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)

Ethanol is easily absorbed from the intestine and diffuses quickly throughout body water. The bulk of ethanol is metabolized in the liver, where alcohol dehydrogenase, a complex mixture of isoenzymes, oxidizes ethanol to acetaldehyde. Ethanol abuse produces functional and structural changes in the gastrointestinal tract, such as in the stomach, small intestine, liver, and pancreas. Accumulating evidence suggests direct toxicity of ethanol and possibly of acetaldehyde. Fatty liver, alcoholic hepatitis, liver cirrhosis, acute and chronic gastritis, deranged structure and function of the small intestine, acute and chronic pancreatitis, and pancreatic lithiasis are some of the sequelae of ethanol abuse. Recent investigations have enhanced our understanding of the functional and structural changes of the gastrointestinal tract produced by the abuse of ethanol.
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PMID:Ethanol, the liver, and the gastrointestinal tract. 719 92

Sodium and water balance of seven patients with decompensated alcoholic hepatic cirrhosis was studied and compared with biochemical and hemodynamic parameters. The pathogenetic factors of sodium and water retention are different also in a relatively homogeneous group of patients; in particular attention is drawn to one case with associated syndrome of likely inappropriate secretion of ADH (SIADH). However our data point out an elevated frequency of spontaneous natriuresis, weight loss and clinical improvement, with bed rest, alcohol withdrawal and dietary sodium intake only moderately reduced. Spontaneous natriuresis was not observed in two cases of decompensated cirrhosis with complication (pre-existing renal failure and oesophagogastric bleeding) and in one patient who needed anti-aldosteronic drugs. Evidence was observed of improper, especially domiciliary use of diuretic drugs. Moreover we suggest a therapeutic strategy in hospitalized cirrhotic patients with sodium and water retention. It is emphasized that studies about water and sodium balance should be systematically extended to any patient, when hospitalized, independently from any previous domiciliary treatment.
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PMID:[Sodium balance in Laennec's cirrhosis]. 727 54

Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH2, ADH3 and ALDH2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH2*2 and ADH3*1 alleles, which encode high maximum velocity beta 2- and gamma 1-ADH subunits, respectively, as well as a lower frequency of the ALDH2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol-related cirrhosis (n = 27), viral hepatitis-related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH2 alleles by using polymerase chain reaction-directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele-specific oligonucleotide probes. We found that the frequencies of the alleles ADH2*2 (57%), ADH3*1 (78%) and ALDH2*2 (9%) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. 790 79

Inherited variations in alcohol and aldehyde dehydrogenases, the principal enzymes of ethanol metabolism, have been implicated in determining susceptibility to alcoholism and alcohol-related organ damage. An association between an RFLP for the alcohol dehydrogenase-2 (ADH2) gene and alcohol-induced liver damage was demonstrated in a Caucasian population. Genotyping studies revealed an increase in the ADH3(2) allele in patients with alcohol-induced cirrhosis. PCR studies of the ALDH5 gene have demonstrated diverse polymorphism within a short segment of its coding region, with marked inter-racial variation in allele frequencies. In addition, the Caucasian alcohol-induced flushing reaction has been characterised and its relationship with phenotypic polymorphism of ALDH1 examined.
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PMID:Alcohol and acetaldehyde dehydrogenase gene polymorphism and alcoholism. 791 53

The presence of atypical liver alcohol dehydrogenase (ADH) was determined in samples of liver tissue from 222 alcoholic and nonalcoholic subjects to determine its prevalence in the Spanish population, and to evaluate the possible relationship between the presence of this isoenzyme and the development of alcoholism and alcoholic liver disease. Alcoholic patients were classified into the following groups: control subjects, with normal liver pathology (group 1), patients with noncirrhotic liver disease (group 2), and patients with cirrhosis of the liver (group 3). Nonalcoholic subjects were also divided, following the same criteria, into groups 4, 5, and 6, respectively. The prevalence of atypical ADH in the population analyzed was 16.2%. Atypical ADH was present in 14.9% of alcoholics and in 17.4% of nonalcoholics (p = NS). There were no significant differences when the prevalence of atypical ADH of alcoholic and nonalcoholic patients with similar degrees of liver pathology was compared (group 1 vs. 4, group 2 vs. 5, and group 3 vs. 6). The prevalence of atypical ADH was also similar in cirrhotic patients with respect to those of noncirrhotic liver disease and control patients, either in alcoholic or nonalcoholic groups. Our findings indicate that the prevalence of atypical ADH in the Spanish population is similar to that reported for other Caucasian groups. Moreover, the presence of atypical ADH does not play a role in the development of alcoholism nor in the development of alcoholic liver disease in the population analyzed.
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PMID:Atypical liver alcohol dehydrogenase in the Spanish population: its relation with the development of alcoholic liver disease. 821 14

Alcohol causes primary malnutrition by displacing nutrients in the diet and secondary malnutrition via malabsorption and cellular injury through direct cytotoxicity. Hepatotoxicity results from metabolic disturbances associated with the oxidation of ethanol via liver alcohol dehydrogenase (ADH) and the redox changes produced by the generated NADH (the reduced form of nicotinamide adenine dinucleotide), which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P450, which contributes to the alcoholic's tolerance and his increased vulnerability to the toxicity of industrial solvents, anesthetics, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and retinoids. Increased acetaldehyde generation, with formation of protein adducts, results in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. Therapy may eventually improve with the use of supernutrients such as S-adenosyl-L-methionine, which replenishes glutathione, restores methylation, and attenuates liver injury, as well as dilinoleoylphosphatidylcholine, which prevents cirrhosis.
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PMID:Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. 823 56

