D-Cycloserine Facilitates Extinction of Conditioned Alcohol-Seeking Behaviour in Rats
Alcohol and Alcoholism 2008 43(6):626-629

The aim of the present study was to examine the influence of partial NMDA receptor agonist D-cycloserine (DCS) on the extinction of conditioned alcohol-seeking behaviour.

We demonstrate that treatment of rats with 5 mg/kg of DCS was capable in facilitating extinction of conditioned alcohol-seeking behaviour, which subsequently reduced the resumption of extinguished operant responding.

Our study suggests a good rationale for the development of new add-on medications for exposure-based psychotherapy so as to extinguish drug-conditioned appetitive memories in alcohol-dependent patients.

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Request Reprint E-Mail: valentina.vengeliene@zi-mannheim.de

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Assessment of GABA_A Benzodiazepine Receptor (GBzR) Sensitivity in Patients with Alcohol Dependence
Alcohol and Alcoholism 2008 43(6):614-618

The aim of this study was to measure GABA_A benzodiazepine receptor (GBzR) sensitivity in alcohol-dependent patients and compare with matched non-dependent drinkers.

Nine abstinent alcohol-dependent male patients, age matched with nine male non-dependent social drinkers, received an intravenous infusion of midazolam. Objective (saccadic eye movement slowing) and subjective (visual analogue scales) measurements were recorded at 15-min intervals for 2 h.

There were no differences in objective or subjective measures.

Our hypothesis that patients with alcohol dependence would have less slowing of their eye movements in response to this challenge, reflecting reduced GBzR sensitivity, was not confirmed.

The reasons for this could mean that GBzR function returns to normal with abstinence, or that this paradigm is unable to measure the subtle subtype-specific changes in GBzR sensitivity that occur following dependent alcohol use.

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Requst Reprint E-Mail: John.Potokar@bristol.ac.uk

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Neuronal reduction in frontal cortex of primates after prenatal alcohol exposure.
Neuroreport. 20(1):13-17, January 7, 2009.


Children with fetal alcohol spectrum disorders (FASD) show behavioral and intellectual impairments that indicate frontal lobe dysfunction, but the extent of damage to this region has not been clarified by brain imaging studies.

This study uses the St Kitts vervet monkey, a species that voluntarily consumes beverage alcohol, to examine the effects of prenatal ethanol exposure. Pregnant vervets were allowed to drink the equivalent of 3-5 standard drinks four times a week during the third trimester.

Using unbiased stereology, we estimated neuronal reduction and found significantly fewer cells in the frontal lobes of FASD offspring as well as an increased density of interstitial white matter neurons.

These cytoarchitectonic effects are consistent with the behavioral and cognitive changes observed in FASD.

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Request Reprint E-Mail: maurice.ptito@umontreal.ca
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Understanding and Overcoming Barriers to Substance Abuse Treatment Access for People with Mental Retardation
Journal of Social Work in Disability & Rehabilitation Volume: 7 Issue: 2

People with mental retardation have experienced increasing levels of freedom and access to community living over the past 40 years. This has included access to alcohol, illicit drugs and the potential for developing substance abuse and related problems.

The manner in which people with mental retardation have handled this access has been recognized since the de − institutionalization era began. Despite this recognition, documented barriers to accessing substance abuse treatment for people with mental retardation exist and there is an overarching lack of knowledge about accessible treatment approaches for this population.

Policy and practice recommendations are presented for disability and rehabilitation social workers in order to better understand and combat barriers to substance abuse treatment.

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Request Reprint E-Mail: elspeth.slayter@salemstate.edu
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Use of Alcohol among Children and Young People

This research sought to understand any barriers that exist to young people getting involved with alcohol or that exist in relation to stopping drinking and to understand what influenced a non-drinking attitude. The project looked to inform the design of interventions (messaging and channel strategy and / or other activity) to young people and parents. The role of current advertising and communication campaigns in the choices of children and young people was assessed.

The research involved parents & young people and included 40 observation sessions, 10 creative conference workshops (239 respondents participating) and interactive galleries involving 79 respondents. In addition, there were two stakeholder group discussions and 10 in-depth interviews involving of a range of stakeholders and experts including teachers, school nurses, healthcare professionals, police officers, youth workers, Portman Group, Alcohol Concern and 4 Children

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Alcoholism in Russia amoung Highest in the World.

In Russia, rates of alcohol consumption and homicide are among the highest in the world, and already-high levels increased dramatically after the breakup of the Soviet Union. Rates of both, however, vary greatly among Russia's 89 regions.

