Who benefits most from the cardioprotective properties of alcohol consumption—health freaks or couch potatoes?
Journal of Epidemiology and Community Health 2008;62:905-908

The cardioprotective properties of moderate alcohol consumption, compared with abstinence or heavy drinking, are widely reported, but whether the benefits are experienced equally by all moderate drinkers is less well known.

To examine the association between average alcohol intake per week and the incidence of fatal and non-fatal myocardial infarction during 17 years of follow-up for 9655 men and women without prevalent disease in the general population; and to test whether the level of cardioprotection differs according to subjects’ other health behaviours (healthy, moderately healthy, unhealthy) at entry to the study.

A significant benefit of moderate drinking compared with abstinence or heavy drinking was found among those with poor health behaviours (little exercise, poor diet and smokers). No additional benefit from alcohol was found among those with the healthiest behaviour profile.

The cardioprotective benefit from moderate drinking does not apply equally to all drinkers, and this variability should be emphasised in public health messages.

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News Release - Key enzyme for regulating heart attack damage found, Stanford scientists report


BY ERIN DIGITALE
September 11, 2008

STANFORD, Calif. — Marauding molecules cause the tissue damage that underlies heart attacks, sunburn, Alzheimer’s and hangovers. But scientists at the Stanford University School of Medicine say they may have found ways to combat the carnage after discovering an important cog in the body’s molecular detoxification machinery.

The culprit molecules are oxygen byproducts called free radicals. These highly unstable molecules start chain reactions of cellular damage—an escalating storm that ravages healthy tissue.

“We’ve found a totally new pathway for reducing the damage caused by free radicals, such as the damage that happens during a heart attack,” said Daria Mochly-Rosen, PhD, professor of chemical and systems biology and the senior author of a study reporting the new findings. The research appears in the Sept. 12 issue of Science.
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Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart
Science 12 September 2008:
Vol. 321. no. 5895, pp. 1493 - 1495


There is substantial interest in the development of drugs that limit the extent of ischemia-induced cardiac damage caused by myocardial infarction or by certain surgical procedures.

Here, using an unbiased proteomic search, we identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models.

A high-throughput screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats before an ischemic event, reduced infarct size by 60%, most likely through its inhibitory effect on the formation of cytotoxic aldehydes. In vitro, Alda-1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is found in 40% of East Asian populations.

Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type or mutant ALDH2 who are subjected to cardiac ischemia, such as during coronary bypass surgery.

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Web-based norms for the Drinker Inventory of Consequences from the Drinker's Checkup
Journal of Substance Abuse Treatment Volume 35, Issue 3, October 2008, Pages 322-327


To date, the only published norms for the Drinker Inventory of Consequences (DrInC) have come from a sample of heavy drinkers in Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) who were enrolling in a treatment program.

We have generated an additional set of norms for the DrInC based on a large sample (N = 1,564) of heavy drinkers who have completed the DrInC as part of a Web-based brief motivational intervention, the Drinker's Checkup (DCU; www.drinkerscheckup.com). Although these drinkers were not seeking formal treatment, they were concerned enough about their drinking to pay $25 to use the DCU.

Comparing the means and decile scores for lifetime and recent total scores and subscale scores between the DCU and MATCH samples revealed that DrInC scores for the DCU sample were significantly lower than the MATCH sample.

These findings have implications for giving normative feedback using the DrInC with non-treatment-seeking populations. The use and limitations of these findings are discussed.

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Request Reprint E-Mail: reidhester@lobo.net
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Guidance for GP alcohol Direcet Enhanced Service

Friday, September 12, 2008

A guidance document has been released to support the delivery of clinical directed enhanced services, alcohol being one of the five key health and service priorities. The DES allows specific funding for GPs to deliver Screening and Brief Interventions (SBIs) to newly registered patients. The DESs began in April 2008 and are scheduled to run for 2 years backed by £50 million funding proposed earlier in the year, with an annual £8 million alcohol allocation.

