Psychological stress and cortisol secretion in anhedonic alcoholic men.

We investigated plasma cortisol in a psychological stress paradigm in seven weaned anhedonic alcoholics in comparison with seven age-matched healthy controls. Alcoholics had significantly higher mean plasma cortisol at baseline and no increase following a psychological stress paradigm. Anhedonic alcoholics judged the experimental situation less agreeable than controls. Anhedonic alcoholics may have blunted cortisol response to psychological stress.

Anhedonia and relapse in alcoholism.

The aim of this study was to determine the role of anhedonia among other psychopathological dimensions in the relapse of alcoholics 6 months after withdrawal. Psychometric assessments included: the Social and Physical Anhedonia Scales, the Sensation Seeking Scale, the Pleasure-Displeasure Scale (including Fawcett-Clark's Pleasure Scale), the Depressive Mood Scale, the Thymasthenic Syndrome Rating Scale and the Comprehensive Psychopathological Rating Scale. Forty-four alcoholics participated in the study. The baseline values recorded during the second week of treatment showed that the more anhedonic the alcoholics were, the less they sought sensations. Type 2 alcoholics (Cloninger's classification) scored higher on the Thrill and Adventure Seeking Subscale. Relapsed alcoholics had higher baseline values on the Thrill and Adventure Seeking Subscale. This was in agreement with the step-wise discriminant analysis which showed that this subscale was the main variable that differentiated abstinent alcoholics from those who relapsed. Our results indicate that anhedonia does not predict relapse.

Impact of long-term ethanol consumption on CYP1A2 activity.

Ethanol is a well-known inducer of CYP2E1; whether or not it is an inducer of other cytochromes has not been investigated systematically. The aim of our study was to evaluate the impact of ethanol consumption on the activity of CYP1A2, which has been shown to be influenced by drugs (inhibited or induced). We evaluated CYP1A2 activity by the ratio of the molar urinary concentrations of the three end products of paraxanthine demethylation of caffeine to the molar concentration of a paraxanthine 8-hydroxylation product. This urinary metabolite ratio has previously been shown to correlate with caffeine clearance. The caffeine metabolites were measured in urine collected during the 3 hours after oral administration of 200 mg caffeine. The caffeine test was performed in 12 smokers (> 25 cigarettes/day) and 12 nonsmokers, all of whom were alcoholic inpatients (daily intake > 100 mg absolute ethanol), within the first 3 days of their hospital stay and after 14 days of abstinence from ethanol. In alcoholic patients who were smokers the molar urinary concentration ratio was 3.14 +/- 0.97 before withdrawal and 4.01 +/- 0.92 after 14 days of abstinence from ethanol. In contrast, in alcoholic patients who were nonsmokers it was 2.62 +/- 0.95 and 2.18 +/- 0.96 before and after withdrawal, respectively. In volunteers who were smokers the molar urinary concentration ratio was 5.02 +/- 1.51, whereas in volunteers who were nonsmokers it was 3.22 +/- 1.46. Our results confirm the well-known induction of CYP1A2 activity by tobacco smoking and show that this induction is masked by long-term ethanol consumption.

A comparative study between carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive drinking in a liver unit.

AIM: To compare the efficacy of carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive alcohol intake in patients admitted in a liver unit. METHODS: The 346 patients were divided into three groups of alcoholics: 57 patients (31 men, 26 women) with a normal liver, 77 patients (51 men, 26 women) with non-cirrhotic alcoholic liver disease, and 61 patients (43 men, 18 women) with alcoholic cirrhosis; and three groups of non-alcoholics: 35 abstainers (21 men, 14 women), and 58 healthy blood donors (26 men, 32 women), and 58 patients (32 men, 26 women) who had a non-alcoholic liver disease. Carbohydrate-deficient transferrin and gamma-glutamyltransferase were measured at admission using commercially available kits. RESULTS: Carbohydrate-deficient transferrin was more sensitive than gamma-glutamyltransferase in patients without alcoholic liver disease, in both men (85 vs 54%) and women (64 vs 36%). Carbohydrate-deficient transferrin sensitivity decreased slightly but not significantly according to the severity of the liver disease in men and women. The sensitivity of gamma-glutamyltransferase which was low in men and women without alcoholic liver disease, improved in groups with moderate or severe alcoholic liver disease: not less than 80% in men and up to 100% in women. The specificity of carbohydrate-deficient transferrin in patients with non-alcoholic liver disease was consistently higher than that of gamma-glutamyltransferase (80% vs 60%). CONCLUSIONS: In liver units, carbohydrate-deficient transferrin can help to identify excessive drinkers without liver disease with a higher efficacy than that of gamma-glutamyltransferase; carbohydrate-deficient transferrin can also be used to distinguish between alcoholics with moderate liver disease and patients with non-alcoholic liver diseases.

Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects.

Susceptibility to cancer or ethanol-related liver diseases may be associated with a large variability in cytochrome P450 2E1 activity. This variability may be of genetic origin or reflect environmental factors. To test the role of genetics, the phenotype and genotype of this enzyme were determined in 42 non-alcoholic and 74 alcoholic patients hospitalized for detoxification treatment. Chlorzoxazone metabolism was used to assess CYP2E1 phenotype. Restriction length fragment polymorphisms with Rsa I or Pst I, and Dra I endonucleases were used to determine the two mutant alleles, Pst I/Rsa I-c2 and Dra I-C. A significant gender difference in basal CYP2E1 activity was observed in non-smoking controls (p < 0.05) but not in alcoholics or smokers. Subjects heterozygous for the C or c2 mutated allele did not show any difference in CYP2E1 activity at the basal level, compared with the wild type homozygotes. Conversely, patients with the mutated genotype appeared less inducible than the others after ethanol induction (p < 0.01).

[Sero-epidemiology of hepatitis A: alcoholic patients are a group at risk]. / Séro-épidémiologie de l'hépatite A: les alcooliques sont un groupe à risque.

OBJECTIVES: The possibility of "community-acquired" viral infection has been suggested in alcoholics. In order to assess this hypothesis, we evaluated the prevalence of antibodies against hepatitis A virus, a oro-fecally transmitted virus, in heavy drinkers. PATIENTS AND METHODS: We retrospectively studied 258 heavy drinkers, 188 males and 70 females, divided into sub-groups of increasing age, and compared them to 277 similarly classified blood donors. RESULTS: The prevalence of serum anti-hepatitis A antibodies was significantly higher in alcoholics than in controls (64.7 vs 52.3%, P < 0.01). The difference was particularly marked in patients younger than 45 years old (56.2 vs 39.1%, P < 0.01). In the alcoholics, there was no correlation between the prevalence of anti-hepatitis A antibodies and the socioeconomic level, the quantity of alcohol ingested, or the severity of the underlying liver disease. CONCLUSION: These results suggest that alcoholism is, per se, a risk factor for viral infections.

Alcohol consumption and visual contrast sensitivity.

Visual contrast sensitivity (VCS) was measured in 30 alcoholic patients and 52 controls. The results showed a significant reduction in VCS for all the spatial frequencies. The mean reduction for all spatial frequencies was 2.49 dB below the level of the control group. Optimal sensitivity corresponded to a lower spatial frequency in patients than controls, i.e. 1 cycle/degree (c/d) versus 2 c/d. Curves for VCS were normal for five patients. Abnormalities in VCS were suggestive of optic nerve dysfunction for 15 patients (50%), which were probable in seven cases (23%) and possible in eight others (27%). For 10 subjects, the abnormalities were indicative of ametropia. Daily alcohol intake and daily tobacco consumption were not significantly different in the patients who displayed VCS abnormalities, reflecting alcohol-tobacco amblyopia, from those who did not. The presence of higher gamma-glutamyl transpeptidase and mean corpuscular volume levels in patients who had VCS abnormalities indicative of alcohol-tobacco amblyopia suggests that alcohol consumption is involved in the development of these abnormalities.

Decrease in cytochrome P4502E1 as assessed by the rate of chlorzoxazone hydroxylation in alcoholics during the withdrawal phase.

To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and chlorzoxazone (CHZ) was measured in blood 2 hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. It was found to be 0.34 +/- 0.03 in 30 controls and 1.05 +/- 0.14 in 41 alcoholic patients within 2 days following ethanol withdrawal. This ratio decreased rapidly during withdrawal as attested by the short half-life of CYP2E1, which was found to be 2.5 days. Patients tested for CHZ metabolism after 8 or 21 days alcohol abstinence displayed the same ratio as controls [0.35 +/- 0.03 (n = 28) and 0.31 +/- 0.03 (n = 34), respectively]. No correlation was observed between gamma-glutamyltransferase, carbohydrate-deficient transferrin values, the amount of alcohol consumed/day, and the 6-OH-CHZ/CHZ ratio. There was no influence of smoking on the rate of CHZ hydroxylation, because smokers displayed the same ratio as nonsmokers [0.33 +/- 0.025 (n = 62) and 0.33 +/- 0.02 (n = 30), respectively]. The CHZ hydroxylation ratio seems to be a good reflection of the hepatic and extrahepatic CYP2E1 activity in humans.

Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics.

Chlorzoxazone is mainly metabolized to 6-hydroxychloroxazone (6-OHchlorzoxazone) by the ethanol-inducible cytochrome P450 2E1 (CYP2E1). To evaluate the impact of ethanol consumption on the enzyme induction, the pharmacokinetics of chlorozoxazone and 6-OHchlorzoxazone were studied in alcoholic and control subjects. Fifteen alcoholic male inpatients (all smokers, daily intake 333 +/- 191 g of absolute ethanol) and 20 healthy male volunteers (10 smokers and 10 non-smokers, weekly intake < 100 g of absolute ethanol) participated in this study. Following a 12 hr fasting period, each subject was orally administered 500 mg of chlorzoxazone. Venous blood and urine samples were collected over a 10 hr period. Areas under the curve of plasma concentration versus time (AUC) of chlorzoxazone and 6-OHchlorzoxazone was calculated. The total plasma clearance of chlorzoxazone was measured as the dose/AUC ratio. The mean total plasma clearance was not different between smoker and non-smoker controls but it was enhanced by 73% in alcoholic patients. These results indicate a negligible and non-significant effect of cigarette smoking in controls but an increased metabolism of chlorzoxazone in alcoholic patients (P < 0.05). This increase was corroborated by the 2-fold enhancement of the 6-OHchlorzoxazone/chlorzoxazone AUC ratio, compared to controls. A good correlation was found between this AUC ratio and the 6-OHchlorzoxazone/chlorzoxazone concentration ratio at t = 2 hr in patients and in controls (r = 0.88 and 0.85, respectively, P < 0.01). The concentration ratio increased by 150% in alcoholic patients and decreased by 65% in the seven alcoholics tested after 7 days of alcohol abstinence. It is therefore concluded that the 6-OHchlorzoxazone/chlorzoxazone concentration ratio at t = 2 hr could constitute a simple and non-traumatic marker of CYP2E1 induction.

Red blood cell deformability and alcohol dependence in humans.

Studies of DPH fluorescence polarization and deformability have shown that alcohol induces rigidification of the red blood cell (RBC) membrane. We investigated a possible link between RBC membrane fluidity and deformability by studying both parameters simultaneously in samples from alcohol-dependent patients (group 1, N = 19), social drinkers (group 2, N = 12) and long-term abstaining alcoholics (group 3, N = 8). The active drinkers showed disturbances of several RBC membrane parameters, including abnormal microorganization of the membrane surface, a decrease in sialic acid content, and resistance to the fluidizing effect of ethanol, that were not completely corrected in the abstinent alcoholics. The RBC transit time was significantly longer in the active drinkers than in the abstainers but not the social drinkers. There were no significant differences between the groups with regard to membrane lipid core fluidity. The main abnormality (fluidization) in RBC from the active alcoholics involved the polar surface of the membrane (probed using TMA-DPH), and correlated with the decrease in sialic acid content but not with RBC deformability.

Increased metabolism of acetaminophen in chronically alcoholic patients.

The aim of this work was to determine whether the metabolism of acetaminophen increases in chronic alcoholics, and consequently whether the production of its hepatotoxic metabolite is enhanced. For this purpose, the pharmacokinetics of acetaminophen were compared in 12 alcoholic men and 12 healthy controls. After a 12-hr fast, the patients (on the 3rd hospital day) and volunteers were given 1 g of oral acetaminophen at 8.00 AM. Venous blood samples were drawn before drug intake and at regular intervals after to evaluate plasma acetaminophen concentrations. The elimination half-life of acetaminophen was significantly shorter in the alcoholic patients than in the controls (1.70 +/- 0.55 vs. 2.84 +/- 0.30 hr, p < 0.001). Similarly, total plasma acetaminophen clearance was significantly higher in the patients than in the controls (29.19 +/- 13.37 vs. 24.45 +/- 11.10 l/hr, p < 0.05). These results confirm that the metabolism of acetaminophen increases in chronic alcoholism and consequently suggest that its potential liver toxicity might be enhanced.