We took advantage of newly available vital statistics and socioeconomic data to examine the regional covariation of drinking and lethal violence. Log-log models were employed to estimate the impact of alcohol consumption on regional homicide rates, controlling for structural factors thought to influence the spatial distribution of homicide rates. Results revealed a positive and significant relationship between alcohol consumption and homicide, with a 1% increase in regional consumption of alcohol associated with an approximately 0.25% increase in homicide rates.
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Press Release - 'Know your limits' at Clothes Show Live

5 December 2008

More than 150,000 young women are expected to visit the new alcohol 'Know Your Limits' stand when it opens at the Clothes Show Live exhibition in Birmingham today.

The government’s £4 million multi-media campaign aims to challenge prevailing attitudes and change behaviour among young adults who binge drink, asking them: ‘you wouldn’t start a night like this, so why end it that way?’ The new interactive stand has exhibits which are designed to encourage young people, in particular young women aged between 18 and 24, to drink responsibly. This is a key audience for the Know Your Limits (new window) campaign: a quarter of women aged between 16 and 24 admit to binge drinking at least once in the previous week.

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75 Years After the Repeal of Prohibition, We’re Still Captives of the ‘Dry’ Crusaders

By Maureen Ogle

Posted December 4, 2008

Prohibition ended on Dec. 5, 1933, not with a bang but with the thud of thousands of pages of new city, state, and federal laws that dictated when, where, and how Americans could make, buy, sell, and drink alcohol. Ratification of the 21st Amendment, repealing Prohibition, was neither a green light to drink nor a victory over the "dry" crusade that had produced Prohibition. Seventy-five years later, we're still captives of that crusade.

. . . . .

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Alcohol consumption and n–3 polyunsaturated fatty acids in healthy men and women from 3 European populations
Am J Clin Nutr (December 3, 2008)


Because high dietary and blood n–3 (omega-3) fatty acids (FAs) are protective against coronary heart disease and sudden cardiac death, the alcohol-associated increase in blood n–3 FAs could be considered an original mechanism of alcohol's cardioprotective effect.

Our objective was to assess whether alcohol consumption is associated with concentrations of very-long-chain "marine" (eg, fish oil) n–3 FAs both in plasma and in red blood cell membranes.

In the framework of the IMMIDIET (Dietary Habit Profile in European Communities with Different Risk of Myocardial Infarction: the Impact of Migration as a Model of Gene-Environment Interaction) Project, 1604 subjects (802 women-men pairs), aged 26–65 y, were enrolled in Italy, Belgium, and England. A 1-y-recall food-frequency questionnaire was used to evaluate dietary intake.

In fully adjusted multivariate analyses, alcohol intake was positively associated with plasma eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and EPA + DHA concentrations (P <>P = 0.036, and P = 0.002, respectively) in women and with EPA and the EPA + DHA index in red blood cells (P < 0.0001 and P = 0.037, respectively). In men, only plasma and red blood cell EPA concentrations were associated with alcohol intake (P = 0.003 and P = 0.004, respectively). Stratified analyses showed an association between alcohol and both plasma and red cell EPA (P = 0.008 and P = 0.002, respectively), DHA (P = 0.014 and P = 0.008, respectively), and the EPA + DHA index (P = 0.010 and P = 0.006, respectively) in wine drinkers, whereas no association was found in those who drink beer and spirits.

Alcohol intake was associated with higher plasma and red blood cell concentrations of marine n–3 FAs. Components of wine other than alcohol (polyphenols) might exert these effects. Part of the alcohol-induced cardioprotection may be mediated through increased marine n–3 FAs.

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Request Reprint E-Mail: licia.iacoviello@rm.unicatt.it
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Substance dependence and psychiatric disorders are related to outcomes in a mixed ICU population
Intensive Care Medicine Volume 34, Number 12 / December, 2008


Substance dependence disorders are common in hospitalized patients and are associated with poor recovery.

We compared mortality and discharge disposition in critically ill patients with and without substance dependence and patients with and without psychiatric disorders. We also compared the prevalence of substance dependence and psychiatric disorders to population data.

There were 742 critically ill patients of whom 54% were male, acute respiratory distress syndrome developed in 5.5% and hospital mortality was 21%. The mean acute physiology and chronic health evaluation II scores were 16.5 ± 7.9, sequential organ failure assessment scores were 6.7 ± 4.2, duration of mechanical ventilation was 5 ± 6.2 days, ICU length of stay (LOS) was 7.3 ± 10.1 days, hospital LOS was 12.3 ± 12.9 days.

Multivariable regression analyses found psychiatric disorders predicted higher hospital mortality (Odds ratio = 1.50), but was not statistically significant (p = 0.08); substance dependence predicted shorter hospital LOS (R ² = 0.08, p = 0.01) after controlling for covariates.

