Genetic polymorphism of liver alcohol dehydrogenase in Spanish subjects: significance of alcohol consumption and liver disease.

Class I alcohol dehydrogenase (ADH) phenotypes have been studied by starch gel electrophoresis and activity analysis in liver tissue obtained at necropsy from 61 non-alcoholic subjects with normal liver (controls), and in biopsies from 60 chronic alcoholics with liver disease and from 24 subjects with non-alcoholic liver disease. Twenty-three per cent of controls exhibited the ADH2 phenotype, which represents the highest frequency for atypical ADH found in a Caucasian population. Both alcoholic and non-alcoholic patients with liver disease showed a lower frequency of the atypical phenotype (6.6% and 8.8%, respectively). No differences in the ADH2 locus were detected among groups of patients with different severity of alcoholic and non-alcoholic liver disease. The allele frequencies of the ADH3 locus for the controls (ADH3 = 0.63, ADH3 = 0.37) are common to those of other Caucasian populations. Similar ADH3 allele frequencies were observed in patients with alcoholic and non-alcoholic liver disease. Discrepancies between the various phenotyping and genotyping studies now known for several populations suggest that local differences may exist in the distribution of the ADH polymorphism in even geographically close regions, and that the effect of ADH polymorphism on vulnerability towards alcohol may not be identical in different populations.

[The use of pulsed echo-Doppler in verifying the patency of by-passes and reconstructions of the humeral artery]. / Utilización de EcoDoppler pulsado en la comprobación de la permeabilidad de by-passes y reconstrucciones de la arteria humeral.

Personal experiences using Duplex as alternative method to the invasive techniques in 17 patients after the surgical restoration of their injured humeral arteries, are presented. Duplex was used during the control and also during the follow-up of the surgical procedures.

Determinants of ethanol and acetaldehyde metabolism in chronic alcoholics.

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.

Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases.

The hepatic activities and the isoenzyme patterns of both alcohol dehydrogenase and aldehyde dehydrogenase have been studied in 60 alcoholics with varying degrees of liver damage (from normal tissue or minimal changes to cirrhosis with alcoholic hepatitis) and in 24 nonalcoholics with chronic hepatitis or cirrhosis in order to ascertain their association with liver damage. In alcoholics both alcohol dehydrogenase and low-Km aldehyde dehydrogenase activities decreased proportionally with the severity of liver disease. In contrast, in nonalcoholics, there was a reduction of low-Km aldehyde dehydrogenase activity related to the severity of liver injury, but alcohol dehydrogenase was similar in patients with chronic hepatitis and nonalcoholic cirrhosis. There were no significant changes in total and high-Km aldehyde dehydrogenase activities among the different histologic groups studied, although the lowest activities were observed in patients with more severe liver injury. The prevalence of atypical alcohol dehydrogenase was similar in alcoholic (6.6%) and in nonalcoholic (8.3%) liver disease. All patients exhibited isoenzyme aldehyde dehydrogenase II, whereas isoenzyme I was not detected in 39.5% of the alcoholic patients and in 9.5% of those with nonalcoholic liver disease. The lack of aldehyde dehydrogenase I was observed in cases with the lowest enzymatic activities. These results suggest that the decrease of alcohol and aldehyde dehydrogenase activities in alcoholics is not a primary defect and, therefore, their decrease is secondary to liver damage. It is speculated that the diminution of alcohol dehydrogenase, found particularly in alcoholics, could be due to centrilobular cell necrosis.

Hepatic alcohol and aldehyde dehydrogenases in liver disease.

To investigate the influence of liver injury on the activities of hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), these enzymes have been measured in tissue from alcoholic and non alcoholic patients with different severity of liver damage. ADH and ALDH activities decreased proportionatelly with the progression of liver disease in alcoholics. By contrast, in non-alcoholics, there was a reduction of Low-Km ALDH related with the severity of liver injury but ADH was similar in patients with chronic hepatitis and non-alcoholic cirrhosis. Furthermore, ADH was significantly lower in alcoholic than in non-alcoholic cirrhotics. These results suggests that the decreased ADH and ALDH in alcoholics are not primary abnormalities predisposing to alcoholism and alcoholic liver disease. The diminution of ADH found only in alcoholics could be due to the loss of the enzyme produced by centrolobulillar cell necrosis, that is often observed in alcoholic liver disease.