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)

1. Mitochondria and microsomal fractions have been isolated from liver biopsies from patients with alcoholic cirrhosis, cryptogenic cirrhosis or chronic aggressive hepatitis. 2. Cirrhotic livers yieled fewer mitochondria than normal liver. 3. The most significant change was a decrease in mitochondrial respiratory control. Cirrhotic microsomal fractions had a 50% diminution in cytochrome b5 and cytochrome P-450 content. 4. The two patients with chronic aggressive hepatitis showed similar mitochondrial and microsomal changes.
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PMID:Mitochondrial functions and content of microsomal and mitochondrial cytochromes in human cirrhosis. 88 31

Electron microscopic findings made on microsomal fractions of rat liver after treatment with microsomal antibodies obtained from the blood of patients diagnosed as having chronic aggressive hepatitis and liver cirrhosis and after incubation with peroxidase-labelled antihuman IgG are described and presented in this paper. Interpretation of these findings as the substrate of an antibody reaction directed against membranes of the endoplasmic reticulum of hepatocytes is discussed.
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PMID:The immunoelectron-microscopical demonstration of antibodies against endoplasmic reticulum (microsomes) in chronic aggressive hepatitis and liver cirrhosis. 88 90

16 patients with acute hepatitis, 18 patients with cirrhosis and a total of 21 volunteers and patients with normal liver function received 7.32 mg/kg hexobarbital by linear intravenous infusion within 60 min. Hexobarbital was determined gaschromatographically in serial blood samples and the hexobarbital-clearance was calculated from the plasma concentration curve versus time. Additional experiments were performed in rats suffering from so called "galactosamine hepatitis". In half of the patients with acute hepatitis a normal hexobarbital clearance could be found. In the other patients this was distinctly reduced but not correlation was found to other liver function tests. Patients with cirrhosis were subdivided into two groups. The patients in group 1 were well compensated. The patients in group 2 had a decompensated state with ascites and oesophageal varices. In nearly all patients with cirrhosis the hexobarbital-clearance was diminished. This was more pronounced in group 2. Ketohexobarbital excretion in healthy subjects was in the range of 40-60% of dose. Patients with acute hepatitis excreted only 10-20% of dose and patients with liver cirrhosis only about 5% of dose. In rats with "galactosamine hepatitis" hexobarbital clearance in vivo was distinctly reduced and this could be explained by diminished microsomal cytochrome p 45- and hexobarbital oxidation rate.
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PMID:[Metabolism of hexobarbital in patients with acute hepatitis and cirrhosis (author's transl)]. 88 88

A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence on withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver, and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.
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PMID:Animal models of ethanol dependence and liver injury in rats and baboons. 94 46

The specific activity of coumarin-7-hydroxylase was measured in liver microsomes from normal subjects and patients with liver disease. Liver specimens were obtained by needle biopsy and the microsomal fraction was separated by differential centrifugation. Its freedom from mitochondria was demonstrated by the absence of succinic dehydrogenase, a marker enzyme for mitochondria. Liver from healthy subjects showed variation in the specific activity of coumarin-7-hydroxylase from 0.16 to 0.65 nmol-mg-1-min-1, which is probably due to genetic factors. Patients with cirrhosis of the liver, chronic fatty hepatitis (chronic alcoholic hepatitis) and chronic active hepatitis showed a significantly lower mean hydroxylase activity. There was no significant difference in the mean level of hydroxylase between patients with subacute viral hepatitis or chronic persistent hepatitis and the normal controls.
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PMID:Coumarin-7-hydroxylase activity in microsomes from needle biopsies of normal and diseased human liver. 96 89

The method of measuring the rate of aminopyrine demethylation by breath analysis was assessed in 23 normal subjects and 20 patients with cirrhosis. Carbon 14 aminopyrine specifically labeled at the two N-methyl groups was administered by mouth in a dose of 9 mg/kg, including a total radioactivity of 2 muCi. The decay of the specific activity of 14CO2 in breath (kb) was found to correlate (r = 0.91) with the disappearance of aminopyrine from plasma (KP). In normal volunteers, kb was 22.4%/hr; in patients with alcoholic and nonalcoholic cirrhosis it was depressed to 8.4%/hr (p less than 0.001). The degree of functional impairment found with the breath test was similar to the sulfobromophthalein (BSP) disappearance curve and the galactose elimination capacity. Although many questions relating to the aminopyrine breath test remain open, our data confirm and extend previous studies of 14CO2 breath analysis after 14C-aminopyrine administration. It is concluded that it represents a simple and noninvasive procedure which quantitatively reflects the microsomal function of the cirrhotic liver.
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PMID:Aminopyrine demethylation measured by breath analysis in cirrhosis. 97 20

