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 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

We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver.
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PMID:Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis. 319 65

The intact cell hypothesis states that a reduced number of intrinsically normal hepatocytes, together with hemodynamic alterations, explains decreased drug metabolism in cirrhosis. We explored this hypothesis by comparing results of the aminopyrine breath test with in vitro measurements of aminopyrine N-demethylation and morphometrically determined liver cell volume in a rat model of cirrhosis. Aminopyrine N-demethylation in vivo (ABT-k) was 0.98 +/- 0.10/h (mean +/- SD) in controls. The cirrhotic rats were separated into those with normal (NCR) and those with abnormal ABT-k (PCR). Microsomal aminopyrine N-demethylase averaged 2.08 +/- 0.77 and 2.09 +/- 0.54 mumol/min in controls and NCRs, respectively; it was reduced to 1.00 +/- 0.81 mumol/min (p less than 0.02) in PCRs. Morphometrically determined hepatocellular volume was 18.8 +/- 2.8, 17.1 +/- 1.9, and 11.6 +/- 6.1 ml in controls, NCRs, and PCRs, respectively, PCRs being lower than controls (p less than 0.01) and NCRs (p less than 0.05). When N-demethylase and cytochrome P450 were related to hepatocellular volume (in milliliters), no significant difference between the three groups was apparent. We conclude that reduced aminopyrine N-demethylation in progressed cirrhosis is mainly due to a loss of liver cell volume. The function per liver cell volume remains constant, however, thus favoring the intact cell hypothesis for the handling of slowly metabolized compounds such as aminopyrine.
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PMID:Aminopyrine N-demethylation by rats with liver cirrhosis. Evidence for the intact cell hypothesis. A morphometric-functional study. 362 18

In vitro drug metabolism studies were carried out in 97 patients with liver disease. Drug-metabolizing enzymes (aminopyrine N-demethylase and bilirubin UDP-glucuronyl transferase) were estimated in livers obtained at the time of biopsy with a Menghini needle. The patients were divided into three groups depending on clinical, biochemical, radiologic, and histologic findings: (i) mild (non-cirrhotic portal fibrosis and extrahepatic portal vein obstruction), (ii) moderate (Budd-Chiari syndrome and amebic liver abscess), (iii) severe (acute hepatitis, chronic active hepatitis, and cirrhosis). Aminopyrine N-demethylase was decreased in all liver disorders as compared to ten control liver samples. Bilirubin UDP-glucuronyl transferase was significantly lower in all liver disorders except for amebic liver abscess and extrahepatic portal vein obstruction. Both the enzymes in (i) and (ii) groups were significantly higher than in group (iii). A significant correlation was obtained between the two enzymes.
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PMID:In vitro drug metabolism in humans with different liver diseases. 664 84

Aminopyrine breath test was investigated in 268 patients with various liver disease. From the specific activity for six hours after ingestion of a tracer dose the elimination rate in percent per hour is calculated. Comparing to 47 controls the elimination rate is reduced about 20% in patients with chronic persistent hepatitis (49 patients) and fatty liver (84 patients). In 42 patients with chronic active hepatitis the elimination rate is reduced to 48% and in 54 patients with cirrhosis to 64%. Between aminopyrine breath test and indocyaningreen test or cholinesterase and albumin no correlations were found. Aminopyrine breath test is a sensitive, non-invasive test and specific in liver function and therefore useful in the follow up of patients with known liver disease.
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PMID:[The diagnostic relevance of the aminopyrine breath test in liver disease]. 718 67