Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The elimination of pindolol was studied in 32 patients suffering from various liver diseases, mainly acute hepatitis and hepatic cirrhosis. The total body clearance of antipyrine was measured simultaneously as a parameter of liver microsomal enzyme activity. The doses given were antipyrine 1000 mg orally and pindolol 3 mg i.v. Plasma samples were taken and urine was collected for up to 72 h for the measurement of drug concentrations. In addition, conventional biochemical laboratory tests were done. The total body clearance of antipyrine was compared with the pharmacokinetic parameters calculated for pindolol, and the results of the biochemical tests. No correlation was found between antipyrine clearance and the routine biochemical parameters in liver disease or with the total body clearance of pindolol. A significant correlation was seen with the nonrenal clearance of pindolol taken as representing its major metabolic degradation. Higher correlation coefficients were observed when two subgroups of patients with acute hepatitis and hepatic cirrhosis were separated. In some patients suffering from hepatic cirrhosis a higher urinary excretion of unchanged pindolol was observed as liver function become decompensated, a finding due to an unknown mechanism but based on intact renal function. In patients with acute hepatitis a much higher nonrenal clearance was found than in many other patients, which might be based on increased liver blood flow.
 ...
PMID:Elimination of pindolol in liver disease. 710 58

The relationship between high-density lipoproteins (HDL) in plasma and hepatic structure and microsomal function has been investigated in 54 patients undergoing diagnostic liver biopsy. Plasma HDL cholesterol and major apoproteins were correlated with hepatic histology and microsomal enzyme activity assessed directly as liver cytochrome P-450 concentration and indirectly by plasma antipyrine clearance rate. HDL cholesterol, the concentrations of apoproteins A-I and A-II, the HDL cholesterol/total cholesterol ratio and cytochrome P-450 were low in subjects with moderate or severe hepatic fatty infiltration or cirrhosis when compared with the values for subjects with a normal live. HDL cholesterol and apoprotein A-I and the HDL cholesterol/total cholesterol ratio were directly proportional to the amount of non-fatty parenchyma in the livers. Subjects with a normal liver undergoing treatment with enzyme-inducing drugs, such as phenytoin, phenobarbital and primidone, had higher HDL cholesterol, apoproteins A-I and A-II, HDL cholesterol/total cholesterol ratio, cytochrome P-450 and antipyrine clearance rate than subjects not receiving such therapy. Treatment with inducers appeared to have compensated for the effect of liver disease in lowering plasma HLD. In the entire population, and also in subjects not taking inducing drugs, when considered separately, plasma HDL cholesterol, apoproteins A-I and A-II and the HDL cholesterol/total cholesterol ratio were significantly correlated with cytochrome P-450 concentration. In subjects on enzyme inducers, HDL cholesterol and apoprotein A-I levels and the HDL cholesterol/total cholesterol ratio were proportional to the magnitude of the induction. Serum triglycerides were inversely proportional to the measures of liver microsomal enzyme activity. The lipoprotein pattern, high HDL cholesterol and apoproteins A-I and A-II, and high HDL cholesterol/total cholesterol ratio that accompany microsomal induction are characterized by a reduced risk of atherosclerotic vascular disease and a prolonged expectation of life. The plasma changes presumably reflect the effect of enzyme inducers, such as phenytoin and phenobarbital on hepatic lipids and proteins.
 ...
PMID:Plasma high-density lipoproteins and hepatic microsomal enzyme induction. Relation to histological changes in the liver. 717 98

The clinical association of decreased serum and hepatic zinc in patients with cirrhosis of the liver presumably arising from excess ethanol ingestion prompted a study of the activities of zinc and alcohol in experimental animals. The purpose of this study was to determine the effect of zinc deficiency upon lipid peroxidation in the liver. The effect of ethanol and zinc deficiency on lipid peroxidation was also evaluated. Rats were used in the experimental design, one group received a control diet, and one was maintained on a zinc-deficient diet. One-half of each group also received 3.85 g ethanol per kilogram body weight daily. Lipid peroxidation in vivo was determined by estimation of diene conjugation of microsomal lipids. The in vitro lipid peroxidation potential was measured by the generation of malonic dialdehyde by enzymatic as well as nonenzymatic reactions. Analysis of this data indicated that increased hepatic microsomal lipid peroxidation was associated with zinc deficiency whether using in vivo or in vitro indices of measurement. Review of the data from individual animals indicated that the lowest levels of serum zinc were associated with increased hepatic content of phospholipids. The degree of lipid peroxidation in the zinc deficient animals was not increased by ingestion of alcohol.
 ...
PMID:Enhanced lipid peroxidation in liver microsomes of zinc-deficient rats. 735 80

