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.


Wednesday, December 31, 2008

Raising a Glass, Perhaps Labeled

By Cindy Skrzycki
Wednesday, December 31, 2008; Page D01

Consumer advocates are toasting the arrival of Timothy Geithner as President-elect Barack Obama's choice to be the new Treasury secretary by urging him to fix -- along with the economy -- labels on alcoholic drinks.

In a Dec. 11 letter, four groups told Geithner that while they recognize the challenges he faces, nutritional details on the ingredients in libations, especially the alcohol content per serving, have gone unaddressed for too long.
. . . . . .

Monday, December 29, 2008

Does Low to Moderate Alcohol Intake Protect Against Cognitive Decline in Older People?
Journal of the American Geriatrics Society Volume 56 Issue 12, Pages 2217 - 2224

To determine whether low to moderate alcohol intake is protective against cognitive decline in older people.

Alcohol consumption was determined at study baseline. Serial measures of cognitive function over 3.2 years mean follow-up included Mini-Mental-State-Examination (MMSE), speed of information processing (Stroop and Letter-Digit Coding tests), and immediate and delayed memory (Picture-Word Learning test).

Forty-two percent of women and 71% of men were alcohol drinkers. Cognitive performance was better for female drinkers than nondrinkers for all cognitive domains over the 3.2-year follow-up; no significant effects were seen for men (linear mixed model, including adjusting for possible confounders). The rate of cognitive decline was similar for drinkers and nondrinkers for all cognitive domains, except for MMSE, which declined significantly less in female drinkers than nondrinkers (linear mixed model attenuated rate of decline=0.05 MMSE units per annum, P=.001).

Drinking low to moderate amounts of alcohol may delay age-associated cognitive decline in older women (including slowing deterioration in global cognitive function), but these apparent benefits were not clearly seen in older men

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A selective Gβγ-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol
PNAS December 23, 2008 vol. 105 no. 51 20523-20528

The current understanding about ethanol effects on the ligand-gated ion channel (LGIC) superfamily has been restricted to identify potential binding sites within transmembrane (TM) domains in the Cys-loop family.
Here, we demonstrate a key role of the TM3–4 intracellular loop and Gβγ signaling for potentiation of glycine receptors (GlyRs) by ethanol. We discovered 2 motifs within the large intracellular loop of the GlyR α1 subunit that are critical for the actions of pharmacological concentrations of ethanol. Significantly, the sites were ethanol-specific because they did not alter the sensitivity to general anesthetics, neurosteroids, or longer n-alcohols. Furthermore, Gβγ scavengers selectively attenuated the ethanol effects on recombinant and native neuronal GlyRs.
These results show a selective mechanism for low-ethanol concentration effects on the GlyR and provide a mechanism on ethanol pharmacology, which may be applicable to other LGIC members.
Moreover, these data provide an opportunity to develop new genetically modified animal models and novel drugs to treat alcohol-related medical concerns.
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Similarities in Drinking Behavior of Twin’s Friends: Moderation of Heritability of Alcohol Use
Behavior Genetics Online First December 28, 2008

Previous research has indicated that friends’ drinking may influence alcohol use in adolescents and young adults.
We explored whether similarities in the drinking behavior of friends of twins influence the genetic architecture of alcohol use in adolescence and young adulthood.
Survey data from The Netherlands Twin Register were available for 1,526 twin pairs aged 16–25 years. We categorized the twin pairs as concordant (both report similar alcohol use in their friends) or discordant for the alcohol use of their friends. Genetic moderator models were tested by carrying out multi-group analyzes in Mplus.
Findings showed a significant moderation effect. Genetic factors were more and common environment less important in the explanation of variation in alcohol use in twins discordant for alcohol use of friends than in twins concordant for alcohol use of friends.
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Three-Year Changes in Adult Risk Drinking Behavior in Relation to the Course of Alcohol-Use Disorders
J. Stud. Alcohol Drugs 69: 866-877, 2008)

This study examines the associations between the course of alcohol-use disorder (AUD) and changes in average daily volume of ethanol intake, frequency of risk drinking, and maximum quantity of drinks consumed per day over a 3-year follow-up interval in a sample of U.S. adults.

There were positive changes in all consumption measures associated with developing an AUD and negative changes associated with remission of an AUD, even among individuals who continued to drink. Increases and decreases associated with onset and offset of dependence exceeded those associated with onset/offset of abuse only, and the decreases associated with full remission from dependence exceeded those associated with partial remission. There were few changes in consumption among individuals whose AUD status did not change.
Interactions of AUD transitions with other factors indicate that development of an AUD is associated with a greater increase in consumption among men, possibly reflecting their greater total body water and lower blood alcohol concentration in response to a given dose of ethanol, and among individuals with high baseline levels of consumption.

Changes in consumption associated with onset and offset of AUD are substantial enough to have important implications for the risk of associated physical and psychological harm.

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Health campaigns to curb binge brinking seen as 'unrealistic', say researchers

By Ben Leach
28 Dec 2008

Health campaigns warning of the dangers of alcohol are being ignored by many young people because they are seen as "unrealistic", a study shows.

Researchers at Birmingham and Bath universities said the Government must stop "demonising" young people in its attempts to promote safe drinking.

The study found that adverts such as this year's Home Office £4m anti-binge-drinking campaign, were viewed as "laughably unrealistic" in the way they portrayed binge drinking.
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Wine and health: state of proofs and research needs
Inflammopharmacology 16 (2008) 265–271

Regular moderate wine consumption is often associated with reduced morbidity and mortality from to a variety of chronic diseases in which inflammation is a root cause. Wine comes in a wide variety of styles that contain quite different ethanol and polyphenol contents.

Controversy remains as to whether the alcohol or polyphenols contribute more to the health benefits of regular moderate wine consumption. The variety of wines available to consumers can be expected to affect health differently in accordance with a particular wine’s total polyphenolic content and spectrum of individual polyphenols.

