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)

Methionine is a sulfur-containing essential amino acid and there are optic isomers of L- and D-type. It has been known that there are two metabolic pathways in methionine metabolism-the transsulfuration and the transamination. The purposes of the present investigation are to clarify the existence of transaminative pathway in human by the quantitative analysis of 3-methylthiopropionate (3-MTP), one of the metabolites of methionine, and to study its clinical significance in patients with liver cirrhosis. 3-MTP in urine was analysed by gas chromatograph equipped with the flame photometric detector (FPD) which has a highly specific sensitivity to the sulfur compounds. Fasting levels of 3-MTP concentration in urine in healthy subjects (n = 20) and patients with liver cirrhosis (n = 21) were 39.1 +/- 9.7 ng/mg. Cr. (Mean +/- SE) and 103.6 +/- 24.2 ng/mg. Cr., respectively. 3-MTP concentration in urine in cirrhotic patients was significantly higher than that in healthy subjects (p less than 0.05). In some cases, 3-MTP concentration in urine was measured every hour for 3 to 6 hours after the oral loading of 2 g of D- or L-methionine. In healthy subjects, 3-MTP concentration in urine increased remarkably at 1 hour period after oral loading of 2 g of D-methionine, and subsequently its concentration showed a tendency to decrease gradually. However, there were no such changes after oral loading of 2 g of L-methionine. When 2 g of D-methionine was loaded orally, decreasing curves of 3-MTP concentration in urine were different between healthy subjects and patients with liver cirrhosis, and half-disappearance time of 3-MTP concentration in urine was remarkably prolonged in cirrhotic patients. These findings seem to indicate that 3-MTP is one of the metabolites of methionine (especially of D-methionine) and the transaminative pathway exists in human. It was also suggested that there was the impairment of the transaminative pathway of methionine metabolism in patients with liver cirrhosis. Pharmacokinetics of 3-MTP in urine seems to contribute to the clinicopathological investigation of the liver cirrhosis.
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PMID:[Analysis of methionine metabolism studied by the gas chromatographic determination of 3-methylthiopropionate in urine and its clinical application]. 399 54

The effects of branched-chain amino acid (BCAA)-enriched nutrient mixture (nutrient-mixture) on the nitrogen metabolism and nutritional state were clinically investigated in 10 patients with liver cirrhosis. Nutrient-mixture-supplemented diet was prepared by adding 150 g nutrient-mixture daily to low-protein diet, and comparisons were made with a regular diet (control diet). Each diet supplied 2,100 kcal energy and 80 g protein per day. Patients were given control diet for 2 weeks and thereafter treated successively with nutrient-mixture-supplemented and control diet each for 2 weeks. Nitrogen balance improvement and positive balance were observed during the feeding of nutrient-mixture-supplemented diet. The composition of nitrogen compounds in urine and the fecal nitrogen excretion did not alter during the test period. Plasma aromatic amino acid (AAA) concentrations decreased and BCAA/AAA molar ratios increased significantly during the 1st and 2nd week of nutrient-mixture-supplemented diet administration. Plasma methionine concentration also decreased in the 1st week. Plasma pre-albumin levels rose significantly during the 1st and 2nd week of nutrient-mixture-supplemented diet administration, and the number connection test improved significantly following the supplemented diet. These results suggest that the use of nutrient-mixture in the nutritional treatment of liver cirrhosis had no deleterious effects on nitrogen metabolism and is useful for the improvement of plasma amino acid imbalance and protein-energy malnutrition.
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PMID:Nutritional treatment of liver cirrhosis by branched-chain amino acid-enriched nutrient mixture. 406 64

An inhibitor of folate metabolism, amethopterin (methotrexate) has been successfully used in the treatment of psoriasis and neoplastic disease. This drug produces several dangerous side effects of both an acute and chronic nature which have widely curtailed its use. A serious chronic side effect of the drug is its hepatotoxicity, which may culminate in hepatic cirrhosis and death. To date the underlying mechanism of methotrexate in producing liver damage is unknown. Results of three studies conducted in this laboratory on the nutritional effects of methotrexate offer some evidence that the hepatotoxicity may possibly be incurred through the effect of the drug on methionine biosynthesis and methylation processes. This thesis is discussed in the light of methylating agents vital to the synthesis of methionine.
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PMID:Methotrexate hepatotoxicity. 620 20

