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)

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

Mitochondrial function and structure in cirrhotic livers from humans or rats show a variety of changes as compared to control livers. Mitochondrial ATP production is reduced in rats with CCl4- or thioacetamide-induced liver cirrhosis and in rats with secondary biliary cirrhosis. Activity of the electron transport chain is decreased in rats with secondary biliary cirrhosis. In rats with CCl4-induced cirrhosis, the mitochondrial content of certain constituents of the respiratory chain (cytochrome a + a3, cytochrome b and ubiquinone) is increased and activities of cytochrome c oxidase and ATPase are elevated. Similarly, in humans with liver cirrhosis, mitochondrial cytochrome a + a3 content is elevated and has been used to assess the risk for hepatectomy. In rats with secondary biliary cirrhosis, compensatory strategies include increased mitochondrial volume per hepatocyte and possibly increased extramitochondrial ATP production (increased glycolysis). Thus, a variety of adaptive mechanisms are used to maintain mitochondrial function in cirrhotic livers.
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PMID:Adaptation of mitochondrial metabolism in liver cirrhosis. Different strategies to maintain a vital function. 129 65

Hepatic resection can be performed safely in carefully selected patients with cirrhosis. To minimize morbidity and mortality, it is essential to reliably estimate functional hepatic reserve and the extent of tumor before resection is performed. Child's classification is a reliable predictor of long term survival, but a more sensitive measure of hepatic function is needed to predict early morbidity and mortality. Child's classification can also be used to stratify patients and exclude those at high risk from hepatic resection. Promising predictors of operative mortality focus on the mitochondrial function of hepatocytes and include cytochrome a (+a3) contents and the redox tolerance index. Patients with advanced cirrhosis are not candidates for extensive hepatic resection and require careful evaluation before consideration for any hepatic resection. In patients with well-compensated cirrhosis and unifocal tumors, the procedure of choice is an anatomic resection of the tumor. If tumor size and location allows, a segmentectomy offers the best outcome, minimizing postoperative liver dysfunction while offering a long term outcome not dissimilar to a major liver resection. In highly selected patients with incidental tumors, a central tumor and perhaps in patients with multifocal hepatocellular carcinoma, hepatic transplantation may be of benefit. By using the appropriate predictors of hepatic function, refined surgical techniques and optimal postoperative care, a mortality rate of less than 10 per cent is achievable in cirrhotic patients with hepatocellular carcinoma who require resection.
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PMID:Hepatic resection in patients with cirrhosis and hepatocellular carcinoma. 131 68

The relationships between histological findings, adaptively increased cytochrome a(+a3) levels in chronic liver disease and complications after hepatectomy were studied in order to clarify the mechanism of mitochondrial derangement. The liver specimens of 53 hepatectomized patients were randomly evaluated by three independent hepatopathologists and were compared with cytochrome a(+a3) levels in the biopsied liver, the extent of operation and postoperative complications. The cytochrome a(+a3) concentrations did not show any significant difference between cases of chronic hepatitis and liver cirrhosis nor groups classified by regeneration. Severity of piecemeal necrosis was categorized into three groups: group A--minimal (n = 20); group B--moderate (n = 19); and group C--severe (n = 14). There were significant differences (P less than 0.01) in cytochrome a(+a3) concentrations between the groups (A: 99 +/- 9; B: 135 +/- 6; C: 155 +/- 10 pmol/mg of mitochondrial protein). Extensive hepatectomy, involving segmentectomy or more, was frequently complicated (four of nine, 44.4%) in group C, whereas there were few complications (two of 16, 12.5%) in group A cases in which extensive hepatectomy was performed. Evidence will be presented which will show that deranged liver function, as indicated by cytochrome a(+a3) levels, is closely correlated with piecemeal necrosis. This may be attributed to the damage of periportal hepatocytes which are the main sites of oxidative phosphorylation.
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PMID:Influence of piecemeal necrosis on the compensatory increase of mitochondrial respiratory enzymes of the tumour-bearing liver: clinical study of 53 surgical cases. 196 77

