McGrath softens drink law position

The highest-profile opponent of Noel Dempsey’s controversial new drink-driving legislation said yesterday he might support the watered-down version the transport minister published last Friday.

Mattie McGrath, the South Tipperary TD who led a backbench revolt within Fianna Fail against the reduction of the blood alcohol limit from 80mg per 100ml to 50mg, said the softer penalties for those caught with readings of less than 80mg was “a step in the right direction”. . . . . . .

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TRENDS IN ALCOHOL- AND DRUG-RELATED ED AND PRIMARY CARE VISITS: DATA FROM THREE U.S. NATIONAL SURVEYS (1995–2005)

To evaluate trends in alcohol- and drug-related ED and primary care visits over the previous decade.

Although an upward trend was observed in alcohol-related ED visits from 1995 to 2005, this increase was not significant. A significant trend was found for drug-related ED visits from 0.6% in 1995 to 3.7% in 2005 In multiple logistic regression, year of survey (2000 vs. 1995) was positively predictive of drug-related ED visits, controlling for gender, age, ethnicity and health insurance coverage; however, year of survey (2005 vs. 2000) was not significant.

These data suggest that drug-related ED visits are continuing to increase, although the increase has not been as substantial between 2000 and 2005, as that which was observed between 1995 and 2000, and highlight the opportunity provided by the ED and primary care settings for screening and brief intervention for substance-related problems. These findings also suggest that Healthy People 2010 objectives calling for a reduction in substance-related visits may not be reached.

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Alcohol, Other Drugs, and Health: Current Evidence

Current Issue: September–October 2009

View PDF of newsletter (Download Adobe Acrobat Reader)

Interventions and Assessments

• Heroin to Treat Opioid Dependence: A Randomized Trial
• Meta-analysis Confirms Methadone Maintenance Reduces Illicit Opioid Use and Improves Treatment Retention in Patients with Opioid Dependence
• Methadone Maintenance Therapy Decreases Arrests
• Impaired Memory in Subjects Receiving Opioid Agonist Treatment Who Also Abuse Benzodiazepines
• Impact of Buprenorphine Inquiries and Treatment on an Urban Community Health Center
• Improving Entry into Post-detoxification Treatment
• Injectable Risperidone for the Treatment of Methamphetamine Dependence

Health Outcomes

• AUDIT-C Scores Greater than 7 Predict Fracture Risk
• Does Heavy Alcohol Use Increase Risk of Prostate Cancer?
• Alcohol Consumption Limits Associated with Alcohol Problems in Older Adults
• Greater Alcohol Intake Increases the Risk for Hypertension, but Perhaps Not for Consumers of Red Wine
• Moderate Alcohol Intake Is Associated with Better Endothelial Function
• More than Half of All Deaths in Russia among People Aged 15–54 Years Are Attributable to Alcohol
• Action toward Change Predicts Reduced Alcohol Consumption among Unhealthy Drinkers, but Recognition of the Problem Does Not

Slide Presentations

• Update on Alcohol, Other Drugs, and Health
• Journal Club

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An Exploratory Study of the Nature of Family Resilience in Families Affected by Parental Alcohol Abuse

Resilient families are able to adapt to adversities, but the nature of family resilience is not well understood.

This study examines patterns of family functioning that may protect families from the negative impact of alcohol abuse. Naturally occurring patterns of family functioning are identified and associations between these patterns and parenting, current parental alcohol use, recent family stressful events, supportive relationships outside the family, and demographic characteristics are assessed.

The study results reveal a continuum of family functioning associated with parenting, child’s perception of teacher caring, and race.

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Request Reprint E-Mail: jcoyle@uwindsor.ca
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Maternal Alcohol Intake and Offspring Pulse Wave Velocity.

Intrauterine exposure to alcohol may affect cardiovascular development, increasing risk of cardiovascular malformations. Intrauterine exposure to light maternal alcohol intake has been reported to affect human umbilical arterial contractility, and adult sheep exposed in utero have had altered cerebrovascular reactivity. In human adults, alcohol intake affects arterial stiffness.

