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)

Serum magnesium (Mg) was measured in 6,252 patients; in 1,246 (19.9%) the value was abnormal. Hypermagnesemia (serum Mg greater than or equal to 3.9 mg/dl) was observed in 51 patients (0.8%) and hypomagnesemia (Mg less than or equal to 1.5 mg/dl) in 165 (2.6%). Hypermagnesemia was found in patients with renal failure treated with Mg-containing antacids or cathartics, or with eclamptic convulsions treated with Mg sulfate. The most frequent clinical finding of hypermagnesemia was urinary disturbance, although various other neurological signs and symptoms were observed. Hypomagnesemia was seen in patients with various diseases such as cancer, hepatic cirrhosis, cerebrovascular disease, and generally poor condition. Abnormalities of electrolytes other than Mg were also frequently observed. The most common clinical findings of hypomagnesemia were personality changes and depression. The differentiation from psychiatric disease is important.
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PMID:An analysis of hypermagnesemia and hypomagnesemia. 227 20

During human and experimental liver fibrogenesis, the pattern of glycosaminoglycans in fibrotic liver matrix is greatly changed by severalfold increases of hyaluronic acid, chondroitin sulfate, and dermatan sulfate, respectively. The present study aimed to determine whether hepatocytes take part during fibrogenesis in the alteration of the glycosaminoglycan profile in liver matrix. Rats received thioacetamide orally for 2 and 10 weeks, respectively. After 10 weeks a typical micronodular cirrhosis had developed. Hepatocytes isolated at these time points were characterized by light and electron microscopy and incubated for up to 4 h in suspension cultures in [35S]-sulfate and [3H]-glucosamine containing medium to study the synthesis and intra-/extracellular distribution of total and specific types of glycosaminoglycans. A biphasic change of glycosaminoglycan synthesis in hepatocytes was found. After 2 weeks of TAA-treatment parenchymal cells synthesized about 25% more labeled glycosaminoglycans than control liver cells, but at 10 weeks the synthesis was reduced by more than 40%. Thus, between 2 and 10 weeks of TAA-treatment hepatocellular glycosaminoglycan synthesis decreased by more than 50%. The major portion of newly synthesized glycosaminoglycans was nitrous acid labile and, hence, identified as heparan sulfate. Its fractional synthesis decreased from 0.90 in control cells to 0.84 (2 weeks TAA) and 0.76 (10 weeks TAA), respectively. Thus, the absolute synthesis of heparan sulfate was reduced by 50% in hepatocytes from cirrhosis liver. Eighty to 90% of labeled glycosaminoglycans remained cell-associated. Hyaluronic acid was detected neither in normal hepatocytes nor in hepatocytes from injured liver. We conclude from these data that parenchymal liver cells will not contribute actively to the accumulation of galactosaminoglycans (chondroitin sulfate, dermatan sulfate) and hyaluronic acid in the extracellular matrix during fibrogenesis. The diminished rate of synthesis of heparan sulfate in hepatocytes from cirrhotic liver might explain its fractional decrease in cirrhotic liver matrix.
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PMID:The synthesis of glycosaminoglycans in isolated hepatocytes during experimental liver fibrogenesis. 235 59

Single dose disposition of oral quinidine (400 mg sulfate) was studied in a control group of subjects (No. = 6) and in hospitalized alcoholic patients involving one group with (No. = 6) and one group without (No. = 11) hepatic cirrhosis. All subjects also underwent an antipyrine and a debrisoquine test. Patients with cirrhosis had a prolonged elimination half-life (29.5 +/- 5.9 h) and low clearance (24 +/- 7 ml.kg-1.h-1) of antipyrine and also a considerably higher debrisoquine metabolic ratio (18.8 +/- 3.3) than the controls, whereas the alcoholics without cirrhosis had metabolic patterns for these two test compounds comparable to those seen in the controls (antipyrine half-life: 8.8 +/- 1.1 h and 9.8 +/- 2.0 h; debrisoquine metabolic ratio: 3.6 +/- 0.7 and 3.8 +/- 1.2 for alcoholics and controls respectively). In patients with cirrhosis the apparent elimination half-life of quinidine was longer (12.8 +/- 1.8 h) whereas after oral administration clearance of quinidine (15.6 +/- 3.5 l.h-1) and quinidine/3-hydroxyquinidine ratio (9.9 +/- 2.1) were not different from controls (quinidine clearance: 13.45 +/- 1.9 l.h-1; quinidine/3-hydroxyquinidine: 10.3 +/- 2.7). A possible change in distribution patterns of quinidine in cirrhotics may explain these findings.
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PMID:Quinidine disposition in relation to antipyrine elimination and debrisoquine phenotype in alcoholic patients with and without cirrhosis. 262 71

