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PubMed2005

Differences in the peripheral levels of beta-endorphin in response to alcohol and stress as a function of alcohol dependence and family history of alcoholism.

BACKGROUND: Evidence indicates that both genetic and environmental factors, such as stress, may play an important role for the development of alcoholism, while beta-endorphin may be implicated in the control of alcohol consumption. The objective of the present studies was to test the hypothesis that there are differences in the response of the pituitary beta-endorphin system to stress as a function of family history of alcoholism and alcohol dependence. METHODS: The response of the pituitary beta-endorphin to a placebo or an alcohol (0.50 g ethanol/kg) drink and to a stress task performed 30 min following ingestion of either the placebo or the alcohol drink was measured in social and heavy drinkers with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism. Thus, each subject participated in 4 experimental sessions given on different days in a randomized order. Four groups of subjects were investigated: 1) low risk nonalcoholics (LRNA); 2) high risk nonalcoholics (HRNA), 3) low risk alcoholics (LRA); and 4) high risk alcoholics (HRA). Plasma beta-endorphin was estimated prior to and for 3.5 hr post-stress. Changes in the concentration of plasma beta-endorphin following ingestion of either the placebo or alcohol drink without performance of the stress task served as controls to compare the stress-induced changes. RESULTS: Basal plasma beta-endorphin levels were higher in LRNA than LRA, HRNA and HRA participants, while basal plasma beta-endorphin levels were higher in LRA than those in HRNA and HRA participants. Furthermore, there was no significant difference in the plasma beta-endorphin levels between HRNA and HRA participants. Stress, induced a significant increase in plasma beta-endorphin concentration in all four groups of participants. However, the stress-induced increase in plasma beta-endorphin levels was more pronounced in LRNA than HRNA, LRA and HRA participants. Thus, alcohol dependence decreased the basal plasma beta-endorphin levels in LR only, as well as the stress induced increase in plasma beta-endorphin levels of participants without, but not of those with, a family history of alcoholism. Alcohol prior to stress attenuated the stress-induced increase in plasma beta-endorphin levels of all four groups of participants. CONCLUSIONS: The present data indicates that there are differences in both, the basal plasma beta-endorphin levels as well as the response of the pituitary beta-endorphin to stress as a function of family history of alcoholism and alcohol dependence. Thus, in HR individuals a dysfunction in the activity of the pituitary beta-endorphin system predates the development of alcoholism, while in LR individuals it develops following alcohol dependence. Furthermore, alcohol dependence did not alter the alcohol-induced attenuation of beta-endorphin response to stress.

Adult↗
PubMed1997

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients.

It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.

Acute Disease↗
PubMed1998

Alcohol-related harm and alcohol consumption in Moscow before, during and after a major anti-alcohol campaign.

AIMS: To examine the rates of alcohol-related harm in relation to levels of alcohol consumption before, during and after a major anti-alcohol campaign in Moscow. DESIGN: Changes in State alcohol sale and alcohol consumption and certain forms of alcohol-related harm were observed as a function of time. FINDINGS: Following the 1985 anti-alcohol campaign, State alcohol sales decreased by 38.0% in 1.5 years in Moscow, and total consumption decreased by 28.6%. At the same time, admissions for alcohol-related mental and behavioural disorders, deaths from liver cirrhosis, alcohol poisoning and other blood alcohol positive violent deaths decreased by 63.3%, 33.0%, 50.8% and 50.9%, respectively. There was a linear correlation between medical variables and alcohol consumption during its decrease in 1985-86. An increase in blood alcohol positive violent deaths began in 1987, before the increases in other variables. Growth of total alcohol consumption began in 1987, and continued during all subsequent years, although it was especially high in 1992-93 at the time of the introduction of market reforms in Russia. Alcohol-related mental and behavioural disorders and liver cirrhosis mortality increased after a time-lag following the rise in alcohol consumption. CONCLUSIONS: The findings provide stark evidence of the potential impact of policy measures applied to general alcohol consumption on alcohol-related harm.