The overall effect of wine consumption on health depends upon the total amounts consumed, the style and possibly the pattern of consumption. The apparent effect of wine consumption may be modified by the non-wine diet composition of the consumer in that alcohol may appear as the primary component in consumers with high fruit, vegetable and whole grain intakes while phytochemical benefit may become significant in diets where wine is the primary dietary source of phytochemical.

In this review, wine polyphenol mechanisms of action will be reviewed in connection with the mechanism the development of atherosclerotic cardiovascular disease (ASCVD). Selected clinical studies published in 2004–2008 were reviewed.

Experimental requirements for valid clinical studies, translation of in vitro to in vivo application and areas where additional evidence needs to be developed were identified.

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Comparison of 3 Data Collection Methods for Gathering Sensitive and Less Sensitive Information
Ambulatory Pediatrics Volume 8, Issue 4, Pages 255-260

When gathering sensitive information about personal experiences such as child abuse, drug and alcohol use, and intimate partner violence (IPV), it is especially important for both research and clinical purposes to use optimal methods to limit socially desirable responses.

The purpose of this paper is to determine which of the following 3 methods is optimal for gathering data: 1) face-to-face interviews, 2) self-administered paper and pencil questionnaires, or 3) audio computer-assisted self-interviews (ACASI).

In general, ACASI yielded the highest rates for sensitive problems such as social isolation and parental stress, with face-to-face interviews occupying an intermediate position. The differences between ACASI and self-administered paper and pencil questionnaires were significant for many items. The differences between ACASI and face-to-face interviews, however, were modest. There were no significant group differences among the 3 methods in the prevalence rates of the neutral, less sensitive items.

ACASI resulted in greater disclosure of sensitive information than did a paper and pencil approach. No significant differences were observed between the computer-assisted interview and the face-to-face interview, both done in a research setting. The 3 methods appeared similar when gathering less sensitive data.

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Press Release - 'Tis the season to be jolly?

As the party season approaches, a timely reminder of the issues surrounding the binge drinking culture are again highlighted by research into 'young people and alcohol' a team led by Professor Christine Griffin, at the University of Bath. The research, funded by the Economic and Social Research Council (ESRC) suggests several considerations for future policy.

Focusing on the role of marketing practices in shaping young people's attitudes to alcohol consumption, the research included analysis of 216 alcohol adverts, both in print and broadcast. While extreme drinking and determined drunkenness may be perceived as the norm amongst young people, there is some positive news from the research. Evidence suggests that increases in young people's alcohol consumption is levelling off.

Previously, representations of binge drinking as a source of entertainment, coupled with pervasive coverage of drunken celebrities has increased the social acceptance of binge drinking. Advertising representing the 'coolness' of excessive drinking, along with the increasing use of internet based social networking sites that are used to share images of drunken nights out,, also enable the linkage between alcohol and 'having fun'.

Looking at what steps society may need to take to tackle the scourge of binge drinking, Professor Griffin says, "Top of my list would have to be to stop demonizing and making generalisations about young people and their drinking. We also need to listen and incorporate their views and perspectives."
. . . . .

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Branded Consumption and Social Identification: Young People and Alcohol

In most British towns and cities, young people drinking alcohol is now a central part of the night-time economy. For young people themselves, drinking to excess has become a normal part of a ‘good night out’ for many, and they are the target of extensive advertising and marketing campaigns by drinks manufacturers. All this has led to concern about risks to young people’s health and social problems related to their drinking.

This study (the Young People and Alcohol project) aimed to present a systematic and in-depth examination of young people’s own accounts of alcohol consumption and the part it plays in their lives. Interviews, focus groups and study visits to drinking venues were carried out in three different UK locations. The researchers analysed the results to assess the views of young people aged 18–25 on alcohol. The researchers also analysed a selected sample of 216 alcohol adverts aimed at young people to assess the influence of advertising and marketing. Finally, the project considered the implications for future policy and practice

Key Findings
  • Drinking alcohol is socially important in young people’s lives

  • Practices differ across gender, and less so across class, ethnicity and place

  • Advertising reflects the idea of drinking as ‘fun’

  • Overall, government policy needs to change to reflect how young people use alcohol

  • Future applications and research

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Regular binge drinking can cause long-term brain damage - study

Denis Campbell, health correspondent
The Guardian, Monday 29 December 2008

• High alcohol intake can affect mental abilities

• Researchers say findings should be a wake-up call

Just a few sessions of heavy drinking can damage someone's ability to pay attention, remember things and make good judgments, research shows

Binge drinkers are known to be at increased risk of accidents, violence and engaging in unprotected sex. But the study is the first to identify brain damage as a danger of consuming more alcohol than official safe limits.

The research, to be published in the journal Alcohol and Alcoholism, is significant because binge drinking is so widespread in the UK. Twenty-three per cent of men and 15% of women drink more than twice the government's recommended daily limit. For men this means consuming more than eight units a day and for women more than six, according to the Office for National Statistics.
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The Overlap in Predicting Alcohol Outcome for Two Measures of the Level of Response to Alcohol
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Two different measures have been used to establish a person's level of response (LR) to alcohol as a risk factor for alcohol use disorders. LR values established by the alcohol challenge protocol and the Self-Report of the Effects of Ethanol (SRE) questionnaire usually correlate at 0.3 to 0.4, up to 0.6. However, it is not clear how this correlation relates to the ability of each measure to predict alcohol outcomes. This paper evaluates that overlap.

Sixty-six Caucasian males (mean age = 22 years) from 2 protocols participated in alcohol challenges with 0.75 ml/kg of ethanol, filled out the SRE, and were followed with a structured interview ∼5 years later. The relationship between the subjective feelings of intoxication at the time of peak breath alcohol levels from the alcohol challenge and the SRE score for a time early in the drinking career were evaluated regarding predicting the drinks per occasion in the 6 months prior to follow-up.