We investigated whether intrauterine exposure to alcohol was associated with childhood pulse wave velocity (PWV), a measure of arterial stiffness.

Carotid-femoral PWV in adults is predictive of cardiovascular morbidity and mortality. The degree of continuity between childhood and adulthood PWV is unknown, but as we found an association between prenatal alcohol exposure and carotid-femoral PWV at 9 years, a permanent change in vessel wall structure or function is possible. These findings need to be confirmed in other and larger cohorts, and mechanistic animal studies are needed

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Request Reprint E-Mail: ruth.morley@mcri.edu.au
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WHO - A response to the need for comprehensive, consistent and comparable information on health risks at global and regional level.

The leading global risks for mortality in the world are high blood pressure (responsible for 13% of deaths globally), tobacco use (9%), high blood glucose (6%), physical inactivity (6%), and overweight and obesity (5%). These risks are responsible for raising the risk of chronic diseases such as heart disease, diabetes and cancers. They affect countries across all income groups: high, middle and low.

The leading global risks for burden of disease as measured in disability-adjusted life years (DALYs) are underweight (6% of global DALYs) and unsafe sex (5%), followed by alcohol use (5%) and unsafe water, sanitation and hygiene (4%). Three of these risks particularly affect populations in low-income countries, especially in the regions of South-East Asia and sub-Saharan Africa. The fourth risk – alcohol use – shows a unique geographic and sex pattern,with its burden highest for men in Africa, in middle-income countries in the Americas and in some high-income countries.

Download the full report [pdf 3.77Mb]

MORE INFORMATION ON THE REPORT
Key figures and graphs [ppt 1.17Mb]

THE REPORT IN SECTIONS

:: Front cover, table of contents and summary [pdf 930kb]
:: Part 1: Introduction [pdf 994kb]
:: Part 2: Results [pdf 1.57Mb]
:: Part 3: Joint effects of risk factors [pdf 443kb]
:: Annex A: Data and methods [pdf 841kb]
:: References [pdf 148kb]

STATISTICS FROM THE REPORT

:: Regional estimates of YLL, YLD, DALYs, and deaths attributable to 24 risk factors for 2004: estimates of exposure prevalence for selected risk factors
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Alcohol Expectancy and Hazardous Drinking: A 6-Year Longitudinal and Nationwide Study of Medical Doctors

The study's aim was to determine whether medical doctors' expectancy that alcohol use reduces tension predicts the extent of their hazardous drinking and whether this effect is mediated by drinking to cope.

Efforts to reduce drinking among medical students and doctors should target both alcohol expectancies (beliefs) and hazardous drinking (behavior)..

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Request Reprint E-Mail: k.s.grotmol@medisin.uio.no
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Craving and Attentional Bias Respond Differently to Alcohol Priming: A Field Study in the Pub

Several experimental laboratory studies have shown that subjective craving for alcohol increases as a result of low-to-moderate levels of alcohol consumption.

Less is known about alcohol prime effects on relatively automatic appetitive motivational processes such as attentional bias (AB). Also, it is not known whether the effects from laboratory studies can be generalized to real-life drinking environments, and whether effects change after higher alcohol doses than those that have been administered in lab studies.

This field study validates earlier experimental research on alcohol prime effects in a real drinking situation. Further, it demonstrates prime effects up to much higher alcohol doses than in previous lab studies.

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Request Reprint E-Mail: schoenmakers@ivo.nl
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When zero tolerance looks like the safest option

It is no longer seen as ''safe'' for families to allow their teenagers an occasional drink.

WHEN the National Health and Medical Research Council guidelines on drinking alcohol were released earlier this year, some parents were surprised to discover that sharing the occasional beer or glass of wine with their teenagers might be dangerous. ''Parents and carers should be advised that children under 15 years of age are at the greatest risk of harm from drinking and that for this age group, not drinking alcohol is especially important,'' says guideline three. ''For young people aged 15-17 years, the safest option is to delay the initiation of drinking for as long as possible.''

