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)

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured by a specific and sensitive tlc-method concomitantly. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced according to endogenous creatinine clearance. In older patients the elimination of TA was impaired.
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PMID:Pharmacokinetics of triamterene. 683 48

A randomized study was performed in order to compare the course of hepatic encephalopathy in patients treated with neomycin plus magnesium sulfate or with lactulose. Admission criteria were: morphological diagnosis of cirrhosis and absence of comorbidity, of contraindications to drugs, or of previous treatments which could influence the outcome. The treatment groups were similar in terms of clinical characteristics, fatalities, recovery rate from grade 1 encephalopathy, and disappearance rate of neuropsychiatric signs. Transitions from severe to grade 1 or 0 encephalopathy showed a 0.17 (NS) difference in favor of neomycin. Early therapy and evidence of precipitating factors showed a favorable prognostic significance. Ascites, hyperbilirubinemia, poor nutritional state, and hypoprothrombinemia showed bad prognostic significance. This is the first large-scale investigation on hepatic encephalopathy. It demonstrated a similar effectiveness of the two drugs in grade 1 encephalopathy and provides a basis for drug selection in the current management of the syndrome.
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PMID:Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy: a randomized clinical study. 701 84

We evaluated, in a randomized double-blind trial, the efficacy of oral paromomycin sulfate administration in the prevention of endotoxemia in 24 cirrhotic patients with endotoxemia. Renal function was evaluated by glomerular-filtration rate and renal plasma flow at the beginning and at the end of the study period. After the administration of paromomycin sulfate, 2 g/day for 4 weeks, endotoxemia disappeared in 10 out of 13 (76.9%) cirrhotic patients with endotoxemia, whereas it became negative in only 3 of the 11 (27.3%) treated with placebo, the difference being significant (P less than 0.05). With regard to correlation of endotoxemia with renal impairment, endogenous creatinine clearance and p-aminohippurate clearance were significantly improved (P less than 0.02) in those patients whose endotoxemia disappeared on paromomycin sulfate administration. We did not find significant improvement, however, neither in liver function or in blood coagulation tests in the same patients. Paromomycin sulfate seems to be effective in the prevention of endotoxemia and the associated renal impairment in cirrhosis in man.
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PMID:Effect of paromomycin sulfate on endotoxemia in patients with cirrhosis. 709 60

In a comparative study absorption and elimination characteristics of p.o. administered paromomycin and neomycin were investigated in healthy volunteers and patients with liver cirrhosis and/or portocaval shunt. Serum and urine concentrations were determined by means of the diffusion test. 1. In a cross-over study 6 volunteers were each administered single p.o. doses of 14.28 g paromomycin sulfate (= 10 g free base = 1.6 X 10(-2) mol) and 16 g neomycin sulfate (= 10.65 g free base = 1.7 X 10(-2) mol). Following these virtually equimolar doses AUC values of neomycin were 2.5 times as high as those of paromomycin (p less than 0.01). Paromomycin serum level time courses could be described by an open one-compartment model with a mean half-life of 2.6 h (harmon. mean). Mean computed maximum levels of 3.6 microgram/ml appeared on an average of 1.9 h after administration. After 32 h the mean recovery in urine was 0.2%. 5 volunteers showed a similar behavior with a mean excretion of 0.1%, whereas one person excreted 0.8% in urine. The time course of neomycin was evaluated according to an open two-compartment model with a distribution half-life of 1.5 h and a terminal half-life of 9 h (harmon. means). Mean computed maximum levels of 5.1 microgram/ml appeared on an average of 2.6 h after administration. The mean lag time was 1.3 h. 32 h after administration 0.3% of the dose were detected in urine. 2. Patients with cirrhosis and/or portocaval shunt were treated with 8 capsules/d of either 357.1 mg paromomycin sulfate or 250 mg neomycinsulfate each over a period of 7 days. Despite the lower dose of neomycin comparable serum levels of both aminoglycosides were observed. This result can be explained by a lower elimination rate and a higher extent of accumulation of neomycin. Mean amounts excreted in the urine of the 7th day were 0.1% for paromycin and 0.2% for neomycin.
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PMID:[Comparative study of serum levels and urinary excretion following oral administration of paromomycin and neomycin (author's transl)]. 719 77