Cross-sectional correlations between alcohol challenge and SRE LR's ranged from −0.25 (p < 0.05) to −0.32 (p = 0.02) for the full sample, and the 2 LR measures correlated with drinking at follow-up (−0.26 and 0.41, respectively). The SRE measure was more robust than the challenge in a regression analysis predicting the outcome in the context of other baseline predictors (e.g., drinking at baseline). As much as 60% of the ability of the more well established (gold standard) alcohol challenge LR to predict outcome was shared with the SRE. The alcohol challenge accounted for as much as 44% of the ability of the SRE to predict outcome.

The SRE-generated LR overlapped considerably with the alcohol challenge LR in the ability to predict future heavier drinking.

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Alcohol and Colorectal Cancer: The Role of Alcohol Dehydrogenase 1C Polymorphism
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Chronic alcohol consumption is a risk factor for colorectal cancer. Animal experiments as well as genetic linkage studies in Japanese individuals with inactive acetaldehyde dehydrogenase leading to elevated acetaldehyde concentrations following ethanol ingestion support the hypothesis that acetaldehyde may be responsible for this carcinogenic effect of alcohol. In Caucasians, a polymorphism of alcohol dehydrogenase 1C (ADH1C) exists resulting in different acetaldehyde concentrations following ethanol oxidation.

Genotype ADH1C*1/1 was more frequent in patients with alcohol-associated colorectal neoplasia compared to patients without cancers in the multivariate model controlling for age, gender, and alcohol intake (odds ratio = 1.674, 95% confidence interval = 1.110–2.524, 2-sided p from Wald test = 0.0139). In addition, the joint test of the genetic effect and interaction between ADH1C genotype and alcohol intake (2-sided p = 0.0007) indicated that the difference in ADH1C*1 polymorphisms between controls and colorectal neoplasia is strongly influenced by the alcohol consumption and that only individuals drinking more than 30 g ethanol per day with the genotype ADH1C*1/1 had an increased risk for colorectal tumors.

These data identify ADH1C homozygosity as a genetic risk marker for colorectal tumors in individuals consuming more than 30 g alcohol per day and emphasize the role of acetaldehyde as a carcinogenic agent in alcohol-related colorectal carcinogenesis.

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Long-Term Ethanol Exposure Impairs Neuronal Differentiation of Human Neuroblastoma Cells Involving Neurotrophin-Mediated Intracellular Signaling and in Particular Protein Kinase C
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Revealing the molecular changes in chronic ethanol-impaired neuronal differentiation may be of great importance for understanding ethanol-related pathology in embryonic development but also in the adult brain. In this study, both acute and long-term effects of ethanol on neuronal differentiation of human neuroblastoma cells were investigated. We focused on several aspects of brain-derived neurotrophic factor (BDNF) signaling because BDNF activates the extracellular signal-regulated kinase (ERK) cascade, promoting neuronal differentiation including neurite outgrowth.

Chronic ethanol interfered with the development of a neuronal network consisting of cell clusters and neuritic bundles. Furthermore, neuronal and synaptic markers were reduced, indicating impaired neuronal differentiation. BDNF-mediated activation of the ERK cascade was found to be continuously impaired by ethanol. This could not be explained by expressional changes monitored for TrkB, Raf-1, MEK, and ERK. However, BDNF also activates PKC signaling which involves RKIP, which finally leads to ERK activation as well. Therefore, we hypothesized that ethanol impairs this branch of BDNF signaling. Indeed, both PKC and RKIP were significantly down-regulated.

Chronic ethanol exposure impaired neuronal differentiation of neuroblastoma cells and BDNF signaling, particularly the PKC-dependent branch. RKIP, acting as a signaling switch at the merge of the PKC cascade and the Raf/MEK/ERK cascade, was associated with neuronal differentiation and significantly reduced in ethanol treatment. Moreover, PKC expression itself was even more strongly reduced. In contrast, members of the Raf-1/MEK/ERK cascade were less affected and the observed changes were not associated with impaired differentiation.

Thus, reduced RKIP and PKC levels and subsequently reduced positive feedback on ERK activation provide an explanation for the striking effects of long-term ethanol exposure on BDNF signal transduction and neuronal differentiation, respectively.

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Ethanol-Induced Conditioned Taste Avoidance: Reward or Aversion?
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue.

The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus.

Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol.

The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose.

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Genomewide SNP Screen to Detect Quantitative Trait Loci for Alcohol Preference in the High Alcohol Preferring and Low Alcohol Preferring Mice
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

The high and low alcohol preferring (HAP1 and LAP1) mouse lines were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice are essentially noninbred lines that originated from the outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice.

QTL analysis detected significant evidence of association on 4 chromosomes: 1, 3, 5, and 9. The region on chromosome 9 was previously found linked in a subset of these F2 animals using a whole genome microsatellite screen.

We have detected strong evidence of association to multiple chromosomal regions in the mouse. Several of these regions include candidate genes previously associated with alcohol dependence in humans or other animal models.

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Sunday, December 28, 2008

Press Release - New power and guidance to tackle alcohol-related crime

23 December 2008

A new power targeting offenders who commit crime under the influence of alcohol was unveiled today.

From next summer, drinking banning orders will allow police and local authorities to stop a person entering certain premises if they have been involved in criminal or disorderly conduct under the influence of alcohol. Breach of a drinking banning order, which can last up to two years, could lead to a fine of up to £2,500. The orders are focused on people whose drinking has been identified as a factor in their irresponsible and disorderly behaviour.

To add to the range of tools and powers to tackle alcohol-related crime and disorder, the government also published new guidance on obtaining designated public place orders and establishing alcohol disorder zones.

. . . . .

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News Release - “A drink or two may be good for baby?”

We are alarmed to learn of many recent news articles reporting the results of a recent epidemiological study entitled “Light drinking in pregnancy, a risk for behavioral problems and cognitive deficits at 3 years of age?” published by Dr. Yvonne Kelly and colleagues in the International Journal of Epidemiology (2008).
A few of the lay press reports include:

2)‐23580602‐‐ details/Light+drinking+in+pregnancy+will+not+be+a+mother% 7s+ruin/

FASDSG assembled a panel of Clinical and Basic Science Investigators who are currently conducting research in the field to discuss the impact of light drinking during pregnancy.

