CDT by Anion-Exchange Chromatography Followed by RIA as a Marker of Heavy Drinking Among Men

Carbohydrate-deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population-based study examined the diagnostic value of CDT among consecutive middle-aged males including 122 social drinkers (mean alcohol consumption 88 ± 79 g per week) and 77 non-alcoholic heavy drinkers (301 ± 195 g/wk). Ninety-six men with a well-documented history of chronic alcoholism (≥1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pl = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean ± SD = 14 ± 5 U/I) were significantly lower than those of heavy drinkers (19 ± 13 U/I, p < 0.01) and alcoholics (34 ± 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption ( r = 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non-alcoholic heavy drinkers.     

Cardiovascular status in asymptomatic alcoholics, with reference to the level of ethanol consumption.

One hundred and forty-five alcoholics without known causes of heart disease, who were serially admitted to the alcohol detoxification centre, were studied to see the incidence of cardiac abnormalities and dose related effects of ethanol. All patients were divided into heavy (consumed more than the equivalent amount of 125 ml of pure ethanol daily for 10 years or more) and moderate drinkers (consumed 75 to 125 ml of ethanol daily). All of them were ambulatory and free from cardiac symptoms. There was no difference among heavy and moderate drinkers in the incidence of abnormalities detected by the electrocardiograms and chest x-ray films. In the alcoholics, the most frequent finding was a prolonged QTc interval of more than 0.44 s on the electrocardiogram (62 patients, 42.8%), unrelated to serum electrolytes imbalance. Cardiomegaly on chest x-ray film was observed in 25 patients (17.2%). M-mode echocardiogram was recorded in randomly selected patients and compared with age and sex matched controls. The interventricular septum and posterior wall were thicker in alcoholics, while left ventricular volume showed no difference. Left ventricular muscle mass was significantly increased only in heavy drinkers. Left ventricular function at rest was not depressed in these patients at an average of 31 days after the last drink of ethanol. Severe heart failure was not found even among the group of heavy drinkers, of whom more than 90% had liver dysfunction. Cardiac hypertrophy seems to occur in heavy drinkers, but is clinically well compensated in the majority of alcoholics.     

High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan

To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80 g of ethanol daily for 5 years or more. Findings for anti-HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.3%) of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/121, 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection.     

Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.     

Carbohydrate-Deficient Transferrin as an Alcohol Marker among Female Heavy Drinkers: A Population-Based Study

Carbohydrate-deficient transferrin (CDT) has previously been reported to be an excellent marker of male alcoholics. Less is known of its efficiency among women and especially of early-phase alcohol abuse in nonselected populations. The present population-based study examined the diagnostic value of CDT among consecutive women, including 13 teetotallers, 135 social drinkers (mean alcohol consumption 45 ± 34 g/week), and 57 nonalcoholic heavy drinkers (197 ± 97 g/week). Sixty-two women with a well-documented history of chronic alcoholism (942 ± 191 g/week) were also studied, as well as 36 pregnant women used as a reference group. Two weeks of abstinence among 11 alcoholics was followed. The CDT (containing part of isotransferrin with pl = 5.7, 5.8, and 5.9) was separated by anion exchange chromatography and assayed by radioimmunoassay. In the whole material, CDT correlated significantly with alcohol consumption (r= 0.43, p < 0.001) but not with conventional markers (γ-glutamyltransferase, AST, ALT, and mean corpuscular volume). The CDT values of alcoholics (34 ± 20 units/liter) were significantly (p < 0.001) higher than those of teetotallers (19 ± 6 units/liter), social drinkers (20 ± 6 units/liter), or pregnant women (16 ± 13 units/ liter). Heavy drinkers also had higher values (25 ± 13 units/liter), but the difference did not reach statistic significance. The specificity of CDT was on the level of conventional markers when the cut-off value was increased from 26 to 29 units/liter. At a specificity of 95%, CDT found 19% of the heavy drinkers and 52% of the alcoholics; the best traditional marker, AST, with a specificity of 97%, found 7% and 56%, respectively. CDT was useful for follow-up of alcohol withdrawal when its initial value was elevated. In general, CDT (as well as conventional laboratory markers) does not seem to be sensitive enough in the detection of alcohol abuse in the female population. This is especially clear among nonalcoholic female heavy drinkers. CDT gives, however, additional information about alcohol abuse, and it may be recommended for parallel use with conventional markers in clinical use.     

