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)

In this paper are presented the results of a study on the elimination kinetics of phenprocoumon in patients concomitantly treated with phenprocoumon and phenobarbital as well as in patients with bioptically proved hepatic cirrhosis. The pre-treatment of the patients with phenobarbital (3 X 100 mg), 4 days before phenprocoumon was started, resulted in an accelerated elimination of phenprocoumon. The biological half-life of phenprocoumon was reduced from 150 to 70 hrs when compared to normal controls, and the elimination constant was found to increase to 9,96 X 10(-3). Phenobarbital at plasma concentrations achieved by usual therapeutical dosage schedules of the drug does not interfere with the protein binding of phenprocoumon as could be shown by equilibrium dialysis. Phenobarbital, therefore, does not accelerate the elimination of phenprocoumon. The inducing effect of phenobarbital on the drug metabolizing enzyme system in the liver results in more rapid biotransformation of phenprocoumon. In patients with bioptically proved hepatic cirrhosis, the elimination kinetics did not differ from the results obtained in normal controls.
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PMID:[Elimination kinetics of phenprocoumon (Marcumar) in liver cirrhosis and after premedication with phenobarbital]. 96 32

The authors report on a comparative study of light and electron microscopy in the diagnosis of tissue obtained in 21 percutaneous liver biopsies in patients known to have cirrhosis. Using light microscopy twelve patients were ascertained to have post-necrotic cirrhosis and twelve had Laennec's cirrhosis. All of these patients were given phenobarbital, 65 mg. every twelve hours, during twenty-one days. A control group of five patients received placebos. With electron microscopic methods, in all of the cirrhotic patients both before and after treatment with phenobarbital, the authors observed bands of fibrous tissue made up of collagen fibers and fibroblasts which originate in the portal spaces and in the Kupffer cells. This makes up the mesenchymal reaction to the liver cell damage, which in the long run proves to be more important than liver cell regeneration. Phenobarbital treatment resulted in hyperplasia of the agranular endoplasmic reticulum in liver cells. The authors agree with other authors that this is related to metabolic activity of enzymes acting on extraneous drugs and chemical substances.
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PMID:[Morphological study of the hepatocyte in cirrhotic patients treated with phenobarbital]. 123 93

The onset of sodium retention in phenobarbital/carbon tetrachloride-induced cirrhosis in rats is preceded by a linear decrease in hepatic function as assessed by the aminopyrine rate constant of elimination. Sodium retention occurs when liver function decreases below a critical aminopyrine rate constant of elimination threshold of 1 min-1 x 10(-3). The objective of this study was to investigate this relationship in a different experimental model of cirrhosis in rats and to learn whether alteration of drug-metabolizing activity by hepatic enzyme induction changes the threshold for urinary sodium retention. Cirrhosis was induced in untreated and phenobarbital-treated rats by bile duct excision. Liver function, assessed by the aminopyrine breath test, and urinary sodium excretion on a constant salt diet were measured weekly for up to 4 wk. In untreated rats, the aminopyrine breath test rate constant of elimination was reduced by about 40% within 1 wk of surgery. Aminopyrine rate constant of elimination then decreased more slowly, but linearly. Urinary sodium excretion was initially unchanged, but sodium retention occurred after 2.5 wk and was maintained until the end of the experiment. Phenobarbital-treated rats had greater initial aminopyrine rate constant of elimination, but we saw a similar fall in aminopyrine rate constant of elimination of about 40% within 1 wk of bile duct excision to a value still above baseline aminopyrine rate constant of elimination of untreated controls. Aminopyrine rate constant of elimination remained at a plateau for 3.5 wk without changes in urinary sodium excretion. After 3.5 wk, a sudden decrease in aminopyrine rate constant of elimination was associated with the sudden onset of sodium retention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenobarbital influences the development of sodium retention in liver disease induced by bile duct ligation in the rat. 234 52

Proliferation of the two types of bile ductules, typical and atypical, in the portal and periportal areas was examined in various liver diseases other than cirrhosis to determine any difference in their immunohistochemical properties and presumed histogenesis. While the typical ductules with a well-formed lumen were frequently seen in a large spectrum of diseases, atypical ductules with a poorly defined lumen were encountered much more frequently in prolonged biliary diseases, including primary biliary cirrhosis and primary sclerosing cholangitis, than in nonbiliary hepatic diseases. Immunocytochemically, cytoplasmic keratin was intensively positive in typical ductules, and the degree of its intensity and extent was variable in atypical ductules. Simultaneously, some of the periportal hepatocytes revealed weak staining for keratin. Luminal borders of typical ductules usually revealed an expression of both carcinoembryonic antigen and epithelial membrane antigen, while atypical ductules and periportal hepatocytes lacked epithelial membrane antigen. The atypical ductules, together with the adjoining hepatocytes, appeared on occasion to form anastomosing cords in prolonged biliary diseases. Thus, atypical ductules seem likely to originate from ductular transformation of the periportal hepatocytes and the typical ductules might result from the proliferation of preexisting interlobular bile ducts and ductules.
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PMID:Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseases. 243 Jan 63