This was a significant change. The previous 2001 guidelines had recommended under-18s not drink above the levels suggested for adults. The new advice challenged entrenched ideas about what sensible drinking means. In many Australian households, parents occasionally serve alcohol to their children as a way of teaching them how to enjoy a drink responsibly. Could it really be safer to ban under-age drinking in the home altogether and allow them to find their own way once they turn 18? . . . . . .

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Alcohol as a risk factor for type 2 diabetes: A systematic review and meta-analysis.

To clarify the dose-response relationship between alcohol consumption and type 2 diabetes.

The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76–1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71–1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52–0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83–1.26]).

Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women.

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Request Reprint E-Mail: dolly.baliunas@utoronto.ca.
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Booze putting teen brains at risk

A GENERATION of Victorian teenagers are drinking themselves into oblivion, with more than a quarter of 15-year-olds bingeing until they black out - the point at which brain damage is likely to occur.

Research has also found that more than a third of 11-year-old boys have consumed alcohol.

The figures, contained in a study by the Murdoch Children's Research Institute, have alarmed brain development experts who say a generation of young people are destroying their chances of reaching their full potential. . . . . . . .

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Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics

Identification of risk alleles for human behavioral disorders through genomewide association studies (GWAS) has been hampered by a daunting multiple testing problem. This problem can be circumvented for some phenotypes by combining genomewide studies in model organisms with subsequent candidate gene association analyses in human populations.

Here, we characterized genetic networks that underlie the response to ethanol exposure in Drosophila melanogaster by measuring ethanol knockdown time in 40 wild-derived inbred Drosophila lines. We associated phenotypic variation in ethanol responses with genomewide variation in gene expression and identified modules of correlated transcripts associated with a first and second exposure to ethanol vapors as well as the induction of tolerance. We validated the computational networks and assessed their robustness by transposon-mediated disruption of focal genes within modules in a laboratory inbred strain, followed by measurements of transcript abundance of connected genes within the module.

Many genes within the modules have human orthologs, which provides a stepping stone for the identification of candidate genes associated with alcohol drinking behavior in human populations. We demonstrated the potential of this translational approach by identifying seven intronic single nucleotide polymorphisms of the Malic Enzyme 1 (ME1) gene that are associated with cocktail drinking in 1687 individuals of the Framingham Offspring cohort, implicating that variation in levels of cytoplasmic malic enzyme may contribute to variation in alcohol consumption.

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Request Reprint E-Mail: anholt@ncsu.edu
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Endogenous BDNF in the Dorsolateral Striatum Gates Alcohol Drinking

We previously found that brain-derived neurotrophic factor (BDNF)-haplodeficient mice exhibit greater ethanol-induced place preference and psychomotor sensitization, and greater ethanol consumption after deprivation, than control mice. We further observed that, in mice, voluntary ethanol intake increases BDNF expression in the dorsal striatum (DS).

Here, we determined whether BDNF within the DS regulates ethanol self-administration in Long–Evans rats trained to self-administer a 10% ethanol solution.

We observed a greater increase in BDNF expression after ethanol self-administration in the dorsolateral striatum (DLS) than in the dorsomedial striatum (DMS). We further found that downregulation of endogenous BDNF using viral-mediated siRNA in the DLS, but not in the DMS, significantly increased ethanol self-administration. Infusion of exogenous BDNF (0.25 µg/µl/side into the DMS; 0.25 and 0.75 µg/µl/side into the DLS) attenuated responding for ethanol when infused 3 h before the beginning of the self-administration session. Although the decrease in ethanol intake was similar in the DLS and DMS, BDNF infused in the DLS, but not in the DMS, induced an early termination of the drinking episode. Furthermore, the action of BDNF in the DLS was specific for ethanol, as infusion of the neurotrophic factor in the DMS, but not DLS, resulted in a reduction of sucrose intake.