Relationship between drinking alcohol and atherosclerotic risk factors in female Japanese workers of different ages

AIM: To determine whether age influences the relationships of drinking alcohol with blood pressure and lipids in women. METHODS: The subjects were 53,911 female Japanese workers (20-69 years old) receiving annual health checkups at each workplace. The subjects were divided into three groups by daily average amount of ethanol consumed (non-drinkers; light drinkers, less than 30g ethanol/day; heavy drinkers, 30g ethanol/day or more). Blood pressure, body mass index (BMI) and total and HDL cholesterol were measured. RESULTS: In the age groups from twenties to fifties, BMI was significantly lower in light drinkers than in non-drinkers. In the forties and fifties age groups, systolic blood pressure in heavy drinkers was higher than that in non-drinkers, while no significant difference was found between non- and heavy drinkers in the twenties and thirties age groups. Diastolic blood pressure was higher in heavy drinkers than in non-drinkers in all age groups. Blood total cholesterol tended to be lower in drinkers than in non-drinkers at ages less than 60 years, while this relation was not observed in the sixties age group. Blood HDL cholesterol and atherogenic index tended to become higher and lower, respectively, with an increase in the amount of alcohol drinking in all age groups. CONCLUSION: In elderly women, the elevating effect of drinking on systolic blood pressure is increased and the lowering effects on BMI and blood total cholesterol are decreased. These results imply that drinking alcohol has less beneficial and more harmful effects on atherosclerotic risk in elderly women.     

Biological markers of alcoholism

The roles of two categories of biological markers — those relating to alcohol consumption and those relating to the risk of developing alcohol related problems - are reviewed. Platelet Mono-amino oxidase levels are low in individuals with a strong inheritance of their drinking problem (Cloninger Type II alcoholics). Elevated gamma-glutamyl transpeptidase (GGT) levels identify regular heavy drinkers with a sensitivity between 40–60%. Mean corpuscular volume (MCV) has a high specificity (95%) and is useful in detecting regular heavy drinkers in the ambulatory care population if other causes of an elevated MCV can be included. Currently there are no laboratory tests with adequate sensitivity to be used as screening tests for alcoholism. (Aust NZ J Med 1992; 22: 209–213.)     

Erythrocyte Mean Cell Volume—Correlation to Drinking Pattern in Heavy Alcoholics

ABSTRACT. Erythrocyte mean cell volume (MCV) correlates well to alcohol intake in moderate alcoholism, but only about 50% of heavy drinkers have increased MCV. To evaluate the influence of the duration and extent of a drinking episode on MCV, 64 addictive alcoholics were investigated prospectively within two weeks after a drinking period. Their daily alcohol intake was 120–480 g and the actual drinking period has lasted for 1–104 weeks. For comparison, 21 non-active alcoholics were investigated. There was no correlation between MCV of active alcoholics and daily alcohol consumption or smoking habits, whereas a significant positive correlation was found between MCV and both duration of actual drinking episode and total alcohol intake in this period. We conclude that MCV is probably of greater value in estimating the duration and extent of actual drinking episodes in heavy alcoholics than in screening for alcoholism.     

