Impact of Chronic Alcohol Ingestion on Cardiac Muscle Protein Expression

Chronic alcohol abuse contributes not only to an increased risk of health-related complications, but also to a premature mortality in adults. Myocardial dysfunction, including the development of a syndrome referred to as alcoholic cardiomyopathy, appears to be a major contributing factor. One mechanism to account for the pathogenesis of alcoholic cardiomyopathy involves alterations in protein expression secondary to an inhibition of protein synthesis. However, the full extent to which myocardial proteins are affected by chronic alcohol consumption remains unresolved.

The purpose of this study was to examine the effect of chronic alcohol consumption on the expression of cardiac proteins. Male rats were maintained for 16 weeks on a 40% ethanol-containing diet in which alcohol was provided both in drinking water and agar blocks. Control animals were pair-fed to consume the same caloric intake. Heart homogenates from control- and ethanol-fed rats were labeled with the cleavable isotope coded affinity tags (ICAT™). Following the reaction with the ICAT™ reagent, we applied one-dimensional gel electrophoresis with in-gel trypsin digestion of proteins and subsequent MALDI-TOF-TOF mass spectrometric techniques for identification of peptides. Differences in the expression of cardiac proteins from control- and ethanol-fed rats were determined by mass spectrometry approaches.

Initial proteomic analysis identified and quantified hundreds of cardiac proteins. Major decreases in the expression of specific myocardial proteins were observed. Proteins were grouped depending on their contribution to multiple activities of cardiac function and metabolism, including mitochondrial-, glycolytic-, myofibrillar-, membrane-associated, and plasma proteins. Another group contained identified proteins that could not be properly categorized under the aforementioned classification system.

Based on the changes in proteins, we speculate modulation of cardiac muscle protein expression represents a fundamental alteration induced by chronic alcohol consumption, consistent with changes in myocardial wall thickness measured under the same conditions.

Read Full Abstract

Request Reprint E-Mail: tvary@psu.edu

____________________________________________________________

Inflexible and Indifferent Alcohol Drinking in Male Mice

Alcoholism is characterized by compulsive alcohol intake, but this critical feature of alcoholism is seldom captured in preclinical studies.

Here, we evaluated whether alcohol-preferring C57BL/6J mice develop compulsive alcohol drinking patterns, using adulteration of the alcohol solution with quinine, in a limited access choice paradigm. We assessed 2 independent aspects of compulsive drinking: (i) inflexible alcohol intake by testing whether mice would drink bitter alcohol solutions if this was their only source of alcohol and (ii) indifferent drinking by comparing intake of aversive and nonaversive alcohol solutions.

C57BL/6J mice rapidly developed compulsive alcohol drinking patterns. Adulteration of the alcohol solution with an aversive quinine concentration failed to reduce intake, indicative of inflexible drinking behavior, after only 2 weeks of alcohol experience, although quinine adulteration did suppress the acquisition of alcohol drinking in naïve mice. After 8 weeks of alcohol consumption, the mice also became indifferent to quinine. They consumed an aversive, quinine-containing alcohol solution, despite the simultaneous availability of an unadulterated alcohol solution. Prolonged alcohol ingestion did not alter the sensitivity to the bitter taste of quinine itself.

These findings demonstrate the staged occurrence in mice of 2 distinct behavioral characteristics of alcoholism, i.e., inflexible and indifferent alcohol drinking.

Read Full Abstract

Request Reprint E-Mail: h.m.b.lesscher@umcutrecht.nl

________________________________________________________

Transcallosal White Matter Degradation Detected With Quantitative Fiber Tracking in Alcoholic Men and Women: Selective Relations to Dissociable Functi

Excessive alcohol consumption can adversely affect white matter fibers and disrupt transmission of neuronal signals.

Here, we examined six anatomically defined transcallosal white matter fiber bundles and asked whether any bundle was specifically vulnerable to alcohol, what aspect of white matter integrity was most affected, whether women were more vulnerable than men, and whether evidence of compromise in specific bundles was associated with deficits in balance, sustained attention, associative learning, and psychomotor function, commonly affected in alcoholics.