Elevated serum estradiol concentrations and specific changes in the biliary excretion of some androstenedione metabolites have been reported in male rats with portal bypass produced by portal vein ligation (PVL). In this study, the hypothesis that male-specific forms of cytochrome P-450 are altered after PVL was tested by measuring microsomal steroid hydroxylase activities. Consistent with earlier findings in the intact animal, androstenedione 16 alpha-hydroxylase activity was reduced after PVL to 44% of control (P less than 0.05). Other pathways of androstenedione hydroxylation, and total estrogen formation (after androstenedione aromatization) were unchanged. Although total estrogen formation was not different, a sevenfold greater proportion of estradiol was produced in PVL rat microsomes. Additional experiments revealed that PVL selectively reduced the rate of microsomal estradiol 16 alpha-hydroxylation (to 56% of control, P less than 0.02). Levels of cytochrome P-450UT-A, the microsomal steroid 16 alpha-hydroxylase, were lower after PVL (56% of control, P less than 0.05), so that the present observations are consistent with the earlier suggestion that portal bypass is associated with the selective downregulation of this enzyme. Since downregulation of cytochrome P-450UT-A also occurs in experimental hepatic cirrhosis, portal hypertension may well contribute significantly to altered drug metabolism in liver disease. Impaired hepatic elimination of androstenedione by hydroxylation may indirectly enhance extrahepatic aromatization of the androgen. The decreased activity of hepatic estradiol 16 alpha-hydroxylation after PVL would enhance the accumulation of estradiol, the biologically more potent estrogen.
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PMID:Downregulation of the male-specific hepatic microsomal steroid 16 alpha-hydroxylase, cytochrome P-450UT-A, in rats with portal bypass. Relevance to estradiol accumulation and impaired drug metabolism in hepatic cirrhosis. 270 29

In the cirrhotic rat liver induced by carbon tetrachloride and phenobarbitone, the concentrations of mitochondrial Coenzyme Q were measured in comparison with other respiratory components. The concentration of cytochrome a(+a3) and Coenzyme Q significantly increased in the cirrhotic liver, without any changes in the ratio of Coenzyme Q to cytochrome a(+a3). It is suggested that such increase of Coenzyme Q plays an important role as one of the adaptive responses to compensate for the prolonged metabolic overload on the mitochondrial respiratory assembly. Also, from the findings that the concentrations of cytochrome a(+a3) in the mitochondria of cirrhotic liver increase concomitant with the severity of cirrhosis, it is suggested that the rise of Coenzyme Q levels may be one of the indicators for the decreased functional reserve capacity in liver cirrhosis.
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PMID:Changes in coenzyme Q level in mitochondria of cirrhotic rat liver. 298 4

The relationship of glucose intolerance and indocyanine green clearance to respiratory enzyme levels in liver mitochondria was studied along with standard liver function tests in 40 patients (8 cirrhosis, 19 cirrhosis with hepatoma, 13 non-cirrhotic with hepatoma). There was a negative correlation between cytochrome a(+a3) concentrations and phosphorylative activity per unit of cytochrome a(+a3) (r = -0.75, p less than 0.01), but no correlation between ICG-K and cytochrome a(+a3) concentrations. Cytochrome a(+a3) concentrations in cirrhotic patients with linear oral glucose tolerance pattern, characterized with no return toward normal glucose levels within 120 minutes after an oral glucose load, increased to 1.45 +/- 0.11 (10(-10) mol/mg of protein) compared with 0.90 +/- 0.07 in cirrhotic patients with parabolic OGTT pattern, characterized with a return toward normal glucose levels within 120 minutes (p less than 0.01) (0.82 +/- 0.02 in control patients without liver diseases). The former had high operative mortality regardless of ICG-K value and the latter had virtually uneventful clinical courses. It was suggested that increased cytochrome a(+a3) concentrations and impaired glucose tolerance might be responsible for decreased hepatic functional reserve and poor prognosis in cirrhotics.
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PMID:Relationship of glucose intolerance and indocyanine green clearance to respiratory enzyme levels in human cirrhotic liver. 299 74

