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 administration of medroxyprogesterone acetate to rats did not induce rapidly progressing cirrhosis in livers damage by carbon tetrachloride, as had occurred after the administration of 17-alpha-hydroxyprogesterone caprate. Even after two months' treatment with medroxyprogesterone acetate and CC14, the cirrhosis did not reach the levels obtained in a single month with the association of 17-alpha-hydroxyprogesterone and CC14.
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PMID:[Diverse action of 17-alpha-hydroxyprogesterone caproate and medroxyprogesterone acetate on the biosynthesis of collagen and cirrhogenous course of CC14-induced hepatic lesions in rats]. 623 3

The carcinogenic potential of cycasin and methylazoxymethanol (MAM) acetate was investigated in nonhuman primates. Old-world monkeys (rhesus, cynomolgus, and African green monkeys) received cycasin and/or MAM acetate by oral or ip routes up to 11 years. Eighteen monkeys survived longer than 2 months after initiation of treatment with cycasin (50-75 mg/kg) or MAM acetate (1.5-3.0 mg/kg) given orally 5 days/week; 9 of the animals were necropsied. Histopathologic examination of a liver tumor from 1 of these monkeys revealed well-differentiated hepatocellular carcinoma. A second monkey had multiple tumors, including hepatocellular carcinoma, intrahepatic bile duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous polyps of the colon. Although liver tumors were not observed in the other monkeys, all but 1 monkey had hepatic lesions such as toxic hepatitis and cirrhosis. These monkeys had received cycasin and/or MAM acetate for an average of 57 months (range, 2-133 mo). A group of 10 monkeys received MAM acetate by weekly ip injections (3-10 mg/kg). Six of these animals developed tumors after receiving an average of 6.14 g (range, 3.58-9.66 g) of MAM acetate for an average of 75 months (range, 50-89 mo). Four of the monkeys developed hepatocellular carcinomas, and 2 had multiple primary tumors including hepatocellular carcinomas, renal carcinomas, squamous cell carcinomas of the esophagus, and adenocarcinomas of the small intestine. Our results showed that long-term administration of cycasin and/or MAM acetate by oral and ip routes was hepatotoxic and carcinogenic in old-world monkeys.
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PMID:Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates. 624 73

In western industrialized countries ethanol is an important etiologic factor in the development of cirrhosis of the liver. Metabolic, immunologic and physico-chemical alterations of the hepatocyte due to ethanol are involved in the pathogenesis of alcoholic liver disease. However, the mechanisms by which ethanol damages the liver are far from clear. During the last two decades, the effect of ethanol on multiple biochemical pathways of the hepatocyte has been investigated intensively. The present paper is focusing on the metabolic aspects of alcoholic liver disease. In the first part of the review, special emphasis has been led on the metabolites of ethanol oxidation, while in the second part microsomal enzyme induction due to alcohol has been discussed. More than 90% of ethanol metabolism takes place in the liver via cytoplasmic alcoholdehydrogenase (ADH) and via a microsomal ethanol oxidizing system (MEOS). The products of these reactions are reduced nicotinadenine dinucleotide phosphate (NADH), acetaldehyde and acetate. NADH alters the redox state of the liver cell favouring all reductive processes. This shift in metabolic pathways results in hyperlactacidaemia, lactacidosis, ketosis and hyperuricaemia. Disturbances of the carbohydrate metabolism may lead either to hypo- or hyperglycaemia. The altered redox state also influences the metabolic pathways of lipid metabolism leading to lipid accumulation within the hepatocyte which can be morphologically observed as alcoholic fatty liver. In addition, porphyrin and collagen metabolism is also affected by the increased NADH/NAD+ ratio. On the other hand, acetaldehyde damages the microtubular system and the mitochondria. Acetaldehyde may also be responsible for the increased lipidperoxidation after chronic ethanol ingestion.
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PMID:[Metabolic aspects of alcoholic liver damage: 1984/5 update. 1. Epidemiology and alcohol metabolism]. 639 85