The following statement has been sent to the editors of several lay press reports.
. . . . .
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Alcohol and drugs in fatally and non-fatally injured motor vehicle drivers in northern Sweden
Analysis & PreventionVolume 41, Issue 1, January 2009, Pages 129-136 Accident

Alcohol and drugs are important risk factors for traffic injuries, a major health problm worldwide. This prospective study investigated the epidemiology and the presence of alcohol and drugs in fatally and hospitalized non-fatally injured drivers of motor vehicles in northern Sweden.

During a 2-year study period, blood from fatally and hospitalized non-fatally injured drivers was tested for alcohol and drugs. The study subjects were recruited from well-defined geographical areas with known demographics. Autopsy reports, medical journals, police reports, and toxicological analyses were evaluated.

Of the fatally injured, 38% tested positive for alcohol and of the non-fatally 21% tested positive; 7% and 13%, respectively, tested positive for pharmaceuticals with a warning for impaired driving; 9% and 4%, respectively, tested positive for illicit drugs. The most frequently detected pharmaceuticals were benzodiazepines, opiates, and antidepressants. Tetrahydrocannabiol was the most frequently detected illicit substance. No fatally injured women had illegal blood alcohol concentration.

The relative proportion of positively tested drivers has increased and was higher than in a similar study 14 years earlier.

This finding indicates that alcohol and drugs merit more attention in future traffic safety work

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Saturday, December 27, 2008

Integration of alcohol use disorders identification and management in the tuberculosis programme in Tomsk Oblast, Russia
The European Journal of Public Health Advance Access published online on December 26, 2008

Alcohol use disorders (AUDs) among tuberculosis (TB) patients are associated with nonadherence and poor treatment outcomes.

We developed a multidisciplinary model to manage AUDs among TB patients in Tomsk, Russia.

First, we assessed current standards of care through stakeholder meetings and ethnographic work. The Alcohol Use Disorders Identification Test (AUDIT) was incorporated into routine assessment of all patients starting TB treatment. We established treatment algorithms based on AUDIT scores. We then hired specialists and addressed licensing requirements to provide on-site addictions care.

Our experience offers a successful model in the management of co-occurring AUDs among patients with chronic medical problems.

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Tuesday, December 23, 2008

ADD Bulletin 5/2008: Malawi and WHO

Invitation to an NGO Alliance for a Global Strategy

NGOs worldwide are now invited to join an information sharing network connected to the WHO process leading up to a Global Strategy on alcohol. More information on how your organization can be affiliated to the network can be found here.
. . . . .

FORUT signs agreement with the Government of Malawi

The Government of Malawi and the Norwegian development NGO FORUT recently signed an agreement to cooperate on alcohol and drug prevention. The new Memorandum of Understanding is outlining the ambitions, intentions and motivation for the cooperation between the Government of the Republic of Malawi and FORUT. The parties have the common understanding that alcohol and drugs are obstacles to development and that it is important to develop evidence based alcohol policy and local prevention strategies to combat the harm of alcohol and drug.
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WHO Commission on Social Determinants of Health

Closing the gap in health inequities in a generation is the ambitious goal described in the report from the WHO Commission on Social Determinants on Health. The Commission calls on the WHO and all governments to lead global action on the social determinants of health with the aim of achieving health equity.
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Monday, December 22, 2008

Alcohol Primes the Airway for Increased Interleukin-13 Signaling
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Using an experimental model of airway fibrosis following lung transplantation, we recently showed that chronic alcohol ingestion by donor rats amplifies airway fibrosis in the recipient. Associated with alcohol-mediated amplification of airway fibrosis is increased transforming growth factor β-1(TGFβ1) and α-smooth muscle actin expression. Other studies have shown that interleukin-13 (IL-13) modulates TGFβ1 signaling during experimentally-induced airway fibrosis.

Therefore, we hypothesized that IL-13 is a component of alcohol-mediated amplification of pro-fibrotic mediators in the alcoholic lung.

Interleukin-13 expression was detected in type II alveolar epithelial cells and human bronchial epithelial cells, but not in lung fibroblasts. IL-13 expression was decreased in whole lung and type II cells in response to alcohol exposure. In all cell types analyzed, expression of IL-13 signaling receptor (IL-13Rα1) mRNA was markedly increased. In contrast, mRNA and protein expression of the IL-13 decoy receptor (IL-13Rα2) were decreased in all cells analyzed. Exposure to alcohol also increased STAT6 phosphorylation in response to IL-13 and lipopolysaccharide.

Data from multiple cell types in the pulmonary system suggest that IL-13 and its receptors play a role in alcohol-mediated activation of pro-fibrotic pathways. Taken together, these data suggest that alcohol primes the airway for increased IL-13 signaling and subsequent tissue remodeling upon injury such as transplantation.

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Alcohol Functionally Upregulates Toll-Like Receptor 2 in Airway Epithelial Cells
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Alcoholics are known to have more severe airway diseases of the lung, such as bronchitis. Little is known about why this phenomenon is observed. We hypothesized that alcohol may modulate Toll-like receptor 2 (TLR2), which regulates inflammation caused by gram-positive bacteria.

Alcohol, at biologically relevant concentrations (25 to 100 mM), caused a 2 to 3-fold time- and concentration-dependent increase in TLR2 mRNA in normal human bronchial epithelial cells and 16HBE 14o- cells. Western blots for TLR2 revealed a qualitative increase in TLR2 protein in cells exposed to 100 mM alcohol. FACS showed that TLR2 was quantitatively increased on the surface of airway epithelial cells that were exposed to alcohol. Airway cells that were primed with alcohol produced nearly twice as much IL-8 in response to 40 ng of peptidoglycan than naive cells.

Alcohol upregulates TLR2 message and protein in the airway epithelium. This leads to exaggerated inflammation in response to environmental stimuli that would normally be well tolerated in airway epithelial cells. This may be a partial explanation of why alcoholics have more severe airway disease than nonalcoholics.