The effect of a choline-deficient diet on microsomal cytochrome P-450 and mixed-function oxidase (MFO) activity was investigated in relation to the development of nutritional cirrhosis. In rats that received the choline-deficient diet for 28 weeks cirrhosis was evident macroscopically and histologically; control rats that received an identical diet supplemented with choline had normal livers. Microsomal cytochrome P-450 and cytochrome b5 were reduced in cirrhotic liver to 50% of control levels. Three MFO activities (ethylmorphine N-demethylase, aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase) were also reduced to 40-70% of control levels. However, the turnover number for the O-deethylation of 7-ethoxycoumarin was not reduced in cirrhotic liver. This finding suggested that certain drug oxidations may be selectively depressed in nutritional cirrhosis. To examine the possibility that selective changes in MFO activity may reflect the suppression of certain cytochrome P-450 isozymes, partially purified fractions of the cytochrome were prepared after solubilisation and hydrophobic affinity chromatography (on n-octylamino-Sepharose 4B) of cirrhotic and control liver microsomes. Analysis of these fractions by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and laser densitometry indicated that a protein band of apparent minimum molecular weight 50.5 kD was primarily affected in cirrhotic rat liver microsomes. Levels of two other bands (apparent minimum molecular weight 48 and 52.5 kD) appeared essentially unaltered. Additional electrophoretic studies, conducted under non-reduced conditions, indicated the haemoprotein nature of protein bands in the 48-55 kD region. These data strongly suggest that cirrhosis produced in rats by a choline-deficient diet is associated with selective decreases in oxidative drug metabolism and individual cytochrome P-450 isozymes.
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PMID:Drug metabolism in cirrhosis. Selective changes in cytochrome P-450 isozymes in the choline-deficient rat model. 371 30

Measurement of cytochrome a(+a(3)) contents in liver mitochondria was made on 52 biopsy specimens of patients with liver tumor. Patients having higher cytochrome a(+a(3)) contents in mitochondria from remaining liver than those of normal human liver mitochondria could survive well major liver resections whether or not associated with liver cirrhosis. However, patients with cytochrome a(+a(3)) contents less than 0.5 x 10(-10) moles per mg protein showed a high rate of postoperative complication (80%) and death (40%) in spite of minor operation. In routinely used liver function tests such as serum albumin, A/G ratio, SGOT, total bilirubin, prothrombin time, BSP and TTT, there were no significant differences between patients with cytochrome a(+a(3)) contents more than 0.5 x 10(-10) moles per mg protein and those less than 0.5. The results indicate that routine laboratory studies do not have much diagnostic value in estimation of a marked decrease of mitochondrial cytochrome a(+a(3)) contents. It is suggested that the measurements of cytochrome a(+a(3)) of the remnant liver should be done prior to a contemplated major resection.
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PMID:Clinical application of cytochrome a(plus a3) assay of mitochondria from liver specimens: an aid in determining metabolic tolerance of liver remnant for hepatic resection. 437 60

In the cirrhotic rat liver induced by phenobarbitone and carbon tetrachloride, adenylate energy charge, mitochondrial oxidative phosphorylation, and respiratory enzyme concentrations were studied along with serum albumin concentrations. Cytochrome a (+a3) concentrations of the liver increased with the severity of cirrhosis and were negatively correlated with the ATP-synthesizing ability per unit of cytochrome a (+a3). These changes were associated with the decrease in hepatic energy charge. Such decreased energy charge may be responsible for the decreased serum albumin level in the cirrhotic rat. It is suggested that such falls in hepatic energy charge may be one of the most important factors contributing to the decreased functional reserve of cirrhotic patients.
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PMID:Adenylate energy charge and cytochrome a (+a3) in the cirrhotic rat liver. 609 79


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