Together, these findings demonstrate that the BDNF pathway within the DLS controls the level of ethanol self-administration. Importantly, our results suggest that an endogenous signaling pathway within the same brain region that mediates drug-taking behavior also plays a critical role in gating the level of ethanol intake.

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Request Reprint E-Mail: dorit.ron@ucsf.edu
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Molecular reconstruction of mGluR5a-mediated endocannabinoid signaling cascade in single rat sympathetic neurons.

Endocannabinoids (eCB) such as 2-arachidonylglycerol (2-AG) are lipid metabolites that are synthesized in a postsynaptic neurons and act upon CB(1) cannabinoid receptors (CB(1)R) in presynaptic nerve terminals. This retrograde transmission underlies several forms of short and long term synaptic plasticity within the CNS.

Here, we constructed a model system based on isolated rat sympathetic neurons, in which an eCB signaling cascade could be studied in a reduced, spatially compact, and genetically malleable system. We constructed a complete eCB production/mobilization pathway by sequential addition of molecular components. Heterologous expression of four components was required for eCB production and detection: metabotropic glutamate receptor 5a (mGluR5a), Homer 2b, diacylglycerol lipase alpha, and CB(1)R. In these neurons, application of l-glutamate produced voltage-dependent modulation of N-type Ca(2+) channels mediated by activation of CB(1)R.

Using both molecular dissection and pharmacological agents, we provide evidence that activation of mGluR5a results in rapid enzymatic production of 2-AG followed by activation of CB(1)R. These experiments define the critical elements required to recapitulate retrograde eCB production and signaling in a single peripheral neuron. Moreover, production/mobilization of eCB can be detected on a physiologically relevant time scale using electrophysiological techniques.

The system provides a platform for testing candidate molecules underlying facilitation of eCB transport across the plasma membrane.

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Request Reprint E-Mail: sikeda@mail.nih.gov
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H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence

Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype.

Here, we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project.

Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA . A similar G × E interaction was associated with protective effects against alcohol dependence risk . For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers.

These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence.

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Request Reprint E-Mail: nelsone@wustl.edu
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Estonia will increase tax on alcohol and tobacco in 2010

The Estonian government agreed yesterday on principle on next the state budget 2010 and in order to cover spending in this budget, the state will increase the excise tax on alcohol and tobacco, Estonian dailies write.

It was agreed that the spending will amount to 89 billion kroons and the revenue volume will be 84 billion kroons. If the decision of the government is finalised, next year the excise tax on alcohol will increase by ten percent and excise tax on tobacco will be raised by 20 percent by the beginning of 2011. . . . . . .

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A Beer Tax Won't Reduce The Clap

Booze, STDs and the irrational exuberance of public health experts.


In the history of medicine, nothing has been used so widely and to so little effect as Hirudo Medicinalis--better known as the leech. For two millennia, leeches were used to balance the humors--or to drain the patient of "excess" blood and other substances thought to be the cause of most of humanity's physical and mental ailments. In a similar vein, some doctors and public health advocates are turning to a modern equivalent of the leech--taxes--in order to draw "excess" money from going to "unhealthy" activities, thereby reducing disease and balancing health care spending.

Recently, taxes on sugary sodas have been hailed as a painless way to tackle obesity, despite the absence of proof that the taxes would actually achieve this goal. Now the latest advice for "leeching" America comes from Dr. Lloyd I. Sederer, medical director for the New York State Office of Mental Health, and Dr. Eric Goplerud, director of the Center for Integrated Behavioral Health Policy at George Washington University. Writing in the Washington Post, they argue that imposing heavy taxes on alcohol would both reduce the harmful effects of heavy drinking and help pay for health reform. The logic is that if teens drink less, they'll have less unprotected sex, reducing their exposure to sexually transmitted diseases. . . . . . .