Rats have been treated for 6 weeks with thioacetamide (0.1% in drinking water). The biochemical changes in liver microsomal metabolism of estradiol which are similar to those observed in human liver cirrhosis become already apparent after one week of treatment. These are diminishment of hepatic microsomal cytochromes P-450 and b5, comparable decrease of 2-hydroxylation and increase of formation of estrone from estradiol. The alterations of estrogen metabolism are reversible within two weeks after ending thioacetamide treatment. These data correspond to the already well established histological response of rat liver to thioacetamide, and its reversibility.
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PMID:[Time course of thioacetamide-induced changes in estrogen metabolism in the rat liver]. 100 99

25 patients suffering from different hepatic diseases were studied in order to investigate the elimination of the beta-receptor blocking drug pindolol in hepatic disease. Following an overnight fasting period the patients received simultaneously 3 mg pindolol intravenously and 1000 mg antipyrine orally. Plasma samples were taken at certain time intervals for 24 hs and urine was collected for 72 hs for the measurements of drug concentrations in plasma and urine. From these measurements different pharmacokinetic parameters were calculated for both drugs used in the present study according to a one-compartment open model. The total body clearance of antipyrine was selected as a parameter of the metabolic capacity of the liver microsomal enzyme system and was compared with the pharmacokinetic parameters calculated for pindolol by means of linear regression. There was no significant correlation between the total body clearance of antipyrine and the kinetic parameters of pindolol in any of the 25 patients irrespective of the differences in liver disease. On the other hand, 14 patients suffering from cirrhosis of the liver showed a significant correlation between the total body clearance of antipyrine and the overall elimination rate constant or metabolic clearance of pindolol. No correlation was found between antipyrine clearance and total body clearance of pindolol, as some patients with intact renal function excreted a higher proportion of pindolol in the urine as liver function decompensated. The mechanism of such compensatory elimination is unknown. In conclusion, the total body clearance of antipyrine known to represent metabolic liver function showed a significant correlation with the metabolic clearance of pindolol in patients with cirrhosis of the liver. For the other liver diseases investigated, too few patients were studied to calculate an adequate correlation.
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PMID:[Comparative study on the elimination of pindolol (visken) and antipyrin in patients with liver diseases]. 101 99

This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.
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PMID:Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets. 105 27

Comparative studies have been conducted of the activity of microsomal mixed-function oxidases from livers of normal, precirrhotic and cirrhotic rats linked with the metabolism of type-I (aminopyrine, hexobarbital), type-II (aniline, metyrapone) and "modified type-II" (corticosterone) substrates. The following factors were investigated: the possible role of cytochrome P-450 content, the state of the "substrate-binding protein" of this enzyme, the degree of affinity of this hemoprotein for both type-I and type-II substrates and finally, the activity of the enzymes of the microsomal electron-transport chain (both in the absence and in the presence of type-I substrate) -- as rate-limiting reactions, "tight spots" in the biotransformation of drugs in experimental microsomes. It was found that the hydroxylation activity for type-II and "modified type-II" substrates during the entire period of liver cirrhosis development is determined by the cytochrome P-450 content and the amplitude of maximal spectral changes observed in the presence of excess substrate. Type-I substrate metabolism, however, is limited in the precirrhotic phase by the state of the "substrate-binding protein" contained in P-450 as well as by the NADPH-cytochrome P-450 reductase activity. On the other hand, the N-demethylating activity in CCl-4-cirrhotic liver microsomes does not depend on either the concentration of P-450, on the amplitude of the maximal spectral changes or on the Ks value. The rate-limiting step in this case is the rate of reduction of the P-450-substrate complex by NADPH.
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PMID:Rate-limiting steps in drug metabolism by microsomes from CCl-4-cirrhotic rat liver. 112 2


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