3 beta-Hydroxy-(delta 5-3 beta-ol), 3 beta,12 alpha-dihydroxy-(delta 5-3 beta,12 alpha-ol), 3 beta,7 alpha-dihydroxy-(delta 5-3 beta,7 alpha-ol) and 3 beta,7 beta-dihydroxy-(delta 5-3 beta,7 beta-ol) 5-cholenoic acids were identified in patients with liver diseases by gas-liquid chromatography-mass spectrometry (GLC-MS). Of these unusual 3 beta-hydroxy-5-en-metabolites, delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found as major components in the urine of patients with liver diseases (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis). Other 3 beta-dihydroxy-5-en-metabolites, delta 5-3 beta,7 alpha-ol and delta 5-3 beta,7 beta-ol, were found as minor components in the urine. The levels of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol in urine were correlated with their levels in serum, with total bile acids in the urine, and with liver function, implying that the degree of their increment correlated well with the severity of liver diseases. The most abundant amounts of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found in the urine as sulfate conjugates in comparison with bile, portal and hepatic venous sera, and liver tissue of the patients. The biliary excretion and hepatic extraction of these 3 beta-hydroxy-5-en-unsaturated bile acids were more impaired and inefficient than those of cholic and chenodeoxycholic acids.
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PMID:Concurrent occurrence of 3 beta,12 alpha-dihydroxy-5-cholenoic acid associated with 3 beta-hydroxy-5-cholenoic acid and their preferential urinary excretion in liver diseases. 276 75

Triamterene is a potassium-sparing diuretic used in patients with cirrhosis for the treatment of ascites. It is extensively metabolized by the liver and is subject to an important first-pass effect after oral dosing. We examined the disposition and diuretic effect of triamterene after repeated oral administration (200 mg daily for 10 days) in 7 healthy controls and 6 patients with cirrhosis and ascites. In the controls the average plasma concentration of triamterene during a dosage interval was 45 +/- 8 ng/ml and that of hydroxy-triamterene sulfate, an active metabolite of triamterene, was 967 +/- 177 ng/ml. In the cirrhotics, the mean concentration of triamterene was 586 +/- 126 ng/ml (a 13-fold increase as compared with the controls) and that of hydroxy-triamterene sulfate was 747 +/- 502 ng/ml. Sodium excretion was correlated with hydroxy-triamterene sulfate levels in the controls (r = 0.81), but in the cirrhotics the diuretic response was correlated with basal sodium excretion (r = 0.86) and was not related to either triamterene or hydroxy-triamterene plasma concentrations. Our results indicate that chronic treatment with triamterene in patients with cirrhosis and ascites results in markedly elevated plasma levels, but these changes do not have a major influence on the magnitude of the diuretic response.
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PMID:Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis. 336 82

Seric and hepatic zinc concentrations are decreased in chronic alcoholics, particularly those with cirrhosis. The purpose of this study was: 1) to assess the duration of zinc intake necessary to normalize seric and hepatic zinc concentrations; 2) to demonstrate that this supplementation did not increase zinc concentrations in other tissues (erythrocytes, leukocytes and hair) and did not induce adverse reactions. Twenty alcoholic patients with (group A: n = 13 or without (group B: n = 7) cirrhosis received zinc sulfate 600 mg daily during 10 days, 10 patients with alcoholic cirrhosis during 30 days (group C) and 7 during 60 days (group D) and were compared with a group of 30 normal subjects. Serum zinc concentrations increased to normal values in all groups of patients. Hepatic zinc increased significantly in groups B (p less than 0.05) and D (p less than 0.01). Zinc concentrations in erythrocytes, leukocytes and hair were unchanged. No adverse reactions were observed. We conclude that seric zinc concentrations reached normal values in alcoholics with or without cirrhosis by daily supplementation of 600 mg zinc sulfate during 10 days to 2 months while hepatic zinc concentrations increased but remained under normal values in some patients, particularly those with cirrhosis.
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PMID:[Serum and tissue concentrations of zinc after oral supplementation in chronic alcoholics with or without cirrhosis]. 344 3

Urinary bile acids from a 3-mo-old boy with cholestatic jaundice were analyzed by ion exchange chromatography and gas chromatography-mass spectrometry (GC-MS). This suggested the presence of labile sulfated cholenoic acids with an allylic hydroxyl group, a conclusion supported by analysis using fast atom bombardment mass spectrometry (FAB-MS). The compounds detected by FAB-MS were separated by thin layer chromatography and high performance liquid chromatography. The sulfated bile acids could be solvolyzed in acidified tetrahydrofuran, and glycine conjugates were partially hydrolyzed by cholylglycine hydrolase. Following solvolysis, deconjugation, and methylation with diazomethane, the bile acids were identified by GC-MS of trimethylsilyl derivatives. The major bile acids in the urine were 3 beta,7 alpha-dihydroxy-5-cholenoic acid 3-sulfate, 3 beta,7 alpha,12 alpha-trihydroxy-5-cholenoic acid monosulfate, and their glycine conjugates. Chenodeoxycholic acid and cholic acid were undetectable in urine and plasma. The family pedigree suggested that abnormal bile acid synthesis was an autosomal recessive condition leading to cirrhosis in early childhood.
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PMID:Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids. 347 Mar 5

