Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

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Tuesday, October 27, 2009

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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Monday, October 26, 2009

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.


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.


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.


Request Reprint E-Mail: peipei.chau@neuro.gu.se
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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.


Request Reprint E-Mail: peipei.chau@neuro.gu.se

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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.


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

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Alcohol Up-Regulates TLR2 Through a NO/cGMP Dependent Pathway
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Heavy alcohol consumption is associated with severe bronchitis. This is likely related to increased inflammation in the airways of alcohol abusers. Toll-like receptor 2 (TLR2) is an important mediator of inflammation in the airway epithelium. TLR2 initiates an inflammatory cascade in response to gram-positive bacteria. We have previously shown that alcohol up-regulates TLR2 in the airway epithelium. However, the mechanism of alcohol-mediated up-regulation of TLR2 has not been identified.

Alcohol up-regulates TLR2 through a NO/cGMP/PKG dependent pathway in the airway epithelium. This is an important observation in the understanding how alcohol modulates airway inflammation. In addition, this is the first time that cyclic nucleotides have been shown to play a role in the regulation of TLR2.

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Request Reprint E-Mail: kbailey@unmc.edu
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Ethanol Upregulates iNOS Expression in Colon Through Activation of Nuclear Factor-kappa B in Rats
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Alcohol inhibits colonic motility but the mechanism is unknown. The goal of this study was to test the possibility that nuclear factor-kappa B (NF-κB) is involved in the upregulation of inducible nitric oxide synthase (iNOS) expression induced by ethanol in colon.

Ethanol inhibited the contraction of LP in colon mainly through activation of NF-κB, the subsequent upregulation of iNOS expression and increase of NO release in myenteric plexus.


Request Reprint E-Mail: liucy@sdu.edu.cn

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Reduced attentional blink for alcohol-related stimuli in heavy social drinkers

Researchers have used various paradigms to show that attentional biases for substance-related stimuli are an important feature of addictive behaviors (e.g. Field & Cox, 2008). However, it is not clear whether these attentional biases occur at the level of encoding or at later postattentive processing stages.

We examined attentional bias at the level of encoding with the attentional blink (AB) paradigm (Raymond et al., 1992) in a sample of non-clinical heavy and light drinking students.

Our results show a diminished AB effect for alcohol-related words compared to soft drink-related words among heavy drinkers. The AB was equally strong for alcohol-related and soft drink-related words among light drinkers.

This suggests that alcohol related information is processed relatively more efficiently in the former group. Even though these results are promising, our study shows that the internal consistency of the AB can be improved.

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Alcohol Consumption, Hypertension, and Total Mortality Among Women
American Journal of Hypertension 2009; 22, 11, 1212–1218.

Moderate alcohol consumption is associated with a reduced risk of total mortality among Caucasian women. Whether moderate alcohol consumption is associated with a reduced risk of total mortality among African-American or hypertensive women is unclear.

Moderate drinking is associated with a lower risk of total mortality among Caucasian women. Current drinking is associated with a lower risk of total mortality among Caucasians, regardless of hypertensive status, and hypertensive but not nonhypertensive African-American women. The latter observation was affected by the low mortality rate among the African-American nonhypertensive lifetime abstainers.

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Influence of Alcohol Intake on Circadian Blood Pressure Variation in Japanese Men: The Ohasama Study
American Journal of Hypertension 2009; 22, 11, 1171–1176

Both a large habitual alcohol intake and a pattern of circadian blood pressure (BP) variation characterized by a high morning/daytime BP have been reported to be risk factors for cerebral hemorrhage. Therefore, the association between these two factors was examined.

Habitual alcohol intake was associated with a higher 2h-BP Dif.

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Impact of Access to Recovery services on alcohol/drug treatment outcomes
Journal of Substance Abuse Treatment Volume 37, Issue 4, December 2009, Pages 435-442

The purpose of this study was to assess the impact of providing recovery support services to clients receiving publicly funded chemical dependency (CD) treatment through the Access to Recovery (ATR) Program in Washington State.

Results indicated that ATR services were associated with a number of positive outcomes including increased length of stay in treatment, increased likelihood of completing treatment, and increased likelihood of becoming employed. The beneficial effects of ATR services on treatment retention were most pronounced when they were provided between 31 and 180 days after treatment began.

The results reported here offer evidence for the value of ATR services.