High Diastolic Blood Pressure: Common Among Women Who Are Heavy Drinkers

The present study evaluates the relationship of different alcohol consumption levels to blood pressure among women. Blood pressure values were compared between four groups of women consuming different amounts of alcohol. Three groups were formed from the middle-aged female population participating in a health survey ( n = 219): 15 consecutive alcohol abstainers, 136 consecutive moderate drinkers, and 68 consecutive heavy drinkers. Also, 78 consecutive female alcoholics reporting for treatment were included, forming the fourth group. The prevalence of systolic blood pressure ≥160 mm Hg did not increase in relation to alcohol consumption. In contrast, the percentage of women showing diastolic blood pressure ≥90 mm Hg clearly increased ( p = 0.004) from abstainers (7%) to moderate drinkers (18%), to heavy drinkers (32%), and to alcoholics (37%). The highest blood pressure values were found among heavy drinkers. Compared with abstainers, the mean difference in systolic blood pressure was –12 mm Hg, with a 95% confidence interval from –2 to –23 mm Hg. For diastolic blood pressure, the difference was –6 mm Hg with a 95% confidence interval from 1 to –13 mm Hg. Among alcoholics, the blood pressure values had returned essentially to normal after 4 days of abstinence. It is concluded that alcohol consumption increases both systolic and diastolic blood pressure values among women. However, only diastolic blood pressure values increase enough to be clinically significant. Moderately elevated diastolic blood pressure, combined with normal systolic blood pressure, might thus be a possible sign of alcohol abuse among women. Abstinence should be emphasized as an inexpensive and rapidly effective treatment for mild hypertension among female alcohol abusers.     

Indicators of Alcohol Consumption: Comparisons Between a Questionnaire (Mm-MAST), Interviews and Serum γ-Glutamyl Transferase (GGT) in a Health Survey of Middle-aged Males

A questionnaire consisting of nine questions about drinking habits was used in a preventive programme for middle-aged males in Malmo. With a cut-off point of two yes-answers to the questions, 66% of a group of heavy drinkers, 73 % of all registered alcoholics and 90% of not previously identified alcoholics were identified. Serum γ-glutamyltransferase (GGT), used as an indicator of heavy alcohol consumption in the screening, was a poor instrument for the detection of alcoholism in the same population, assigning correctly only 35%. In combination, the two tests identified 82% of all registered alcoholics, and 97% of the alcoholics who were registered in the period following the screening investigation. Thus Mm-MAST is a useful screening test for alcoholism in medical screening examinations and may successfully be used in combination with biochemical tests.     

Polymorphisms of Alcohol Dehydrogenase‐1B and Aldehyde Dehydrogenase‐2 and the Blood and Salivary Ethanol and Acetaldehyde Concentrations of Japanese Alcoholic Men

Background: The effects of genetic polymorphism of aldehyde dehydrogenase‐2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase‐1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers. Methods: We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before. Results: The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes. Conclusions: The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner from nonalcoholics, and clear effects of ADH1B genotype and less clear effects of ALDH2 were observed in the alcoholics. Alterations in alcohol metabolism as a result of alcoholism may modify the gene effects, and these findings provide some clues in regard to associations between the genotypes and the risks of alcoholism and UADT cancer.     

Effect of Alcohol on Blood Dolichol Concentration

Serum dolichol levels were studied in 95 active alcoholics and 16 abstinent alcoholics (at the time of blood sampling) and compared to those of 41 social drinkers. Active alcoholics had a significantly higher mean serum dolichol concentration (182.7 +/- 5.1 ng/ml, p less than 0.001 than either abstinent alcoholics (138.7 +/- 5.4 ng/ml) or social drinkers (142.1 +/- 4.1 ng/ml). During weekend (48 hr) heavy drinking (5.5 g of alcohol per kg b.w.) no significant changes were seen in mean serum dolichol concentrations in 10 healthy, nonalcoholic volunteers. Neither did moderate drinking for 10 days (60 g of alcohol daily)--preceded and followed by a period of abstinence--produce any significant changes in serum dolichol levels in 10 nonalcoholic subjects. During detoxification treatment of 12 alcoholics, mean serum dolichol concentration stayed constant for the first 7 days; on entering treatment it was 227.7 +/- 15.0 ng/ml, on the 3rd day 238.5 +/- 15.9 ng/ml, and on the 7th day of treatment 222.6 +/- 18.6 ng/ml. Our results show that as well as increasing urinary dolichol excretion, chronic alcohol abuse also produces increased serum dolichol concentrations. However, contrary to urinary dolichols, serum dolichol levels do not react significantly to heavy drinking lasting for 48 hr in nonalcoholic volunteers. Furthermore in alcoholics increased serum dolichol concentrations do not decrease as rapidly during abstinence as urinary dolichol concentrations do.     

