Erythrocyte aldehyde dehydrogenase activity in alcoholic subjects and its value as a marker for hepatic aldehyde dehydrogenase in subjects with and without liver disease

Erythrocyte aldehyde dehydrogenase activity was assayed in actively drinking alcoholics, patients with alcoholic liver disease who claimed to be abstaining, patients with non-alcoholic liver disorders and normal controls. Hepatic cytosolic aldehyde dehydrogenase was also assayed in the majority of the subjects. Actively drinking alcoholics had significantly lower erythrocyte aldehyde dehydrogenase activity than controls (P less than 0.01) but abstaining alcoholic liver disease and non-alcoholic liver disorder subjects did not. There was a significant correlation between erythrocyte and hepatic cytosolic aldehyde dehydrogenase activity in the control group (r = 0.94, P less than 0.05) but not in the other study groups.     

Multiple Changes in Apoprotein B Containing Lipoproteins after Ethanol Withdrawal in Alcoholic Men

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol: triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospho-lipid: cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol: triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.     

Multiple changes in apoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol:triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.     

Psychiatric outcome in alcoholic liver transplant patients

We investigated drinking behaviour and psychiatric outcome ofpatients with alcoholic liver disease after liver transplantation,to help assess the advisability of the procedure in these patients.English-speaking patients (n = 20) transplanted for alcoholicliver disease and informants, and patients transplanted fornon-alcoholic liver disease (n = 54), were assessed by semi-structuredinterviews and standardized questionnaires 1–6 years followingtransplantation. All alcoholics were abstinent for several monthsafter transplantation, but only one patient remained totallyabstinent. Sixteen of the 20 alcoholics later returned to regulardrinking; the mean daily alcohol consumption was 3.5 units.Forty percent of the group were drinking above the recommendedsafe levels for the general population and over 50% were ‘binge’drinking intermittently. The alcoholic liver transplant patientsdid not have higher levels of psychiatric or physical morbiditythan controls. Patients with alcoholic liver disease returnto drinking after a period of abstinence following liver transplantation,although at lower levels than before. Their vulnerability toalcohol abuse is not explained by higher levels of physicalor psychiatric morbidity.     

Effects of ethanol on platelet thromboxane formation after ethanol withdrawal in chronic alcoholics: An in vitro study

The effect of ethanol on the formation of platelet thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2) was studied in vitro in six chronic alcoholics, admitted for detoxification, and in six healthy volunteers. Immediately after cessation of heavy drinking platelet count and ADP-induced TXB2 formation were lower in alcoholics than in nonalcoholic volunteers (P less than 0.05). Ten days after withdrawal of ethanol platelet count increased, and skin bleeding time shortened (P less than 0.05). Ethanol had no effect on arachidonate-induced platelet TXB2 formation, whereas ethanol added to platelet suspension prior to stimulation by ADP resulted in a concentration-related inhibitory tendency in both alcoholics and nonalcoholic control subjects. This effect of ethanol may be of significance for primary hemostasis in alcoholics.     

Free and total carnitine and acylcarnitine content of plasma, urine, liver and muscle of alcoholics

1. Plasma and urine free and total carnitine and acylcarnitine levels were assayed in 12 control subjects and 20 chronic alcoholics with fatty liver. Although the alcoholics had a wider range of values than the controls, there was no significant difference between the two groups. 2. Hepatic free and total carnitine and long- and short-chain acylcarnitines were assayed by a radioenzymatic method in samples from seven control subjects and seven alcoholics. No significant differences in any of the indices were noted between the patient and control groups and it was concluded that carnitine deficiency did not contribute to alcoholic fatty liver in patients without cirrhosis. 3. Skeletal muscle free and total carnitine and long- and short-chain acylcarnitines were assayed in eight alcoholics and seven control subjects. The alcoholics had significantly higher total and free carnitine levels. It is suggested that this reflects a selective enrichment of the biopsy sample with type I carnitine-rich fibres due to the type II fibre atrophy found in approximately half the patients.     

Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers

Recently detoxified men with alcohol dependence (n = 15) and healthy volunteers (n = 14) were administered oral and intravenous imipramine and desipramine. Alcoholics had significantly greater total body clearance of imipramine (0.93 vs. 0.48 L/hr/kg; P less than 0.05) and desipramine (1.00 vs. 0.62 L/hr/kg; P less than 0.05) than did control subjects. Intrinsic clearance of unbound imipramine was greater in the alcoholic group (19.80 vs. 6.56 L/hr/kg; P less than 0.05), as was the intrinsic clearance of unbound desipramine (14.52 vs. 9.05 L/hr/kg; P less than 0.05). The mean elimination half-life for imipramine was significantly decreased in alcoholics (8.7 vs. 19.9 hours after intravenous infusion and 10.9 vs. 19.6 hours after oral administration; P less than 0.05). The mean elimination half-life for desipramine was decreased in alcoholics after intravenous infusion (16.5 vs. 22.4 hours; P less than 0.05). Unbound fractions of drug in plasma were decreased in the alcoholic group for both imipramine and desipramine after both routes of administration. alpha 1-Acid glycoprotein levels were elevated in the alcoholic group whereas total protein and albumin levels did not differ between groups. These findings suggest that recently detoxified alcoholics may require higher doses of imipramine than do nonalcoholic subjects. Desipramine clearance was affected to a lesser degree than imipramine, suggesting that from a pharmacokinetic standpoint it may be the preferred drug for the treatment of alcoholics with depression. Periodic monitoring of plasma levels may be required for recently abstinent alcoholics treated with antidepressants.     

Erythrocyte and leukocyte lipids in alcoholic macrocytosis

Erythrocytes and leukocytes were obtained from patients with alcoholic macrocytosis and their lipid composition compared with those from normal subjects. The patients had normal plasma cholesterol and fasting triglyceride levels with mild and fully compensated liver disease. There was no difference in the lipid composition of leukocytes from alcoholics compared with controls. Erythrocytes from patients with alcoholic macrocytosis had increased cholesterol content. The increased cholesterol content correlated with the MCV but there was no correlation between plasma and erythrocyte cholesterol. There was a decrease in erythrocyte phosphatidylethanolamine in alcoholic macrocytosis. There was no change in the fatty acid composition of the phospholipid fraction but there was an increase in the amount of linoleic acid in phosphatidylethanolamine. The double bond index, non-essential-to-essential fatty acid ratio and double bond index to saturated fatty acid ratio for the erythrocyte phospholipids were unchanged in alcoholic macrocytosis. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of erythrocyte membrane proteins from patients with alcoholic macrocytosis and control subjects showed no significant differences.     

Enhancing the self-esteem of inpatient alcoholics

This study examined the effect of pairing inpatient alcoholics with nursing home residents (NHRs) on the alcoholics' self-esteem. In this PALS program, the alcoholic inpatients assumed a helping-companion relationship with the NHRs for 2 hr per day during their last 2 weeks of treatment. Fifty alcoholic inpatients were randomly assigned to the PALS program (n = 25) or to the library for free reading time (n = 25). The Tennessee Self-Concept Scale (TSCS) was administered to all subjects in both groups before and after the interventions. Of the nine TSCS scales, the improvement on the Moral-Ethical scale was significantly greater in the PALS group. Because the alcoholic inpatients in the PALS group engaged in altruistic (moral) behavior, this study provides a logical link between the intervention and the outcome, which has been a prevalent weakness in previous studies of self-esteem in alcoholics.     

Locus of control among alcoholics, recovering alcoholics, and non-alcoholics

An alcoholic's relapse to drinking is thought to be related to various interpersonal and intrapersonal factors. Drinking-Related Locus of Control (DRIE) scores among alcoholics, recovering alcoholics, and non-alcoholics were compared in this investigation. Each group consisted of 22 males similar in age and other socioeconomic factors. Results indicated significant differences among the three groups. The non-alcoholic group scored more internally than the alcoholic or recovering alcoholic groups; the recovering alcoholic group scored more internally than the alcoholic group. The findings suggest that assessment of the alcoholic's DRIE scores may be useful in planning and monitoring the treatment of this disease.     