Alcohol Drinking↗
PubMedDate not supplied

Acute alcohol tolerance in social drinkers: changes in subjective effects dependent on the alcohol dose and prior alcohol experience.

Using subjective ratings of the degree of alcohol intoxication, the interaction between the drinking history of the subjects, the alcohol dose, and acute alcohol tolerance were examined in light and moderate alcohol consumers (N = 10). Both groups of subjects were tested with doses of alcohol corresponding to 0.5 and 1.0 g/kg. Dose order was random and tests were carried out with an interval of 1 week. Reports of the subjects' previous experience with these doses of alcohol indicated that the moderate consumers ingested the lower (but not the higher) of the doses quite regularly, whereas light consumers were rather inexperienced with both of the doses. Comparison of blood alcohol concentrations as measured by breath and blood analysis yielded slightly different results, the concentrations being significantly higher as measured by breath analysis. This result was mainly associated with the initial phases, where this difference was greatest. Acute tolerance was assessed by comparing the ratings at equal concentrations of alcohol on the ascending and the descending limbs of the alcohol concentration curve. Due to the lag in the measurements of breath and blood alcohol concentrations, the outcome of the evaluations of acute tolerance was also influenced by whether breath or blood alcohol concentrations were used to obtain similar concentrations in both phases. Results based on the breath alcohol concentrations showed that in light alcohol consumers, acute tolerance was demonstrated for both of the doses. In moderate alcohol consumers only the higher of the doses produced evidence for acute tolerance. However, if comparisons are based on blood alcohol concentrations, moderate alcohol consumers also show an apparent acute tolerance for the lower of the doses tested. The present results clearly demonstrate the complexity of the acute tolerance phenomenon, and emphasize the fact that the results are dependent on the dose of alcohol, the subjects' prior experience with alcohol as well as the procedure used for measuring alcohol concentration.

Adult↗
PubMedDate not supplied

Acute alcohol tolerance in cognitive and psychomotor performance: influence of the alcohol dose and prior alcohol experience.

Using tests for cognitive performance (the Pauli test) and psychomotor coordination (the Pursuit Rotor test), the interaction between the drinking history of the subjects, the alcohol dose, and acute alcohol tolerance were examined in light and moderate alcohol consumers (N = 10). Both groups of subjects were tested with doses of alcohol corresponding to 0.5 and 1.0 g/kg. Dose order was random and tests were carried out at an interval of 1 week. Reports of the subjects' previous experience with alcohol indicated that the moderate consumers ingested alcohol in higher quantities than the light consumers. The light consumers were rather inexperienced with frequent alcohol consumption at the quantities investigated, as were the moderate consumers for the higher of the alcohol doses used. Acute tolerance was assessed by comparing performance at equal concentrations of alcohol on the ascending and the descending limbs of the alcohol concentration curve. In the test for cognitive performance, both doses of alcohol in light alcohol consumers yielded significant differences between the ascending and descending limbs of the alcohol concentration curve, suggesting the existence of acute tolerance. In the moderate alcohol consumers, only a tendency to acute tolerance was observed for the higher of the doses tested. In the test for the psychomotor performance, both of the measures of frequency (of misses) and duration (of time outside the target area) were used. The results showed that in the light consumers, acute tolerance was seen for both of the doses, and to some extent for both of the dependent measures (frequency and duration) investigated. However, in the moderate alcohol consumers, acute tolerance was only observed for the higher of the doses and only for the duration measure. Given the difference in drinking history between the two groups of subjects, the implication would be that when the dose of alcohol exceeds the subjects' prior experience, acute tolerance seems inevitable. The present results clearly demonstrate the complexity of the acute tolerance phenomenon, and emphasize the fact that the results are dependent on the subjects' prior experience with alcohol as well as the dose of alcohol ingested, and consequently suggest the interaction between acute and chronic alcohol tolerance.

Adult↗
PubMed1996

Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat.

Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is now pending in most European countries. The basic mechanisms by which acamprosate elicits its anti-craving action, thereby leading to reduced relapse rates, is not known at the moment. In the present study we describe a rat model of long-term alcohol-drinking which mimics relapse behavior in human alcoholics. The effect of acamprosate was studied in this model. Wistar rats had a free choice between water and alcohol solutions of different concentrations (5, 10, 20% v/v). After two months of continuous alcohol access, rats were deprived of alcohol for three days. Following this deprivation phase, all alcohol solutions were presented again. This procedure was repeated monthly for the following six months. The rats consumed 3.5 +/- 0.3 g/kg alcohol a day. After alcohol deprivation, alcohol intake rose to 5.2 +/- 0.3 g/kg per day resulting in blood alcohol levels of 30 +/- 6 mg/dl. Interestingly, the addition of quinine to the alcohol solutions or the additional presentation of a 5% sucrose solution did not affect the alcohol-deprivation effect after eight months of this intermittent alcohol exposure. However, when acamprosate (50-200 mg/kg i.p.) was administered twice daily, alcohol-drinking following an alcohol-deprivation phase was decreased dose dependently. Given at the highest dose alcohol intake even dropped significantly below baseline drinking. Together, these results show that acamprosate effectively diminishes the alcohol-deprivation effect. Furthermore, the described model seems to be a suitable animal model to screen compounds for their anti-relapse properties and subsequently for their anti-craving action.

Acamprosate↗
PubMed1998

Prenatal alcohol exposure and family history of alcoholism in the etiology of adolescent alcohol problems.

OBJECTIVE: To examine the relative importance of prenatal alcohol exposure and family history of alcoholism for the prediction of adolescent alcohol problems. METHOD: In 1974-75, a population-based, longitudinal prospective study of alcohol and pregnancy began with self-report of alcohol use by pregnant women. In a 14-year follow-up, 439 parents provided information on the family history of alcohol problems for these adolescent offspring. The 14-year-old adolescents provided information on the frequency and quantity of their own alcohol consumption within the past month, on the consequences of their drinking over the past 3 years, and on their age at first intoxication. Additional covariates were assessed prenatally and at follow-up. RESULTS: Prenatal alcohol exposure was more predictive of adolescent alcohol use and its negative consequences than was family history of alcohol problems. Prenatal exposure retained a significant predictive effect even after adjustment for family history and other prenatal and environmental covariates. By contrast, the nominally significant correlation of family history with adolescent drinking is weaker after adjustment for prenatal alcohol exposure and disappears entirely after adjustment for other relevant covariates. We observed no evidence for an interactive effect of fetal exposure and family history in predicting adolescent alcohol use. CONCLUSIONS: Fetal alcohol exposure is a risk factor for adolescent alcohol involvement and alcohol-related problems and may account for variance in prediction of problems otherwise attributed to family history of alcoholism. Studies of alcoholism etiology and family history need to include consideration of even modest levels of fetal alcohol exposure.

Adolescent↗
PubMed2001

Pharmacogenetics of alcohol response and alcoholism: the interplay of genes and environmental factors in thresholds for alcoholism.

Recent advances in neuroscience and genetics have enabled a better understanding of genetically influenced differences in ethanol ("alcohol")-related responses and differential vulnerability to alcohol dependence at the cellular and molecular levels. Heritability studies reveal that the role of genetic factors in alcoholism is largely substance-specific, with the exception of nicotine. One focus of genetic research in alcoholism is the study of functional polymorphisms influencing alcohol metabolism, such as the aldehyde dehydrogenase type 2 Glu487Lys and alcohol dehydrogenase type 2 His47Arg polymorphisms, which affect vulnerability to alcoholism via pharmacokinetic mechanisms, and cross-population studies have begun to reveal important gene-environment interactions. The other focus is on functional genetic variants of proteins involved in the neuronal response to alcohol, including alcohol sensitivity, reward, tolerance, and withdrawal. Studies on the roles of GABA(A) alpha6-amino acid substitutions in rodents in alcohol and benzodiazepine sensitivity, and potential roles in human alcohol and benzodiazepine sensitivity are reviewed. These studies, together with recently developed knowledge on a GABA(A) receptor gene cluster at a quantitative trait loci for alcohol withdrawal on mouse chromosome 11, indicate that research investigation of variation at GABA(A) neurotransmission is a promising area in the pharmacodynamics of alcohol and in differential susceptibility to alcoholism. Genes for proteins involved in alcohol-mediated reward include genes for transporters and receptors for dopamine, serotonin, opioids, and GABA. These genes and their functional variants also represent important targets for understanding alcohol's effects in humans. Identification of genes for alcoholism vulnerability is important in the near future, not only for prevention, but also for development and targeting treatments.