There was a higher prevalence of substance dependence compared to Utah.

Our data suggest that substance dependence increases hospital LOS and that patients with drug or alcohol dependence are at higher risk for ICU admission compared to the general population.

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Spousal and Alcohol-Related Predictors of Smoking Cessation: A Longitudinal Study in a Community Sample of Married Couples
AJPH First Look, published online ahead of print Dec 4, 2008

We investigated the longitudinal influence of spousal and individual heavy drinking and heavy smoking on smoking cessation among married couples.

Couples’ (N=634) past-year smoking, alcohol problems, and heavy drinking were assessed.

We used an event history analysis and found that spousal and one’s own heavy smoking and one’s own heavy drinking decreased the likelihood of smoking cessation.

Heavy drinking and spousal behavior should be considered when developing public health interventions and policies for smoking cessation.

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Request Reprint E-Mail: kdollar@buffalo.edu
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Improving 24-Month Abstinence and Employment Outcomes for Substance-Dependent Women Receiving Temporary Assistance for Needy Families With Intensive Case Management
AJPH First Look, published online ahead of print Dec 4, 2008

We examined abstinence rates among substance-dependent women receiving Temporary Assistance for Needy Families (TANF) in intensive case management (ICM) over 24 months and whether ICM yielded significantly better employment outcomes compared with a screen-and-refer program (i.e., usual care).

Abstinence rates were higher for the ICM group than for the usual care group through 24 months of follow-up (odds ratio [OR]=2.11; 95% confidence interval [CI]=1.36, 3.29). A statistically significant interaction between time and group on number of days employed indicated that the rate of improvement over time in employment was greater for the ICM group than for the usual care group (incidence rate ratio=1.03; 95% CI=1.02, 1.04). Additionally, there were greater odds of being employed full time for those in the ICM group (OR=1.68; 95% CI=1.12, 2.51).

ICM is a promising intervention for managing substance dependence among women receiving TANF and for improving employment rates among this vulnerable population.

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Request Reprint E-Mail: jm977@columbia.edu

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Association Between Residential Exposure to Outdoor Alcohol Advertising and Problem Drinking Among African American Women in New York City
AJPH First Look, published online ahead of print Dec 4, 2008

We evaluated the association between residential exposure to outdoor alcohol advertising and current problem drinking among 139 African American women aged 21 to 49 years in Central Harlem, New York City.

We found that exposure to advertisements was positively related to problem drinking (13% greater odds), even after we controlled for a family history of alcohol problems and socioeconomic status.

The results suggest that the density of alcohol advertisements in predominantly African American neighborhoods may add to problem drinking behavior of their residents.

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Request Reprint E-Mail: nak2106@columbia.edu
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Alcohol Environments and Disparities in Exposure Associated with Adolescent Drinking in California
AJPH First Look, published online ahead of print Dec 4, 2008


We investigated sociodemographic disparities in alcohol environments and their relationship with adolescent drinking.

We geocoded and mapped alcohol license data with ArcMap to construct circular buffers centered at 14595 households with children that participated in the California Health Interview Survey. We calculated commercial sources of alcohol in each buffer. Multivariate logistic regression differentiated the effects of alcohol sales on adolescents’ drinking from their individual, family, and neighborhood characteristics.

Alcohol availability, measured by mean and median number of licenses, was significantly higher around residences of minority and lower-income families. Binge drinking and driving after drinking among adolescents aged 12 to 17 years were significantly associated with the presence of alcohol retailers within 0.5 miles of home. Simulation of changes in the alcohol environment showed that if alcohol sales were reduced from the mean number of alcohol outlets around the lowest-income quartile of households to that of the highest quartile, prevalence of binge drinking would fall from 6.4% to 5.6% and driving after drinking from 7.9% to 5.9%.

Alcohol outlets are concentrated in disadvantaged neighborhoods and can contribute to adolescent drinking.

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Request Reprint E-Mail: tdkhoa9@yahoo.com

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New alcohol measures tackle irresponsible drinks deals - but not 'loss-leading'

Government officials today announced new measures to tackle irresponsible retailing practice such as 'happy hours' and 'buy one get one free' promotions. The measures will be delivered through a new code of practice that retailers will be legally obliged to comply with following findings that the existing voluntary code was widely flouted. Although the new mandatory code is yet to be produced, a Home Office/DoH press release announced key measures were to include:

• banning offers like 'all you can drink for £10'
• ensuring that customers in supermarkets are not required to buy very large amounts of a product to take advantage of price discounts
• ensuring staff selling alcohol are properly trained
• requiring that consumers are able to see unit content of all alcohol when they buy it
• requiring bars and pubs to have the minimum sized glasses available for customers who want them

. . . . . .