According to the guidance, practices are required to screen newly registered patients using a shortened screening tool such as FAST. Those identified as positive will be given the full AUDIT test to determine if they are drinking at hazardous or harmful levels, and then offered the recommended intervention of 5 minutes brief advice in line with University of Newcastle's primary care guidance 'How Much is too much?'. Dependant drinkers should be referred to local treatment services.

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Ethanol Enhances Glutamate Transmission by Retrograde Dopamine Signaling in a Postsynaptic Neuron/Synaptic Bouton Preparation From the Ventral Tegmental Area
Neuropsychopharmacology advance online publication 10 September 2008


It is well documented that somatodendritically released dopamine is important in the excitability and synaptic transmission of midbrain dopaminergic neurons. Recently we showed that in midbrain slices, acute ethanol exposure facilitates glutamatergic transmission onto dopaminergic neurons in the ventral tegmental area (VTA). The VTA is a brain region critical to the rewarding effects of abused drugs, including ethanol.

We hypothesized that ethanol facilitation might result from an increase in somatodendritically released dopamine, which acts retrogradely on dopamine D₁ receptors on glutamate-releasing axons and consequently leads to an increase in glutamate release onto dopaminergic neurons. To further test this hypothesis and to examine whether ethanol facilitation can occur at the single-cell level, VTA neurons were freshly isolated from rat brains using an enzyme-free procedure. These isolated neurons retain functional synaptic terminals, including those that release glutamate. Spontaneous excitatory postsynaptic currents (sEPSCs) mediated by glutamate -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors were recorded from these freshly isolated putative dopaminergic neurons.

We found that acute application of clinically relevant concentrations of ethanol (10–80 mM) significantly facilitated the frequency of sEPSCs but not their mean amplitude. Ethanol facilitation was mimicked by the D₁ agonist SKF 38393 and by the dopamine uptake blocker GBR 12935 but was blocked by the D₁ antagonist SKF 83566, and by depleting dopamine stores with reserpine, as well as by chelating postsynaptic calcium with BAPTA.

Furthermore, the sodium channel blocker tetrodotoxin eliminated the facilitation of sEPSCs induced by ethanol but not by SKF 38393. These results constitute the first evidence from single isolated cells of ethanol facilitation of glutamate transmission to dopaminergic neurons in the VTA.

In addition, we show that ethanol facilitation has a postsynaptic origin and a presynaptic locus.

Furthermore, ethanol stimulation of a single dopaminergic neuron is capable of eliciting the release of somatodendritic dopamine, which is sufficient to influence glutamatergic transmission at individual synapses.

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Alcohol Abuse/Dependence Symptoms Among Hospital Employees Exposed to a SARS Outbreak
Alcohol and Alcoholism Advance Access published online on September 12, 2008


The aim of this study was to examine alcohol abuse/dependence symptoms among hospital employees exposed to a severe acute respiratory syndrome (SARS) outbreak, and the relationship between types of exposure to the SARS outbreak and subsequent alcohol abuse/dependence symptoms.

Current alcohol abuse/dependence symptom counts 3 years after the outbreak were positively associated with having been quarantined, or worked in high-risk locations such as SARS wards, during the outbreak. However, having had family members or friends contract, SARS was not related to alcohol abuse/dependence symptom count. Symptoms of PTS and of depression, and having used drinking as a coping method, were also significantly associated with increased alcohol abuse/dependence symptoms. The relationship between outbreak exposure and alcohol abuse/dependence symptom count remained significant even when sociodemographic and other factors were controlled for. When the intrusion, avoidance and hyperarousal PTS symptom clusters were entered into the model, hyperarousal was found to be significantly associated with alcohol abuse/dependence symptoms.

Exposure to an outbreak of a severe infectious disease can, like other disaster exposures, lead not only to PTSD but also to other psychiatric conditions, such as alcohol abuse/dependence. The findings will help policy makers and health professionals to better prepare for potential outbreaks of diseases such as SARS or avian flu.