Alcoholism↗
PubMed2006

Relationships among the level of response to alcohol and the number of alcoholic relatives in predicting alcohol-related outcomes.

BACKGROUND: The low level of response (LR) to alcohol is related to a family history (FH) of alcohol use disorders (AUDs), and each predicts alcohol-related outcomes. Few studies have evaluated the interrelationships between the number of alcoholic relatives, LR, and a range of alcohol-related outcomes. This study tests the hypotheses that there will be an inverse relationship between LR and FH and that LR will be a better predictor of the maximum quantity of alcohol consumed. METHODS: Data were extracted from personal interviews with 376 males from 20 years of follow-up in the San Diego Prospective Study. Level of response had been established at about age 20 through alcohol challenges in this population, about half of whom had at least one alcoholic relative. Face-to-face follow-ups with both the subjects and additional informants were carried out 10, 15, and 20 years later. These analyses used correlations and regressions to evaluate the relationship between the 2 major predictors (FH and LR) and 5 alcohol-related outcomes over 20 years of follow-up. RESULTS: As predicted, the alcohol challenge-based LR correlated significantly with the number of alcoholic relatives (up to -0.17 for subjects with clearly high and low LR scores). Each of the 2 predictors correlated with the 5 outcomes, including the maximum quantity of alcohol consumed since original testing, maximum frequency, nondiagnostic alcohol-related problems, the number of 11 DSM-IV (Fourth Diagnostic and Statistical Manual of Mental Disorders) abuse and dependence items, and having developed alcohol abuse or dependence. In hierarchical regression analyses, LR contributed significantly to the prediction of all 5 outcomes, even when considered in the context of FH, with only LR predicting drinking quantity and frequency, but both items adding to the prediction of alcohol-related problems and diagnoses. These results were not affected by the intensity of usual drinking when LR had been measured at age 20. CONCLUSIONS: Both FH and LR contributed to a range of alcohol-related outcomes, with LR alone significantly predicting maximum quantity and frequency in regression analyses.

Adult↗
PubMed1999

Clinical characteristics of alcoholism in alcohol-dependent subjects with and without a history of alcohol treatment.

BACKGROUND: Most clinical alcohol research is carried out on alcoholics who are in treatment, usually inpatients. However, most alcohol-dependent men and women never enter treatment, and even fewer ever receive inpatient care. Thus, some generally accepted data on the clinical course of alcoholism, derived from treatment samples, might not generalize to the entire population of alcohol-dependent individuals. This article characterizes the clinical characteristics of alcohol dependence in three groups of alcoholics, based on their histories of treatment for alcohol problems: those without prior rehabilitation; those with only outpatient approaches or Alcoholics Anonymous (AA); and subjects with an inpatient experience. METHODS: Semistructured interviews were administered to 3572 DSM-III-R-defined alcohol-dependent subjects from the Collaborative Study on the Genetics of Alcoholism. The clinical patterns were compared across the three groups of alcoholics: Group 1, never-treated (n = 1582; 44%); Group 2, histories of outpatient or AA only (n = 399; 11%); and Group 3, at least one inpatient experience (n = 1591; 45%). RESULTS: A progression was shown from Groups 1 to 3 for more general life problems (e.g., unemployment, marital instability); higher rates of additional drug dependencies and psychiatric disorders; and more alcohol-related adverse events. Logistic regression analyses revealed that those with no prior treatment were more likely to be women, Caucasian, and employed, and to report a lower rate of divorce/separation, lower levels of alcohol intake, and fewer alcohol problems. Among those who received help, inpatient care was predicted by an opposite profile. CONCLUSIONS: These results indicate that studies using data from inpatient populations may give a skewed picture of the clinical characteristics of alcohol dependence.