The possibility of a relationship between hepatic and renal cytochrome P-450 contents was assessed in rats with liver disease. In rats killed 3 days after two-thirds hepatectomy (a model for hepatocellular insufficiency), the total microsomal cytochrome P-450 content of the whole liver was decreased by 60% as compared to that in control rats; renal cytochrome P-450 was increased by 30% while the 7-ethoxycoumarin deethylase activity of kidney microsomes was increased by 80%. In rats killed 7 days after bile duct ligation (a model for cholestasis) or 35 days after bile duct ligation (a model for biliary cirrhosis), hepatic cytochrome P-450 was decreased by 60% and 45%, respectively, while renal cytochrome P-450 content was increased by 50% and 150%, respectively. In contrast, in rats killed 15 days after the last dose of carbon tetrachloride, 1.3 ml/kg twice weekly for 3 months (a model for post-necrotic cirrhosis), both hepatic and renal cytochrome P-450 contents remained unchanged. Phenobarbital (80 mg/kg daily for 3 days) was a poor inducer of renal cytochrome P-450 in sham-operated rats but became a potent inducer of renal cytochrome P-450 in rats with two-thirds hepatectomy. We conclude that renal cytochrome P-450 is increased in three models in which hepatic cytochrome P-450 contents are decreased (two-thirds hepatectomy, cholestasis and biliary cirrhosis), but remains unchanged in a model of severe liver pathology, in which hepatic cytochrome P-450 content is not modified (late, post-necrotic cirrhosis). The hypothetical role of endogenous inducer(s) is discussed.
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PMID:Regulation of renal cytochrome P-450. Effects of two-thirds hepatectomy, cholestasis, biliary cirrhosis and post-necrotic cirrhosis on hepatic and renal microsomal enzymes. 391 37

An experimental animal model designed specifically to simulate liver fibrosis and cirrhosis in childhood is described. Phenobarbitone was administered continuously from the 4th day of life and carbon tetrachloride intermittently from the 13th day to developing rats for 10 weeks. Treated animals showed hepatic necrosis, hepatic regeneration and a progressive increase in hepatic fibrosis; cirrhosis developed before the animals reached sexual maturity at 72 days or were fully grown. Hepatic prolyl hydroxylase activity increased to a maximum level after 20 days of treatment, before increased hepatic collagen could be detected, and fell to a lower level as cirrhosis became established. Serum activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase gave a similar pattern, a marked increase at 20 days of age followed by a fall to near normal levels as hepatic damage became more severe. By the 26th day of life hepatic collagen levels were increased significantly and rose thereafter progressively as fibrosis became more widespread throughout the liver. Cirrhosis developed between the 38th and 75th days. Cirrhosis remained 10 weeks after discontinuation of treatment with phenobarbitone and carbon tetrachloride treatment.
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PMID:Carbon tetrachloride-induced hepatic fibrosis and cirrhosis in the developing rat: an experimental model of cirrhosis in childhood. 630 21

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

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

We here show the application of mRNA differential display to investigate changes in gene expression in rat liver cirrhosis and address problems inherent in the technique when applied to this complex disease model. A number of differentially expressed mRNA species could be identified and two were analyzed in more detail here. One was found to derive from a new gene while the other corresponded to fetuin, a 41 kDa N-glycoprotein that specifically inhibits tyrosine kinase activity of the insulin receptor when phosphorylated. Fetuin expression was reduced by 45% in liver cirrhosis induced by bile duct ligation, but not in cirrhosis induced by carbon tetrachloride/Phenobarbital, as compared to controls. Our results raise the possibility that fetuin plays a regulatory role in the proliferation of parenchymal liver cells.
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PMID:Application of mRNA differential display to liver cirrhosis: reduced fetuin expression in biliary cirrhosis in the rat. 875 72

Recent results have suggested a role for prolactin (PRL) as a regeneration factor in the liver. In order to investigate the involvement of prolactin in the pathogenesis of liver cirrhosis, we studied the expression of the prolactin receptor (PRLR) and PRL during the development of cirrhosis in an animal model. 30 male rats were exposed to CCl4 by inhalation. Phenobarbitone was added to the drinking water to accelerate the formation of toxic metabolites by enzyme induction. Two control groups of 30 animals each were treated with phenobarbitone only or received no treatment. 10 animals of each group were sacrificed 35, 55, and 70 days after initiation of treatment. Liver tissue was subjected to histological examination, which demonstrated fibrosis of different grades and cirrhosis in the CCl4-treated rats. Expression of PRLR mRNA was investigated by mRNA extraction, RT-PCR and computer-supported densitometric evaluation. Compared to control liver, PRLR mRNA was expressed at a higher level in fibrotic and cirrhotic liver specimens. In normal tissue, immunohistochemical staining showed a high concentration of PRLR around the central vein and in the epithelium of the bile ducts. This pattern of distribution was lost in fibrosis and cirrhosis. An accumulation of PRLR was demonstrated within the damaged cells. Neither PRL nor PRL mRNA was detectable in normal, fibrotic, or cirrhotic liver. We conclude that PRLR is distributed in normal rat liver in a typical pattern which is lost with increasing fibrosis. PRL is not produced by rat liver, indicating that PRL does not act through autocrine or paracrine mechanisms.
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PMID:Expression and distribution of the prolactin receptor in normal rat liver and in experimental liver cirrhosis. 1150 75


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