Diffusion tensor imaging quantitative fiber tracking assessed integrity of six transcallosal white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy controls (42 men, 46 women). Measures included orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, quantified separately for axial (longitudinal; λL) and radial (transverse; λT) diffusivity. The Digit Symbol Test and a test of ataxia were also administered.

Alcoholism negatively affected callosal FA and λT of all but the sensory-motor bundle. Women showed no evidence for greater vulnerability to alcohol than men. Multiple regression analyses confirmed a double dissociation: higher diffusivity in sensory-motor and parietal bundles was associated with poorer balance but not psychomotor speed, whereas higher diffusivity in prefrontal and temporal bundles was associated with slower psychomotor speed but not balance.

This study revealed stronger alcohol effects for FA and radial diffusivity than axial diffusivity, suggesting myelin degradation, but no evidence for greater vulnerability to alcohol in women than men. The presence of brain-behavior relationships provides support for the role of alcoholism-related commissural white matter degradation as a substrate of cognitive and motor impairment. Identification of a double dissociation provides further support for the role of selective white matter integrity in specific domains of performance.

Read Full Abstract

Request Reprint E-Mail: edie@stanford.edu

_____________________________________________________________

MAOA Interacts With the ALDH2 Gene in Anxiety–Depression Alcohol Dependence

Alcohol dependence is usually comorbid with anxiety disorder, depressive disorder, or both; this comorbidity may increase drinking behavior. We previously hypothesized that anxiety–depressive alcohol dependence (ANX/DEP ALC) was a genetically specific subtype of alcohol dependence. ANX/DEP ALC may be related to dopamine and serotonin, which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2).

The aim of this study was to determine whether the interaction between the MAOA and the ALDH2 genes is associated with ANX/DEP ALC.

We recruited 383 Han Chinese men in Taiwan: 143 ANX/DEP ALC and 240 healthy controls. The diagnosis of ANX/DEP ALC (alcohol dependence with a past or current history of anxiety, depressive disorder, or both) was made using DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR (variable number of tandem repeat located upstream) were determined using PCR-RFLP.

The ALDH2, but not the MAOA-uVNTR, polymorphism was associated with ANX/DEP ALC. After stratifying the MAOA-uVNTR polymorphism, we found a stronger association between the ALDH2*1/*2 and *2/*2 genotypes and the controls in the MAOA-uVNTR 4-repeat subgroup. Logistic regression significantly associated the interaction between ALDH2 and MAOA variants with ANX/DEP ALC.

We conclude that the MAOA and ALDH2 genes interact in ANX/DEP ALC. Although the MAOA gene alone is not associated with ANX/DEP ALC, we hypothesize that different variants of MAOA-uVNTR polymorphisms modify the protective effects of the ALDH2*2 allele on ANX/DEP ALC in Han Chinese in Taiwan.

Read Full Abstract

Request Reprint E-Mail: rblu@mail.ncku.edu.tw

_________________________________________________________

Paradoxical Effects of Alcohol Information on Alcohol Outcome Expectancies

Cognitive associations with alcohol predict both current and future use in youth and young adults. Much cognitive and social cognitive research suggests that exposure to information may have unconscious influences on thinking and behavior.

The present study assessed the impact of information statements on the accessibility of alcohol outcome expectancies.

The 2 studies reported here investigated the effects of exposure to alcohol statements typical of informational approaches to prevention on the accessibility of alcohol outcome expectancies. High school and university students were presented with information statements about the effects of alcohol and other commercial products. The alcohol statements were taken from expectancy questionnaires. Some of these statements were presented as facts and others as myths. The retention of detailed information about these statements was manipulated by (i) divided attention versus focused attention or (ii) immediate versus delayed testing. Accessibility of personal alcohol outcome expectancies was subsequently measured using an open-ended question about the expected effects of alcohol.

Participants reported more alcohol outcomes seen during the information task as personal expectations about the effects of alcohol use than similar unseen items. Paradoxically, myth statements were also more likely to be reported as expectancies than unseen items in all conditions. Additionally, myth statements were generated less often than fact statements only under the condition of immediate testing with strong content processing instructions.