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Characterization of White Matter Microstructure in Fetal Alcohol Spectrum Disorders
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure.

Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed.

These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.

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Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis
Human Molecular Genetics Advance Access published online on November 7, 2008

Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated.
This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use, and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSMIIIR criteria for AD.
There were study-wide significant associations (p<2.3x10–4) p="8.2x10–7)," p="2.7x10–6)," p="2.7x10–6)" p="8.9x10–8)">
After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (p=4.7x10–5) and suggestive associations (p<0.001)>
These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake.
The absence of study-wide significant effects on alcohol dependence results from the low p-value required when testing multiple SNPs and phenotypes.
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NHS must take long term approach to tackling unhealthy lifestyles

A new report states the NHS needs to change its approach to health prevention in order to successfully impact on key health risks including alcohol misuse, obesity and smoking. 'Commissioning and behaviour change; Kicking Bad Habits', produced by the King's fund, says more work is needed to ensure NHS staff are suitably skilled to ensure people choose and maintain healthier lifestyles. A long term approach from the NHS must be delivered as the UK's unhealthy habits are deep-rooted within society and can not be addressed by short term measures. . . . . .
Editorial: Raise Wisconsin's alcohol tax to help address issue

December 22, 2008

We know that too many people in Wisconsin drive drunk. We read about repeat drunken driving offenders almost every day.

And, as The Post-Crescent revealed in its extensive State of Drinking series last summer, Wisconsinites have a litany of other alcohol-related problems that rank high among states in the nation.

We appreciate that the Wisconsin District Attorneys Association wants to raise the state's beer and liquor taxes. This is long overdue. The beer tax hasn't been raised in almost 40 years and the tax on alcohol hasn't gone up since 1981. . . . . .

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Sunday, December 21, 2008

Social anxiety disorder as a risk factor for alcohol use disorders: A prospective examination of parental and peer influences
Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 128-137
Elucidation of mechanisms underlying the high rates of alcohol use disorder (AUD) remains a pressing clinical and research concern. Despite data indicating that social anxiety disorder (SAD) may be a psychological vulnerability that increases AUD risk, no known prospective research has examined underlying mechanisms. Given the nature of SAD, social support and peer alcohol use may be implicated.
The present study set out to clarify the SAD–AUD link in several ways using a prospective dataset comprised of 1803 (47% female) young adults at T1, 1431 of whom were assessed again approximately 3 years later. First, stringent criteria were used to directly test whether SAD was a risk for AUD. Second, we examined whether social support and peer alcohol use moderated the prospective SAD–AUD link. Structured diagnostic interviews were conducted to assess DSM-IV Axis I disorders, negative life events, social support, and peer alcohol use.
Among men, Time 1 (T1) SAD was not significantly related to Time 2 (T2) AUD. Yet, among women, T1 SAD was related to T2 AUD. Further, T1 SAD was the only internalizing disorder to significantly predict T2 AUD after controlling for relevant variables (e.g., T1 depression, other anxiety, alcohol and marijuana use disorders). The SAD–AUD relation demonstrated directional specificity. Family cohesion and adverse family relations significantly moderated this relation.
Findings highlight the important role of SAD and familial support in the onset of AUD among women.
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Change over time in alcohol consumption in control groups in brief intervention studies: systematic review and meta-regression study
Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 107-114
Reactivity to assessment has attracted recent attention in the brief alcohol intervention literature. This systematic review sought to examine the nature of change in alcohol consumption over time in control groups in brief intervention studies.
Primary studies were identified from existing reviews published in English language, peer-reviewed journals between 1995 and 2005. Change in alcohol consumption and selected study-level characteristics for each primary study were extracted. Consumption change data were pooled in random effects models and meta-regression was used to explore predictors of change. Eleven review papers reported the results of 44 individual studies. Twenty-six of these studies provided data suitable for quantitative study.
Extreme heterogeneity was identified and the extent of observed reduction in consumption over time was greater in studies undertaken in Anglophone countries, with single gender study participants, and without special targeting by age. Heterogeneity was reduced but was still substantial in a sub-set of 15 general population studies undertaken in English language countries.
The actual content of the control group procedure itself was not predictive of reduction in drinking, nor were a range of other candidate variables including setting, the exclusion of dependent drinkers, the collection of a biological sample at follow-up, and duration of study.
Further investigations may yield novel insights into the nature of behaviour change with potential to inform brief interventions design.
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Acute effects of alcohol on inhibitory control and information processing in high and low sensation-seekers
Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 91-99
Sensation-seeking is a personality characteristic that has been associated with drug abuse. Some evidence suggests that sensation-seekers might experience increased rewarding effects from drugs of abuse, possibly contributing to the association between sensation-seeking and risk for drug abuse.
The present study examined the effects of three doses of alcohol (0.0 g/kg, 0.45 g/kg, and 0.65 g/kg) on inhibitory control, information processing, and subjective ratings in a group of high sensation-seekers and a group of low sensation-seekers (N = 20). Inhibitory control was measured by a cued go/no-go task and speed of information processing was assessed by the Rapid Information Processing (RIP) task.
Alcohol impaired inhibitory control and information processing. Group differences were also observed. Compared with their low sensation-seeking counterparts, high sensation-seekers demonstrated increased sensitivity to the subjective rewarding effects of alcohol and a poorer degree of inhibitory control that was further impaired by alcohol.
The findings highlight reward- and cognitive-based mechanisms by which sensation-seeking could operate to increase risk for alcohol abuse.
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Induction of brain CYP2E1 changes the effects of ethanol on dopamine release in nucleus accumbens shell
Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 83-90
CYP2E1 is an important enzyme involved in the brain metabolism of ethanol that can be induced by chronic consumption of alcohol. Recent works have highlighted the importance of this system in the context of the behavioural effects of ethanol. Unfortunately, the underlying neurochemical events for these behavioural changes, has not been yet explored.
In this work, we have started this exploration by analyzing the possible changes in the neurochemical response of the mesolimbic system to ethanol after pharmacological induction of brain CYP2E1. We have used the dopamine extracellular levels in nucleus accumbens (NAc) core and shell, measured by means of microdialysis in vivo, as an index of the effects of ethanol.
Acetone 1% in the tap water was used to induce brain CYP2E1. Efficacy of the induction protocol was assessed by immunoblotting. Intravenous administration of 1.5 g/kg of ethanol in control rats provoked a significant increase of the dopamine levels in both the core (up to 127% of baseline) and the shell (up to 122% of baseline) of the NAc. However, the same dose of ethanol in acetone-treated rats only increased the dopamine extracellular levels in the core (up to 142% of baseline) whereas dopamine levels in the shell subregion remain unaltered relative to baseline.
The results of this study indicate that induction of CYP2E1 changes the response of the mesolimbic system to ethanol in a region-dependent manner. Two hypotheses are postulated to explain the observed effects.
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The Alcohol Use Disorders Identification Test revisited: Establishing its structure using nonlinear factor analysis and identifying subgroups of respondents using latent class factor analysis
Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 71-82
Previous research used principal components as well as exploratory and confirmatory factor analysis to establish continuous dimensions underlying answers to the 10-items of the Alcohol Use Disorders Identification Test (AUDIT). The majority of these studies conclude that one consumption dimension and an adverse consequences dimension explain the answers to the AUDIT sufficiently. However, most of the methods used presuppose normal answer distributions and linear relations between indicators and constructs, which are unrealistic assumptions for AUDIT answer.
First, to investigate the continuous factor analytic structure underlying the answers to all AUDIT items. Second and third, to assess the impact of consumption as well as age and gender on AUDIT consequences dimension. Fourth and fifth, to categorize respondents into subgroups based on the AUDIT consequences items and adjusting the subgroups for differences in consumption, age and gender. Sixth, to describe the subgroups with respect to further adverse consequences of drinking.