Hepatic drug-metabolizing capacity was investigated in 56 diabetics. The antipyrine test was selected as an in vivo index, since its kinetics indirectly reflect the metabolically active liver mass. Hepatic cytochrome P-450 (P-450), determined from the biopsy samples, was used as an in vitro parameter, since it is a direct measure of microsomal drug-metabolizing enzyme activity. There was a wide interindividual variation in the indexes of drug metabolism in the diabetics: 40 fold in P-450 content and eightfold in antipyrine metabolism. P-450 levels were higher and antipyrine metabolism faster in the subjects with normal liver than in those with fatty liver, parenchymal inflammatory changes, or cirrhosis. Thus the in vivo and in vitro parameters of drug metabolism were related to the alterations in liver histology. On the other hand, the diabetes per se did not seem to alter the drug-metabolizing capacity of the liver. Also, drug metabolism in diabetics classified by treatment regimen did not differ significantly.
 ...
PMID:The evaluation of the drug-metabolizing capacity in patients with diabetes mellitus. 743 38

The influence of cholestyramine and chenodeoxycholic acid on the induction of liver cirrhosis by carbon tetrachloride was investigated in the Wistar rat. The addition of 1.3% cholestyramine to the diet of the experimental animals inhibited to a large extent the induction of cirrhosis. While all the animals subjected to carbon tetrachloride exposure plus basal diet and those to carbon tetrachloride intoxication plus chenodeoxycholic acid diet developed cirrhosis, the morphological manifestation of cirrhosis occurred in the livers of only two out of 18 rats under carbon tetrachloride treatment plus cholestyramine diet. The administration of cholestryamine induces reactions which correspond to the physiological protective mechanisms of the liver. These are the bile acid binding, bacteriostatic, and microsomal enzymatic stimulating properties of cholestyramine.
 ...
PMID:Protective effects of cholestyramine on liver cirrhosis induced by carbon tetrachloride in the rat. 743 6

Hepatitis C virus is a positive single-strand RNA virus distantly related to flaviviruses. Therefore RNA replicase, an RNA-dependent RNA polymerase, may be essential for the replication of hepatitis C virus, as well as other RNA viruses. In this study we synthesized the recombinant polypeptide (HCV-NS5 antigen) with a 576 bp cDNA encoding a part of the NS5 region of the HCV genome that has the Gly-Asp-Asp motif. The antibody against this polypeptide was obtained from rabbit serum. In Western-blot analysis with NS5 IgG HCV antibody, an 84-kD protein was clearly detected as a single band in the microsomal fraction but not in the nuclear and mitochondrial fractions or in the cytosol fraction. Immunohistochemically, HCV-NS5 antigen was clearly stained in the cytoplasm of hepatocytes but not in the nucleus or cell membrane. Moreover, as determined on immunoelectron microscopy, HCV-NS5 antigen was demonstrated with fine granular distribution along the endoplasmic reticulum but not in other organelles, including the nucleus and mitochondria. Immunoreaction in other cell types was negative. These results indicate that replication of HCV may occur only in hepatocytes and that HCV-NS5 may be produced in the endoplasmic reticulum of these cells. HCV-NS5 antigen was stained only in the livers of hepatitis C virus-positive patients but not in sections from patients with chronic type B hepatitis or alcoholic fibrosis. In chronic type C liver disease, the overall detection rate of HCV-NS5 antigen was 56% (33% in chronic persistent hepatitis, 52% in chronic active hepatitis and 86% in cirrhosis).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Detection of antigens related to hepatitis C virus RNA encoding the NS5 region in the livers of patients with chronic type C hepatitis. 750 61

Trimethadione (TMO) was chosen as an indicator of quantitative hepatic microsomal function, and its pharmacokinetics were studied in 52 patients with chronic hepatitis. Findings in these patients were compared with those for 26 healthy subjects and 13 patients with renal failure. Patients with chronic hepatitis, but not those with renal failure, showed significant reduction in clearance (CL) and prolongation of half-life (t1/2), and the extent of abnormalities was found to reflect the severity of histologic changes in liver tissue. The serum dimethadione (DMO)/TMO ratio 4 h after the administration of TMO altered in parallel with the CL and t1/2 of TMO, and abnormalities in this simple ratio were also related to the histologic severity of changes in the liver tissue. A low DMO/TMO ratio (< 0.4) was associated with advanced histologic changes (chronic active hepatitis with bridging or chronic active hepatitis with cirrhosis), whereas a high DMO/TMO ratio (> 0.4) was associated with mild histologic changes (chronic persistent hepatitis or chronic active hepatitis) (sensitivity, 0.81; specificity, 0.86). These results indicate that the DMO/TMO ratio, which can be obtained from a single blood sampling, reflects the histologic severity of changes in tissue liver, and that the TMO tolerance test is a useful indicator of quantitative liver function.
 ...
PMID:Clinical significance of the trimethadione tolerance test in chronic hepatitis: a useful indicator of hepatic drug metabolizing capacity. 755 Aug 58