The incorporation of [35S]sulfate into total and specific types of serum glycosaminoglycans was studied in rats with acute, subacute or chronic liver injury (liver cirrhosis), and compared with that of normal rats. The macromolecular (protein-bound) nature of serum glycosaminoglycans in normal and diseased animals was also analysed. The results show a strong increase in rate and extent of [35S]sulfate incorporation into total serum glycosaminoglycans for acutely but a decrease for subacutely and chronically liver damaged rats. The time-course of distribution of label between serum chondroitin sulfate and dermatan sulfate exhibits significant changes in liver-injured animals, in particular a relatively high proportion of dermatan [35S]sulfate in rats with cirrhotic livers. In comparison with serum glycosaminoglycans the labeling profile of glycosaminoglycans in the cirrhotic liver was quite different (heparan sulfate:dermatan sulfate:chondroitin sulfate = 1:0.34:0.09) and changed only insignificantly during a 1 h labeling period. The protein-bound moiety of serum glycosaminoglycans was not affected by liver disease; but the elution profile of chondroitin [35S]sulfate from Dowex 1 X 2 for treated rats was altered, thus indicating a structural modification of its carbohydrate chain.
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PMID:Metabolic and structural studies on serum- and liver-glycosaminoglycans in normal and liver-injured rats. 743 Sep 57

We have used three tests of paracoagulation in patients with chronic liver diseases: ethanol test, protamine sulfate test and agglutination test. The best results were obtained with agglutination test specially in liver cirrhosis.
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PMID:[Comparison between paracoagulation tests in chronic liver disease]. 744 60

The metabolism of 14C-labeled chenodeoxycholic, cholic, and deoxycholic acids was studied in patients with intrahepatic cholestasis. Radioactively labeled metabolites were isolated from urine and were identified by gas-liquid chromatography-mass spectrometry. About 5% of the radioactivity was recovered in urine after administration of labeled chenodeoxycholic acid to a patient with mild intrahepatic cholestasis. In urine collected 0-24 hr after the injection, 20% of the radioactivity appeared in the combined glycine and taurine conjugate fractions, and the predominant metabolite in these fractions was identified as hyocholic acid. Eighty percent of the activity was eluted in the sulfate fraction presumably representing mainly sulfated chenodeoxycholic acid conjugates. Twenty percent of the radioactivity was recovered in urine following administration of labeled cholic acid to a patient with biliary cirrhosis and severe cholestasis. In urine collected on the fifth day, half of this radioactivity appeared in the glycine and taurine conjugate fractions, and 10% of this activity was present as tetrahydroxycholanoates. The major metabolites in this fraction were 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta- and 1 xi, 3 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholanoic acids. The former compound constituted about 50% of the tetrahydroxycholanoates. Three additional minor tetrahydroxy bile acids were present, one of which was tentatively identified as 6 beta-hydroxycholic acid. About 5% of the radioactivity appeared in urine after oral administration of labeled deoxycholic acid to a patient with mild intrahepatic cholestasis. Twenty-two percent of the activity appeared in the glycine and taurine conjugate fractions isolated from urine collected on the second day after the administration. About 75% of this activity was associated with trihydroxycholanoates. The main metabolite was 1 beta-hydroxydeoxycholic acid with small amounts of, tentatively, 6 alpha-hydroxydeoxycholic acid.
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PMID:Hydroxylation of cholic, chenodeoxycholic, and deoxycholic acids in patients with intrahepatic cholestasis. 746 3