Nonlinear factor analyses suggested two continuous correlated factors reflecting the adverse consequences of alcohol use: (1) harmful alcohol use, (2) alcohol dependence (aim 1). Consumption items did not prove to be reasonable construct indicators, but adverse consequences were predicted by consumption (aim 2), and also by age and gender (aim 3). Latent class factor analysis identified four subgroups based on the AUDIT consequences items (aim 4): one not affected (66%), and three subgroups defined by either harmful (15%) or dependent (9%), or combined harmful and dependent use (10%). These groups differed also with respect to further alcohol use consequences. Adjusting the subgroups for differences in consumption, age and gender (aim 5) reduced the non-affected subgroup and increased the subgroup with harmful and dependent use.

The AUDIT items cover three separable domains, i.e. consumption, harmful and dependent use, as originally intended. Hence, assessment of alcohol use does not substitute for assessing adverse consequences, as assumed in short versions of the AUDIT comprising only the AUDIT consumption items. Further, the dimensional as well as the LCFA subgroup solution imply that the respondents cannot be ordered along a single severity dimension without loss of information.
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Alcohol use disorders in patients with obsessive–compulsive disorder: The importance of appropriate dual-diagnosis
Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 173-177

To evaluate the prevalence and clinical associated factors of alcohol use disorders (AUD) comorbidity in a large clinical sample of patients with obsessive–compulsive disorder (OCD).

Forty-seven patients (7.5%) presented AUD comorbidity. Compared to OCD patients without this comorbidity they were more likely to be men, to have received previous psychiatric treatment, to present lifetime suicidal thoughts and attempts and to have higher scores in the hoarding dimension. They also presented higher comorbidity with generalized anxiety and somatization disorders, and compulsive sexual behavior. Substance use was related to the appearance of the first O.C. symptoms and symptom amelioration.

Although uncommon among OCD treatment seeking samples, AUD comorbidity has specific clinical features, such as increased risk for suicidality, which deserve special attention from mental health professionals. Future studies focused on the development of specific interventions for these patients are warranted.

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Saturday, December 20, 2008

Age of Onset and Temporal Sequencing of Lifetime DSM-IV Alcohol Use Disorders Relative to Comorbid Mood and Anxiety Disorders
Drug Alcohol Depend. 2008 April 1; 94(1-3): 234–245.

Understanding the temporal sequencing of alcohol use disorders (AUDs) nd comorbid mood and anxiety disorders may help to disentangle the etiological underpinnings of comorbidity. Methodological limitations of previous studies, however, may have led to inconsistent or inconclusive findings.

To describe the temporal sequencing of the onset of AUDs relative to the onset of specific comorbid mood and anxiety disorders using a large, nationally representative survey.

AUD onset tended to follow the onset of 2 of the 9 mood and anxiety disorders (specific and social phobia). The onset of alcohol abuse tended to precede the onset of 5 of the 9 mood and anxiety disorders (GAD, panic, panic with agoraphobia, major depression, and dysthymia), whereas the onset of alcohol dependence tended to precede the onset of only 2 of the 9 mood and anxiety disorders (GAD and panic). Lag times between primary and subsequent disorders generally ranged from 7–16 years. Comorbid individuals whose alcohol dependence came after panic with agoraphobia, hypomania, and GAD had increased risk of persistent alcohol dependence.

Alcohol abuse, but not dependence, precedes many mood and anxiety disorders. If the primary disorder does in fact play a causative or ontributing role in the development of the subsequent disorder, this role can best be described as “temporally distal.” However, in assessing the risk for persistent alcohol dependence, clinicians should not only consider the type of comorbid mood/anxiety disorder, but also the temporal ordering of these disorders.

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Association of NFKB1, which encodes a subunit of the transcription factor NF-[kappa]B, with alcohol dependence.
Human Molecular Genetics. 17(7):963-970, April 1, 2008.