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Children, young people and alcohol: how they learn and how to prevent excessive use

What influences how children and young people behave towards alcohol.

Two linked research reviews examine:

• How young people acquire their knowledge, attitudes, expectations and intentions about alcohol, and:
• What interventions work best to prevent excessive use of alcohol

'Influences on how children and young people learn about and behave towards alcohol: A review of the literature for the Joseph Rowntree Foundation (part one)' (PDF, 420KB) looks in detail at the influences on children, including family processes and structures, peers, marketing and cultural representations, and other major forces such as religion, school and community.

Alcohol prevention programmes: A review of the literature for the Joseph Rowntree Foundation (part two) (PDF, 390KB) reviews what interventions have been attempted to try to prevent excessive use of alcohol by young people, summarises the findings and suggests how a universal prevention programme might be delivered.

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Press Release - Alcohol more harmful than many illegal drugs, claims drugs expert

Alcohol probably poses the biggest drugs harm challenge today, according to a new briefing from the Centre for Crime and Justice Studies. In `Estimating drug harms: a risky business', Professor David Nutt, of Imperial College London argues that the relative harms of legal drugs such as alcohol and tobacco are greater than those of a number of illegal drugs, including cannabis, LSD and ecstasy.

Professor Nutt proposes a `drug harm ranking', which compares the harms caused by legal as well as illegal drugs. Alcohol ranks as the fifth most harmful drug after heroin, cocaine, barbiturates and methadone. Tobacco is ranked ninth. Cannabis, LSD and ecstasy, while harmful, are ranked lower at 11, 14 and 18 respectively. Professor Nutt argues that simply focussing on the harms caused by illegal drugs, without assessing them against those of drugs such as alcohol and tobacco, results in an `isolated and arbitrary' debate about relative drug harms. . . . . . .

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SNP left high and dry as Labour rejects minimum alcohol pricing

Angus Macleod, Scottish Political Editor

The minority SNP government’s plans to adopt a minimum price for alcohol appear doomed after Labour’s appointment of a new shadow health secretary who is strongly against the move.

Jackie Baillie, whose constituency includes a big whisky firm employing 600 people, was appointed to the shadow health portfolio this week by Iain Gray, the Labour leader at Holyrood. . . . . . .

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Alcohol, Tobacco, and Nonmedical Drug Use in Older U.S. Adults: Data from the 2001/02 National Epidemiologic Survey of Alcohol and Related Conditions

Journal of the American Geriatrics Society Early View 26 Oct 2009

To examine the prevalence and sociodemographic and health-related correlates of substance use, including alcohol, tobacco, and nonmedical drug use, in adults aged 65 and older.

Most older adults had used substances over their lifetimes and in the previous 12 months. Alcohol is the substance of choice for this age group, followed by tobacco; few report nonmedical drug use.

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Request Reprint E-Mail: aamoore@mednet.ucla.edu

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Alcohol Consumption, Mortality and Morbidity - Key Findings

Key findings from Professor Martin Plant, Alcohol Health and Research Unit, Faculty of Health and Sciences, University of the West of England and Alcohol Concern, the national agency on alcohol misuse.

Professor Plant and his team were commissioned by Alcohol Concern in April 2009 to investigate what the future may hold for the nation’s drinking habits nd associated harms1. Professor Plant’s forecasting allows us to answer how our drinking patterns are likely to affect the state of the nation’s health in 2035.

For the first time in the UK, the relationship between alcohol consumption and mortality has been calculated. The research indicates a definitive link: the higher our society’s alcohol consumption, the more deaths occur as a result. Based on this, it is possible to forecast how health harms from alcohol may ncrease in the next 10 years if we continue to drink at the rate of the last 15 years.

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Alcohol in moderation, premorbid intelligence and cognition in older adults: results from the Psychiatric Morbidity Survey

Journal of Neurology, Neurosurgery, and Psychiatry 2009;80:1236-1239

To test the hypothesis that the association previously reported between moderate alcohol use and better cognition is an artefact of confounding by (a) higher premorbid education and socioeconomic status; (b) a lifestyle of moderation (using smoking as a risk marker); and (c) decreased alcohol consumption in people with physical illnesses.