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Cheap alcohol ban will hit wine drinkers most

Alan Travis and John Carvel
The Guardian, Thursday December 4 2008

Plans will have little effect on lager, research shows

Raising cost of alcohol will reduce crime and NHS bill

Wine drinkers will be hit hardest by government proposals to ban cut-price alcohol promotions in supermarkets and off-licences, according to government-commissioned research published yesterday.

The Sheffield University study says that bans on discounts of over 30%, such as "three for the price of two" offers, will affect wine consumption most but will have little effect on cheaper alcohol, such as lager and beers, that sell for less than 30p a unit.

The research, commissioned by the Department for Health, looked at 40 separate policy options, including setting minimum prices per unit of alcohol. It showed that reducing the quantity of cut-price alcohol on sale can reduce consumption and have significant effects on reducing alcohol-related crime and ill-health.

Over 50% of alcohol sold in supermarkets is sold at a discount, albeit a small one in most cases.

The Sheffield research also shows that targeting price increases at cheaper types of alcohol, particularly in bars and pubs where at-risk groups such as younger people do most of their drinking, would have an impact without unduly penalising moderate drinkers.
. . . . .

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Sheffield report analyses effects of alcohol pricing and promotion policies

03 December 2008

A University of Sheffield report, commissioned by the Department of Health to help Government Ministers decide future alcohol policy, shows that policies which lead to price increases reduce alcohol consumption and can have significant effects on reducing alcohol-related harm.

The findings, which were published today (Wednesday 3 December 2008) by the Department of Health, are the results of the second phase of an independent review. As part of the review the Sheffield researchers examined the potential effects of different pricing policies on patterns of alcohol consumption and the resulting impact on the nation´s health, crime, absenteeism in the workplace and unemployment.

To compile the report the Sheffield team analysed over 40 separate policy scenarios, including setting minimum prices per unit of alcohol at different levels and bans on price-based promotions in off licences and supermarkets. The research examines how policies affect alcohol purchasing and consumption by different population groups, including moderate, hazardous, harmful and underage drinkers both in the on-trade (such as pubs, clubs and restaurants) and the off-trade (supermarkets, off licenses) sectors.
. . . . .

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Independent Review of the Effects of Alcohol Pricing and Promotion

In December 2008, the Department of Health published an independent review, by the School of Health and Related Research at the University of Sheffield (ScHARR) to better understand the link between alcohol related harm and how alcohol is promoted and priced. Government is evaluating the findings.

• Download Independent Review Of The Effects Of Alcohol Pricing And Promotion: Part B (PDF, 1199K)

• Download Independent Review Of The Effects Of Alcohol Pricing And Promotion Part A: Systematic Reviews (PDF, 1959K)

• Download The Independent Review Of The Effects Of Alcohol Pricing And Promotion Summary of Evidence to Accompany Report on Phase 1: Systematic Reviews (PDF, 176K)

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Press Release - Time’s up for irresponsible drink deals

3 December 2008

A ban on 'all you can drink' promotions in pubs and bars is among a range of new measures announced today by Home Secretary Jacqui Smith and Health Secretary Alan Johnson.

The measures are supported by a new £4.5 million crackdown on alcohol-fuelled crime and disorder.

Following an independent review, which found that many retailers are not abiding by their own voluntary standards for responsible selling and marketing of alcohol, the government now intends to introduce a new mandatory code of practice to target the most irresponsible retail practices.

This will set out compulsory licensing conditions for all alcohol retailers and will give licensing authorities new powers to clampdown on specific problems in their areas. Licensing authorities will also be able to impose these new powers on several premises at once.

. . . . .

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A Recent Perspective on Alcohol, Immunity, and Host Defense
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system.

This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed.

Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects.

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Request Reprint E-Mail: gyongyi.szabo@umassmed.edu

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Role of Potassium Channel Gene Kcnj10 in Ethanol Preference in C57bl/6J and DBA/2J Mice
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

Inwardly-rectifying potassium channel protein Kir4.1 is encoded by Kcnj10 which maps to a quantitative trait locus on chromosome 1 for the voluntary alcohol consumption phenotype in mice. Kcnj10 brain expression differences have been established between ethanol-preferring C57Bl/6J and ethanol-avoiding BALB/cJ mice, but its differential expression in other tissues and strains have largely been overlooked. A nonsynonymous single nucleotide polymorphism exists between C57Bl/6J and ethanol-avoiding DBA/2J mice which changes amino acid 262 from threonine (C57Bl/6J) to serine (DBA/2J). This Kcnj10 SNP and its expression may serve as valuable markers in predicting the ethanol preference phenotype in mice.