These observations are consistent with findings from cognitive research where familiarity in the absence of explicit memory can have an unconscious influence on performance. In particular, the exposure to these items in an informational format increases accessibility of the seen items even when the participants were told that they were myths. The findings have implications for the development of effective prevention materials.

Read Full Abstract

Request Reprint E-Mail: marvin.krank@ubc.ca

____________________________________________________________

Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol

A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol.

This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption.

A total of 30 matched high- and low-LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level-dependent response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task were examined across 120 fMRI sessions.

Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p <>

Alcohol had differential effects on brain activation for low- and high-LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.

Read Full Abstract

Request Reprint E-Mail: mschuckit@ucsd.edu

___________________________________________________________

Age-Related Changes in Drinking Patterns From Mid- to Older Age: Results From the Wisconsin Longitudinal Study

Drinking has generally been shown to decline with age in older adults. However, results vary depending on the measure of alcohol consumption used and the study population.

The goals of this study were to (i) describe changes in drinking in a current cohort of older adults using a variety of measures of drinking and (ii) examine a number of different possible predictors of change.

From age 53 to 64, average drinks per drinking day and heavy drinking decreased. Frequency of drinking increased for men and women, and total drinks per month increased for men. The most consistent predictors of drinking changes were gender, health, and education. Other factors predicted drinking change but were not consistent across drinking measures including: adolescent IQ, income, lifetime history of alcohol-related problems, religious service attendance, depression, debt, and changes in employment.

Heavy drinking decreases with age, but we may see more frequent moderate drinking with current and upcoming cohorts of older adults. Components of quantity and frequency of drinking change differently. Composite measures of total alcohol consumption may not be adequate for describing relevant changes in drinking over time. A number of factors predicted patterns of change in drinking and warrant further exploration.

Read Full Abstract

Request Reprint E-Mail: r.molander@hosp.wisc.edu

_______________________________________________________

Age of Drinking Onset as a Moderator of the Efficacy of Parent-Based, Brief Motivational, and Combined Intervention Approaches to Reduce Drinking and

The current study tested age of onset as a moderator of intervention efficacy on drinking and consequence outcomes among a high-risk population of college students (i.e., former high school athletes).

Students were randomized to one of four conditions: assessment only control, combined parent-based intervention (PBI) and brief motivational intervention (BMI), PBI alone, and BMI alone. Participants (n = 1,275) completed web-administered measures at baseline (summer before starting college) and 10-month follow-up.

Overall, the combined intervention demonstrated the strongest and most consistent reductions across all outcomes, particularly with the youngest initiators. Participants who initiated drinking at the youngest ages had significantly lower peak drinking, typical weekly drinking, and reported consequences at follow-up when they received the combined intervention when compared to the control group. The BMI and PBI groups, when examined independently, demonstrated significant effects across outcomes but were inconsistent across the different age groups.

Results suggest the combination of a PBI and a peer-delivered BMI is an appropriate and efficacious way to reduce drinking and related consequences among individuals who initiated drinking earlier in adolescence and are at an increased risk of experiencing alcohol problems.

Read Full Abstract

Request Reprint E-Mail: kmallett@psu.edu

_________________________________________________________

---

ERP and RT Delays in Long-Term Abstinent Alcoholics in Processing of Emotional Facial Expressions During Gender and Emotion Categorization Tasks

There is considerable evidence that alcoholics differ from nonalcoholics in the processing of stimuli that have emotional content. The current study examines those differences that are present in multi-year abstinent individuals.

We compared reaction time (RT), accuracy, and Event Related Potentials (ERP) measures in long-term abstinent alcoholics (LTAA, n = 52) with that in age- and gender-comparable nonalcoholic controls (NAC, n = 47). Subjects were presented with male and female faces exhibiting happy, neutral, or sad facial expressions and were instructed to identify the picture gender in 1 task and the emotion being expressed in a subsequent task.