[Alcohol dependence. Financial aspect and socio-occupational consequences]. / La dépendance à l'alcool. Aspect financier et conséquences socio-professionnelles.

The financial cost of alcohol dependence was evaluated in 133 alcoholic patients. The main amount of money spent daily on alcoholic beverages was 94 French francs, a figure that was unrelated to the patients' monthly incomes and highest in those living alone and in those drinking exclusively out of home. These results suggest that the economic cost of alcohol dependence plays a key role in the socio-professional degradation of alcoholics.

Effect of abstinence from alcohol on the depression of glutathione peroxidase activity and selenium and vitamin E levels in chronic alcoholic patients.

Glutathione peroxidase activity and selenium and vitamin E levels were measured in the plasma and erythrocytes of 25 chronic alcoholic patients without liver cirrhosis before and after 14 days of abstinence from alcohol, and compared with the levels in 25 sex- and age-matched healthy controls. Before abstinence, all three levels were shown significantly depressed in the alcoholic patients compared with the controls, in both plasma (80, 71, and 89% of control values) and erythrocytes (68, 70, and 83% of control values). After a 14-day abstinence period with no dietary supplementation, a trend towards normalization was noted in erythrocyte (vitamin E and glutathione peroxidase 74 and 91% of control values respectively), in whole blood selenium (82%) and plasma in vitamin E (74%). However, plasma selenium and glutathione peroxidase values were lower than pre-abstinence values (76% and 86% of control values respectively). Our results point to a deficiency in the antioxidant defense system of chronic alcoholics before the occurrence of severe liver disease. This lack of protection against lipoperoxides is all the more important in circumstances like chronic alcohol consumption, in which lipid peroxidation is known to increase. However, the present study also demonstrated that during 14 days of a normal diet free of ethanol, a rapid trend occurred towards the normalization of the factors.

High blood lead level in alcoholics: wine vs. beer.

One hundred and sixty one alcoholics (121 men and 40 women) were studied during a social rehabilitation program. All had a daily intake of ethanol higher than 1 g/kg/day. The mean lead blood level was 28 micrograms/100 ml and was as high as 72.5 micrograms/100 ml in one subject. Wine drinkers had a higher blood lead level (29.8 micrograms/100 ml) than beer or spirit drinkers (23.8 micrograms/100 ml). A significant correlation was found between the blood lead level and systolic and diastolic arterial blood pressure and this relation was independent of sex, weight or age. We conclude that a high blood lead level can be a risk factor for hypertension in alcoholics.

[Increase of blood lead in alcoholism. Relation with blood pressure]. / Elévation de la plombémie au cours de l'alcoolisme. Relation avec la pression artérielle.

Blood lead levels and blood pressure were measured on admission in 161 chronic alcoholic patients (121 men and 40 women) hospitalized for detoxification. The mean lead level was 280 micrograms/l and the highest value, in one patient, was 725 micrograms/l. These figures were as high as those of subjects under occupational exposure to lead. Blood lead level was correlated with blood pressure, and the statistical correlation appeared to be independent. Blood lead level was also correlated with serum gamma-glutamyl-transferase concentration and with the mean corpuscular volume. Wine drinkers had higher blood lead level than beer and/or liquor drinkers (mean: 298 micrograms/l versus 225 micrograms/l respectively), which fits with the higher lead content of wine.

[Subclinical alcoholic optic neuritis without vitamin deficiency]. / Névrites optiques alcooliques infra-cliniques sans carences vitaminiques.

Vitamin B1, Folic acid Vitamin B12, whole blood Lead level, and plasma Zinc level were determined in 82 patients admitted to an alcoholism rehabilitation program. Each patient was examined for an optic neuritis. Thirty-two of the patients had sub-clinical abnormalities suggestive of optic neuritis like dyschromatopsias and/or field visual defects. No differences were found in the blood levels of Vitamin B1, Folic acid, and Vitamin B12 between the 32% affected and the 68% unaffected subjects. Moreover vitamins blood levels were found to be within the limits of normal values in both groups. A negative correlation between whole blood Lead levels and plasma Zinc levels was found. When an optic neuritis occurs the lead level tends to be higher and the Zinc lower. Abnormalities of the more usual alcoholism tests: gamma glutamyl Transpeptidase (gamma GT), mean red cell volume (V.G.M.) and glutamic Oxaloacetic transferase (T.G.O.), were more pronounced in alcoholics with optic neuritis.