In people who were not problem drinkers, higher alcohol intake was not associated with improved current cognition after controlling for premorbid intelligence and physical health. Our findings suggest that, despite previous suggestions, moderate alcohol consumption does not protect older people from cognitive decline.

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Request Reprint E-Mail: ccooper@doctors.org.uk

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Underage Drinking Research Initiative

Welcome

Steering Committee Roster
The Surgeon General's Call to Action toPrevent and Reduce Underage Drinking

Print and Multimedia Resources
Statistics on Underage Drinking

Other Resources
NIAAA Interdisciplinary Team

Selected Research Literature
Research Findings on Underage Drinking and the Minimum Legal Drinking AgeResearch Findings on College Drinking and the Minimum Legal Drinking AgePediatrics 2008;121: Issue Supplement

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Alcohol-related hospital admissions data for 2008/09 released

Provisional alcohol-related hospital admissions data for 2008/09 is now available from the North West Public Health Observatory (download the Quarterly data excel sheet from the data download tab). The data shows the overall rate of alcohol-related hospital admissions is still rising, though the rate of increase is slowing down. . . . . . .

Read More
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Falls in alcohol consumption but longer term trend and impact not clear

Levels of alcohol consumption have been on a downward trend since 2004, prompting the British Beer and Pub Association (BBPA) to call out against 'population' based approaches to alcohol harm reduction such as pricing measures and the mandatory licensing code.

Based on figures from HM Revenues and Customs data, sales have been falling since their 2004 peak, although 2007 levels showed a slight increase on the previous year. Nonetheless the longer term trend has been one of a more significant increase as demonstrated in the recent report from the Alcohol Health and Research Unit 'Future Proof'.

However consideration is urged when interpreting the data and assessing trends - consumption falls may be predominantly determined by significant decreases in consumption levels amongst younger drinkers in particular (16-24 age group). This was highlighted in the report released earlier this year by the JRF 'Drinking in the UK: an exploration of trends'. The impact of the recession, continued rise in home consumption and issues such as convergence between men and women's drinking patterns is also unclear. . . . . . .

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Association of Substance Use Disorders With Childhood Trauma but not African Genetic Heritage in an African American Cohort

Am J Psychiatry. Author manuscript; available in PMC 2009 October 27.

Genetic variation influences differential vulnerability to addiction within populations. However, it remains unclear whether differences in frequencies of vulnerability alleles contribute to disparities between populations and to what extent ancestry correlates with differential exposure to environmental risk factors, including poverty and trauma.

These results suggest that African genetic heritage does not increase the likelihood of genetic risk for addictions. They highlight the complex interrelation between genetic ancestry and social, economic, and environmental conditions and the strong relation of those factors to addiction. Studies of epidemiological samples characterized for genetic ancestry and social, psychological, demographic, economic, cultural, and historical factors are needed to better disentangle the effects of genetic and environmental factors underlying interpopulation differences in vulnerability to addiction and other health disparities.

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Chronic alcoholism: Insights from neurophysiology

Neurophysiologie Clinique/Clinical Neurophysiology Volume 39, Issues 4-5, October-November 2009, Pages 191-207

Increasing knowledge of the anatomical structures and cellular processes underlying psychiatric disorders may help bridge the gap between clinical signs and basic physiological processes. Accordingly, considerable insight has been gained in recent years into a common psychiatric condition, i.e., chronic alcoholism.

The heterogeneity of alcoholic disorders in terms of symptomatology, course and outcome is the result of various pathophysiological processes that physiological parameters may help to define. These alterations may be related to precise cognitive processes that could be easily monitored neurophysiologically in order to create more homogeneous subgroups of alcoholic individuals.