LTAA had slower RTs than NAC when instructed to identify emotion, while RT was comparable when identifying gender. There were no differences between groups on task accuracy. P160 latency was increased in LTAA for both tasks compared to NAC, though P160 amplitude did not differ between groups. The P160 effect was about 5 × as large as the RT effect and was statistically independent of the RT effect, while the RT effect was no longer present after removing variance because of the P160 effect.

Our data demonstrate slower early processing of emotional facial stimuli in alcoholics that is unresolved by long-term abstinence and is most sensitively indexed by delayed P160 latency in LTAA.

Read Full Abstract

Request Reprint E-Mail: george@nbresearch.com

______________________________________________________

Ethanol Acutely Modulates mGluR1-Dependent Long-Term Depression in Cerebellum

Acute and chronic ethanol exposure produces profound impairments in motor functioning. Individuals with lower sensitivity to the acute motor impairing effects of ethanol have an increased risk of developing alcohol dependence and abuse, and infants with subtle delays in motor coordination development may have an increased risk for subsequently developing alcoholism. Thus, understanding the mechanism by which ethanol disrupts motor functioning is very important.

We determined whether ethanol acutely affects parallel fiber LTD using whole-cell patch-clamp recordings from Purkinje cells. Application of ethanol both externally (50 mM) and internally (17 and 10 mM) significantly suppressed mGluR-mediate slow currents. Short-term external ethanol exposure (50 but not 17 mM) during tetanus blocked mGluR-dependent parallel fiber LTD. Furthermore, internal 17 and 10 mM ethanol completely inhibited this LTD.

The results of the current study demonstrate that ethanol acutely suppresses parallel fiber LTD and may influence the mGluR-mediated slow current intracellularly. This study, plus previous evidence by Carta and colleagues (2006) and Belmeguenai and colleagues (2008), suggests significant actions of ethanol on mGluR-mediated currents and its dependent plasticity in brain.

Read Full Abstract

Request Reprint E-Mail: yshen@zju.edu.cn

_____________________________________________________________

Nearly Four Million California Adults Are Victims of Intimate Partner Violence

Nearly 1 in 6 adults in California, about 3.7 million persons, report experiencing physicalintimate partner violence (IPV) as adults. Over one million Californians were forced to have sex (5%) by an intimate partner during adulthood.

Overall, 17.2% of adults—nearly four million Californians—report being a victim of physical and/or sexual IPV as an adult (Exhibit 1). These acts of violence are not merely a criminal justice problem, but a public health problem with deep and lingering social, psychological and health-related costs.

Beyond the immediate trauma facing adult victims, IPV incidents may have a prolonged impact on the emotional and mental health of the victims, affect their ability to complete school or maintain employment, and result in adverse health behaviors to cope with the trauma, such as engaging in risky alcohol, tobacco or other drug use.

Violence that occurs between intimates or family members is especially damaging when it takes place in the presence of children; previous studies have shown that witnessing violence can lead to intergenerational cycles of violence.


Read Full Report (PDF)


________________________________________________________

Alcohol blamed for kick-starting suicide bids

A new study has found that alcohol is to blame for most suicide attempts by overdosing.

Wellington Hospital emergency doctor Paul Quigley says at least 80 per cent of the 127 people who turned up at his emergency department last year after taking an overdose had alcohol as "the initiating agent".

Most (56 per cent) arrived at the weekend, mainly on the "party nights" of Friday and Saturday.

"When you analyse it, where their situation started from is the two bottles of wine they had to start with, or the four bottles of wine," he told the Alcohol Advisory Council's annual conference in Manukau yesterday. . . . . .

Read More

____________________________________________________________

Media Release - AER WELCOMES HENRY RECOMMENDATIONS ON ALCOHOL TAXATION ALCOHOL REFORM MUST BE PUT BACK ON THE FEDERAL GOVT AGENDA

The Alcohol Education and Rehabilitation Foundation (AER), Australia's leading alcohol harm minimisation body, today welcomed the Henry Review recommendations on alcohol taxation reform, but said it is disappointed with the Federal Government’s response. . . . . .