To determine the zonal distribution of alcohol dehydrogenase in normal and cirrhotic human livers, we measured activities of this enzyme by quantitative cytochemical analysis along the liver cell plate in liver specimens from 10 normal organ donors and from 7 children with extrahepatic biliary atresia cirrhosis. In normal human liver samples, a continuous increase in alcohol dehydrogenase activity was observed along the sinusoid from the periportal to the perivenular hepatocytes (mean extinction units from 16.2 +/- 10.0 to 58.0 +/- 14.8). A similar observation was made in cirrhotic nodules, with activity increasing continuously from nodule periphery to center (7.6 +/- 4.1 to 44.9 +/- 13.3). This study demonstrates a heterogeneous pattern of alcohol dehydrogenase distribution along the sinusoid in normal human liver specimens. In addition, demonstration of this heterogeneity in human cirrhosis suggests that the cirrhotic liver is able to maintain a parenchymal functional organization, with persistence of metabolic zonation.
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PMID:Continuous increase of alcohol dehydrogenase activity along the liver plate in normal and cirrhotic human livers. 842 16

We have studied the factors determining the rate of ethanol and acetaldehyde metabolism in a group of 25 alcoholics with varying degrees of liver lesion (from normal liver to cirrhosis) and in six nonalcoholic cirrhotics. In alcoholics the ethanol metabolic rate was related to hepatic function, estimated either by the aminopyrine breath test (r = 0.70, p < 0.001) or the indocyanine green clearance (r = 0.76, p < 0.01), and was independent of the activity of hepatic alcohol dehydrogenase and hepatic blood flow. In nonalcoholic cirrhotics blood acetaldehyde was always below the detection limit (0.5 microM), but elevated levels were found in 14 out of the 25 alcoholics. Alcoholics with elevated blood acetaldehyde showed a significantly higher ethanol metabolic rate than alcoholics with undetectable acetaldehyde (120 +/- 17 mg/kg/hr vs 104 +/- 11 mg/kg/hr, p < 0.02), but no differences were observed in the activities of alcohol and aldehyde dehydrogenases. Peak blood acetaldehyde levels were directly related to the ethanol metabolic rate (r = 0.48, p < 0.02), but not to activities of hepatic alcohol or aldehyde dehydrogenases. These results indicate that in chronic alcoholics the main determinant of the ethanol metabolic rate is hepatic function, while the rise of blood acetaldehyde is mainly dependent on the ethanol metabolic rate. Alcohol and aldehyde dehydrogenase activities do not seem to be rate-limiting factors in the oxidation of ethanol or acetaldehyde.
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PMID:Determinants of ethanol and acetaldehyde metabolism in chronic alcoholics. 845 8

Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. To investigate whether genetic polymorphism of alcohol-metabolizing enzymes [including alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the ADH2 and ALDH2 genes in 77 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. Digestion with MaeIII and MboII after polymerase chain reaction amplification showed that the ADH2(1) gene frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (chi 2 = 9.274, p < 0.01), whereas no significant association was observed between brain atrophy and the ALDH2 gene Multivariate analysis (including age, total alcohol intake, liver cirrhosis, and ADH2 genotype) showed that the ADH2(1)/ADH2(1) genotype was associated with alcoholic brain atrophy. These findings suggest that the ADH2(1) allele may be associated with alcoholic brain atrophy.
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PMID:Association of restriction fragment-length polymorphisms in the alcohol dehydrogenase 2 gene with alcoholic brain atrophy. 865 84

Excessive ethanol consumption has been related with the development of liver cirrhosis, as well as with rapid intestinal transit time and diarrhea. Moreover, heavy drinking is associated with an increased incidence of cancer of the oropharynx, larynx, esophagus, and colorectum. Acetaldehyde of microbial origin has recently been suggested as a possible pathogenic factor behind this alcohol-associated gastrointestinal morbidity. The present in vitro study was aimed to investigate alcohol dehydrogenase activity and acetaldehyde formation capacity of some major aerobic bacteria representing the normal colonic flora in man. Cytosolic alcohol dehydrogenase activity and cytosolic protein concentration were determined spectrophotometrically. Alcohol dehydrogenase activity was then calculated as nmoles of reduced substrate produced by milligrams of protein per minute. The ability of different bacteria to produce acetaldehyde was determined by incubating the intact bacterial suspension in closed vials containing ethanol (final concentration 22 mM) for 1 hr at 37 degrees C. The acetaldehyde formed during the incubation was analyzed by headspace gas chromatography. Marked differences in the alcohol dehydrogenase activity and acetaldehyde forming capacity were found among the strains tested. The alcohol dehydrogenase activity varied from 606 +/- 91 nmol/min/mg protein (Escherichia coli IH 50546) to 1 +/- 0.2 nmol/min/mg protein (E. coli IH 50817), and acetaldehyde formation varied from 1,717 +/- 2 nmol acetaldehyde/10(9) colony-forming units (Klebsiella oxytoca IH 35403) to 5 +/- 2 nmol acetaldehyde/10(9) colony-forming units (Pseudomonas aeruginosa ATCC 27853). There was a statistically significant correlation (r = 0.77; p < 0.001) between alcohol dehydrogenase activity and acetaldehyde production from ethanol, strongly suggesting the catalytic role of bacterial alcohol dehydrogenase in this reaction.
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PMID:In vitro alcohol dehydrogenase-mediated acetaldehyde production by aerobic bacteria representing the normal colonic flora in man. 889 13


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