Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since S-adenosylmethionine (SAMe) plasma levels are highly reduced in cirrhotic patients, this, showing that a more or less overt deficiency of SAMe-dependent biological transmethylations does exist in the hepatocyte pathology, mostley affecting the albuminopoyesis. Treatment with 15 mg SAMe i.v. or i.m. administered four times a day for 30 days' period, induced in 15 patients with hepatic cirrhosis a statistically significant improvement of the afore mentioned livel cell function, albuminopoyesis: a significant improvement was also observed in the other biohumoral parameters considered to test hepatic function. Administration of equimolecular (with respect to SAMe) doses of L-methionine and ATP to a group of 15 cirrhotic patients under clinical conditions similar to those of the group previously studied, induced none of the modifications observed in the latter. This proved that the therapeutic effects are due only to S-adenosylmethionine.
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PMID:[S-Adenosylmethionine: plasma levels in hepatic cirrhosis and preliminary results of its clinical use in hepatology. Double-blind study]. 109 62

After a diffuse introductory discussion on S-adenosylmethionine methyltransferase activity, the results of an experimental trial carried out on 70 hospitalized patients with chronic hepatitis either persistent or aggressive, and with hepatic cirrhosis at various degrees, are reported. A first group of patients was treated with SAMe (S-adenosylmethionine) intravenously administered for 20 days at two daily doses of 15 mg. The second group was instead-receiving, still by i.v. route, 20 mg of fructose-1-6-diphosphage sodium salt, as a drug for comparison given twice a day at the doses of 2.5 over a 20 days' period. The protidemia picture and in particular the albuminic fraction, generally altered in all the cases under study, have been rapidly and significantly restored only in the group of patients treated with SAMe this indicating the efficacy of this molecule on the liver function.
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PMID:[Relations between protidopoiesis and biological transmethylations: action of S-adenosylmethionine on protein crasis in chronic hepatopathies]. 109 63

Two comparable groups of patients with hepatic cirrhosis of different genesis in a compensation phase have been treated for 30 days with S-adenosylmethionine and vitamine B-12 (28 cases) or with vitamine B-12 alone (25 cases). The drugs were given by slow intravenous route at the daily dose of 150 mg of SAMe and 2000 gamma of vit. B-12 or of 2000 gamma of vit. B-12 alone, in two adminstrations. An evaluation of the results was carried out mostly on the laboratory data testing the liver function. Only the group of patients who had received SAMe showed significant modifications of all the parameters considered. This is confirming SAMe ability to restore hepatocyte activity bringing also to normal the protein synthesis.
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PMID:[Double-blind polycentric study of the action of S-adenosylmethionine in hepatic cirrhosis]. 109 64

Six oral administrations per day of 30 mg S-adenosylmethionine (SAMe) for 30 days, in addition to 6000 gamma/day of Vitamine B12 induced marked improvements of biochemical parameters in 20 patients with hepatic cirrhosis or various chronic hepatites. Particularly, the protidemia, bilirubinemia and radial immunodiffusion have shown the highest favorable drug responses. These improvements were still lasting and even further increasing 30 days after the end of therapy. In another group of patients with similar diagnosis and under clinical conditions comparable to the previous group of twenty, the administration of Vitamine B12 alone, in the same doses as above, has not induced any alteration in the biochemical parameters.
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PMID:[Double-blind studies of the therapeutic action of S-Adenosylmethionine (SAMe) in oral administration, in liver cirrhosis and other chronic hepatitides]. 109 65

Albuminopoyesis, prothrombin activity, BSF clearance, bioptic and sometimes also laparoscopic pictures have been examined in order to test the hepatic activity of SAMe. This study has been carried out in patients suffering from liver cirrhosis and other chronic hepatites. The above-mentioned parameters proved to be significantly improved in almost all the 25 patients studied and checked after 30 and 60 days' treatment with 30-45 mg SAMe administered by slow intravenous route.
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PMID:[Therapeutic action of S-adenosylmethionine in some chronic hepatopathies]. 114 92

Administration of carbon tetrachloride to rats resulted in induction of hepatic fibrosis and a 60% reduction of hepatic S-adenosylmethionine synthetase activity without producing any significant modification of hepatic levels of S-adenosylmethionine synthetase messenger RNA. The reduction of S-adenosylmethionine synthetase activity was corrected by treatment with S-adenosylmethionine (3 mg/kg/day, intramuscularly). Administration of carbon tetrachloride also produced a 45% depletion of liver glutathione (reduced form) that was corrected by S-adenosylmethionine treatment. After the rats received carbon tetrachloride, a 2.3-fold increase in liver collagen was observed; prolyl hydroxylase activity was 2.5 times greater than that seen in controls. These increases were attenuated in animals treated with carbon tetrachloride and S-adenosylmethionine. The attenuation by S-adenosylmethionine treatment of the fibrogenic effect of carbon tetrachloride was associated with a decrease in the number of rats in which cirrhosis developed.
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PMID:S-adenosylmethionine treatment prevents carbon tetrachloride-induced S-adenosylmethionine synthetase inactivation and attenuates liver injury. 139 82