Read Full Release (PDF)




__________________________________________________________

Energized Alcohol

Vodka and Red Bull has been the choice of concert and club goers almost since it was launched in the U.S. back in 1997. With more than one billion cans sold worldwide every year, and a significant percentage of those mixed with booze, it was only a matter of time before enterprising liquors decided to spare us all the effort of mixing the two - bottling their own premixed energy drinks with varying amounts of alcohol. . . . . . .

Read More

_____________________________________________________________

Treatment with Neuropeptides Attenuates c-fos Expression in a Mouse Model of Fetal Alcohol Syndrome

Fetal alcohol syndrome (FAS) is the most common nongenetic cause of mental retardation and is characterized by neurodevelopmental anomalies. C-fos is a cellular marker of transcriptional activity in the stress-signal pathway. Previously, we showed the treatment with NAP (NAPVSIPQ) + SAL (SALLRSIPA) reversed the learning deficit after prenatal alcohol exposure in FAS.

Our objective was to evaluate if the mechanism of actions of NAP + SAL involves the stress-signal pathway differentiating c-fos expression in mouse brains after prenatal alcohol exposure.

Adult treatment with NAP + SAL restored the down-regulation of c-fos in the hippocampus after prenatal alcohol exposure (p < class="ITALIC">c-fos expression in the cortex.

Adult treatment with NAP + SAL restored the down-regulation of c-fos expression in hippocampus attenuating the alcohol-induced alteration of the stress-signal pathway.

Read Full Abstract

Request Reprint E-Mail: incertim@mail.nih.gov

____________________________________________________________

Pen portraits: alcohol segmentation series report 4

To further understand population segmentation in alcohol misuse, the North West Public Health Observatory has published a series of four reports utilising segmentation tools to discuss alcohol consumption, attitudes and related admission.

The first three reports in the series discuss attitudes to alcohol consumption, consumption and related hospital admissions respectively.

This report, the fourth in the series, summarises the findings and presents them by classification in order to present an overview of the attitudes, consumption and harms experienced by each segmentation type.

Read Full Report (PDF)


_______________________________________________________

Alcohol-attributable hospital admission: segmentation series report 3

To further understand population segmentation in alcohol misuse, the North West Public Health Observatory has published a series of four reports utilising segmentation tools to discuss alcohol consumption, attitudes
and related admission.

This is the third report in the series and focuses on different types of alcohol-related hospital admissions.

Read Full Report (PDF)


________________________________________________________

Alcohol consumption: segmentation series report 2

Approximately a fifth of the population in England are thought to drink at hazardous levels of consumption, and a further 5% at harmful levels. Such levels of consumption are associated with a wide range of health, crime and economic harms. However, neither consumption nor harms are universally experienced, and in order to effectively target interventions, it is vital to understand which populations are most at risk.

Segmentation tools are one way of doing this, allowing the grouping of populations by age, gender, lifestyle, attitude and motivation. To further understand population segmentation in alcohol misuse, the North West Public Health Observatory has published a series of four reports utilising segmentation tools to discuss alcohol consumption, attitudes and related admission.

This is the second report in the series and focuses on alcohol, consumption levels, quantities and types of drinks consumed.

Read Full Report (PDF)


________________________________________________________

Attitudes to alcohol: segmentation report series 1

Approximately a fifth of the population in England are thought to drink at hazardous levels of consumption, and a further 5% at harmful levels. Such levels of consumption are associated with a wide range of health, crime and economic harms. However, neither consumption nor harms are universally experienced, and in order to effectively target interventions it is vital to understand which populations are most at risk.

Segmentation tools are one way of doing this, allowing the grouping of populations by age, gender, lifestyle, attitude and motivation. To further understand population segmentation in alcohol misuse, the North West Public Health Observatory has published a series of four reports utilising segmentation tools to discuss alcohol consumption, attitudes and related admission.

This is the first report in the series and focuses on attitudes and motivations around consumption. The second and third report discuss,consumption and hospital admissions respectively, whilst the fourth report in the series summarises the findings and presents them by classification in order to present an overview of the attitudes, consumption and harms experienced by each segmentation type.