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Request Reprint E-Mail: pw11@columbia.edu
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An Intervention for Treating Alcohol Dependence: Relating Elements of Medical Management to Patient Outcomes With Implications for Primary Care
Annals of Family Medicine 6:435-440 (2008)


Alcohol dependence, frequently seen in medical settings, is a major problem that affects the health and well-being of many individuals and their families.

The purpose of this study was to examine the relationship between treatment outcomes and patient and clinician factors specifically associated with a medically oriented intervention given for the treatment of alcohol dependence. The intervention was developed for the National Institute on Alcohol Abuse and Alcoholism–sponsored COMBINE Study, a randomized controlled trial combining 2 medications, naltrexone and acamprosate, with Medical Management, with or without specialty alcohol treatment.

We examined the effect of patient adherence to treatment (number of Medical Management visits, total minutes in treatment, alliance or therapeutic relationship with the clinician, patient satisfaction with treatment, and clinician adherence to the Medical Management protocol) on abstinence from alcohol, amount of heavy drinking, and clinical improvement during treatment.

More Medical Management visits attended and less total time spent in Medical Management treatment was associated with more days of abstinence from alcohol, reductions in heavy alcohol drinking, and a higher likelihood of clinical improvement. The patients’ positive perceptions of their alliance with their clinician and their satisfaction with treatment was significantly associated with more days of abstinence from alcohol during treatment. Two clinician factors clinician confidence in the Medical Management treatment and flexibility in delivering Medical Management were also associated with better patient outcomes.

Medically trained clinicians with minimal specialty training in alcohol dependence treatments were able to deliver a brief and effective medication management intervention that was designed to be consistent with primary care practice.

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Request Reprint E-Mail: dernst@unm.edu
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News Release - Novel Compound Shows Promise for Treatment of Alcoholism

BIRMINGHAM, Ala. (September 11, 2008) - Southern Research Institute and Gallo Research Center today announced that peer-reviewed results from a study testing Naltrexone-derived pyridomorphinan (SoRI-9409) will be published in the December 2008 issue of the journal Biological Psychiatry. The publication is available online today at the journal's website, and suggests that a new compound that causes selective and long-lasting reduction in ethanol consumption might be a promising candidate as a novel treatment for alcoholism.

The article, "A Novel Delta Opioid Receptor Antagonist, SoRI-9409, Produces a Selective and Long-Lasting Decrease in Ethanol Consumption in Heavy-Drinking Rats" by Selena Bartlett, BPharm PhD, Director of Preclinical Development Group at the Gallo Research Center at University of California San Francisco, et al presents the effects of SoRI-9409 on ethanol consumption. These are promising developments for the treatment of alcoholism. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) estimates 15.1 million people are alcohol-abusing or alcohol-dependent individuals. There are currently only three FDA-approved options for the treatment of alcoholism.

The compound, SoRI-9409, was first designed and synthesized in Southern Research's Drug Discovery research division by Dr. Subramaniam (Sam) Ananthan under U.S. Government Grant DA008883. "Southern Research has been particularly interested in ligands that interact with opioid delta receptor subtype since such ligands hold promise as therapeutic agents for treatment of drug addictions and other disorders," said Dr. Ananthan, senior scientist and manager of Computational Chemistry and CNS Discovery Chemistry at Southern Research Institute. "The present findings by Dr. Bartlett and her group on the effect of SoRI-9409 on its ability to reduce alcohol intake not only provides us with a new drug lead, but also serves as the impetus for further research aimed at discovery of new therapeutic compounds for treating alcoholism and related disorders."

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A Novel Delta Opioid Receptor Antagonist, SoRI-9409, Produces a Selective and Long-Lasting Decrease in Ethanol Consumption in Heavy-Drinking Rats
Biological Psychiatry Article in Press, 6 September 2008

Naltrexone, a compound with high affinity for the μ opioid receptor (MOP-R) reduces alcohol consumption. SoRI-9409 is a derivative of naltrexone that has highest affinity at δ opioid receptors (DOP-Rs).