Evolutionary analysis supports gene duplication and genetic recombination as likely sources of diversity within the Kir gene family. Semiquantitative RT-PCR analysis revealed significantly higher Kcnj10 expression in the brain, spleen, and kidney of both strains when compared to other tissues from the same strain. There were no significant differences in tissue-specific mRNA levels between strains except in the testes. Genotype distributions of the Kcnj10 Thr262Ser SNP were different between low- and high-drinkers. A significant difference in the average ethanol preference level of each genotype was also observed.

Our results suggest a role for Kcnj10 in ethanol preference determination in mice. However, further experiments are needed to establish if this association is due to the nonsynonymous SNP or other additional factors associated with Kcnj10.

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Request Reprint E-Mail: ssingh@uwo.ca

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Low Bone Mineral Density and Impaired Bone Metabolism in Young Alcoholic Patients Without Liver Cirrhosis: A Cross-Sectional Study
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol's direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors.

In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z-score ≤ −2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D <>

Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism.

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Request Reprint E-Mail: peter.malik@i-med.ac.at

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Central and Peripheral Timing Variability in Children With Heavy Prenatal Alcohol Exposure
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system.

Mean inter-response interval for the 4 groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 millisecond interval and all other groups for the 900 millisecond interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced.

Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central and peripheral timing variability between the older alcohol-exposed children and controls.

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Request Reprint E-Mail: rsimmons@mail.sdsu.edu

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OPRM1 Asn40Asp Predicts Response to Naltrexone Treatment: A Haplotype-Based Approach
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

Individualized pharmacotherapy requires identification of genetic variants predictive of treatment response. In OPRM1, Asn40Asp has been reported to be predictive of response to naltrexone treatment. Nevertheless, the in vitro function of the polymorphism remains elusive and over 300 OPRM1 sequence variants have been identified to date. Therefore we used a haplotype-based approach to capture information of other genetic variants that might predict treatment response to naltrexone in the COMBINE Study.

A significant haplotype by medication interaction (p = 0.03) was found in OPRM1 block 1. Naltrexone-treated alcoholics with haplotype AGCCC, the single haplotype carrying the Asp40 allele had the highest percent of good clinical outcome. When interaction of genotypes at each of the 5 loci comprising block 1 with medication was examined, only the Asn40/Asp40 and Asp40/Asp40 genotypes were found to significantly interact with naltrexone treatment. No haplotype by medication interaction was documented in OPRM1 block 2.

Our haplotype-based approach confirms that the single OPRM1 locus predictive of response to naltrexone treatment is Asn40Asp in exon 1. A substantial contribution of any other OPRM1 genetic variant to interindividual variations in response to naltrexone treatment (at least in terms of good clinical outcome) is not supported by our findings.

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Request Reprint E-Mail: antonr@musc.edu

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Ethanol Exposure Impairs LPS-Induced Pulmonary LIX Expression: Alveolar Epithelial Cell Dysfunction as a Consequence of Acute Intoxication
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

Alcohol intoxication impairs innate immune responses to bacterial pneumonia, including neutrophil influx. Lipopolysaccharide (LPS)-induced chemokine (LIX or CXCL5) is a recently described chemokine produced by type-II alveolar epithelial (AE2) cells which facilitates neutrophil recruitment. The effect of acute alcohol intoxication on AE2 cell expression of LIX is unknown.

LIX protein is readily detectable in the lung but not in plasma following LPS administration, demonstrating "compartmentalization" of this chemokine during pulmonary challenge. In contrast to the CXC chemokines keratinocyte-derived chemokine and macrophage inflammatory protein-2, which are abundantly expressed in both lung tissue and alveolar macrophages, LIX expression is largely confined to the lung parenchyma. Compared to controls, intoxicated animals show a decrease in LIX and neutrophil number in bronchoalveolar lavage fluid following LPS challenge. Ethanol inhibits LIX at the transcriptional level. In vitro studies show that LPS and TNF-α are synergistic in inducing LIX by either primary AE2 or MLE-12 cells.

Acute ethanol exposure potently and dose-dependently inhibits LIX expression by AE2 cells. Activation of nuclear factor-κB is critical to LIX expression in MLE-12 cells, and acute ethanol treatment interferes with early activation of this pathway as evidenced by impairing phosphorylation of p65 (RelA). Inhibition of p38 mitogen-activated protein kinase signaling, but not ERK1/2 activity, in MLE-12 cells by acute alcohol is likely an important cause of decreased LIX expression during challenge.

These data demonstrate direct suppression of AE2 cell innate immune function by ethanol and add to our understanding of the mechanisms by which acute intoxication impairs the lung's response to microbial challenge.