The in vivo formation of the sulfate ester of glycolithocholate is a critical step in the elimination of this hepatotoxic bile salt. Rhesus monkeys fed chenodeoxycholate or ursodeoxycholate, the precursors of lithocholate, develop frank cirrhosis in association with accumulation of nonsulfated glycolithocholate in bile. An enzyme catalyzing the formation of glycolithocholate-3-sulfate has been isolated from hepatic cytosol of adult female rhesus monkeys and has been purified 146-fold. When reduced it appears as a 30 kD band on an SDS-polyacrylamide gradient gel. It has a pH optimum of 7.0 and is stimulated by low concentrations of Mg2+ (up to 2 mM), but does not have an absolute requirement for this metal ion. The kinetics of this enzyme have been investigated to ascertain whether its reaction mechanism can account for the poor in vivo rate of glycolithocholate sulfation. Inhibitor studies with an oxidized metabolite of lithocholate, 3-keto-5 beta-cholanoate, showed that the latter is a competitive inhibitor of glycolithocholate and is noncompetitive with the active form of sulfate, 3'phosphoadenosine-5'-phosphosulfate. The monophosphonucleotide 3'-AMP is a competitive inhibitor of 3'phosphoadenosine-5'-phosphosulfate, and is noncompetitive with glycolithocholate. These observations are consistent with a sequentially ordered Bi Bi reaction mechanism in which the bile salt is the first substrate to bind to the enzyme. Such a reaction mechanism for bile salt:3'phosphoadenosine-5'-phosphosulfate:sulfotransferase would be, therefore, the first time in which the sulfate acceptor (the bile salt) is the initial substrate to bind to a sulfotransferase. These studies have shown that although rhesus monkeys have a liver enzyme capable of forming the sulfate ester of glycolithocholate, its reaction mechanism and the potent inhibition caused by simple metabolites, such as 3-keto-5 beta-cholanoate, may serve to under-express the activity of the enzyme in vivo.
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PMID:Evidence for an ordered reaction mechanism for bile salt: 3'phosphoadenosine-5'-phosphosulfate: sulfotransferase from rhesus monkey liver that catalyzes the sulfation of the hepatotoxin glycolithocholate. 347 Apr 20

Supplementation may benefit patients with liver cirrhosis. Zinc uptake from zinc-histidine complex 1:2 was assessed in eight patients with liver cirrhosis. Influence of the time of application was also studied. Compared with healthy controls, patients showed a 40% lower uptake of zinc after 20 mg zinc from zinc histidine. Bioavailability was identical when zinc was taken 6 h or 1 h before a meal but an order of magnitude greater than with or 1 h after a meal. No significant increase of serum zinc was found when zinc was given with a meal or 1 h after. Lower doses of zinc-histidine complexes than of zinc sulfate may be used to supplement patients with liver cirrhosis. Time of application is of great importance if this substitution is to be successful.
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PMID:Bioavailability of zinc from zinc-histidine complexes. II. Studies on patients with liver cirrhosis and the influence of the time of application. 359 29

3 beta-Hydroxy-5-cholenoic acid in the serum of control subjects and 62 patients with various hepatobiliary diseases was quantitated by mass fragmentography after separation into nonglucuronidated-nonsulfated, glucuronidated, and sulfated fractions. Deuterium-labeled deoxycholic acid and its glucuronide and sulfate were used as internal standards. Mean concentrations of total 3 beta-hydroxy-5-cholenoic acid in serum (mumole/liter) were as follows: Control subjects (14), 0.184; obstructive jaundice (15), 6.783; liver cirrhosis, compensated (12), 0.433, and decompensated (12), 1.636; chronic hepatitis (12), 0.241; and acute hepatitis (11), 2.364. Most of the 3 beta-hydroxy-5-cholenoic acid was glucuronidated or sulfated. Only in patients with obstructive jaundice did glucuronidation (60 +/- 14%) exceed sulfation (31 +/- 14%), sulfation exceeding glucuronidation in the others. The UDP-glucuronyltransferase might have different substrate specificities for 3 beta-hydroxy-5-cholenoic acid and other common bile acids, especially in the cholestatic state.
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PMID:Determination of 3 beta-hydroxy-5-cholenoic acid in serum of hepatobiliary diseases--its glucuronidated and sulfated conjugates. 401 37


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