We have investigated the effects of SoRI-9409 on ethanol consumption to determine the consequences of altering the naltrexone compound to a form with increased efficacy at DOP-Rs.

In high- but not low-ethanol–consuming animals, SoRI-9409 is threefold more effective and selective at reducing ethanol consumption when compared with naltrexone or naltrindole for up to 24 hours. SoRI-9409 administered daily for 28 days continuously reduced ethanol consumption, and when the administration of SoRI-9409 was terminated, the amount of ethanol consumed remained lower compared with vehicle-treated animals. Furthermore, SoRI-9409 inhibits DOP-R–stimulated [³⁵S]GTPγS binding in brain membranes of high-ethanol–consuming rats.

SoRI-9409 causes selective and long-lasting reductions of ethanol consumption. This suggests that compounds that have high affinity for DOP-Rs such as SoRI-9409 might be promising candidates for development as a novel therapeutic for the treatment of alcoholism.

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Request Reprint E-Mail: selenab@gallo.ucsf.edu

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News Release - MillerCoors Under Fire for Raunchy, Soft Porn Ads for Controversial "Sparks" Energy Brew


Sponsored Videos on Heavy.com Aimed at 18+ Violate Industry�s Voluntary Advertising Code

WASHINGTON�Megabrewer MillerCoors is coming under fresh fire for advertising its caffeinated alcoholic drink Sparks with web videos that portray drug use, explicit sexual content, misogyny, and that otherwise exude general raunchiness. The company was already under investigation by state attorneys general and the target of a civil lawsuit filed earlier this week by the nonprofit Center for Science in the Public Interest.

The video series, which casts men with dwarfism in a parody of HBO�s Entourage, is sponsored by Sparks, framed by ads for Sparks, and has cans of Sparks placed throughout two of the three episodes available on the Heavy.com web site. CSPI today notified the Beer Institute and the Federal Trade Commission that the "Tiny Entourage" ads violate the letter of the industry's voluntary marketing code and will serve as an important test of how, or whether, the industry can continue to self-regulate.

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Culture Alcohol & Society Quarterly
Newsletter of Kirk/CAAS Collections at Brown

Vol. III no. 6 January/February/March 2008

CONTENTS

News and Notes pp. 2-5
News: AHA/ADHS Panels Jan 2009 pp. 2-3
A Washingtonian Anniversary p. 3
Notes on Early AA and Early AAs pp. 3-5
The Messengers to Ebby: A Letter to the Editor from Jack G. pp. 5-8
From Samuel George Blythe , The Old Game (1914, pp. 9-25), pp. 8-11
From Margie Lee Rumbeck, Answer Without Ceasing (1949), pp. 11-23
Washingtonian Notes and Queries (no. 20) pp.23-24


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Factors Mediating the Association Between Drinking in the First Year After Alcohol Treatment and Drinking at Three Years
J. Stud. Alcohol Drugs 69: 728-737, 2008


Previous research has shown a significant relationship between alcohol consumption in the first year following alcohol treatment admission and longer term functioning. This finding is clinically important and pertains to the clinical course of alcohol-use disorders(AUDs).

This study investigated mediators of these relationships, focusing on the first year after treatment admission and alcohol consumption 3 years later.

Model tests by use of structural equation modeling methods showed poor model fit, owing primarily to problems involving the psychosocial-functioning variable. Consequently, a reduced model was tested that dropped the psychosocial factor. Initial tests of this model showed an excellent fit to the data that replicated across subsamples and 3-year drinking variables at the overall model and individual path levels. There was strong support for the hypothesis that the total effects of first-year alcohol use on 3-year drinking is mediated in part (31% and 23% for the two drinking outcomes) through self-efficacy to abstain from alcohol at 15 months.

First-year posttreatment admission alcohol use predicts longer term (3-year) alcohol use, and a substantial portion of this relationship seems to be mediated through self-efficacy at 15 months to abstain from alcohol use. The apparent benefit of sustained abstinence in the first year may be in part the result of facilitation in the rate or strength of the acquisition of self-efficacy. Discussed are the clinical implications of these findings as well as directions for future research involving longitudinal studies of alcohol use, treatment experiences, psychosocial factors, and their interaction both within the first year and afterward in the determination of the clinical course of alcohol-use disorders.