To determine the prevalence and clinicopathologic features of cholangiocarcinoma (CC) associated with nonbiliary cirrhosis, we performed a clinicopathologic study. Among the 5,563 autopsies in our laboratories during the past 14 years, 85 (1.5%) were CCs. Four (4.7%) were associated with cirrhosis, due to hepatitis B virus in one case and cryptogenic (probably non-A non-B hepatitis virus) in the remaining three. Clinically, patients with CC and cirrhosis were characterized by male preponderance, lower age, past history of liver injury, and elevated values of zinc sulfate and thymol turbidity tests. Pathologically, all CCs with cirrhosis were basically adenocarcinoma; other histologic features included adenocarcinoma resembling bile ductules without mucin (one case), adenocarcinoma with broad areas of signet ring cell carcinoma (one case), adenocarcinoma with extensive sarcomatoid transformation (one case), and adenocarcinoma associated with hepatoliths (one case). Immunohistochemically, immunophenotypes of carcinoma cells of CC with cirrhosis were not different from those of CC without cirrhosis. Carcinoembryonic antigens, CA19-9, DU-PAN-2, and biliary-type cytokeratins were positive and alpha-fetoprotein was negative, suggesting that our CCs are not hepatocellular neoplasms but true CCs. It must be stressed that there are actual CCs arising in nonbiliary cirrhotic livers.
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PMID:Intrahepatic cholangiocarcinomas associated with nonbiliary cirrhosis. A clinicopathologic study. 807 22

We examined the serum levels of testosterone (T), androstenedione (delta 4-A), estrone (E1), estradiol (E2), and dehydroepiandrosterone sulfate (DHEA-S) in the non-alcoholic cirrhotic male patients when divided into compensated or decompensated state. Serum level of T was significantly elevated in compensated cirrhotic patients (9.63 +/- 1.00 ng/ml, mean +/- SE) compared to that in decompensated cirrhotic patients (5.63 +/- 0.69 ng/ml, p < 0.01) and in aged-matched normal controls (4.95 +/- 0.38 ng/ml, p < 0.01). Serum levels of E1, E2 and delta 4-A tended to be increased in decompensated cirrhotic patients, while there was not a significant difference decompensated cirrhosis compared to those of normal controls. Serum concentration of cholinesterase, indicative one of the representative residual liver function, showed a good positive correlation to T (r = 0.53, p < 0.01), and a negative correlations to E1 (r = -0.67, p < 0.01), E2 (r = -0.77, p < 0.01), delta 4-A (r = -0.57, r = p < 0.01). Also, we examined the relationship of the serum levels to gynecomastia or esophageal varices. The cirrhotics with gynecomastia showed significantly higher serum levels of E1, E2, and delta 4-A, and lower level of T than those without gynecomastia. And the cirrhotics with esophageal varices showed the greater level of T than those without esophageal varices. Our study suggests that low serum testosterone level of men with nonalcoholic cirrhotic is not a common finding, especially in compensated state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The re-evaluation of sex steroids metabolism in patients with non-alcoholic liver cirrhosis. 808 66

An analytical method for the determination of cholesterol sulfate (CS) in plasma using gas-liquid chromatography was developed. We measured plasma CS concentrations in patients with liver cirrhosis and hypercholesterolemia as examples of disorders that involve aberrations in cholesterol metabolism. Patients with liver cirrhosis had plasma CS concentrations that were significantly higher than those of control subjects (444.6 +/- 51.7 vs. 253.0 +/- 24.6 micrograms/dL, mean +/- SE). The levels of other lipids were lower in cirrhotics, although the differences were not significant. There was no correlation between the levels of CS and sulfated bile acids in cirrhotic patients. CS levels in plasma were also higher in subjects with hypercholesterolemia (413.7 +/- 44.5 micrograms/dL); however, the ratio of CS to total cholesterol (TC) clearly differed between cirrhotics and hypercholesterolemic subjects (1.44 +/- 0.11 x 10(-3) vs. 3.31 +/- 0.63 x 10(-3); P < 0.05). Both in subjects with hypercholesterolemia and in healthy controls, the CS/TC ratio was similar and CS accounted for roughly 0.14% of the TC concentration.
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PMID:Higher levels of plasma cholesterol sulfate in patients with liver cirrhosis and hypercholesterolemia. 823 59


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