A broad region on chromosome 4q has been linked to alcohol dependence (alcoholism). We hypothesized that such broad linkage regions represent the combined action of multiple genes.
Seeking to identify genes within that region that are associated with alcoholism, we have tested the association of NFKB1, located at 4q24, with alcoholism. NFKB1 encodes a 105 kDa transcription inhibitor that is cleaved to the 50 kDa DNA-binding subunit of the ubiquitous transcription factor NF-B. NF-B regulates many genes relevant to brain function, and its actions can be potentiated by ethanol; thus, NFKB1 is an excellent candidate gene for alcoholism.
Nineteen SNPs in and near NFKB1 were analyzed in a sample of 219 multiplex alcoholic families of European American descent. Family-based association analyses detected significant evidence of association with eight SNPs and marginal evidence for five more. The association was driven by the affected individuals with earlier onset of alcoholism (55% of the sample with onset 21 years). Further analysis of the age of onset as a quantitative variable provided evidence for the association of 12 SNPs in this gene.
Thus, variations in NFKB1 appear to affect the risk for alcoholism, particularly contributing to an earlier onset of the disease.

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News Release - UCSF Researchers Shed Light on Genetic Factors Behind Alcohol Dependence

By Robin Hindery

Understanding the genetic factors behind alcohol dependence — and using that information to improve treatment — has been the goal of many scientific studies. Now, a group of UCSF researchers has moved one step closer to unraveling what one called the “complicated web” of components that determine an individual’s response to alcohol and likelihood to abuse it.

In a recently published study, scientists from UCSF’s Ernest Gallo Clinic and Research Center took 367 white siblings with a family history of alcohol abuse and had each consume three alcoholic drinks over a 10-minute period at 10 a.m. . . . . .

Molecular Genetics of Alcohol-Related Brain Damage
Alcohol and Alcoholism Advance Access published online on December 18, 2008

In the scientific literature it has been repeatedly hypothesized that there is a heritable susceptibility to thiamine deficiency comparable to other hereditary metabolic disorders.

The aim of this paper is to review the most recent knowledge on the genetic susceptibility to the development of alcohol-related Wernicke–Korsakoff syndrome (WKS).

A literature review was carried out looking at the molecular genetics studies performed in alcohol-dependent patients affected by WKS.

A genetic component in the pathogenesis of WKS has been postulated since the late seventies. Since then, very few genetic studies have been carried out on candidate genes such as thiamine-dependent enzymes, alcohol-metabolizing enzymes and GABA receptors. The findings are controversial and not conclusive. Several authors reported the important role of the thiamine transporters in the pathogenesis of the thiamine deficiency disorders. Our findings on SLC19A2 and SLC19A3 suggest a potential role of these two genes in the pathophysiology of alcohol-related thiamine deficiency but further studies need to be carried out.

The WKS may be a very complex, multifactorial disorder where the interaction of multiple genes and environment plays an important role in the pathogenesis. However, it is still plausible that megaphenic gene effects are responsible for WKS susceptibility and the thiamine transport genes are good candidates for having such a role. Further genetic studies are definitely needed to investigate the association with candidate genes or linkage with hot spot areas.

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Involvement of A2A receptors in anxiolytic, locomotor and motivational properties of ethanol in mice
Genes, Brain and Behavior Volume 7 Issue 8, Pages 887 - 898

We have shown previously that mice lacking the adenosine A2A receptor (A2AR) generated on a CD1 background self-administer more ethanol and exhibit hyposensitivity to acute ethanol.
We aimed to investigate if the increased propensity of A2A−/− mice to consume ethanol is associated with an altered sensitivity in the motivational properties of ethanol in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms and with an altered development of sensitization to the locomotor effects of ethanol. We also tested their sensitivity to the anxiolytic effects of ethanol.
Our results show that A2A−/− mice produced on a CD1 background displayed a reduced ethanol-induced CPP and an increased sensitivity to the anxiolytic and locomotor-stimulant effects of ethanol, but they did not show alteration in ethanol-induced CTA and locomotor sensitization.
Ethanol-induced CPP, ethanol consumption and the locomotor effects of ethanol were also tested in A2A−/− mice produced on a C57BL/6J background.
Our results emphasized the importance of the genetic background because alteration in ethanol consumption and preference, ethanol-induced CPP and locomotor-stimulant effects were not found in knockout mice produced on the alcohol-preferring C57BL/6J genetic background. Finally, the A2AR agonist, 2-p-(2-carboxyethyl)-phenylethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice.
In conclusion, A2AR deficiency in mice generated on a CD1 background leads to high ethanol consumption that is associated with an increased sensitivity to the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in ethanol-induced CPP.
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Children admitted to hospital due to alcohol increasing

By Rebecca Smith, Medical Editor
17 Dec 2008

The number of children admitted to hospital due to alcohol has risen with those living in rural and isolated areas worst affected, official figures have revealed.

Almost 8,000 children under the age of 18 were admitted to hospital in 2006/7 a rise of more than five per cent in three years.

The data from the North West Public Health Observatory has calculated the alcohol-related health problems for each local authority area and found despite awareness campaigns and warnings from doctors illnesses and deaths caused by drinking continue to rise.

Areas with the highest child admissions due to drink are in rural places such as Copeland in Cumbria, the Isle of Wight, Rossendale in Lancashire, Wirral, and Halton in Cheshire.

The highest adult admissions though tended to be in major towns and cities, especially in the North West. . . . . .

Changes in the Episodic Memory and Executive Functions of Abstinent and Relapsed Alcoholics Over a 6-Month Period
Alcoholism: Clinical and Experimental Research Published Online: 16 Dec 2008

It is still unclear whether episodic memory and executive functions capacities can return to normal in abstinent patients over a 6-month period. Furthermore, the role of interim drinking in cognitive recovery is still not well known. Finally, further research is required to specify the predictive value of cognitive abilities at initial testing in the treatment outcome (abstinence or relapse).

The aims of the present study were therefore to measure changes in episodic memory and executive functions over a 6-month period in abstinent and relapsed alcoholics and to ascertain whether neuropsychological results at treatment entry can predict treatment outcome at follow-up.