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Request Reprint E-Mail: samaisto@syr.edu
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Multiple-Domain Predictors of Problematic Alcohol Use in Young Adulthood
J. Stud. Alcohol Drugs 69: 649-659, 2008


The goal of this study was to identify predictors of problematic young adult alcohol use.

The sample consisted of 141 subjects (81 females) participating in a national study of genetic risk factors for alcoholism. All subjects were evaluated first as children or adolescents, then approximately 5 years later as young adults. Outcome consisted of the number of alcohol symptoms (0-10) endorsed at this second time point. Predictors of outcome were drawn from five domains representing: (1) Demographic Characteristics, (2) Child/Adolescent Problematic Alcohol Use, (3) Biological Risk, (4) Externalizing Behaviors, and (5) Family Environment. A two-stage analytic strategy was used in which (1) separate multiple regression analyses were conducted within each of the five domains and (2) statistically significant predictors of problematic alcohol use from each domain were combined into one regression model to determine which remained significant.

In the final model, 31% of the variance in the number of alcohol symptoms in young adulthood was predicted by a high number of alcohol symptoms in childhood and adolescence, low initial sensitivity to alcohol, and a negative child/adolescent relationship with the father.

These results demonstrated that GABRA2 originally associated with a diagnosis of alcohol dependence in adults also predicted the onset of symptoms among subjects in their 20s, confirmed specific hypotheses about three other predictors in the final model, and suggested the utility of incorporating biological and nonbiological predictors to optimally predict young adult alcohol problems.


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Request Reprint ER-Mail: john-kramer@uiowa.edu

Neighborhood Socioeconomic Status Effects on Adolescent Alcohol Outcomes Using Growth Models: Exploring the Role of Parental Alcoholism
J. Stud. Alcohol Drugs 69: 639-648, 2008


There is conflicting evidence regarding the impact of neighborhood socioeconomic status (SES) on adolescent alcohol use. The current study tested whether the prospective effects of neighborhood SES on adolescent alcohol outcomes varied across parental alcoholism subgroups.

Among non-COAs, higher neighborhood SES predicted increased rates in alcohol use and consequences, whereas among COAs, lower neighborhood SES was predictive of increased rates in alcohol use and marginally predicted rates of consequences. There were also time-specific effects of family mobility on alcohol outcomes.

The current study provides evidence for differential effects of neighborhood SES on adolescent alcohol use and consequences for non-COAs and COAs. The group differences found in this study may help explain the equivocal findings from previous neighborhood studies, which may use samples with an unmeasured mix of high- and low-risk adolescents.

Future research should identify pathways to alcohol use and problems for high- and low-risk adolescents living in neighborhoods that span the range of the socioeconomic spectrum.

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Request Reprint E-Mail: ryan.trim@asu.edu

Alcohol Dependence and Reproductive Onset: Findings in Two Australian Twin Cohorts
Alcoholism: Clinical and Experimental Research Published Online: 5 Sep 2008

Although early alcohol use is a strong predictor of future alcohol problems and adolescent drinking is associated with risky sexual behavior predictive of early childbearing, reproductive dysfunctions associated with delayed childbearing have been reported in adult drinkers.

We examine the relationship between lifetime history of alcohol dependence (AD) and timing of first childbirth across reproductive development.

Results suggest alcoholic women in both cohorts show overall delayed reproduction, with little effect of AD on timing of first reproduction in men. Effects of AD are particularly strong for women in the older cohort, where AD is associated with 73% decreased likelihood of first childbirth after age 29 [hazard ratio (HR) = 0.27, 95% CI: 0.10–0.75]. In adjusted models, effects reduce only slightly (HR = 0.29, 95% CI: 0.11–0.80). For women in the young cohort, AD is associated with delayed reproduction after age 24, with 40% decreased likelihood of first childbirth (HR = 0.60, 95% CI: 0.48–0.75). AD remains predictive in adjusted models, but without age interaction (HR = 0.72, 95% CI: 0.62–0.85).