Request Reprint E-Mail: krupski@u.washington.edu

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Behavioral couple therapy for gay and lesbian couples with alcohol use disorders
Journal of Substance Abuse Treatment Volume 37, Issue 4, December 2009, Pages 379-387

Gay (n = 52) and lesbian (n = 48) patients with alcohol use disorder (AUD) and their non-substance-abusing same-sex relationship partners were randomly assigned to equally intensive interventions consisting of (a) behavioral couples therapy (BCT) plus individual-based treatment (IBT) or (b) IBT only.

This study reports two separate trials, one with gay male participants and one with lesbian female participants.

For both gay and lesbian patients with AUD, those who received BCT had a significantly lower percentage of days of heavy drinking during the year after treatment than patients who received IBT only. In addition, both gay and lesbian couples who received BCT reported higher levels of relationship adjustment at the end of treatment and in the year after treatment than those who received IBT only.

Thus, the response of gay and lesbian couples with an alcoholic member to BCT was consistent with what has been observed with heterosexual couples.



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College students rarely seek help despite serious substance use problems
Journal of Substance Abuse Treatment Volume 37, Issue 4, December 2009, Pages 368-378

The prevalence of substance use disorders (SUD) and aspects of the help-seeking process among a high-risk sample of 946 students at one large public university were assessed in personal interviews during the first 3 years of college.

After statistically adjusting for purposive sampling, an estimated 46.8%wt of all third-year students met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for SUD involving alcohol and/or marijuana at least once.
College students have high rates of substance use problems but rarely recognize a need for treatment or seek help. Results highlight the opportunity for early intervention with college students with SUD.


Request Reprint E-Mail: mailto:aarria@cesar.umd.edu
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Dually diagnosed patients' responses to substance use disorder treatment
Journal of Substance Abuse Treatment Volume 37, Issue 4, December 2009, Pages 335-345

Few studies have investigated whether dually diagnosed patients with co-occurring substance use and psychiatric disorders (DD) respond as well to substance use disorder (SUD) treatments as patients with SUD do.

Here we assessed whether male veteran DD and SUD patients with alcohol dependence diagnoses differed in the process and outcomes of residential SUD treatment.

The main findings showed that (a) DD patients did not perceive SUD programs as positively as patients with SUD did and had worse proximal outcomes at discharge from treatment; (b) DD patients did as well as SUD patients on 1- and 5-year substance use outcomes but had worse psychiatric outcomes; and (c) patients who perceived treatment more positively and had better outcomes at discharge had better longer term outcomes.

Thus, residential SUD programs are relatively effective in reducing DD patients' substance use problems; however, they are less successful in engaging DD patients in treatment and addressing their psychiatric problems.


Request Reprint E-Mail: mailto:mboden@stanford.edu

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Short-term exposure to ethanol causes a differential response between NGF and BDNF ligand/receptor systems in the mouse cerebellum
Neuroscience Article in Press 25 October 2009

Alcohol ingestion affects both neuropsycological and motor functions. We hypothesized that one of the key factors involved in such functions are neurotrophins and their receptors.

We have therefore examined the effects of short-term ethanol exposure on the mRNA expression and protein levels of neurotrophin ligands and receptors in the cerebellum using real-time RT-PCR and Western blotting techniques.

We found that exposure to ethanol resulted in elevated levels of nerve growth factor (NGF) and TrkA mRNA expression but a decreased level of brain-derived neurotrophic factor (BDNF) mRNA expression. The expression of TrkB and p73 mRNA was unchanged. Changes in the level of these proteins were found to mirror these mRNA expression levels.

We conclude that exposure to ethanol for a short period can cause a differential responsive in the various neurotrophin ligand/receptor systems. The functional consequences of these changes are unknown at present.


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Request Reprint E-Mail: mikit@med.kagawa-u.ac.jp

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Agonism of the endocannabinoid system modulates binge-like alcohol intake in male C57BL/6J mice: involvement of the posterior ventral tegmental area.
Neuroscience Volume 164, Issue 2, 1 December 2009, Pages 424-434


Recent studies have indicated a role for the endocannabinoid system in the behavioral and physiological effects of alcohol (ethanol), particularly ethanol seeking behaviors. However, its role in modulating binge-like intake and/or the mechanism by which it may exert these effects remain poorly understood.