Serum methionine levels increased to a greater extent in patients with severe liver diseases such as fulminant hepatitis and liver cirrhosis with and without hepatic encephalopathy. However, the concentrations remained unchanged in non-encephalopathic cirrhotic cases associated with hepatocellular carcinoma, and their serum methionine levels increased only moderately even at the time of encephalopathy. At least two different mechanisms of serum methionine elevations, possibly due to release from injured hepatocytes or diminished catabolisms of this amino acid in the damaged liver, could be differentiated; the former would be involved mainly in fulminant hepatitis and the latter in liver cirrhosis. A methionine-loading test performed in cirrhotic patients supported the validity of these considerations. No significant increase of serum methionine levels in cirrhotic patients with hepatocellular carcinoma was observed, possibly by remarkable consumption of this amino acid in hepatoma tissues. During the clinical course of several patients, serial determinations of serum methionine concentrations indicated that the levels varied depending upon alterations in the pathophysiological state of the damaged liver; much higher levels were observed concomitantly with decompensated signs such as ascites, jaundice and hepatic encephalopathy. These results suggest that monitoring of serum methionine levels would be very valuable, especially for judging prognosis and predicting hepatic encephalopathy in severe liver disease.
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PMID:Impaired metabolism of methionine in severe liver diseases. I. Clinical and pathophysiological significance of elevated serum methionine levels. 628

The influence of intravenous infusion of branched-chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until "wake up". Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA administration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p less than 0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients. It is concluded that BCAA administration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy.
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PMID:Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. 634 30

Repeated plasmaphereses were done in 7 patients with acute hepatic failure (5 of them with coma stage IV and two with stage III). Acute liver insufficiency was induced by fulminant viral hepatitis in 4 cases, by drugs in one case, and was caused by a dystrophic exacerbation of liver cirrhosis in two further cases. Four of the 7 treated patients have survived. Beginning improvement of hepatic function was evidenced by an increase of factor VII and prothrombin in plasma. Significant lowering of bilirubin could be observed in all cases. While ammonia values decreased continuously in the four successfully treated patients while on plasmapheresis, the opposite behaviour was observed in the decreased patients. The influence of plasmapheresis on the pathologically altered aminoacid pattern in hepatic coma was investigated in two patients: Before treatment clearly to excessively increased values of methionine and aromatic aminoacids (phenylalanine and tyrosine) were seen. Branched-chain aminoacids leucine, isoleucine and valine were normal to moderately decreased. After termination of plasmapheresis methionine and aromatic aminoacids were significantly lower, branched-chain aminoacids were slightly below the initial values. Improvement of consciousness correlated with increase of the quotient (val+leu+ile)/(phe+tyr).
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PMID:[Treatment of acute liver failure by plasmapheresis]. 640 57

Plasma contains three forms of cyst(e)ine: cysteine, cystine, and protein-bound cysteine. The former is a thiol and the latter two are disulfides. The levels of all three types of cyst(e)ine, as well as the cysteinyl tripeptide glutathione, were measured in the plasma of 14 normal and 10 cirrhotic individuals. All subjects ate mixed foods. Some cirrhotic patients were studied during nasogastric hyperalimentation with Vivonex (Norwich Eaton Pharmaceuticals, Norwich, N.Y.) as well as during total parenteral nutrition with FreAmine III (American McGaw, Irvine, Calif.); neither formula contains cyst(e)ine. Regardless of the nature of the diet, cirrhotic patients had significantly subnormal values for cysteine, glutathione, and albumin. In addition, the following significant changes were found to be diet-dependent: (a) elevated methionine during Vivonex, (b) subnormal taurine during mixed foods and total parenteral nutrition, (c) depressed protein-bound cysteine during total parenteral nutrition, (d) depressed cyst(e)ine thiol/disulfide ratio during mixed foods, and (e) depressed total thiol during Vivonex and total parenteral nutrition. The data indicate multiple abnormalities in sulfur metabolism in cirrhosis.
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PMID:Plasma cysteine, cystine, and glutathione in cirrhosis. 646 68