Findings of delayed reproductive onset in alcoholic women are consistent with alcohol-related reproductive dysfunctions, although underlying mechanisms remain largely unknown. To better understand AD differences in reproductive onset, continued research on both biological and psychosocial risks is needed.

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Request Reprint E-Mail: maryw@matlock.wustl.edu

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Expression of Renin-Angiotensin System and Peroxisome Proliferator-Activated Receptors in Alcoholic Cardiomyopathy
Alcoholism: Clinical and Experimental Research Published Online: 9 Sep 2008

Alcoholic cardiomyopathy (ACM) develops in response to chronic alcohol intake and it is hypothesized that activation of the renin-angiotensin system (RAS) and disorders in energy metabolism may play important roles in its onset. Given that the expression of peroxisome proliferator-activated receptors (PPARα and PPARγ) changes with alterations in cardiac metabolism and myocardial remodeling, this study was designed to test the hypothesis that protein expression of PPARα and PPARγ is correlated with RAS activation in ACM.

Compared with controls, myocardial angiotensin (Ang) I, Ang II, and renin levels were progressively increased at 2, 4, and 6 months of alcohol intake. mRNA expression of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and AT1 was increased at 6 months. Moreover, activated RAS downregulated PPARα and upregulated PPARγ protein expression as ACM progressed. Finally, extracellular signal regulated kinase 1 and 2 (ERK1/2) was shown to play a key role in the regulation of protein expression of PPARα and PPARγ.

These results suggest that RAS is activated during the development of ACM. Moreover, ERK1/2 plays a key role in the regulation of protein expression of PPARα and PPARγ by RAS in ACM.

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Khama still battling alcohol

PATRICIA MAGANU
Staff Writer

FRANCISTOWN: President Ian Khama has challenged the private sector to be 'proactive rather than reactive'.He was speaking at the 10th National Business Conference (NBC) going on at Tati River Lodge in Francistown where he conducted the official opening and devoted some time to the topic of alcohol.

He said the private sector was late in its recent interest in the challenge posed by alcohol abuse.

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Schedule-induced Polydipsia in Lines of Rats Selectively Bred for High and Low Ethanol Preference
Behavior Genetics September 09, 2008


Ethanol drinking was assessed in the P/NP, HAD1/LAD1, and HAD2/LAD2 lines of rats under environmental conditions that produce schedule-induced polydipsia.

Female rats (n = 8/line), maintained at 85% of free-feeding body weights, underwent daily 1-h sessions during which 45-mg food pellets were delivered every 60 s. Water, 2, 4, 8, 16, or 32% w/v ethanol solution was available from a single bottle for 8 consecutive sessions at each concentration, with blood-ethanol levels (BELs) determined after selected sessions.

P and HAD2 rats drank more water and ethanol than their non-preferring counterparts, while HAD1 and LAD1 rats did not differ. Ethanol intake and BELs were positively correlated (r = 0.75) across lines. Finally, rats were allowed 14 daily choice sessions with 8% ethanol and water concurrently available. Water intake generally exceeded ethanol intake in all lines, while P rats drank similar amounts of both fluids.

These line differences indicate pleiotropic effects of genes that mediate ethanol intake and schedule-induced behaviors.

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Request Reprint E-Mail: nickg@scripps.edu
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'Success' of under-21 alcohol ban is mere SNP spin, says professor

12 September 2008

By Michael Howie

Home Affairs Correspondent

LOCAL underage drinking crackdowns have provided no evidence that a national under-21 alcohol ban in shops and off-licences will reduce youth disorder, according to the country's top public health statistician.

Professor Sheila Bird, vice-president of the Royal Statistical Society, said it was "disappointing" that the Scottish Government's hugely controversial proposal had not been tested in properly controlled trials.
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