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Request Reprint E-Mail: khappe@lsuhsc.edu

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Effect of Extended-Release Naltrexone (XR-NTX) on Quality of Life in Alcohol-Dependent Patients
Alcoholism: Clinical and Experimental Research Published Online: 2 Dec 2008

Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation for the treatment of alcohol dependence previously shown to reduce drinking and heavy drinking relative to placebo (Garbutt et al., 2005). A 24-week, randomized, double-blind, placebo-controlled study established the efficacy and safety of XR-NTX in this patient population. In this report, the effect of XR-NTX on quality of life (QOL) was examined.

Alcohol-dependent patients were randomly assigned to receive XR-NTX 380 mg (N = 205), XR-NTX 190 mg (N = 210), or placebo (N = 209), combined with a standardized psychosocial intervention. QOL was assessed using the Medical Outcomes Study 36-item short-form health survey, administered at baseline and at 4-week intervals during 24 weeks of treatment

Compared with U.S. population norms, patients showed initial impairment in the health-related QOL domains of mental health, social functioning, and problems with work or other daily activities due to emotional problems. Adherence to all 6 injections was 65% for XR-NTX 190 mg, 63% for XR-NTX 380 mg, and 64% for placebo. Generalized estimating equations analyses using an intention-to-treat sample revealed that XR-NTX 380 mg was associated with significantly greater improvements from baseline in mental health (p = 0.0496), social functioning (p = 0.010), general health (p = 0.048), and physical functioning (p = 0.028), compared with placebo. Linear regression analyses revealed that reductions from baseline in drinking (percentage of drinking days and percentage of heavy drinking days in the last 30 days) were significantly (p <>

Extended-release naltrexone 380 mg in combination with psychosocial intervention was associated with improvements in QOL, specifically in the domains of mental health, social functioning, general health, and physical functioning.

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Request Reprint E-Mail: Pettinati_H@mail.trc.upenn.edu

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Ethanol inhibits neuronal differentiation by disrupting activity-dependent neuroprotective protein signaling
PNAS Published online before print December 1, 2008

The mechanisms by which ethanol damages the developing and adult central nervous system (CNS) remain unclear.

Activity-dependent neuroprotective protein (ADNP) is a glial protein that protects the CNS against a wide array of insults and is critical for CNS development. NAPVSIPQ (NAP), a potent active fragment of ADNP, potentiated axon outgrowth in cerebellar granule neurons by activating the sequential tyrosine phosphorylation of Fyn kinase and the scaffold protein Crk-associated substrate (Cas).

Pharmacological inhibition of Fyn kinase or expression of a Fyn kinase siRNA abolished NAP-mediated axon outgrowth. Concentrations of ethanol attained after social drinking blocked NAP-mediated axon outgrowth (IC₅₀ = 17 mM) by inhibiting NAP activation of Fyn kinase and Cas.

These findings identify a mechanism for ADNP regulation of glial–neuronal interactions in developing cerebellum and a pathogenesis of ethanol neurotoxicity.


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Request Reprint E-Mail: mcharness@hms.harvard.edu
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Study commissioned into alcoholism in American Samoa

02 December, 2008

A preliminary study about the genetics of alcoholism in American Samoa has been commissioned by the U.S. National Institute of Health.

The study will be carried out by addiction psychiatrist Dr. Robert Swift from Brown University in Providence Rhode Island, and the Director of Brown International Health Institute Dr. Stephen McGarvey.

Dr. Swift says Samoan levels of alcoholism are no different to the rest of the world but they have chosen Samoans to study because they are very genetically similar.

He says it’s easier to find the genetic basis of different conditions in a group of people with similar genes.

. . . . .

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Clinical Course of Alcohol Dependence in African Americans
Journal of Addictive Diseases Volume: 27 Issue: 4


The sequence and progression of alcohol related life events were investigated in a sample of African Americans and compared with findings from a predominantly Caucasian sample.

Alcohol dependent participants were recruited from treatment facilities. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism to assess the physical, psychological and social manifestations of alcoholism and related disorders.

The sequence and mean age of appearance of alcohol-related life events were similar for this sample of African-American men and women. While there were similarities in the progression of alcohol related life problems between the African American and the Caucasian samples, the frequency of symptom endorsement for most problems was significantly higher in the Caucasian sample.

Identifying ethnic differences in the clinical course of alcohol dependence may be of importance in developing treatment plans and assist in the development of culturally sensitive intervention and prevention programs.

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Request Reprint E-Mail: d_m_scott2@howard.edu
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Alcohol Consumption and Risk of Incident Atrial Fibrillation in Women
JAMA. 2008;300(21):2489-2496.

