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 delta-6-desaturase (D6D) activity was evaluated in microsomes from liver fragments of cholecystectomized subjects without any liver pathology and from explanted liver of patients affected by cirrhosis of different etiologies. We observed a significant decrease in D6D activity, evaluated by a radiochemical technique using 1-[14C]-linoleic acid as substrate, in cirrhotic patients with no correlation with the etiology of the cirrhosis. The D6D activity within the pathological group was quite similar. No alteration in the 20:4/18:2 ratio obtained by gas chromatographic analysis of fatty acid methyl esters of microsomal membranes was found. Liver disease seems to be the main cause of the decreased enzyme activity independent of its etiology.
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PMID:Delta-6-desaturase activity of human liver microsomes from patients with different types of liver injury. 233 35

The monoclonal antibody MBr1 defines the blood group H determinant with beta 1----3N-acetylgalactosamine linkage (Fuc alpha 1----2Gal beta 1----3GalNAc----R) carried by type 3 or 4 backbone. The distribution of the antigen detected by this antibody was studied immunohistochemically in liver tissues. Although bile ducts with a diameter of more than about 100 microns normally expressed the MBr1-reactive antigen supranuclearly, smaller bile ducts and bile ductules did not express the antigen. In cirrhotic liver, proliferated bile ductules extensively expressed the MBr1-reactive antigen. In spite of the absence in normal liver cells, the antigen was expressed membranously in some cirrhotic liver cells. Under subcellular fractionation, MBr1 reactivity was almost exclusively recovered in the microsomal fraction. By HPTLC immunostaining, the major MBr1-reactive antigen was shown to be carried by type 4 chain H glycolipid (globo-H, Fuc alpha 1----2Gal beta 1----3GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc beta 1----1Cer). MBr1 reactive glycoprotein was not found. In conclusion, although type 4 chain H glycolipid is not expressed by normal bile ductules and liver cells, it is actively synthesized and expressed by proliferated bile ductules and some of the liver cells in cirrhosis in the absence of any neoplastic change.
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PMID:Type 4 chain H expression by bile ductules and hepatocytes in cirrhosis. 246 83

In order to see if the term of "plasma cell hepatitis", dating back to the early sixties, is still valid as a morphological diagnosis for autoimmune chronic hepatitis (AICH), and to find out if the existence of several subgroups is reflected by histopathology, we investigated 26 patients with chronic hepatitis, who met the criteria of autoimmune hepatitis based on tests for antinuclear, anti-smooth muscle antibodies (SMA) and on immunoassays for liver-kidney-microsomal (LKM) antigen, liver membrane antigen (LMA), and soluble liver antigen (SLA). In our material autoimmune hepatitis represent the entire spectrum of chronic hepatitis with variable inflammatory activity ranging from chronic persistent hepatitis to severe inflammatory lesions in chronic active hepatitis with transition to cirrhosis. When compared to viral chronic hepatitis A and non-A, non-B, however, characteristic features can be evaluated consisting in broad hypocellular areas of collapse and microacinar transformation of hepatocytes with hydropic swelling being the predominant type of cell lesion. Eosinophilic clumping and acidophilic necrosis were insignificant. Plasma cells were not a constituent feature of AICH. From this histopathologic pattern it may be concluded that the disease seems to run a sluggish course in most patients, however, in few cases a dramatic development may determine the disease with fatal acute episodes which are terminated by death or fade into slow progression. The different subgroups could not be distinguished by histopathology.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histologic features in autoimmune hepatitis. 250 55

The features of the pharmacokinetics of preparations of alpha-lipoic acid (lipoic acid, thioctacide) as compared with their pharmacodynamic effects were studied in 125 patients with chronic diffuse diseases of the liver of viral and alcohol etiology. After a single administration of the preparations, the authors found an elevation of the maximal blood concentrations and an increase of alpha-lipoic acid elimination half-life in patients with liver cirrhosis as compared with chronic hepatitis patients. During the replacement therapy and elimination of alpha-lipoic acid deficiency by using the preparations containing lipoic acid, there is commonly an increase ATP content, an elevation of functioning mass of hepatocytes and activation of liver detoxifying function according to the data of the tests of galactose cytosol oxidation, microsomal oxidation of antipyrine and conjugation of bilirubin.
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PMID:[Pharmacokinetics of preparations of lipoic acid and their effect on ATP synthesis, processes of microsomal and cytosol oxidation in hepatocytes in liver damage in man]. 250 39