Adult↗
PubMedDate not supplied

Long-term alcohol self-administration with repeated alcohol deprivation phases: an animal model of alcoholism?

In order to study the neurobiological and molecular mechanisms of alcohol dependence and addiction, appropriate animal models are warranted. Although animal models cannot incorporate all aspects and criteria of an addictive behaviour to alcohol seen in human alcoholics, they can at least reflect some of the criteria given in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association (1994). Novel aspects of addictive behaviour to alcohol, craving and relapse might be uncovered by animal models of long-term, free-choice, alcohol self-administration followed by alcohol deprivation phases. After several months of voluntary alcohol consumption, the drug-taking behaviour following a deprivation (withdrawal) phase is characterized by increased alcohol intake and preference (alcohol deprivation effect) and changes in alcohol intake patterns where animals consume large amounts of highly concentrated alcohol solutions even at inappropriate times (e.g. during the inactive light phase when drinking activity is minimal). Altogether, alcohol drinking following alcohol deprivation seems to become uncontrolled and inelastic, reflecting an incentive demand for the drug in such a model. Furthermore, the alcohol deprivation effect outlasts very long abstinence phases, which indicates the persistence of a drug memory for alcohol.

Alcohol Drinking↗
PubMed1998

More vasopressin mRNA in the paraventricular hypothalamic nucleus of alcohol-preferring rats and high alcohol-drinking rats selectively bred for high alcohol preference.

Both the selectively bred alcohol-preferring (P) and high alcohol-drinking (HAD) rats exhibit alcohol preference, and develop tolerance to alcohol more quickly than their counterparts, the alcohol-nonpreferring (NP) and low alcohol-drinking (LAD) rats, respectively. It has been shown that the P rats retain developed tolerance longer than do NP rats, and alcohol drinking increases concurrently with the development of tolerance. Although alcohol preference and tolerance are fundamental elements of alcoholism, the exact mechanisms underlying these two phenotypes in P and HAD rats are not well understood. Recent studies have suggested that arginine vasopressin (AVP) may be involved in modulation of alcohol tolerance. Accordingly, this study was designed to examine whether the AVP mRNA level in the hypothalamus differs in rats that have been selectively bred for alcohol preference and nonpreference. A 35S-AVP antisense oligodeoxynucleotide probe was used for in situ hybridization to localize AVP mRNA in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), two major sites for AVP synthesis in the hypothalamus. Quantitative autoradiography demonstrated that P rats had higher levels of AVP mRNA in the PVN than NP rats. Similarly, higher levels of AVP mRNA were also found in the PVN of HAD rats, compared with LAD rats. The AVP mRNA levels in the SON were similar in the alcohol-preferring and alcohol-nonpreferring rat lines. Basal plasma AVP levels were higher in NP rats than in P rats as determined by radioimmunoassay, whereas plasma AVP levels were not significantly different between HAD and LAD rats. The results suggest that increased AVP gene expression in the PVN may contribute to alcohol preference and the development of alcohol tolerance.

Alcohol Drinking↗
PubMed2006

Alcoholism in the elderly: a study of elderly alcoholics compared with healthy elderly and young alcoholics.