Dogs with portal cirrhosis but without portal hypertension (end-to-side portacaval anastomosis) retain sodium and expand plasma volume before ascites formation. In our study, dogs were subjected to bile duct ligation and simultaneous side-to-side portacaval anastomosis (PCA) in order to create a canine model of hepatic cirrhosis without intrahepatic or portal hypertension. The effect of normalizing intrahepatic pressures in the face of venous outflow block on sodium handling was studied. 13 dogs survived the surgical procedures and were followed. Two dogs developed sodium retention and ascites at 5-6 wk (livers were cirrhotic) when the PCA spontaneously closed. 11 dogs were free of sodium retention and ascites for as long as 12 wks after surgery, while ingesting 35 meq/d of sodium. In this group glomerular filtration rate remained normal throughout the period of observation and there was no expansion of plasma volume. Nine of these dogs were then fed 85 meq/d of sodium; eight remained in sodium balance and one retained sodium and went on to develop ascites. When 10-15 mg i.m. of desoxycorticosterone acetate (DOCA) was given daily, five dogs developed sodium retention and ascites, while four escaped from DOCA. Dogs who developed ascites had either a partially occluded PCA (4/5) or a patent PCA, but with a significant portacaval pressure gradient of 9.5 cm H2O (1/5). In all four dogs who escaped from DOCA, the PCA was widely patent and the mean pressure gradient was only 1.6 cm H2O. Both groups were equally cirrhotic, as judged by histological and biochemical parameters. We conclude that normalizing intrahepatic pressure by providing an outflow tract for the cirrhotic liver will abolish that component of early renal tubular sodium retention not due to portal venous hypertension or ascites sequestration.
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PMID:Dogs with experimental cirrhosis of the liver but without intrahepatic hypertension do not retain sodium or form ascites. 663 May 20

Therapy with enzyme inducing drugs may improve the clinical state of alcoholics with liver cirrhosis. The histological changes associated with the therapy were investigated by comparing liver biopsies before and after phenobarbital and medroxyprogesterone acetate treatment, known inducers of hepatic microsomal enzyme system, in eight alcoholics with cirrhosis and two control groups, subjects with normal liver and endstage alcoholic cirrhosis. Pericellular collagen, determined morphometrically, reduced from a point value of 87.6 +/- 28.3 to 63.4 +/- 16.7 (p less than 0.01), while the fibrous septa as well as the non-fatty and fatty parenchyma did not alter significantly. Antipyrine metabolism, an index of hepatic cell function, improved from 17.4 +/- 6.4 to 45.6 +/- 22.2 ml/min (p less than 0.01). Although direct correlation between the decrease of pericellular collagen fibres and antipyrine metabolism was not significant (r = 0.410) the findings suggest that accumulation of pericellular collagen prevents mechanically and availability of the compound to the cell, thus delaying its metabolism.
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PMID:Pericellular collagen in alcoholics with liver cirrhosis. 705 84

Hepatic encephalopathy in patients with severe liver disease was associated with marked elevation of either serum methionine or blood ammonia levels or with simultaneous moderate increases in both parameters. CSF methionine levels also increased in encephalopathic patients with fulminant hepatitis and liver cirrhosis. Increased influx of methionine into the brain over the theoretical values predicted from Pardridge's equation suggested that accelerated transport of serum methionine across the blood-brain barrier was observed in these cases with hepatic encephalopathy. Hepatic encephalopathy in acute carbon tetrachloride liver injury could be obtained experimentally following intraperitoneal injection of ammonium acetate in rats, which already received intragastric administration of methionine. However, similar encephalopathy could not be observed by the administration of glycine or leucine in place of methionine. These results suggest at least that methionine and ammonia act synergistically on inducing hepatic encephalopathy.
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PMID:Impaired metabolism of methionine in severe liver diseases. II. Clinical and experimental studies on role of impaired methionine metabolism in pathogenesis of hepatic encephalopathy. 710 99