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Request Reprint E-Mail: salvatore.campanella@chu-brugmann.be

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A History of Alcohol Dependence Increases the Incidence and Severity of Postoperative Cognitive Dysfunction in Cardiac Surgical Patients

Int. J. Environ. Res. Public Health 2009, 6(11), 2725-2739

Postoperative cognitive dysfunction (POCD) commonly occurs after cardiac surgery.

We tested the hypothesis that a history of alcohol dependence is associated with an increased incidence and severity of POCD in male patients undergoing cardiac surgery using cardiopulmonary bypass.

The results suggest that a history of alcohol dependence increases the incidence and severity of POCD after cardiac surgery.

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Invitation to attend the REAP Stakeholder Meeting in London on Monday 23rd November

The REAP (Research for Effective Alcohol Policies) is a grouping of researchers at British universities established by the Medical Research Council. This major new initiative will take stock of what we know, assess practice around the country, and place evaluation research skills in the service of community responses to alcohol.

We are working to develop a broadly based multi-disciplinary UK partnership to support alcohol policy research and development, informed by the views of key stakeholders in alcohol harm reduction.

We believe that the success of this initiative will depend critically on the development of a strong alliance of community organisations operating at local level including local authorities, the voluntary sector, police and other elements of the criminal justice system, primary care trusts and other non-health sector agencies.

We very much hope that you or a named colleague will be able to attend our first full stakeholder meeting, where we will present our initial ideas, and discuss how we can best develop and evaluate community interventions that are responsive to local needs and based on evidence, with the goal of reducing harm from alcohol.

This meeting will take place in London at the UCL Cruciform Building (Lecture Theatre 2) on Gower Street (nearest tube Euston Square, also close to Euston Station - map attached) from 1.30-3.30 on Monday November 23rd. If you or a colleague are able to come, please contact Despoina.Xenikaki@lshtm.ac.uk no later than November 13th, indicating your role and e-mail address. Also, if you are aware of any groups or individuals whom we have overlooked, please feel free to ask them to contact us.

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Packages of Care for Alcohol Use Disorders in Low- And Middle-Income Countries

PLoS Med 6(10): e1000170.

Alcohol use disorders (AUDs)—conditions that range from hazardous and harmful alcohol use to alcohol dependence—are a low priority in low- and middle-income countries (LMICs), despite causing a large health burden.

Most alcohol-related harm is attributable to hazardous/harmful drinkers who make disproportionate use of primary health care systems, but often go undetected and untreated for long periods, even though brief, easily delivered interventions are effective in this group of people.

Health care systems in LMICs currently focus on providing tertiary care services for the treatment of dependence (where there is often a poor outcome). This focus needs to shift towards the cost-effective strategy of providing brief interventions for early AUDs.

Effective evidence-based combinations of psychosocial and pharmacological treatments for AUDs are available in LMICs but are costly to implement. Policy makers need to ensure that people with AUDs are offered the most appropriate services using stepped-care solutions that start with simple, structured advice for risky drinkers and progress to specialist treatment services for more serious AUDs.

LMICs also need to improve their implementation of proven population-level preventive measures to reduce the health burden due to AUDs. An international Framework Convention on Alcohol Control may help them do this.

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EUCAM Alcohol Marketing Conference

Brussels Date: 23-Nov-2009

The 2nd annual conference will offer an overview of the activities by the alcohol industry to prevent the implementation of effective policy instruments; information on new trends in activities and alcohol marketing in Europe and US; and a place for discussion on "how to react?"

Download Invitation


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Genetical genomic determinants of alcohol consumption in rats and humans
BMC Biology 2009, 7:70

We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs).

Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations.

Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption.

The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption.

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Alcohol, Signaling, and ECM Turnover

Alcoholism: Clinical and Experimental Research Early View 23 oct 2009

Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways that are important for the initiation and progression of alcohol-induced tissue injury are not completely understood. The current understanding of alcohol toxicity to organs suggests that alcohol initiates injury by generation of oxidative and nonoxidative ethanol metabolites and via translocation of gut-derived endotoxin.