An experimental model of toxic liver injury in rats was employed to assay the effect of Nifedipine (a calcium antagonist blocker) and S-Adenosylmethionine (a precursor of glutathione). An important decrease in both perivenular fibrosis and cirrhosis was found. Furthermore, a significant decrease in lactic acid levels was found in the group of animals treated with pharmacologic therapy, although no correlation was seen between lactic acid levels and the different degrees of perivenular fibrosis. No significant variations in ALT and AST enzymes were observed between both groups, as opposed to a significant decrease in LDH enzyme in the Nifedipine+S-Adenosylmethionine group. The results indicate an improvement in the histologic picture of the liver in rats treated by means of pharmacological association, without any change in inflammatory infiltrate and with a slight decrease in necrosis, indicating an action mechanism via creeping fibrosis (instead of a hepatitis pathway).
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PMID:Effect of nifedipine and S-adenosylmethionine in the liver of rats treated with CCl4 and ethanol for one month. 151 99

Parenteral S-adenosylmethionine proved to be effective in reversing intrahepatic cholestasis in pregnant women. Based on these findings, a prospective multicenter, double-blind, placebo-controlled trial was planned to assess whether oral S-adenosylmethionine is effective in cholestatic patients with chronic liver disease. Accordingly, 220 inpatients (26% chronic active hepatitis, 68% cirrhosis, 6% primary biliary cirrhosis) with stable (1 month or more) at least twofold increases in serum total and conjugated bilirubin and alkaline phosphatase volunteered for the trial. Serum markers of cholestasis significantly (P less than 0.01) decreased after oral S-adenosylmethionine administration (1600 mg/day), and their values were significantly (P less than 0.01) lower than the corresponding values in the placebo group. S-adenosylmethionine significantly (P less than 0.01) improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell, whereas placebo was ineffective. Two patients in the S-adenosylmethionine group and 9 controls (P less than 0.05) withdrew from the trial for reduced compliance because of inefficacy of treatment. Oral S-adenosylmethionine was tolerated to the same extent as placebo. In conclusion, short-term administration of oral S-adenosylmethionine is more effective than placebo in improving clinical and laboratory measures of intrahepatic cholestasis and offers a new therapeutic modality for the symptomatic management of this syndrome.
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PMID:Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. 218 71

Catalytically active human and rat liver S-adenosylmethionine synthetase exists mainly in tetramer and dimer form. In liver biopsy samples from cirrhotic patients a marked reduction in total S-adenosylmethionine synthetase activity and a specific loss of the tetrameric form of the enzyme exist. We have investigated the possible role of sulfhydryl groups in maintaining the structure and activity of S-adenosylmethionine synthetase. Both forms of S-adenosylmethionine synthetase are rapidly inactivated by N-ethylmaleimide, and the loss of enzyme activity correlates with the incorporation of approximately 2 moles N-ethylmaleimide per mole of subunit. In addition, reaction with N-ethylmaleimide resulted in displacement of the tetramer-dimer equilibrium of the enzyme toward the dimer, but no monomer was detected under these conditions. A catalytically active monomeric S-adenosylmethionine synthetase was detected in the cytosolic extract from a liver biopsy sample from a cirrhotic patient, supporting our model for the structure of S-adenosylmethionine synthetase. Because treatment of S-adenosylmethionine synthetase with N-ethylmaleimide resembles the situation of this enzyme in cirrhotic patients, it is proposed that impaired protection of the enzyme from oxidizing agents caused by a decreased synthesis of glutathione can explain the diminished synthesis of S-adenosylmethionine in liver cirrhosis.
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PMID:Inactivation and dissociation of S-adenosylmethionine synthetase by modification of sulfhydryl groups and its possible occurrence in cirrhosis. 230

The lipotropes (choline, methionine, folate, and vitamin B12) have a rich history, with many fluctuations in scientific effort and popularity, covering the past 6 decades. A thin thread of common interest in 1-carbon metabolism and a small band of dedicated individuals have kept this area of biology alive. Today, the lipotropes are enjoying a resurgence of interest and effort with promise for significant contributions to some of our most serious chronic diseases. Between 1920, when Banting and Best initiated a work that led to the discovery of insulin, and 1982-83, when investigators working in 3 laboratories announced that lipotrope deficiency alone could result in liver cancer in rodents, many have used this model to study nutritional problems and, more recently, carcinogenesis. Lipotropes are important to lipid metabolism and to synthesis and maintenance of cellular membranes. When weanling rats were fed a diet low in lipotropes, within a few days the liver accumulated lipid, first in the centrilobular zone and later throughout the entire lobule and lobe. If the diet was continued for a longer period, the liver underwent fibrosis and cirrhosis with some rats ultimately developing hepatocellular carcinoma. Although lipotrope deficiency can result in liver cancer, all hepatocarcinogens tested thus far were enhanced in their activity by diets low in lipotropes. Important changes associated with lipotrope deficiency included membrane damage, decreased serum very low density lipoprotein and drug metabolizing enzymes, decreases in S-adenosylmethionine and in methylation of cytosine, increases in cellular peroxidation products and free radicals, decreased immunocompetence, and a markedly shortened lag time for chemical induction of liver cancer in animals. The overall effect of lipotrope deficiency is an increase in the susceptibility to cancer in animals; the exact mechanisms are unclear.
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PMID:Lipotropic factors and oncogenesis. 303 98


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