Read Full Report (PDF)


_______________________________________________________

BRIEF ALCOHOL INTERVENTION RESEARCH AND PRACTICE—TOWARDS A BROADER PERSPECTIVE

The researchers who responded to my overview of brief alcohol intervention and implementation challenges for research and practice [1] seemed to agree with me on most issues. Perhaps there is little within this subject that is up ‘for debate’, then. Nevertheless, I would like to comment on some of the issues addressed by Allamani [2], Kaner [3] and Moyer & Finney [4]. . . . . .

Read Full Text (PDF)


__________________________________________________________

MEETING THE CHALLENGES FOR RESEARCH AND PRACTICE FOR BRIEF ALCOHOL INTERVENTION

Nilsen’s excellent essay [1] on remaining challenges in implementing brief intervention (BI) for hazardous and harmful drinkers calls for efforts to consider the context in which BIs occur, particularly at the organizational level, and to expand BI’s targets and reach. Here we note promising examples of steps toward meeting these challenges. . . . . . .

Read Full Text (PDF)


________________________________________________________

UNEXPLORED TERRITORIES

The conclusions on future challenges for brief intervention (BI) research and for BI dissemination into practice [1], as well as the summary of key BI research findings that the text provides, raise some stimulating issues. As found in the past, a major consideration when interpreting research findings is the difference between northern and southern Europe regarding alcohol research [2], and particularly research into BIs. As the references Nilsen’s paper demonstrate, there is no published BI material generated in southern European countries, even if there are a few exceptions that focus upon primary health care [3–5] or emergency rooms [6]. This i due probably to a combination of both little tradition of alcohol studies and less concern about drinking in southern Europe, where the meaning of alcohol beverages, drinking patterns and presumably hazardous drinking is divergent from other European regions and Englishspeaking countries.

As a consequence, it is worth asking whether further research on the effectiveness of BI is needed for southern Europe,where such a cultural diversity in drinking exists. This may be particularly useful when ‘obtaining knowledge for . . . understanding . . . under what conditions’ BI implementation interventions may work. . . . . . .

Read Full Text (PDF)


_________________________________________________________________

BRIEF ALCOHOL INTERVENTION: TIME FOR TRANSLATIONAL RESEARCH

Heavy drinking is the third greatest risk to public health in developed countries [1], although most of this risk is avoidable [2]. In the United Kingdom, a quarter of the population is affected adversely by their drinking behaviour [3]. Thus, preventing alcohol-related harm is a key public health imperative. This conclusion was reached by the World Health Organization (WHO) some 30 years ago, and it led to the emergence of screening and brief intervention techniques to help reduce heavy drinking. A veritable industry of research has ensued, and there have
now been more than 60 controlled trials of brief alcohol interventions spanning two decades [4,5]. Hence, Nilsen’s review [6] is a timely stock-take of this substantial evidence base and directions for future research and practice. . . . . .

Read Full Text (PDF)


______________________________________________________

Brief alcohol intervention—where to from here? Challenges remain for research and practice

Brief intervention (BI) is intended as an early intervention for non-treatment-seeking, non-alcohol-dependent, hazardous and harmful drinkers.

This text provides a brief summary of key BI research findings from the last three decades and discusses a number of knowledge gaps that need to be addressed.

Five areas are described: patient intervention efficacy and effectiveness; barriers to BI implementation by health professionals; individual-level factors that impact on BI implementation; organization-level factors that impact on BI implementation; and society-level factors that impact on BI implementation.

BI research has focused largely upon the individual patient and health professional levels, with the main focus upon primary health care research, and studies are lacking in other settings. However, research must, to a larger degree, take into account the organizational and wider context in which BI occurs, as well as interaction between factors at different levels, in order to advance the understanding of how wider implementation of BI can be achieved in various settings and how different population groups can be reached.

It is also important to expand BI research beyond its current parameters to investigate more ambitious long-term educational programmes and new organizational models. More widespread implementation of BI will require many different interventions (efforts, actions, initiatives, etc.) at different interlinked levels, from implementation interventions targeting individual health professionals' knowledge, skills, attitudes and behaviours concerning alcohol issues,

BI and behaviour change counselling to efforts at the organizational and societal levels that influence the conditions for delivering BI as part of routine health care.