OBJECTIVES: To test the hypothesis that early-onset alcoholism can be differentiated from alcoholism in the elderly by more severe substance related problems, more frequent family history, higher mortality rate, and antisocial behaviour. METHODS: 73 elderly (E) alcoholics (mean age 70.2 yrs) were compared with 90 young (Y) alcoholics (mean age 43.9 yrs) and 70 elderly non alcoholics (mean age 76 yrs). We focused on, family history (FH), co morbidity, mortality, biological markers (AST, GGT, MCV), and demographics. Geriatric Scale of Depression, Standardized Mini-Mental State Examination and Munich Alkoholism Test were also used. All results analysed by the SPSS. RESULTS: FH was significantly (p<0.001) more often positive in Y (52%) than in E (15%) and C (10%). Significantly (p<0.001) more E (57.5%) are married than Y (37.8%) and C (21.4%), significantly (p<0.001) more E (72. 6%) has elementary education compared with Y (44.4%). E alcoholics abstain significantly (p<0.001) more (>27 months) than Y ones (approximately 11 months). Significantly (p<0.001) more Y (43%) had forensic history than E (8.2%). Significantly (p<0.01) more death rate was found in E (19.2%) than in Y (5.6%) and C (1.4%). Significantly (p<0.01) more E (61%) prefer spirits than Y (21%), but significantly more Y (>63%) combine spirits with beer and wine than E (>32%). Significantly (p<0.001) more alcoholics (E and Y) had elated levels of MCV (>70%), AST and GGT (>60%) than C. We have found significantly (p<0.001) higher rate of comorbidity of CNS diseases, GIT, injuries, haematological and infectious diseases in the groups of elderly and young alcoholics than in C subjects. On the other hand, prevalence of cardiovascular, ORL, ophtalmological, endocrine and orthopedic diseases were significantly (p<0.01) higher in C. To compare elderly patients with young ones, we found significantly (p<0.01) higher rate of respiratory, endocrine, cardiovascular and CNS diseases, and dementia in E alcoholics (p<0.001). Depression and abuse of prescribed medication was significantly (p<0.01) more often in the C, but suicide attempts, neurotic spectrum disorders and personality disorders were significantly (p<0.01) often in group of Y. CONCLUSION: Young alcoholics have significantly more often positive FH, drink significantly bigger amounts of alcohol, have more forensic history, and personality disorders in comparison to elderly ones. On the other hand elderly alcoholics tend to have more somatic complication due to alcohol abuse, but drink less alcohol, tend to abstain longer, and have less psychopathic traits. In contrast to literature, the majority of elderly alcoholics are married, have low education and do not belong to high social classes.

Adult↗
PubMed2004

Kudzu root extract suppresses voluntary alcohol intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol.

Alcohol-preferring (P) rats, given free choice to drink water or 15% alcohol, drank 7-10 g of alcohol/kg/day, giving blood alcohol values ranging from 16 to 24 mg/dL. Body weight and food and total fluid intake values in control and alcohol-drinking P rats did not differ significantly, while water intake was inversely related to the amount of alcohol consumed. Alcohol withdrawal after 50 days of alcohol drinking caused withdrawal symptoms such as hypersensitivity, poor landing coordination, and tremors. A daily 0.5, 0.75, and 1.0 g/kg dose of kudzu root (KdR) did not affect body weight and food and water intake values in control (no alcohol) P rats. Subchronic feeding of relatively higher KdR doses (0.75 and 1.0 g/kg) caused a 25-30% reduction in weight gain. The 0.5 g/kg KdR dose caused a 50-60% reduction in alcohol consumption, abolished the development of alcohol withdrawal symptoms, but did not affect blood alcohol levels. The higher KdR doses did not further reduce alcohol consumption. Alcohol suppressed the weight-reducing effects of KdR. The KdR extract used in this study contained 150 mg/g of puerarin, 13 mg/g of daidzin, 4 mg/g of daidzein, 3 mg/g of genistin, 0.2 mg/g of genistein, and 1 mg/g of glycetin. Blood and liver samples contained mostly puerarin and a trace amount of daidzein that may have been formed by the hydrolysis of daidzin by liver enzymes. An important observation was that brain samples obtained from KdR-fed or alcohol + KdR-fed rats did not contain any of the KdR isoflavones. Thus, KdR isoflavones suppressed alcohol drinking and withdrawal symptoms without entering the brain.