Previous studies suggest that consuming moderate to high amounts of alcohol on a regular basis might increase the risk of developing atrial fibrillation in men but not in women. However, these studies were not powered to investigate the association of alcohol consumption and atrial fibrillation among women.

To prospectively assess the association between regular alcohol consumption and incident atrial fibrillation among women.

Over a median follow-up of 12.4 years, 653 cases of incident atrial fibrillation were confirmed. Age-adjusted incidences among women consuming 0 (n = 15 370), more than 0 and less than 1 (n = 15 758), 1 or more and less than 2 (n = 2228), and 2 or more (n = 1359) drinks per day were 1.59, 1.55, 1.27, and 2.25 events/1000 person-years of follow-up. Thus, compared with nondrinking women, women consuming 2 or more drinks per day had an absolute risk increase of 0.66 events/1000 person-years. The corresponding multivariate-adjusted hazard ratios (HRs) for incident atrial fibrillation were 1, 1.05 (95% CI, 0.88-1.25), 0.84 (95% CI, 0.58-1.22), and 1.60 (95% CI, 1.13-2.25), respectively. The increased hazard in the small group of women consuming 2 or more drinks per day persisted when alcohol intake was updated at 48 months (HR, 1.49; 95% CI, 1.05-2.11) or when women were censored at their first cardiovascular event (HR, 1.68; 95% CI, 1.18-2.39).

Among healthy middle-aged women, consumption of up to 2 alcoholic beverages per day was not associated with an increased risk of incident atrial fibrillation. Heavier consumption of 2 or more drinks per day, however, was associated with a small but statistically significant increased risk of atrial fibrillation.

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Press Release - Pernod Ricard accelerates its responsible consumption initiatives - 30 countries concerned in 2008

Paris, 2 December 2008

Since its creation, Pernod Ricard has increased its responsible consumption initiatives with the founding of IREB (Alcoholic Drinks Scientific Research Institute), that of the “European Forumfor Responsible Drinking” in 1990 and the introduction of internal advertising monitoring procedures in 2005.

Today, Pernod Ricard is accelerating and internationalising its initiatives. Thus in 2008, 30 countries were concerned by the rollout of the Group’s responsible consumption policy. A report entitled “Alcohol: staying in control – Best practice around the world by Pernod Ricard” lists the steps taken, focusing on the following:

o Promoting sensible consumption,
o Avoiding drink driving,
o Making young people aware of the risks of alcohol,
o Dissuading pregnant women from drinking,
o Making staff aware of their responsibilities.


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News Release - Baylor Study Finds Alcohol During Adolescence Leads to Alcohol Tolerance Later in Life

Dec. 1, 2008

Results indicate alcohol alters teen brain, liver functions

A Baylor University study has found that exposure during adolescence to moderate doses of alcohol in a binge-like fashion does in fact produce tolerance to high doses of alcohol later in life.

Baylor researchers found that the alcohol a person might ingest when they are between 12 and 20, even at moderate doses, can alter brain and liver function, and produce alcohol tolerance when the person is older.

The results appeared on-line in the journal Alcohol. It is among the first studies that link long-term tolerance consequences when adolescents are exposed to alcohol.

. . . . .

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Modulation of ethanol state-dependent learning by dorsal hippocampal NMDA receptors in mice
Alcohol Volume 42, Issue 8, December 2008, Pages 667-674


The possible role of N-methyl-d-aspartate (NMDA) receptors of dorsal hippocampus on ethanol state-dependent learning was studied in adult male mice (Pasteur Institute, Iran).

As a model of memory, a single-trial step-down passive avoidance task was used. All animals were bilaterally implanted with cannulae into the CA1 regions of dorsal hippocampi.

Results show that intraperitoneal (i.p.) administration of ethanol (0.5 and 1 g/kg) 30 min before training impaired memory performance in animals when tested 24 h later. Pretest administration of the same doses of ethanol-induced state-dependent retrieval of the memory acquired under pretraining ethanol (1 g/kg, i.p.) influence. Pretest intra-CA1 microinjection of NMDA (0.001, 0.01, and 0.1 μg/mouse) by itself had no effect on memory retrieval and ethanol-induced amnesia. However, pretest intra-CA1 administration of the same doses of NMDA with an ineffective dose of ethanol (0.25 g/kg, i.p.) significantly restored the retrieval and potentiated ethanol state-dependent learning.

On the other hand, pretest administration of a competitive NMDA receptor antagonist d-AP5 (d-(−)-2-Amino-5-phosphonopentanoic acid) (0.01, 0.1, and 1 μg/mouse, intra-CA1) or a noncompetitive NMDA receptor antagonist MK-801 maleate [(5S, 10R)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine maleate] (0.25, 0.5, and 1 g/mouse, intra-CA1) 5 min before the administration of ethanol (1 g/kg, i.p.) significantly inhibited ethanol state-dependent learning.