The efficacy of hepatic enzyme-inducing drugs in improving liver function and drug metabolism was investigated in 18 chronic alcoholics with cirrhosis. Five subjects treated continuously with the inducing drugs, phenytoin or prednisolone, for concomitant diseases showed more rapid metabolism than the other patients. Phenobarbital (PB) and medroxyprogesterone acetate (MPA), both known inducers, improved drug metabolism in patients with normal or decreased serum albumin. Serum albumin levels rose in alcoholics with low pretherapy levels, whereas serum albumin in subjects with normal pretherapy levels did not change. Serum thrombotest levels rose in six of seven subjects with low pretreatment values. There was a trend toward normal conventional liver tests during the experiment. There was a relationship between in vivo and in vitro drug metabolism in the alcoholics with cirrhosis. Our results demonstrate that by activating liver function, enzyme-inducing drugs may be of therapeutic value in alcoholics with liver cirrhosis and hepatic failure.
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PMID:Treatment of alcoholic cirrhosis with enzyme inducers. 743 82

Monocytes appear to play a role in immunological abnormalities observed in primary biliary cirrhosis (PBC). Monocytes not only produce fibroproliferative factors, such as IL-1, TNF, and PDGF but also produce superoxide anion which can directly damage tissues, and thus may lead to fibrosis. The aim of this study was to compare the superoxide production in monocytes obtained from 12 control persons, 9 patients with non biliary cirrhosis, 6 untreated PBC patients, 6 patients with gallstones under urso- and chenodeoxycholicacid (Lithofalk) treatment and 32 PBC patients under ursodeoxycholicacid (UDCA) therapy. Monocytes were isolated and the production of superoxide anions with and without phorbol-myristate-acetate (PMA) stimulation was determined. In two occasion, the monocytes from control patients were preincubated with 10, 50, 100 microM UDCA. Unstimulated monocytes from PBC patients under UDCA therapy produce an average 43% more and the PMA stimulated monocytes an average 42% more superoxide than monocytes from the control or from the other cirrhotic patients. The UDCA preincubation did not influence the superoxide production of monocytes obtained from control patients. These findings suggest that the increased activity of monocytes may also play a role in liver damage and fibrosis in PBC.
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PMID:[Comparative study of superoxide production of monocytes in primary biliary cirrhosis]. 747 83

Ascites often appears as a complication of several illnesses. The therapy is essentially based on the use of low-sodium diet, plasma or albumin infusion, diuretics and low-dosed ACE-inhibitors. To use the simple paracentesis or special techniques as Rhodiascit or Lee Veen Shunt means not to resolve definitively the problem and sometimes to cause undesirable complications. The authors present a new therapeutic tactics that joins the use of technique of double filtration of ascitic fluid and reinfusion of concentrated proteins (DFAF) with the injection in the peritoneal cavity of beta-interferon and the venous infusion of ATIII. Twenty patients affected by hepatic cirrhosis with the presence of ascitic fluid not treatable with the usual therapy have been subjected to this treatment. All the patients showed an immediate improvement of the clinical situation. After one year of observation, we describe our results. Twelve patients needed a further treatment with the DFAF technique, two patients died for the original pathology and six patients just needed an adjustment of pharmacologic therapy.
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PMID:[Reinfusion ascites therapy: considerations after a year's experience]. 748 Sep 64

Fosinopril is distinguished from other ACE inhibitors by a pharmacokinetic pecularity in the sense that is can be metabolized either by liver or kidney. This was the rationale of the present research the aim of which was to verify if administered to patients with liver cirrhosis the drug was liable to alter global liver function and ability to metabolize drugs. Eight cirrhotic males, mean age 56 years, also suffering from high blood pressure, were studied. In these patients, liver and kidney function tests (BUN, creatinine blood level, serum and urinary electrolytes, creatinine clearance, calcium and phosphor blood level, transaminases, alkaline phosphatase prothrombin time, cholinesterase, gamma-glutamyl-transpeptidase) were carried out at baseline and after 30 days' fosinopril treatment (1 capsule every morning in the fasting state); in addition total functioning liver mass was assessed by the galactose test, and drug-metabolizing capacity by the antipyrine test. Treatment resulted in a significant improvement of pressure values in all patients (p < 0.01) and did not alter liver and kidney function parameters. Besides, no side effects were registered, especially no case of orthostatic hypotension. The antipyrine test was not influenced by fosinopril treatment. Therefore, short-term treatment with this ACE-inhibitor can be concluded to be effective and not to cause additional alterations of liver function in patients with liver cirrhosis.
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PMID:[Evaluation of the total hepatic function after treatment with fosinopril in hypertensive patients with liver cirrhosis]. 772 Mar 55


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