These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. With continuing alcohol abuse, the injury progresses through impairment of tissue regeneration and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, the predominant being stellate cells, macrophages, and parenchymal cells. In response to alcohol, growth factors and cytokines activate many signaling cascades that regulate fibrogenesis.

This mini-review brings together research focusing on the underlying mechanisms of alcohol-mediated injury in a number of organs. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, susceptibility to infection, ECM turnover and fibrogenesis in the liver, pancreas, and lung triggered by alcohol abuse.

Read Full Abstract

Request Reprint E-Mail: devanshi.seth@email.cs.nsw.gov.au
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Alcohol Stimulates Activation of Snail, Epidermal Growth Factor Receptor Signaling, and Biomarkers of Epithelial–Mesenchymal Transition in Colon and Breast Cancer Cells

Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Alcohol consumption is associated with the risk of progressive cancers including colon and breast cancer. The mechanisms for the alcohol-induced aggressive behavior of these epithelial cancer cells have not been fully identified. Epithelial–mesenchymal transition (EMT) is a developmental program recently shown to play a role in cancer progression and metastases. We hypothesized that alcohol might promote cancer progression by inducing EMT in cancer cells and tested this hypothesis by assessing alcohol-stimulated changes in phenotypic markers of EMT as well as the EMT transcription factor Snail and its related cell signaling.

Collectively, our data support a novel mechanism for alcohol promoting cancer progression through stimulating the EMT program in cancer cells via an EGFR-Snail mediated pathway. This study reveals new pathways for alcohol-mediated promotion of cancer that could be targeted for therapy or prevention of alcohol-related cancers.

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Request Reprint E-Mail: ali_keshavarzian@rush.edu

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Glycine Receptors Involved in Acamprosate's Modulation of Accumbal Dopamine Levels: An In Vivo Microdialysis Study

Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) have been suggested to be involved in the positive reinforcing and dopamine elevating effects of ethanol. Recent studies have also shown that ethanol high-preferring rats substantially decrease their ethanol intake when treated with a glycine transporter 1 inhibitor (ORG 25935). Acamprosate, a drug used for relapse prevention in treatment of alcohol dependence, has also been demonstrated to elevate extracellular dopamine levels in the nAc. However, the underlying mechanism of action of acamprosate is not fully understood.

Here we investigated whether acamprosate interferes with a neuronal circuitry that previously has been demonstrated to be involved in the dopamine elevating effects of ethanol and taurine.

These results suggest that both systemic and local application of acamprosate elevate extracellular dopamine levels in the nAc by activating accumbal GlyRs, and, secondarily, tegmental nAChRs.

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Glycine Receptors in the Nucleus Accumbens Involved in the Ethanol Intake-Reducing Effect of Acamprosate

Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

We have previously demonstrated that strychnine-sensitive glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area are involved in mediating ethanol (EtOH)-induced elevation of dopamine in the rat mesolimbic dopamine system. This neuronal circuitry was also demonstrated to mediate dopamine elevation in the nAc after both taurine, an endogenous agonist of GlyRs, and acamprosate, a synthetic derivate of homotaurine. The aim of this study was to investigate whether the EtOH intake-reducing effect of acamprosate involves accumbal GlyRs.

Based on current and previous results, we suggest that acamprosate primarily interacts with accumbal GlyRs and secondarily with ventral tegmental nAChRs, in a similar manner to that previously observed with EtOH and taurine. The interaction between acamprosate and GlyRs does not only influence dopamine output in the nAc but also EtOH consumption, giving further support for our hypothesis that GlyRs are of importance in EtOH reinforcement.

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Increased Acid Sphingomyelinase Activity in Peripheral Blood Cells of Acutely Intoxicated Patients With Alcohol Dependence

Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol-induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.

Alcohol-induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol.

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Request Reprint E-Mail: martin.reichel@uk-erlangen.de

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