The current study used a newly developed strain-specific animal model of binge drinking, dubbed ‘Drinking In the Dark’ (DID), to determine if facilitation of the endocannabinoid system with the synthetic cannabinoid agonist WIN 55-212,2 (WIN) modulates binge-like ethanol intake in male C57BL/6J (B6) mice.

Based on the results of these systemic (i.p.) manipulations, and evidence in support of the involvement of subregions of the Ventral Tegmental Area (VTA) in governing self-administration of ethanol (Rodd-Henricks et al., (2000) Psychopharmacology (Berl) 149(3):217–224) as well as binge-like intake using the DID model (Moore & Boehm, (2009 Behav Neurosci 123(3):555–563), we extended these findings to evaluate the role of the endocannabinoid system within the anterior and posterior sub regions of the VTA using site-specific microinjections.

Consistent with previous research, the lowest systemic dose of WIN (0.5 mg/kg) significantly increased ethanol intake in the first 30 minutes of access whereas the two highest doses (1 and 2 mg/kg) decreased ethanol intake within this time interval. Intra-posterior ventral tegmental area (pVTA) (but not aVTA (anterior ventral tegmental area) microinjections elicited time-dependent and dose-dependent increases (0.25 and 0.5 μg/side) and decreases (2.5 μg/side) in ethanol intake. Importantly, follow-up studies revealed that in some cases alterations in fluid consumption may have been influenced by competing locomotor activity (or inactivity).

The present data are consistent with previous research in that agonism of the endocannabinoid system increases ethanol intake in rodents and implicate the pVTA in the modulation of drinking to intoxication. Moreover, the dose-dependent alterations in locomotor activity emphasize the importance of directly assessing multiple (possibly competing) behaviors when evaluating drug effects on voluntary consumption.


Request Reprint E-Mail: dlinsenb@iupui.edu

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Sunday, October 25, 2009

Galanin Knockout Mice Show Disturbances in Ethanol Consumption and Expression of Hypothalamic Peptides That Stimulate Ethanol Intake
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat-rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice.

These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat-rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males.


Request Reprint E-Mail: leibow@rockefeller.edu

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Heavy Episodic Drinking and Alcohol Consumption in French Colleges: The Role of Perceived Social Norms
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

The effect of normative perceptions (social norms) on heavy episodic drinking (HED) behavior is well known in the U.S. college setting, but little work is available in other cultural contexts.

The objective of this study is therefore to assess whether social norms of alcohol use are related to HED in France, taking account of other influential predictors.

Overestimation of peer student prevalence is not uncommon among French university students. Furthermore, perceived peer student prevalence of HED is linked to HED frequency, even after adjusting for other correlates. Interventions correcting misperceived prevalences of HED among peer students have therefore the potential to reduce the frequency of HED in this population.


Request Reprint E-Mail: leonel@worldonline.fr

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Age-Related Gray Matter Shrinkage in a Treatment Naïve Actively Drinking Alcohol-Dependent Sample
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

We previously demonstrated, in a small sample, steeper age-related gray matter shrinkage in treatment naïve alcohol-dependent (TxN) men compared to nonalcoholic controls, but could not separate out the contributions of age and lifetime duration of alcohol use (which were highly correlated) to this effect.

In the current study, we have quadrupled the sample size and expanded it to include both men and women to try to replicate and extend the previous findings and to separate the contributions of age and alcohol use to the phenomenon.

We found greater age-related gray matter shrinkage in TxN than in controls. Partial correlation analysis showed that the effect was a function of age and not lifetime alcohol burden.

Implications of the findings are discussed in terms of their contribution toward our knowledge of differences between different subpopulations of alcoholics and in terms of their implications for the morbidity of alcohol dependence in an aging national population.


Request Reprint E-Mail: george@nbresearch.com
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Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1*c2 Allele
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture.

We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out.

Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary.

The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype.

This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI.

Request Reprint E-Mail: bastidas@cencar.udg.mx

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Students' Drinker Prototypes and Alcohol Use in a Naturalistic Setting
Alcoholism: Clinical and Experimental Research Early View 23ct 2009

Perceptions about the type of people who drink, also referred to as drinker prototypes, may strengthen young people's motivation to engage in alcohol use. Previous research has shown that drinker prototypes are related to alcohol consumption in both adolescents and young adults. However, the evidence for the strength of these relationships remains inconclusive. One of the caveats in former studies is that all insights about prototype relations are based on self-reported data from youngsters themselves, mostly gathered in a class situation, which may contain bias due to memory distortions and self-presentation concerns.