Results showed that over the 6-month interval, the abstainers' episodic memory and executive performances had returned to normal, whereas the relapsers performed lower than before in the flexibility task. Episodic memory and executive functions recovery was correlated, in abstainers, with drinking history and age respectively. Finally, there was no significant difference regarding neuropsychological scores at baseline between abstainers and relapsers.

Over the 6-month interval, abstainers normalized episodic memory and executive performances whereas relapsers obtained executive results which were more severely impaired, emphasizing the influence of interim drinking on cognitive changes. Episodic memory, executive functions, the slave systems of working memory and attentional abilities did not appear to be reliable predictors of treatment outcome over a 6-month interval.

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Middle class over 45-year-olds now the most frequent drinkers

By Kate Devlin Medical Correspondent
17 Dec 2008

The middle class people over the age of 45 are now the most frequent drinkers in England, new NHS figures show.

Middle aged people who are on high incomes are the most likely to drink five or more nights a week, according to the statistics.

The findings add to growing concern over middle class drinkers and the damage their habits are doing to their bodies.

Earlier this year a report by the National Audit Office, the Government watchdog, warned that 10 million Britons were now drinking to "hazardous" levels. . . . . .

Chronic voluntary ethanol intake hypersensitizes 5-HT1A autoreceptors in C57BL/6J mice
Journal of Neurochemistry Volume 107 Issue 6, Pages 1660 - 1670

Alcoholism is a complex disorder involving, among others, the serotoninergic (5-HT) system, mainly regulated by 5-HT1A autoreceptors in the dorsal raphe nucleus. 5-HT1A autoreceptor desensitization induced by chronic 5-HT reuptake inactivation has been associated with a decrease in ethanol intake in mice.

We investigated here whether, conversely, chronic ethanol intake could induce 5-HT1A autoreceptor supersensitivity, thereby contributing to the maintenance of high ethanol consumption. C57BL/6J mice were subjected to a progressive ethanol intake procedure in a free-choice paradigm (3–10% ethanol versus tap water; 21 days) and 5-HT1A autoreceptor functional state was assessed using different approaches.

Acute administration of the 5-HT1A receptor agonist ipsapirone decreased the rate of tryptophan hydroxylation in striatum, and this effect was significantly larger (+75%) in mice that drank ethanol than in those drinking water. Furthermore, ethanol intake produced both an increased potency (+45%) of ipsapirone to inhibit the firing of 5-HT neurons, and a raise (+35%) in 5-HT1A autoreceptor-mediated stimulation of [35S]GTP-γ-S binding in the dorsal raphe nucleus.

These data showed that chronic voluntary ethanol intake in C57BL/6J mice induced 5-HT1A autoreceptor supersensitivity, at the origin of a 5-HT neurotransmission deficit, which might be causally related to the addictive effects of ethanol intake,

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Does Low to Moderate Alcohol Intake Protect Against Cognitive Decline in Older People?
Journal of the American Geriatrics Society Volume 56 Issue 12, Pages 2217 - 2224
To determine whether low to moderate alcohol intake is protective against cognitive decline in older people.

Forty-two percent of women and 71% of men were alcohol drinkers. Cognitive performance was better for female drinkers than nondrinkers for all cognitive domains over the 3.2-year follow-up; no significant effects were seen for men (linear mixed model, including adjusting for possible confounders). The rate of cognitive decline was similar for drinkers and nondrinkers for all cognitive domains, except for MMSE, which declined significantly less in female drinkers than nondrinkers (linear mixed model attenuated rate of decline=0.05 MMSE units per annum, P=.001).

Drinking low to moderate amounts of alcohol may delay age-associated cognitive decline in older women (including slowing deterioration in global cognitive function), but these apparent benefits were not clearly seen in older men.

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Mandatory drinks code closer to reality

19 December, 2008
By James Wilmore

But details of conditions not specified in Policing and Crime Bill

Government plans to introduce a national mandatory code of practice for the industry took a step closer yesterday with the official tabling of a new Bill.

If passed, the Policing and Crime Bill, first announced in the Queen’s Speech, will give Home Secretary Jacqui Smith the power to impose mandatory conditions on on-trade and off-trade premises. . . . .

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Limited Competition: Collaborative Study on the Genetics of Alcoholism (COGA) (U10)

This Funding Opportunity Announcement (FOA) issued by the National Institute on Alcoholism and Alcohol Abuse (NIAAA), National Institutes of Health, is a limited competition FOA soliciting a cooperative agreement (U10) application from investigators currently supported under an existing study, entitled “Collaborative Study of the Genetics of Alcoholism (COGA)” to (i) identify genetic variants that affect the susceptibility to develop alcohol dependence in adult and adolescent populations, (ii) determine molecular and functional mechanisms of these variants, (iii) identify and characterize gene x gene and gene x environment interactions leading to alcoholism, (iv) develop and refine phenotypes that will facilitate genetic analysis. (v) perform prospective studies of COGA probands.

The Collaborative Study of the Genetics of Alcoholism (COGA) is a joint multi-disciplinary project that has been supported by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) since 1989 and more recently also by the National Institute on Drug Abuse (NIDA). It seeks to identify the role of genes in susceptibility to (or protection from) developing alcohol dependence and related phenotypes. The ultimate goal is to understand the functional effects of variation at genes identified in these studies, including effects on expression, at the molecular and cellular level. Investigators with complementary expertise in molecular and cellular biology, neurophysiology, and psychiatry have collaborated over the years to identify genes in which nucleotide sequence variation affects the risk for alcoholism and related disorders. This approach was built on linkage and association studies in severely affected individuals within families. COGA collected data from more than 300 extended families consisting of more than 3,000 individuals. This dataset is a rich resource for alcohol researchers and for investigators interested in determining the genetic basis of other complex disorders that frequently influence the development of alcoholism, such as anxiety and major depression. The COGA dataset has also served the larger research community as a resource for examining functionally-based endophenotypes and in testing new analytical approaches