Activated Lymphocytes (CD25+ CD69+ Cells) and Decreased CD19+ Cells in Well-Nourished Chronic Alcoholics without Ethanol-Related Diseases

To assess lymphocyte subsets and expression of activation antigens in peripheral blood lymphocytes (PBLs) in chronic alcoholism, a cross-sectional study with 30 well-nourished chronic alcoholics and 30 controls was performed. Studies included detailed clinical and laboratory evaluation, nutritional status assessment, and determination of lymphocyte subpopulations, as well as activation antigens. A significant decrease of B cells (CD19⁺) was observed in chronic alcoholics, compared with controls ( p < 0.001). A significant increase of PBLs expressing CD69 and CD25 ( p < 0.01, both) in chronic alcoholics was also detected, whereas CD71 expression was unaffected. In addition, T lymphocytes expressing HLA-DR were significantly higher in chronic alcoholics than controls ( p < 0.05). The serum level of soluble interleukin-2 receptor was also significantly higher in the alcoholic group, compared with controls ( p = 0.04). Moreover, the estimated total lifetime dose of ethanol consumed correlated positively with the percentage of PBLs expressing CD25 ( r = 0.48; p = 0.01) and negatively with PBLs expressing CD71 ( r = -0.39; p = 0.04). By contrast, the changes were not related to age, nutritional status, or the presence of other ethanol-related diseases. In conclusion, chronic alcoholics present a significant decrease of B cells and an "incomplete activation state" of PBLs that depends on the dose of ethanol consumed.     

Relationship Between Alcohol Intake and Immunoglobulin A Immunoreactivity with Acetaldehyde-Modified Bovine Serum Albumin

Acetaldehyde, the main metabolite of ethanol, is a highly reactive species that reacts with macromolecules to produce unstable and stable adducts. Acetaldehyde-modifled proteins are immunogenic and have been detected in the liver and blood of alcoholics. Furthermore, antibodies reactive with acetaldehyde-modified proteins have been detected in the plasma of social drinkers and alcoholics. However, the class distribution of immunoglobulins reactive with modified proteins was different in the two groups, being predominantly immunoglobulin (Ig)M in social drinkers, but IgM and IgA in alcoholics. In this study, we demonstrate that heavy drinkers (alcohol intake > 130 g/week for females and 150 g/week for males) also exhibit IgA reactivity with acetaldehyde-modified proteins. The IgA adduct-spe-cific reactivity (IgA reactivity with acetaldehyde-modified bovine serum albumin-reactivity with native bovine serum albumin) showed a moderate correlation with self-reported alcohol intake, but did not correlate with markers such as plasma transaminase, γ-glutamyl-transferase activity, or mean corpuscular volume. IgA adduct-spe-cific reactivity had similar specificity to the conventional tests of alcohol abuse, but had higher sensitivity than the other tests, especially with heavy drinkers. Data presented herein demonstrate that elevated IgA reactivity with acetaldehyde-modified epitopes is associated with heavy drinking and is a potential marker for high alcohol intake.     

Urinary Markers of Chronic Excessive Ethanol Consumption

A gas chromatographic mass spectrometric procedure is described for the measurement of free ethanol and conjugates of ethanol and acetaldehyde. It was demonstrated that conjugates of ethanol and acetaldehyde were present in urine of alcoholics. Urinary levels of free ethanol and the conjugates in abstaining alcoholics were higher than those of social drinkers. On the average, alcoholics excreted equal amounts of free ethanol and ethanol conjugates while controls eliminated three parts of ethanol conjugates to one part of free ethanol. After 14 days of abstinence, 16/23 (70%) of alcoholics had levels of free ethanol and acetaldehyde conjugates higher than the mean +2 SD of social drinkers for these substances. When the molar ratio of ethanol conjugates/free ethanol was considered, five more subjects who were alcoholics could be classified as being alcoholics. There was one false positive among 46 control subjects.     