In order to investigate the reason for the elevation of serum gamma-glutamyltranspeptidase (GGT) after chronic alcohol consumption, the activity of this enzyme, together with the activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in serum (parameters of liver cell damage) and the excretion of D-glucaric acid (D-GA) in urine (parameter of microsomal enzymatic induction) were determined in 72 chronic alcoholics. Of these, 32 had no significant liver disease (1st group) and 40 had an overt liver disease varying from fatty liver to liver cirrhosis (2nd group). The GGT was elevated in only 62% of the patients of the first group, but in 95% of the second group. Of the latter group, patients with cirrhosis had significantly higher GGT mean levels than the patients with fatty liver. On the other hand, increased D-GA excretion was only found in 23% of the group 1 patients and in 44% of the group 2 patients. Moreover, in all patients there was a significant correlation between the values of GGT and aspartate aminotransferase, but not between GGT and D-GA. From these results, the GGT increase in chronic alcoholics, would seem to be better related to cellular damage than to enzymatic induction assessed on the basis of D-GA urinary excretion.
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PMID:Abnormal serum gamma-glutamyltranspeptidase in alcoholics. Clues to its explanation. 256 72

The metabolism of lidocaine to its major metabolite monoethylglycinexylidide (MEGX) was studied in human liver microsomes of 13 kidney transplant donors and of one patient with liver cirrhosis. Interindividual variation in metabolite formation was considerable. Biphasic kinetics indicated the involvement of at least two distinct enzymatic activities. With use of a series of antisera that recognize different human cytochrome P450 isozymes, we were able to identify an enzyme of the P450III gene family as one of two enzymes. By expressing human P450IIIA4 complementary deoxyribonucleic acid (cDNA) in HepG2 cells, we directly demonstrated lidocaine-deethylase activity for this P450 isozyme. These data suggest that P450IIIA4 is at least in part responsible for microsomal MEGX formation.
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PMID:Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4. 258 9

Elevated serum ammonia may play a role in central nervous system derangement after transurethral resection of the prostate. Glycine used as a surgical irrigant for prostate resection produces ammonia as a by-product after liver and renal metabolism. The presence of liver dysfunction often leads to an inability to remove generated ammonia from the circulation. To determine whether the presence of cirrhosis allows significant metabolism of glycine and the resulting serum ammonia levels generated, the production of ammonia after glycine infusion was examined in normal and cirrhotic rats. Hepatic microsomal enzyme induction was produced in male Sprague-Dawley rats given sodium phenobarbital, added to the drinking water to hasten the development of cirrhosis, by increasing the toxicity of carbon tetrachloride given intragastrically to one group at weekly intervals for production of cirrhosis. A control group was maintained under similar conditions except for carbon tetrachloride dosing. The end point for production of cirrhosis was the development of ascites. Two weeks after the development of ascites in the cirrhotic rats and the discontinuation of phenobarbital in both groups, both control and cirrhotic rats were anesthetized with IP pentobarbital and glycine (1.25 g/kg; 7.5%) was given intravenously. Venous blood samples were taken at intervals up to 120 min for serum ammonia analysis. After the final serum ammonia sample, lethal pentobarbital injection was given and livers and kidneys removed for histologic analysis. Terminal body weight, glycine dose, and renal histology were not different between groups. Liver weights were greater in cirrhotic rats. Baseline serum ammonia levels were also greater int he cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum ammonia levels in response to glycine infusion in normal and cirrhotic rats. 258 60

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

Mitochondrial function is impaired in patients and experimental animals with liver cirrhosis. The relationship between mitochondrial impairment and severity of cirrhosis is unknown, however. We therefore characterized the severity of cirrhosis in rats with phenobarbital/CCl4-induced cirrhosis by the aminopyrine breath test, a microsomal function test reflecting hepatocellular mass. Mitochondrial function was evaluated by measuring oxygen consumption, enzyme activities and ATP production in mitochondria isolated from cirrhotic (N = 8) and control livers (N = 4). Oxygen consumption and mitochondrial enzyme activities calculated per liver were significantly reduced in the presence of cirrhosis. This decrease corresponded to the loss of hepatocytes calculated from the reduction in aminopyrine breath test. The effect of atractylate, oligomycin and dinitrophenol on state 3 respiration was equal between the two groups. The respiratory control ratio was significantly reduced in mitochondria from cirrhotic livers with beta-hydroxybutyrate (4.01 +/- 0.94 vs 5.45 +/- 0.40), but not with succinate as substrate. The rate of ATP production was significantly decreased in mitochondria from cirrhotic rats for both substrates. In contrast, the static head (state 4) phosphate potential was fully developed after 10 min and was equal between the two groups. We conclude that cirrhosis of the liver leads to a loss of hepatocytes which is paralleled by reduced oxygen uptake and reduced mitochondrial enzyme activities.
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PMID:Mitochondrial function in carbon tetrachloride-induced cirrhosis in the rat. Qualitative and quantitative defects. 273 Jun 74

The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (Vz) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2 h). There were no significant differences between renal failure and control patients in clotiazepam Vz, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.
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PMID:Effect of cirrhosis and renal failure on the kinetics of clotiazepam. 287 61


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