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)

Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.
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PMID:Monooxygenase enzyme activity in alcoholics with varying degrees of liver damage. 11 58

Basal and reactive peripheral hyperinsulinism recorded in alcoholic hepatic disease may result from decreased hepatic breakdown or pancreatic hypersecretion. C-peptide (CPR) and insulin (IRI) concentrations were measured in 3 groups of 8 alcoholic patients--steatosis, compensated and decompensated cirrhosis--and compared with 8 normal subjects in order to determine the importance of these two possibilities. At basal state, the molar ratio CPR/IRI was near the normal (8.7 +/- 0.9) but is diminished in the 8 hyperinsulinaemic patients (5.9 +/- 0.6). After i.v. glucose tolerance test and tolbutamide stimulations, an hyperreactivity of IRI and CPR may be noted in cirrhotics. A relative insensitivity of the B-cell to glucose appeared after comparison with the effect of tolbutamide. Thus basal hyperinsulinism resulted of decreased hepatic breakdown and stimulated hyperinsulinism resulted of hypersecretion. Glucose intolerance and anomalies of the insulin secretion were more apparent with severe hepatic disease.
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PMID:[Insulin secretion in alcoholic hepatopathy: analysis by measurement of C-peptide (author's transl)]. 73 68

Of the many information obtainable from the urine of diabetic patients, urinary C-peptide (CPR), albumin and anti-diuretic hormone (ADH) were representatively described using my clinical and experimental data. C-peptide excretion in 24h collection of urine is a good estimate of insulin secretion from the pancreas and thus low in IDDM patients and even in NIDDM patients at a later stage, but high in pathological conditions including Graves' disease, obesity, liver cirrhosis and Cushing's syndrome. Urinary albumin excretion in small amounts (microalbuminuria) is usually observed in diabetic patients who have been under a poor control state of diabetic hyperglycemia for over 5 years and provides a good tool for monitoring early diabetic nephropathy. The grade of microalbuminuria (30-300 mg/day) is positively correlated with the HbA1 level in diabetic patients, showing that microalbuminuria is reversible along with an improvement of diabetic control at least in an early phase of diabetic nephropathy. As the albumin level measured in a spot urine sample correlates well with the value in the 24h collection of urine, the albumin measurement is conveniently feasible with a spot urine sample at every patient's visit. The amount of ADH excreted in urine is 7-10% of that secreted from the posterior pituitary. The excretion of ADH in a day was in the urine of diabetic patients positively correlated with HbA1, urinary osmolarity and concentration of sodium in urine, although the pathological meaning of the observed ADH hypersecretion in the development of diabetic complications is currently unknown.
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PMID:[Pathophysiological analysis of diabetes mellitus and complications from the urine of diabetic patients]. 150 92

Plasma level of immunoreactive insulin (IRI) and C-peptide (CPR), and their responses to intravenous administration of glucagon were studied in 37 patients with cirrhotic portal hypertension during hepatic vein catheterization. IRI and CPR in peripheral vein and hepatic vein were compared with development of portal vein collaterals measured by indocyanine green disappearance tests and portal venograms. In additional 2 cases, the values were compared with those of portal vein blood obtained by percutaneous transhepatic catheterization. Plasma IRI of peripheral vein in cirrhotic patients, those who had only esophageal varices but did not have remarkable amount of portal vein collateral blood flow, revealed the changes closely resembling the controls. On the contrary, peripheral vein IRI elevated significantly in cirrhotics with large shunt and the values exceeded those of hepatic vein, although responses to the glucagon test were normal. In experimental study using dogs, peripheral IRI revealed significant increase after the portocaval anastomosis diverting the portal blood containing high IRI into the inferior vena cava, and the values exceeded those of hepatic vein. It is important to know the development of portal vein collaterals as a major cause of hyperinsulinemia in liver cirrhosis.
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PMID:[Clinical and experimental studies on elevated plasma level of insulin in cirrhotic patients with portal hypertension and portosystemic collateral circulation]. 637 13