Low-molecular hydrocarbons (butan, pentan) from the exhaled air as lipid peroxidation (LPO) markers were quantified in patients with chronic diffuse liver diseases. The study was also made of microsomal oxidation enzymic activity by antipirin metabolism. The above parameters were followed up in the course of antioxidant treatment. As shown by total butan and pentan levels, LPO activity varied with the disease, being high in hepatic cirrhosis and primary biliary cirrhosis, but low in chronic active hepatitis and fat dystrophy. Increased levels of butan and pentan occurred in association with inhibited activity of P450-dependent monooxygenases. This was determined by antipirin biotransformation and confirmed by a strong inverse correlation between the amount of hydrocarbons and antipirin metabolites (4-hydroxy- and norantipirin) clearance. In the course of antioxidant therapy the most pronounced inhibiting action on formation of low-molecular hydrocarbons was distinctive of essenciale, pikamilon and copmplivit. Relevant efficacy of carsil was weaker. Similar regularity for these drugs takes place in relation to activation of microsomal oxidation.
 ...
PMID:[Lipid peroxidation markers in the exhaled breath and microsomal oxidation in patients with chronic diffuse liver diseases]. 778 77

The aim of this study was to evaluate the changes in fatty acid composition of lipids of plasma, erythrocytes, and liver microsomes in rats with liver cirrhosis induced by oral intake of thioacetamide and to determine to what extent the experimental model reproduces the fatty acid tissue alterations reported in human cirrhosis. Two groups of rats were studied. The control group received water ad libitum, and the experimental group received 0.03% w/v thioacetamide in drinking water for 2, 4, and 6 months. At these times, lipids of plasma, erythrocytes, and liver microsomes were extracted, and their fatty acid compositions were determined. Thioacetamide intake led to macronodular and micronodular cirrhosis at 2 months. These alterations progressed at 4 months and eventuated in liver tumors at 6 months. Thioacetamide-treated rats showed a drop in total plasma fatty acids, higher percentages of palmitic acid in all lipid fractions, and lower levels of stearic acid in erythrocyte lipids and liver microsomal phospholipids. Oleic acid increased in plasma cholesteryl esters and phospholipids, as well as in erythrocyte lipids and liver microsomal phospholipids. In plasma lipids and liver microsomal phospholipids, the percentages of arachidonic and docosahexaenoic acids decreased. The latter also decreased in erythrocyte lipids. In addition, liver microsomes showed a higher cholesterol/lipid phosphorus molar ratio. The experimental model of cirrhosis obtained by intake of thioacetamide in drinking water for 4 months reproduces many of the fatty acid tissue alterations that appear in human cirrhosis and may serve to ascertain the biochemical mechanisms involved in these changes.
 ...
PMID:Changes in fatty acid composition of plasma, liver microsomes, and erythrocytes in liver cirrhosis induced by oral intake of thioacetamide in rats. 780 55

There are several inherited and acquired disorders that can result in chronic iron overload in humans, and the major clinical consequences are hepatic fibrosis, cirrhosis, hepatocellular cancer, cardiac disease, and diabetes. It is clear that lipid peroxidation occurs in experimental iron overload if sufficiently high levels of iron within hepatocytes are achieved. Lipid peroxidation is associated with hepatic mitochondrial and microsomal dysfunction in experimental iron overload, and lipid peroxidation may underlie the increased lysosomal fragility that has been detected in liver samples from both iron-loaded human subjects and experimental animals. Reduced cellular ATP levels, impaired cellular calcium homeostasis, and damage to DNA may all contribute to hepatocellular injury in iron overload. Long-term dietary iron overload in rats can lead to increased collagen gene expression and hepatic fibrosis, perhaps due to activation of hepatic lipocytes. The mechanisms whereby lipocytes are activated in iron overload remain to be elucidated; possible mediators include aldehydic products of iron-induced lipid peroxidation produced in hepatocytes, tissue ferritin, and/or cytokines released by activated Kupffer cells.
 ...
PMID:Pathophysiology of iron toxicity. 788 29


<< Previous 1 2 3 4 5 6 7 8 9 10