β-Carbolines in Chronic Alcoholics Undergoing Elective Tumor Resection

The prevalence of chronic alcoholism in patients with carcinomas of the upper digestive tract exceeds 60%. The patient's history and laboratory markers, preoperatively, are often not sensitive or specific enough to detect alcohol-dependent patients, preoperatively, who are at risk of developing alcohol withdrawal syndrome (AWS) during their postoperative intensive care unit (ICU) stay. Previously, it was found that plasma norharman was elevated in chronic alcoholics, suggesting marker characteristics for chronic ethanol misuse and possibly alcohol dependence. We investigated whether β-carbolines (i.e., harman and norharman) were different between chronic alcoholics and nonalcoholics with carcinoma, and how the levels change in alcohol-dependent patients during their hospital stay. Ninety-seven patients with oral, pharyngeal, laryngeal, or esophageal carcinomas were evaluated regarding their drinking habits. Sixty patients were transferred to the ICU following tumor resection. Chronic alcoholics met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in chronic alcoholics was ≥60 g. Blood samples were collected on admission to the hospital, preoperatively, on admission to the ICU and on days 2, 4, and 7 in the ICU. Harman and norharman were determined by HPLC. Elevated norharman was found in chronic alcoholics on admission to the hospital, whereas harman did not differ between groups. On admission, the area under the receiver operating characteristics curve was significantly larger for carbohydrate-deficient transferrin and preoperatively for norharman. The preoperative norharman levels were significantly correlated with the period of mechanical ventilation and the length of ICU stay. Postoperatively, norharman decreased in all patients, except a group of 11 alcohol-dependent patients who developed AWS during their ICU stay. The finding that elevated norharman levels were found in chronic alcoholics on admission to the hospital and preoperatively supports the view of a specific marker for alcoholism. Preoperative norharman was superior to carbohydrate-deficient transferrin and was associated with a prolonged ICU stay and a prolonged period of mechanical ventilation. Further studies are required to determine whether norhaman aids in the preoperative diagnosis of chronic alcohol misuse with respect to the prevention of postoperative complications.     

Liver Galbeta1,4GlcNAc alpha2,6-sialyltransferase is down-regulated in human alcoholics: possible cause for the appearance of asialoconjugates

Galbetal,4GlcNAc alpha2,6-sialyltransferase (ST6GalI) mediates the glycosylation of proteins and lipids to form functionally important glycoproteins and glycolipids in the Golgi compartment. Our previous work demonstrated that long-term ethanol feeding in rats caused a marked 59% decrease in ST6GalI activity as well as ST6GalI messenger RNA (mRNA) level in the liver that was due to decreased stability of the mRNA. Clinical observations show that down-regulation of ST6GalI gene and consequent impaired activity of ST6GalI seems to be the major cause for the appearance of asialoconjugates in the blood of long-term alcoholics. The plasma carbohydrate-deficient transferrin (CDT) and sialic acid index of plasma apolipoprotein J were also altered in the alcoholic group compared with the nondrinkers. We have now investigated how alcohol affects the gene regulation of ST6GalI and the possible mechanism in postmortem human liver specimens taken from nondrinkers, moderate alcohol drinkers, and heavy alcohol drinkers. Real-time polymerase chain reaction analyses of the liver RNA extract showed that ST6GalI mRNA level was progressively decreased by 49% in moderate drinkers (P < .01) and by 69% in heavy drinkers (P < .01) compared with nondrinkers. Western blot analysis showed that liver ST6GalI protein level was negligibly decreased in moderate drinkers but decreased by 30% (P < .05) in heavy drinkers compared with nondrinkers. We further demonstrated a single ST6GalI mRNA-binding protein complex in the normal human liver extract, which progressively decreased in the liver extracts of moderate and heavy alcohol drinkers. Thus, it is concluded that the appearance of asialoconjugates in alcoholics is possibly due to the down-regulation of ST6GalI gene expression.     