These findings further establish the value of drinker prototypes in predicting young adults' drinking behavior and suggest that people's motivation to drink alcohol in real-life drinking situations is related to their perceptions about heavy drinkers.


Request Reprint E-Mail: r.spijkerman@pwo.ru.nl

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Maternal Alcohol Use During Pregnancy Causes Systemic Oxidation of the Glutathione Redox System
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Increased systemic oxidant stress contributes to a variety of maternal complications of pregnancy. Although the antioxidant glutathione (GSH) and its oxidized component glutathione disulfide (GSSG) have been demonstrated to be significantly altered in the adult alcoholic, the effects of maternal alcohol use during pregnancy on oxidant stress in the postpartum female remain under investigation.

We hypothesized that maternal alcohol use would increase systemic oxidant stress in the pregnant female, evidenced by an oxidized systemic GSH redox potential.

Alcohol use during pregnancy, particularly at levels >3 drinks/occasion, caused significant oxidation of the systemic GSH system in the postpartum women. The clinical ramifications of the observed alcohol-induced oxidation of the GSH redox system on high risk pregnancies or on the exposed offspring require more accurate identification and further investigation.


Request Reprint E-Mail: tgauthi@emory.edu
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Alcohol, Cocaine, and Brain Stimulation-Reward in C57Bl6/J and DBA2/J Mice
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward.

These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine.

C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBA mice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique.

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Request Reprint E-Mail fishe@neurology.unc.edu
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Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent Rats
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals.

Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal.

Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant.


Request Reprint E-Mail: roberto.ciccocioppo@unicam.it ___________________________________________________________
Systemic Administration of Arecoline Reduces Ethanol-Induced Sleeping Through Activation of Central Muscarinic Receptor in Mice
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Epidemiological evidence of co-use of alcohol and areca nuts suggests a potential central interaction between arecoline, a major alkaloid of areca and a muscarinic receptor agonist, and ethanol. Moreover, the central cholinergic system plays an important role in the depressant action of ethanol and barbiturates.

The purpose of this study was to investigate the effects of arecoline on pentobarbital- and ethanol-induced hypnosis in mice.

These results suggest that central muscarinic receptor is a pharmacological target for the action of arecoline to modulate ethanol-induced hypnosis.


Request Reprint E-Mail: liangjh@hotmail.com

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Initial Evidence of an Association Between OPRM1 and Adolescent Alcohol Misuse
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

Considerable research efforts have attempted to identify genes associated with alcoholism among adults, yet few studies have examined adolescents. Identifying genes associated with alcohol misuse in youth is important given that the relative contribution of genetic and environmental influences on alcoholism varies across development.

The purpose of this study was to examine the association between a polymorphism of the μ-opioid receptor gene (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened sensitivity to the reinforcing effects of alcohol mediated this relationship.

These data build on findings from adult studies and provide the first evidence that a polymorphism of the OPRM1 receptor gene is associated with the development of early-onset alcohol-related problems during adolescence, in part, by heightening sensitivity to the reinforcing effects of alcohol.


Request Reprint E-Mail: robert_miranda_jr@brown.edu

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Linkage Analysis of Alcohol Dependence Symptoms in the Community
Alcoholism: Clinical and Experimental Research Early View 23 Oct 2009

We have previously identified suggestive linkage for alcohol consumption in a community-based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms.

Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously identified in alcohol linkage studies using clinical populations. Linkage signal strength was found to vary between full and truncated samples and when samples differed only on the collection age for a sample subset.

The results support the finding that large community samples can be informative in the study of alcohol-related traits.


Request Reprint E-Mail: Narelle.Hansell@qimr.edu.au

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Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7
Alcoholism: Clinical and Experimental Research Early View 23 October 2009

This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment.

The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects.

Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development.


Request Reprint E-Mail: eamyers@med.unc.edu
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CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn-Hooded Rats
Alcoholism: Clinical and Experimental Research Early View 23 Odct 2009

This study was undertaken to identify the neurochemical changes underlying the attenuation of voluntary ethanol intake induced by the cannabinoid CB1 receptor antagonist AM251 in fawn-hooded rats.

Taken together, these results revealed that blockade of cannabinoid CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol-habituated rats by normalizing the neurochemical alterations induced by ethanol.


