these alternative forms, short-form (SF) Ron, is generated from an alternative start site in intron 10 of the Ron gene that eliminates most of the extracellular portion of the receptor and is overexpressed in several human cancers. To test the physiological significance of SF-Ron in vivo, mice were generated that solely express the full-length form of Ron (FL-Ron). Our results show that elimination of the capacity to express SF-Ron in vivo leads to augmented production of IFN-gamma from splenocytes following stimulation ex vivo with either concanavalin A or anti-CD3/T cell receptor monoclonal antibody. Moreover, in a concanavalin A-induced murine model of acute liver injury, FL-Ron mice have increased production of serum INF-gamma and serum alanine aminotransferase levels and worsened liver histology and overall survival compared with wild-type control mice. Taken together, these results suggest for the first time that SF-Ron impacts the progression of inflammatory immune responses in vivo and further support a role for the Ron receptor and its various forms in liver pathophysiology.
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PMID:Short-form Ron receptor is required for normal IFN-gamma production in concanavalin A-induced acute liver injury. 1700 58

To elucidate the roles of enteric bacteria and immunological interactions among liver, spleen and intestine in the pathogenesis of liver injury during obstructive jaundice, we studied the effects of antibiotics and splenectomy on bile-duct-ligated C57BL mice. When animals were subjected to bile-duct-ligation (BDL), plasma levels of bilirubin, alanine aminotransferase and aspartate aminotransferase increased markedly. However, the increases in plasma transaminases were significantly lower in splenectomized or antibiotics-treated groups than in the control BDL group. Histological examination revealed that liver injury was also low in the two groups. BDL markedly increased plasma level of interferon-gamma (IFN-gamma) and the expression of inducible nitric oxide synthase (iNOS) in liver and spleen. These changes were suppressed either by splenectomy or administration of antibiotics. Kinetic analysis revealed that BDL-induced liver injury and the increase of interleukin-10 (IL-10) and INF-gamma were lower in iNOS(-/-) than in wild type animals. BDL markedly increased the expression of IgA in colonic mucosa. These observations suggest that enteric bacteria, nitric oxide and cytokines including IFN-gamma and IL-10 derived from spleen and intestines form a critical network that determines the extent of liver injury during obstructive jaundice.
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PMID:Mechanism of Liver Injury during Obstructive Jaundice: Role of Nitric Oxide, Splenic Cytokines, and Intestinal Flora. 1839 95

In this study, the effects of fucoidan on aspirin-induced ulcers in rats were evaluated: both biochemical and immunological parameters were taken into consideration. The status of stomach tissue glycogen storage and histological changes were also examined. Examination of basic biochemical parameters showed significant (p<0.01) alterations in aspartate (AST) and alanine (ALT) transaminases in ulcer-induced rats. Also, moderate alterations (p<0.05) were observed in the levels of cholesterol and blood urea nitrogen (BUN). Histopathological examination showed neutrophil infiltration and inflammation in oxyntic cells with altered glycogen storage. Analysis of serum cytokines of aspirin-induced rats showed a moderate decrease in interleukin-10 (IL-10) with considerable increase of interleukin-6 (IL-6) and interferon-gamma (INF-gamma) when compared with control. Administration of fucoidan showed considerable (p<0.05) protection against ulceration by inhibiting the acute alterations of AST, ALT, cytokines and stomach glycogen. However, aggravated serum INF-gamma was observed in the fucoidan-pretreated group. These findings suggest that the anti-ulcer property of fucoidan might contribute in protecting the inflammatory cytokine-mediated oxidative damage to gastric mucosa.
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PMID:Effect of fucoidan on aspirin-induced stomach ulceration in rats. 1978 92


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