Intra-CA1 pretest administration of d-AP5 (0.01, 0.1, and 1 μg/mouse) or MK-801 maleate [5S, 10R)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine maleate] (0.25, 0.5, and 1 μg/mouse) alone did not affect memory retention.

It may be concluded that dorsal hippocampal NMDA receptors are involved in mediating ethanol state-dependent learning.


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Chronic binge ethanol-mediated acidemia reduces availability of glutamine and related amino acids in maternal plasma of pregnant sheep
Alcohol Volume 42, Issue 8, December 2008, Pages 657-666

Heavy drinking during pregnancy can result in fetal alcohol syndrome (FAS), of which, fetal and postnatal growth retardation and central nervous system deficits are cardinal features. Although a number of mechanisms have been proposed, none fully account for these deficiencies. W

We have previously reported that maternal ethanol exposure (1.75 g/kg) results in transient acidemia in the mother and fetus. Alterations in pH are known to regulate glutamine homeostasis. Therefore, we hypothesized that chronic binge ethanol-mediated acidosis reduces glutamine concentrations in maternal plasma that result in decreases in the circulating levels of amino acids related to glutamine metabolism.

Pregnant ewes were divided into three groups: ethanol (1.75 g/kg), saline control, and acidemia (inspired fractional carbon dioxide [CO₂] was manipulated to mimic the maternal arterial pH pattern created by ethanol). The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109, continuing to GD 132. Plasma samples were analyzed for nutrients and metabolites using HPLC and spectrophotometric methods.

Maternal plasma concentrations of glutamate increased (58%), whereas glutamine, citrulline, and arginine decreased (between 14 and 53%) in response to an acute challenge after the chronic exposure in ethanol-treated ewes. No differences in these amino acid concentrations were noted between the ethanol and acidemic group subjects. Maternal plasma lactate levels increased by 100% in response to ethanol, whereas glucose and urea levels did not change in any group.

We conclude that maternal chronic binge ethanol consumption results in acidosis-mediated reductions in circulating levels of glutamine and related amino acids that could be responsible for neuronal deficits, altered fetal growth, development, and programming. We also speculate that the consequent increase in fetal glutamate during critical periods of brain development may contribute to the pathogenesis of FAS.

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Binge alcohol treatment of adolescent rats followed by alcohol abstinence is associated with site-specific differences in bone loss and incomplete recovery of bone mass and strength
Alcohol Volume 42, Issue 8, December 2008, Pages 649-656


We previously demonstrated that alcohol-fed adolescent rats exhibit reductions in lumbar spine bone mineral density (BMD) and vertebral body height, suggesting that chronic alcohol consumption has negative consequences for skeletal development during adolescence.

Binge alcohol consumption is common in adolescents and young adults, yet little is known about its consequences on skeletal integrity or the attainment of peak bone mass.

We used a previously validated binge alcohol exposure model to test the hypothesis that binge alcohol treatment of adolescent rats would be associated with distinct temporal and site-specific bone loss profiles, with incomplete recovery from bone loss following a period of alcohol abstinence.

Seventy-two male adolescent Sprague-Dawley rats were assigned to one of six treatment groups (n = 12/group) receiving binge alcohol (3 g/kg) or saline intraperitoneal, 3 consecutive days (acute binge), 4 consecutive weekly (3-day) binge cycles (chronic binge), or 4 weekly binge cycles followed by a 30-day abstinence period without alcohol or saline injections (chronic binge with abstinence). Cancellous BMD was determined by quantitative computed tomography and compressive strength determined by biomechanical testing. Serum testosterone and osteocalcin levels were measured by enzyme-linked immunosorbent assay.

Tibial cancellous BMD was significantly reduced by 25% (P < .05) after both acute and chronic binge alcohol treatment and vertebral cancellous BMD was significantly reduced by 15% (P < .05) after chronic binge exposure. Vertebral compressive strength was also significantly decreased by 31% (P < .05) after chronic binge alcohol treatment. Tibial cancellous BMD returned to control levels after the 30-day alcohol abstinence period, but vertebral cancellous BMD remained 15% below control values (P < .05) 30 days after termination of binge alcohol exposures. Serum osteocalcin levels were significantly decreased following acute binge alcohol exposure (P < .05).

These results show that binge alcohol exposure can produce both short- and long-term skeletal damage in the adolescent rat. These data might have relevance to peak bone mass attainment and future risk of skeletal disease in adolescents and young adults who engage in repeated binge-drinking episodes.


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