Alcohol Drinking↗
PubMed2006

Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women.

BACKGROUND: The relationship of polymorphisms of the genes that encode for alcohol-metabolizing enzymes and individual vulnerability to alcoholism and alcoholic liver disease (ALD) in women is unclear. We determined the genotypes of ADH1B, ADH1C, CYP2E1 (Dra-I and Pst-I) and ALDH2 in a group of Caucasian Spanish women. METHODS: We performed a cross-sectional case-control study. The study group was made of 220 women. Of these, 85 were alcoholic (27 without liver disease and 58 with alcoholic liver disease) and 135 were non-alcoholic (42 healthy controls and 93 with liver disease unrelated to alcohol). Genotyping of alcohol-metabolizing enzymes was performed using PCR-RFLP methods. RESULTS: The distribution of the allelic variants (alleles 1 and 2) in the whole subjects analyzed was: ADH1B 91.6% and 8.4%; ADH1C 58.4% and 41.6%; CYP2E1 Dra-I 15% and 85%; CYP2E1 Pst-I 96.8% and 3.2%; and ALDH2 100% and 0%, respectively. Carriage of genotypes containing the ADH1B*2 mutant allele significantly protected against alcoholism [odds-ratio (OR)=0.00; 95% confidence interval (95% CI): 0.00-0.94; p=0.02] but was associated with an increased risk for alcoholic liver disease among alcohol-dependent women [OR=0.43; 95% CI: 0.18-0.41; p=0.004]. Analysis of the remaining loci showed no significant associations. CONCLUSIONS: In Caucasian Spanish women the ADH1B*2 allele modulates the risk for alcohol dependence and for alcoholic liver disease. Given the small number of alcoholic women analyzed here, these data need further validation in larger cohorts.

Alcohol Dehydrogenase↗
PubMed2005

RSA 2004: combined basic research satellite symposium-mechanisms of alcohol-mediated organ and tissue damage: inflammation and immunity and alcohol and mitochondrial metabolism: at the crossroads of life and death session one: alcohol, cellular and organ damage.

This article summarizes content proceedings of a satellite meeting held at the 2004 Research Society on Alcoholism Annual Scientific Meeting in Vancouver, Canada. The aim of the satellite conference was to facilitate the interaction of scientists investigating the mechanisms of alcohol-mediated organ or tissue damage, and enable the discussion and sharing of new ideas and concepts that may be common in each of the organs or tissues affected by chronic ethanol consumption. The original planned program on immunity was expanded to incorporate a session on a closely related topic "Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death" organized by Dr. Jan Hoek and Dr. Sam Zakhari. The conference was arranged into four sessions: 1) Alcohol, Cellular and Organ Damage 2) Toll-like receptors and Organ Damage 3) Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death and 4) Hepatitis virus and alcohol interactions in Immunity and Liver Disease. The keynote address was given by Dr. Bruce Beutler from the Scripps Institute on "TLRs in Inflammation and Immunity."The Combined Basic Research Satellite Symposium entitled, "Mechanisms of Alcohol-Mediated Organ and Tissue Damage: Inflammation and Immunity and Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death" was convened at the 2004 Research Society on Alcoholism meeting in Vancouver, BC. Session One featured five speakers who discussed various aspects of the role of the immune system in initiating or exacerbating cellular and organ damage following alcohol consumption. The presentations were (1) Innate Immune responses of Alcohol-exposed mice and macrophage-like cells following infections with Listeria monocytogenes by Robert T. Cook 2) Alcohol, cytokines and host defense by Kyle Happel 3) Decreased antigen presentation and anergy induced by alcohol in myeloid dendritic cells by Pranoti Mandrekar 4) Transcriptional regulation of TNF-alpha in human monocytes by chronic ethanol: role of the cellular redox state by Jay Kolls 5) Estrogen and gender differences in inflammatory responses after alcohol and burn injury by Elizabeth Kovacs. This session highlighted the growing information on the role of pattern recognition molecules in alcohol-mediated tissue damage or dysfunction. The new techniques and ideas presented will be helpful in future studies in this area of research, and should result in some exciting avenues of study.