Abuse of ethanol has shown to induce the drug-metabolizing enzyme activity of the liver in rats and in humans. Therefore, we studied cytochrome P-450 dependent monooxygenase and conjugating enzyme activity in needle liver biopsy specimens of patients using the following substrates and enzyme assays: 7-ethoxycoumarin O-deethylase (EOD), p-nitroanisol O-demethylase (PNA), NADPH-cytochrome c reductase, 1-naphtol glucuronyltransferase (NGT). Among alcoholics induction of EOD, PNA and NGT was only found in patients with active alcoholic liver damage (elevated transaminases and necrosis of the liver cells). The other groups had either normal enzyme activity (abstinent alcoholics, residual alcoholic liver damage) or low activity (liver cirrhosis, cholestatic liver disease). Surprisingly, nonabstinent alcoholics with normal liver histology did not reveal enzyme induction. Enzyme induction was dependent on time of abstinence. Within 20 days of abstinence the induction tapered off concomitantly with the resolution of active liver injury. The hyperactive ethanol-induced enzyme system could produce toxic oxygen radicals leading to liver injury and also toxify drugs (paracetamol, halogenated hydrocarbons, INH). Induction of hepatic monooxygenase activity by ethanol, although originally an adaptive response, might therefore increase the risk of hepatotoxicity of certain drugs.
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PMID:[Enzyme induction of the liver caused by chronic alcoholism as risk factor in hepatotoxicity]. 670 35

In order to clarify the mechanism of insulin secretion, responses of insulin (IRI) and C-peptide (CPR) in plasma to various stimuli were investigated in normal subjects and patients with diabetes mellitus, liver cirrhosis, chronic nephritis or insulinoma. The response of plasma IRI and CPR to oral glucose load was less marked in the mild and moderate diabetes groups than in the normal controls. Neither IRI nor CPR in the severe diabetes group responded to oral glucose. The patients with liver cirrhosis revealed an exaggerated and delayed response of IRI and CPR, and a lowered CPR/IRI ratio, indicating a remarkable response of IRI to glucose. In contrast, the patients with chronic nephritis showed a prominent rise of CPR alone. In the insulinoma patients, both plasma IRI and CPR increased after glucose load. In the response to glucose, there was approximately 30-min lag time between the peaks of IRI and CPR in the normal controls and the patients with various diseases. Following arginine infusion, plasma IRI and CPR increased in the normal subjects and the patients with moderate diabetes. In the normal subjects, plasma IRI reached a peak at 6 min and 3 min in response to tolbutamide and glucagon, respectively, which elicit an abrupt and sharp rise of insulin from B-cells. However, diabetic patients showed a minimal change in plasma IRI and CPR, whereas there was an exaggerated response of plasma IRI and CPR in insulinoma patients. In analysis of responses of plasma IRI and CPR to tolbutamide or glucagon, there was a lag time longer than 10 min in the normal subjects. The present study confirms the concurrent release of C-peptide from the B-cells in the secretion of insulin. In addition, it was suggested that insulin and C-peptide are mainly handled in the liver and the kidney, respectively. Furthermore, a longer lag time between the peaks of IRI and CPR in response to tolbutamide or glucagon did not necessarily indicate a simultaneous release of insulin and C-peptide from the B-cell, but a delayed release of the latter.
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PMID:Analysis of insulin secretion based on changes in plasma insulin and C-peptide in man. 676 99

To determine whether cytochrome P450 proteins were differentially altered in severe chronic liver diseases, we examined 50 livers removed at liver transplantation from patients with end-stage cirrhosis, including 18 with and 32 without cholestasis, and compared the results with 21 histologically normal livers. NADPH-cytochrome c reductase activities were unaltered in microsomes from cirrhotic livers. Total cytochrome P450 content was significantly reduced. The catalytic activities of four xenobiotic-metabolizing P450s and the level of the corresponding proteins were differentially altered. Thus, P450 3A-supported testosterone 6 beta-hydroxylase activity and 3A protein appeared to be reduced, but only in the subgroup without cholestasis was this change significant. In contrast, 2E1 and the related N,N-dimethylnitrosamine N-demethylase activity were clearly reduced in livers from patients with cholestatic forms of cirrhosis but appeared not to be changed in other cirrhotic livers. Similarly, P450 2C protein was reduced only in patients with severe chronic cholestasis. Finally, P450 1A2 and 1A2-supported ethoxyresorufin O-deethylase activity were significantly reduced in hepatic microsomes from patients with both types of advanced liver disease. In summary, these data demonstrate that cytochrome P450 proteins are selectively altered in severe chronic liver disease, some being profoundly decreased, others less so or not at all. Our results also suggest that there may be different patterns of altered hepatic P450 expression according to the presence or absence of cholestasis in patients with cirrhosis severe enough to require transplantation.
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PMID:Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. 780 44

For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.
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PMID:Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy. 1474