Vitamin D deficiency and muscle strength in male alcoholics

1. Chronic alcoholism may be complicated by proximal muscle weakness associated with a selective atrophy of type II skeletal muscle fibres. The histopathological findings are non-specific as identical changes are seen in proximal muscle weakness associated with various metabolic myopathies, including osteomalacia. 2. The maximum voluntary contraction (MVC) of the dominant quadriceps and plasma 25-hydroxycholecalciferol [25-(OH)D] were measured in male alcoholics and control subjects to determine whether vitamin D deficiency contributed to proximal muscle weakness. 3. In both groups MVC declined with age and was related to body build. The distribution of plasma 25-(OH)D was skewed in alcoholics, with the mean significantly lower than in control subjects. Seventeen per cent of patients (but none of the control subjects) had pronounced biochemical deficiency [plasma 25-(OH)D less than 10 nmol/l]. 4. Alcoholics were significantly weaker than control subjects, even after correcting for the effects of age, height and weight. The severity of associated liver disease (cirrhosis vs no cirrhosis) did not influence muscle strength. Variation in plasma 25-(OH)D and albumin made an insignificant contribution to the difference in MVC observed between patients and control subjects. 5. We conclude that proximal muscle strength is reduced in chronic alcoholism but that this is not due to associated vitamin D [25-(OH)D] deficiency or alcoholic cirrhosis.     

急性酒精干预对长期嗜酒者左心功能的超声心动图观察

目的 通过超声心动图观察急性酒精摄入对长期哮酒者左心功能的影响，评价其早期诊断酒精性心肌病的价值。方法 嗜酒组42例，对照组18例，分别测定急性饮酒及及饮酒后1h、2h、3h每搏输出量将结果进行统计学处理。结果 饮酒前嗜酒组与对照组左室收缩功能无明显差异，但哮酒组急性酒精摄入前后EF、SV无变化，CO增大，其中21例EF、SV下降；对照组EF、SV、CO均增大。左室舒张功能E值无变化，A值明显升高，酒后1h、2h、3hE／A下降。结论 虽饮酒前与对照组相比，哮酒组左室收缩功能无明显变化，E／A＞1，但哮酒组急性酒精摄入后左室收缩、功能均有不同程度下降，急性酒精摄入实验可作为酒精性心肌病早期敏感指标之一。     

Serum carnosinase activities in patients with alcoholic chronic skeletal muscle myopathy

1. Serum carnosinase activity was assayed in a group of alcoholic patients with and without histologically proven atrophy of type II skeletal muscle fibres, and in control subjects. No significant activity was detected in muscle biopsy samples or washed erythrocytes. 2. Serum carnosinase activity was significantly lower in chronic alcoholic patients compared with a group of age-matched controls. Alcoholics with abnormal muscle biopsies had significantly lower enzyme activities than either those patients with normal muscle biopsies or the controls. Serum enzyme activities in patients with normal muscle biopsies were not significantly different from controls. 3. Serum carnosinase activity was inversely correlated with the degree of muscle atrophy as measured by the type II fibre atrophy factor. There was a positive correlation between the enzyme activity and skeletal muscle mass as reflected by the creatinine-height index. Furthermore, the enzyme activity significantly increased, with resolution or improvement in the myopathy, in patients who abstained from alcohol. 4. Kinetic studies showed that the reduced carnosinase activity was due mainly to a decrease in the apparent Vmax. The apparent Km was significantly higher in the myopathic compared with non-myopathic alcoholics. Mixing serum from controls and patients with myopathy gave the expected values, indicating the absence of a serum enzyme inhibitory factor. Acute alcohol loading had no effect on the serum carnosinase activity. 5. The decrease in serum carnosinase activity in alcoholics was not related to the severity of their liver disease. Assays of serum carnosinase in chronic alcoholics, can thus be used as a marker of their associated myopathy.     

Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients

In liver biopsy material of eighty-nine patients with suspected liver disease the drug-metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P-450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7-ethoxycoumarin, p-nitroanisol and cytochrome c). From the eight-nine patients sixty-one had various liver diseases not related to ethanol and twenty-eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7-ethoxycoumarin O-deethylase (EOD: 76.9 +/- 31.1 pmol min-1 mg-1 protein, mean +/- SD) than the non-alcoholic liver disease group (42.7 +/- 14.1). The inducing effect of ethanol was most striking on the EOD activity, less for the O-demethylation of p-nitroanisol (PNA) and not present for the NADPH-cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n = 7) had the highest EOD activities (108.9 +/- 25.0), patients with alcoholic hepatitis (n = 10) had significantly less activity (66.0 +/- 1.9) than the former group. However, alcoholics without liver damage (n = 6) had activities not significantly different (46.0 +/- 15.8) from controls (39.4 +/- 9.1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethanol and galactose metabolism as influenced by 4-methylpyrazole in alcoholics with and without nutritional deficiencies. Preliminary report of a new approach to pathogenesis and treatment in alcoholic liver disease.

4-Methyl pyrazole (4-MP, a specific inhibitor of alcohol dehydrogenase) reduced ethanol elimination by 30-50% and completely removed the ethanol-induced inhibition of galactose elimination in 2 control subjects. Ethanol elimination was accelerated in 2 alcoholics with adequate nutrition, but the effect of 4-MP was comparable to that in controls. In 2 other alcoholic subjects, who reported poor nutritional intake, intermediate rates of ethanol elimination were observed and 4-MP had almost no effect on ethanol or galactose elimination. These results suggest that alcohol abuse may result in an increased contribution to ethanol elimination by pathways other than that involving alcohol dehydrogenase (ADH) and that the decreased contribution from ADH, possibly potentiated by inadequate nutrition, may diminish the ethanol-induced shift in the NAD-coupled redox state. Since liver damage produced by alcohol abuse is believed to be related to changes from the normal redox state caused by ethanol, these results may explain why alcoholic liver damage is uncommon in alcoholics living on a marginal diet. Since 4-MP effectively eliminates the ethanol-induced shift in the redox state, a therapeutic trial with 4-MP in alcoholics with a high risk for liver disease is indicated.     

Assessment in vitro and in vivo of muscle degradation in chronic skeletal muscle myopathy of alcoholism

1. Muscle protein breakdown in vivo has been studied by measurements of urinary 3-methyl-histidine/creatinine ratios. No differences were found between control subjects and chronic alcoholics either with or without proximal muscle wasting or cirrhosis. 2. Calculation of muscle turnover rates, with the correction of Afting et al. (1981, Biochemical Journal, 200, 449-452) for non-skeletal muscle contributions of 3-methylhistidine and creatinine, showed lower values for alcoholics compared with controls. 3. Tissue activities of a neutral protease, assayed by a novel, rapid and sensitive fluorimetric method, were similar in patients and controls. The activity did not vary with severity of atrophy or the presence of cirrhosis. 4. No evidence was therefore obtained to suggest that alcoholic myopathy is due to increased muscle breakdown.     

Gastroduodenal morphology and related symptoms in chronic alcoholics

Twenty-four chronic alcoholics admitted to hospital for detoxification after a drinking spree were examined by upper gastrointestinal endoscopy. Biopsy specimens were taken from corpus/fundus, antrum and duodenum for tissue histology (eosin stain). From the duodenum villus index and ultrastructure (scanning electron microscopy, SEM) were also performed. As a control group 12 subjectively healthy non-alcoholics referred to upper gastrointestinal endoscopy mainly for dyspepsia were chosen.Gastrointestinal symptoms were common in alcoholics (88%). Endoscopic and histological gastroduodenitis were not more common in the alcohol group. There was no correlation between gastrointestinal symptoms and endoscopic or histological gastroduodenitis in both groups. In the duodenum, 50% of the alcoholics and 82% in the control group had alterations by scanning electron microscopy. Ten of the 11 alcoholics with an abnormal ultrastructure had diarrhoea. In the control group dyspepsia (ulcus suspect) was correlated to a pathological SEM.     

Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease

OBJECTIVES: To investigate the relationship between serum paraoxonase-1 and liver damage in chronic alcoholic patients. To assess the diagnostic accuracy of paraoxonase-1 plus standard biochemical tests in the assessment of liver damage in alcoholics. DESIGN AND METHODS: We studied 328 chronic alcoholics and 368 healthy individuals. RESULTS: Paraoxonase-1 activity was decreased and the concentration was increased in alcoholics (P<0.001). The enzyme activity was correlated with albumin (r=0.45; P<0.001) and prothrombin time (r=0.49; P<0.001). Addition of paraoxonase-1 activity measurement to a battery of biochemical tests increased the sensitivity in differentiating between patients and controls up to 96.6% but did not improve the sensitivity in differentiating between subgroups of alcoholics. CONCLUSIONS: Paraoxonase-1 was related to the severity of alcoholic liver disease. Its measurement was useful in discriminating between patients and healthy subjects, but did not add any valuable information in subgroups of alcoholics.     

Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy

Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease.During an afterload test of LV function the pressor response to angiotensin evoked a threefold rise of enddiastolic pressure in the alcoholic group which was substantially greater than the 4 mm Hg rise in control subjects. The stroke volume and stroke work response in the noncardiac alcoholic was significantly less than in controls. Diminished LV function was corroborated in the noncardiac alcoholic at rest, using a contractility index.To evaluate the dose-response relationship of ethanol in the production of cardiac malfunction, two groups of noncardiac alcoholic subjects were studied acutely at low and moderate dose levels. After 6 oz, ventricular function, myocardial blood flow, and metabolism were not significantly affected. After 12 oz, there was a progressive rise of end-diastolic pressure and decrease of stroke output at a mean blood alcohol level of 150 mg/100 ml, reverting toward control by 4 hr. The coronary effluent transiently evidenced leakage of cell constituents, despite an increase of coronary blood flow, suggesting a direct but reversible cardiac injury. Myocardial extraction of triglyceride was enhanced, whereas FFA uptake was reduced. A possible role of myocardial triglyceride accumulation in heart muscle was considered in pathogenesis.Chronic ingestion of 16 oz of Scotch daily by an alcoholic subject while on a normal diet produced, after 12 wk, a progressive increase of heart rate and size, circulation time, and venous pressure, and a ventricular diastolic gallop. Normal values were restored within 7 wk after interrupting alcohol.These several studies suggest that the cumulative effects of repeated ingestion of ethanol in intoxicating doses can produce diminished LV function before clinical evidence of cardiac abnormality, or heart disease not necessarily related to malnutrition.     

Hormone and metabolite profiles in alcoholic liver disease

Abstract. Circulating hormone and metabolite profiles have been studied in ten patients with alcoholic cirrhosis, five patients with alcoholic hepatitis and/or fatty liver, and nine normal controls over a 12-h period of meals and activity. Blood glucose was elevated throughout the day in both cirrhotic and non-cirrhotic alcoholics (mean 12-h glucose; controls 5.38 ± 0.16 (SEM) mmol/l; cirrhotics 6.98 ± 0.30 mmol/l, P < 0.001; non-cirrhotics 7.18 ± 0.26 mmol/l, P < 0.001). Non-cirrhotic alcoholics had an exaggerated insulin response to meals, whereas cirrhotic patients had hyperinsulinaemia throughout the day (mean 12-h insulin; controls 16.3 ± 2.3 mU/l; cirrhotics 35.8 ± 6.6 mU/l, P < 0.02). Growth hormone levels were elevated only in patients with cirrhosis (mean 12-h growth hormone, 7.06 ± 1.35 v. 0.85 ± 0.17 μg/l, P < 0.001). Serum Cortisol was persistently elevated in cirrhotics but only in the evening in non-cirrhotic alcoholics. Lactate and pyruvate responses to meals were exaggerated in non-cirrhotic patients whereas in cirrhotics, levels were persistently raised. Blood glycerol was elevated in all alcoholic patients whereas ketone body levels were normal. Hypertriglyceridae-mia was observed only in non-cirrhotic patients. No relationship between the endocrine and metabolic state was observed in either cirrhotic or non-cirrhotic patients.