The potential promoting and/or complete carcinogenic activity of a methyl group-deficient (MD) diet lacking methionine, choline, vitamin B12, and folate on liver tumor induction in weanling male F344/NCr rats was examined. Each of 50 rats per group received one injection 20 mg diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine]/kg body weight at 4 weeks of age, and then each was maintained on a methyl group-adequate (MA) diet for 52 weeks (groups 2 and 5) or on an MD diet for 15 weeks followed by the MA diet for 37 weeks (group 4). Controls received injections of saline and were maintained on the same two respective diet regimens (groups 1 and 3, respectively). Histologic results from sacrifices at 6, 10, 15, 22, 39, and 52 weeks revealed early development of foci of eosinophilic gamma-glutamyltransferase (GGT)-positive hepatocytes by week 6 in DENA-MD diet-treated rats, with subsequent development of a diffuse hyperplasia of hepatocytes, oval cell proliferation, cholangiofibrosis, nodular cirrhosis, and neoplastic nodule (NN) formation and, at 52 weeks, hepatocellular carcinomas (HCC) in 13 of 15 rats. Similar but significantly fewer lesions were observed at slightly later sacrifice times in the livers of saline-MD diet-treated rats, with development of NN in 5 of 12 rats and an HCC in 1 of 12 rats at 52 weeks. DENA-treated rats on MA diets developed relatively few GGT-positive foci, and none developed any neoplastic lesions. Except for basophilic foci, areas and foci of cellular alteration containing glycogen-rich hepatocytes frequently exhibited diminished uptake of injected iron and decreased glucose-6-phosphatase and ATPase contents focally or throughout. This study indicates that a relatively brief exposure of both untreated and DENA-treated weanling rats to a severely MD diet produces classical preneoplastic and neoplastic lesions in their livers.
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PMID:Profound postinitiation enhancement by short-term severe methionine, choline, vitamin B12, and folate deficiency of hepatocarcinogenesis in F344 rats given a single low-dose diethylnitrosamine injection. 659 43

Twenty-two patients with cirrhosis and acute encephalopathy who were refractory to medical therapy were entered into a randomized, double-blind prospective trial. This trial consisted of either neomycin or a modified amino acid solution rich in branched chains and low in aromatic amino acids and methionine (F080) in the presence of isocaloric amounts of dextrose. The groups were indistinguishable from each other by clinical or laboratory criteria; they were primarily patients who had undergone operation and they would tolerate only 30 gm of oral protein or intravenous standard amino acids. The group receiving F080 had a faster and more complete improvement in encephalopathy. This improvement correlated with the plasma molar ratio and occurred with a lower mortality rate. In addition, the patients also tolerated twice the amino acid load without encephalopathy and were in positive nitrogen balance. Modified metabolic support is effective in the setting of acute liver failure in chronic cirrhosis, particularly in patients who have undergone operation.
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PMID:Cirrhosis, encephalopathy, and improved results with metabolic support. 662 61

A new nutritional product (SF-1008C) containing a high proportion of branched chain amino acids (BCAA) and low proportion of aromatic amino acids (AAA) and methionine was tested to see its effect on the impaired protein metabolism and abnormal nutritional state frequently observed in patients with advanced liver cirrhosis. A sharp increase in plasma BCAA levels and fall of AAA and methionine levels were found following the administration of an SF-1008C-supplemented diet to healthy controls and cirrhotic patients, which the BCAA levels increased only slightly following an isocaloric control diet. Blood ammonia levels increased within the normal range transiently following the diets. The SF-1008C-supplemented diet was given for 2 weeks to cirrhotic patients with histories of hepatic encephalopathy, who were taking a low-protein diet because of hyperammonemia. Serum prealbumin levels, nitrogen balance, molar ratio of plasma BCAA/phenylalanine and tyrosine, the number connection test and electroencephalograms improved during the period of the experimental diet. The results, therefore, indicate that a BCAA-supplemented diet is well tolerated by patients with advanced cirrhosis and useful for treatment of impaired protein metabolism. Furthermore, this product is beneficial in preventing hepatic encephalopathy in cirrhotics.
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PMID:Effect of a branched chain amino acid-enriched nutritional product on the pathophysiology of the liver and nutritional state of patients with liver cirrhosis. 662 32


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