Animals↗
PubMed2004

The co-occurrence of DSM-IV alcohol abuse in DSM-IV alcohol dependence: results of the National Epidemiologic Survey on Alcohol and Related Conditions on heterogeneity that differ by population subgroup.

BACKGROUND: In DSM-IV, an alcohol abuse diagnosis is preempted by dependence, although the symptoms of each disorder are different. Consequently, little is known about the extent to which dependence occurs with or without abuse. The distinction is important because of potential heterogeneity in dependence as a phenotype in genetic research, as well as potential underestimation of alcohol dependence when surveys cover dependence symptoms only among those who screen positive for alcohol abuse. OBJECTIVE: To present the prevalence of DSM-IV alcohol dependence with and without alcohol abuse in national and population subgroups. DESIGN: Face-to-face interviews. SETTING: The United States, including Alaska, Hawaii, and the District of Columbia. PARTICIPANTS: Household and group-quarters residents, 18 years and older, in the National Epidemiologic Survey on Alcohol and Related Conditions (N = 42 392). MAIN OUTCOME MEASURES: DSM-IV alcohol dependence with and without DSM-IV alcohol abuse, assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule. RESULTS: Among respondents with current alcohol dependence, 33.7% did not additionally meet criteria for abuse (29.0% among men and 46.1% among women). Current dependence without abuse was especially common among minority women (48.5% among African Americans, 55.2% among Hispanics). Among respondents with lifetime diagnoses of dependence, 13.9% did not additionally meet criteria for abuse (10.1% among men, 22.1% among women): proportions were highest among minorities, eg, 29.1% among Hispanic women and 19.2% among Hispanic men. CONCLUSIONS: Alcohol abuse does not always accompany alcohol dependence in the general population, especially among women and minorities. Dependence with and without abuse may represent heterogeneous phenotypes for genetic research. Use of alcohol abuse as a screening method for alcohol dependence in large epidemiologic studies will differentially underestimate the prevalence of dependence by subgroup, affecting time trend and comorbidity research. Such underestimation may also perpetuate a lack of services for traditionally underserved groups.

Adolescent↗
PubMed2004

Effects of purified puerarin on voluntary alcohol intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol.

Alcohol preferring (P) rats, given "free choice" of water, exhibited daily intake of 60-75 g of water/kg of body weight. When given "free choice" of water and 15% ethanol, P rats consumed 7-13 g of alcohol/kg. Their water intake decreased proportionally to the alcohol intake, but total fluid intake did not differ significantly. Alcohol withdrawal after 50 days of alcohol drinking caused withdrawal symptoms such as hypersensitivity, poor coordination, and tremors. A daily 50 mg/kg dose of puerarin (PU) caused approximately 50% suppression in alcohol intake, but did not affect body weight and food and total fluid intake in P rats receiving "free choice" of water and 15% ethanol. Alcohol ingestion gradually returned to the control level despite consistent PU intake. However, alcohol intake following alcohol withdrawal was suppressed in PU-fed P rats. PU suppressed the severity of alcohol withdrawal symptoms. Thus, withdrawal symptoms do not occur in PU-fed rats even though their alcohol ingestion is comparable to that in control P rats. Brain, plasma, and liver samples were analyzed for the presence of kudzu root isoflavones, which are mostly PU (>90% of total isoflavones) and a trace amount of daidzin. Liver samples obtained from PU-fed P rats contained 20-30 microg/g of PU. An important observation was that plasma or brain samples obtained from PU-fed or alcohol + PU-fed rats did not contain PU. This study indicated that PU feeding transiently suppressed alcohol intake and abolished withdrawal symptoms at a time when alcohol intake had returned to the control level. The absence of PU in plasma and brain indicates the possibility that some nonspecific mechanism may be involved in the anti-alcoholism effects of PU in P rats.

Alcohol Drinking↗