Request Reprint E-Mail: jmanzanares@umh.es

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14th Annual Mark Keller Lecture - November 19, 2009
Event:
14th Annual Mark Keller Lecture on "Alcoholism and Its Impact on Energy Metabolism: Implications for Tissue Injury and Repair"

Location:
Lipsett AmphitheaterNIH Clinical Center (Bldg. 10)Bethesda, MD

Start Date:
11/19/2009 1:30 PM
End Date:
11/19/2009 3:30 PM

Event Details:
Presented by:Jan B. Hoek, Ph.D.Department of Pathology, Anatomy and Cell Biology Thomas Jefferson University

Contact: Nancy Colladay,

NIAAA 301-443-4733 ncollada@mail.nih.gov

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How to give grog-free clubs a sporting chance
JILL STARK
ALCOHOL experts are increasingly concerned by a growing number of violent attacks linked to community sporting clubs, warning that Australian sport's entrenched boozy culture must be reversed.

The Australian Drug Foundation is leading a world-first trial comparing levels of violence, drink-driving and alcohol-related harm at clubs that adopt responsible alcohol policies with those without such programs. . . . . . . .

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The auditory-visual integration of anger is impaired in alcoholism: an event-related potentials study
J Psychiatry Neurosci 2008;33(2):111-22.

Chronic alcoholism leads to impaired visual and auditory processing of emotions, but the cross-modal (auditory-visual) processing of emotional stimuli has not yet been explored. Our objectives were to describe the electrophysiological correlates of unimodal (visual and auditory) impairments in emotion processing in people suffering from alcoholism, to determine whether this deficit is general or emotion-specific, and to explore potential deterioration in the specific cross-modal integration processes in alcoholism.

These results suggest that the specific deficit that people with alcoholism demonstrate in processing anger stimuli, widely described in clinical situations but not clearly identified in earlier studies (using unimodal stimuli), is particularly obvious during cross-modal processing, which is more common than unimodal processing in everyday life.

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Case Ascertainment to Estimate the U.S. Prevalence of Fetal Alcohol Spectrum Disorders in Young Children

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) seeks grant applications from institutions that propose to determine within defined geographical areas of the U.S. a prevalence rate for fetal alcohol spectrum disorders (FASD), including fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorders, among young children in the United States.

This funding opportunity will support research by the Collaboration on FASD Prevalence (CoFASP), the final group of awardees funded through this RFA, comprising multi-disciplinary teams using active case ascertainment to establish reasonable, reproducible and generalizable estimates of FASD prevalence across one or more geographic sub-divisions (counties cities) reflective of the general population of that area.

This research effort will require the development and/or use of a standardized diagnostic system to evaluate clinical characteristics of FASD among affected children.


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Saturday, October 24, 2009

Impact of Alcoholism on Sleep Architecture and EEG Power Spectra in Men and Women
SLEEP 2009;32(10):1341-1352.

To determine the impact of alcoholism on sleep architecture and sleep EEG power spectra in men and women with uncomplicated alcoholism.

Long-term alcoholism affects sleep even after long periods of abstinence in both men and women. Measures of frontal slow wave activity were particularly sensitive markers of this long-lasting effect. Sleep EEG measures would thus seem to provide a functional correlate of the changes in brain structure seen in frontal cortex of long-term alcoholics.


Request Reprint E-Mail: ian.colrain@sri.com

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Selective and Brain Penetrant Neuropeptide Y Y2 Receptor Antagonists Discovered by Whole-Cell High Throughput Screening.
Molecular Pharmacology Fast Forward First published on October 16, 2009

The role of neuropeptide Y Y2 receptor (Y2R) in human diseases such as obesity, mood disorders and alcoholism could be better resolved by use of small molecule chemical probes that are substantially different from the currently available Y2R antagonist, BIIE0246.

Presented here are five potent, selective and publicly available Y2R antagonists identified by a high throughput screening (HTS) approach. These compounds belong to four chemical scaffolds that are structurally distinct from the peptidomimetic BIIE0246.

Profiling against a panel of 40 receptors, ion channels, and transporters found in the central nervous system showed that the five Y2R antagonists demonstrate greater selectivity than BIIE0246.

Furthermore, the ability of these antagonists to penetrate the blood-brain barrier makes them better suited for pharmacologic studies of Y2R function in both the brain and periphery.


Request Reprint E-Mail: hodderp@scripps.edu


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