Low Platelet Gamma-Aminobutyrate Aminotransferase and Monoamine Oxidase Activities in Chronic Alcoholic Patients

The activities of gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) were estimated in blood platelets from 25 male chronic alcoholics and from 27 healthy male volunteers without histories of alcohol abuse. Based on clinical criteria, the alcoholics were classified into type 1 or type 2 alcoholism. The activity of GABA-T was found to be lower both in type 1 and type 2 alcoholics than in healthy volunteers. With regard to MAO, the platelet activity was found to be significantly lower only in type 2 alcoholics in concordance with previous reports. No significant correlation was found between the activities of GABA-T and MAO in the blood platelets of healthy volunteers. The inhibitory effect of 400 mM ethanol on the platelet MAO activity increased with decreasing concentrations of the substrate phenylethylamine. The degree of inhibition of ethanol on the platelet MAO activity, however, did not differ significantly between alcoholics and controls.     

Down-regulation of liver Galβ1, 4GlcNAc α2, 6-sialyltransferase gene by ethanol significantly correlates with alcoholic steatosis in humans

Hepatic steatosis and steatohepatitis are frequent results of long-term ethanol exposure. We have previously demonstrated that long-term ethanol down-regulates Galβl, 4GlcNAc α2, 6-sialyltransferase (ST6Gal1), leading to defective glycosylation of a number of proteins including apolipoprotein (apo) E and apo J and the appearance of asialoconjugates in the blood of continuously alcohol-fed animals as well as in human alcoholics. In the current study, we have explored the possibility of whether ethanol-induced down-regulation of ST6Gal1 could contribute toward alcoholic steatosis in human alcoholics presumably because of impaired lipid and lipoprotein transport caused by this down-regulation. Real-time quantitative polymerase chain reaction analyses of liver samples from nondrinkers, moderate drinkers, and heavy drinkers as well as from subjects with and without alcoholic liver disease revealed direct evidence that the down-regulation of ST6Gal1 may be due to ethanol per se. The ST6Gal1 messenger RNA level was reduced by as much as 70% in moderate and heavy drinkers as well as in patients with alcoholic liver disease, but was not changed in subjects with liver disease due to causes other than alcohol exposure. Biochemical and histopathologic analysis demonstrated that the liver total cholesterol was increased by more than 30% (P < .05) and 75% (P < .01), respectively, in moderate and heavy drinkers compared with nondrinkers, with even more dramatic changes in triglyceride levels. Significantly, there was a strong inverse correlation between ST6Gal1 messenger RNA level and liver lipid deposit (F = 8.68, P < .001) by statistical analysis. Thus, it is suggested that alcohol-mediated down-regulation of hepatic ST6Gal1 gene leads to defective glycosylation of lipid-carrying apolipoproteins such as apo E and apo J, resulting in defective intracellular lipid and lipoprotein transport, which in turn may contribute to alcoholic steatosis.     

Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Male Patients with Liver Disease

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcohol abuse. However, its value in patients with associated liver disease is still controversial. The aim of the study was to investigate the usefulness of CDT as a marker of alcohol consumption in patients with liver disease. We measured serum levels of CDT and those of commonly used hematological and biochemical markers, mean corpuscular volume (MCV), transaminases (AST and ALT), and γ-glutamyltransferase in 179 male subjects divided into four groups: 45 active drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls. Serum CDT in active alcoholics was 37.5 ± 3.6 units/liter, being significantly higher than that of abstinent alcoholics (20.3 ± 1.5 units/liter), patients with nonalcoholic liver disease (18.1 ± 1.1 units/liter), and controls (13.1 ± 0.8 units/liter). Contrary to the other markers, no significant differences were observed in CDT values in relation with the presence and severity of liver disease in either the active drinkers or in the abstinent alcoholics. The sensitivity and specificity of CDT as a marker of alcoholism in the series as a whole was 64% and 82%, respectively, similar to the best conventional marker, MCV (64 and 82%). In patients with liver disease, CDT maintained good sensitivity (72%) and specificity (83%). Receiver operating characteristic analysis confirmed that CDT had a similar diagnostic value to that of MCV, but better than γ-glutamyltransferase and transaminases for the detection of alcohol abusers. The good diagnostic efficacy of CDT remained unchanged when analyzing only patients with liver disease. We conclude that serum CDT is a good marker of alcoholism and is less influenced than the currently used biochemical markers for associated liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse regardless of the presence of alcoholic liver disease.