Read Full Text (PDF)

____________________________________________________________

Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: A trial on pigs.

Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction.

The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) verify the functioning of a prototype of a new intraoral device in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery.

The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment.

The administration of I.V. NLX induced a sharp increase in blood levels after 5 minutes and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90 minutes, followed by a slow decrease. After 6 hours the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted.

These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route.

Read Full Abstract

Request Reprint E-Mail: campisi@odonto.unipa.it

______________________________________________________________

Differences in Substance Abuse Treatment Admissions between Mexican-American Males and Females

Among Mexican admissions, males reported alcohol as their primary substance of abuse more often than other substances, and females most commonly reported methamphetamine.

The majority of Mexican admissions reported that they first used their primary substance of abuse before the age of 18 (60.7 percent for males and 56.1 percent for females); overall, 7.4 percent reported using their first substance before the age of 12.

About three quarters of Mexican admissions had no health insurance (78.8 percent for males and 71.5 percent for females), a substantially higher proportion than non-Mexican admissions (62.6 percent for males and 50.9 percent for females).


Read Full Report (PDF)


______________________________________________________

Evidence-based alcohol screening and brief intervention in Aboriginal Community Controlled Health Services: Experiences of health-care providers

Alcohol screening and brief intervention (SBI) is a cost-effective treatment for reducing alcohol misuse in non-Indigenous populations. To increase the likelihood of alcohol SBI proving cost-effective for Indigenous Australians in practice, strategies to increase its uptake in Aboriginal Community Controlled Health Services (ACCHSs) should be implemented.

The aim of this study is to describe the experiences of health-care providers supported to implement evidence-based alcohol SBI in two ACCHSs.

Pre- and post-surveys were administered to health staff (n = 32) participating in training workshops, followed by group interviews with health-care providers delivering alcohol SBI. Patient group interviews were also conducted. Survey results were summarised using descriptive statistics and interviews were analysed using a phenomenological approach.

Thirty-two per cent (n = 10) of workshop participants were confident or very confident at baseline to deliver alcohol SBI, increasing significantly to 81% (n = P < 25) post-training (McNemar Test,0.05). Fifty-seven per cent (n = 16) of health-care providers attending workshops reported delivering alcohol SBI in the following 6 months. Group interviews with health-care providers elicited five themes relating to their experiences of alcohol SBI delivery. Patients in group interviews expressed a preference to be screened for alcohol as part of health assessments.

Training workshops appear to be an acceptable initial strategy for disseminating alcohol SBI to ACCHSs. Outreach support is required to assist health-care providers to tailor guidelines and resources, and optimally integrate their clinical skills with evidence-based practice. Patients' needs should inform the tailoring process. Tailored collaborative and supportive strategies are probably required to optimally disseminate alcohol SBI in ACCHSs.

Read Full Abstract

Request Reprint E-Mail: a.shakeshaft@unsw.edu.au


_______________________________________________________

Comparison of Outcomes Among Moderate Alcohol Drinkers Before Acute Myocardial Infarction to Effect of Continued Versus Discontinuing Alcohol Intake

Light-to-moderate alcohol consumption has been previously associated with a lower risk of acute myocardial infarction (AMI) and mortality. The association of changes in drinking behavior after an AMI with health status and long-term outcomes is unknown.

Using a prospective cohort of patients with AMI evaluated with the World Health Organization's Alcohol Use Disorders Identification Test, we investigated changes in drinking patterns in 325 patients who reported moderate drinking at the time of their AMI. One-year alcohol consumption, disease-specific (angina pectoris and quality of life) and general (mental and physical) health status and rehospitalization outcomes, and 3-year mortality were assessed. Seattle Angina Questionnaire Angina Frequency and Quality of Life, Short Form-12 Mental and Physical Component Summary Scales were modeled using multivariable hierarchical linear models within site.

Of the initial 325 moderate drinkers at baseline, 273 (84%) remained drinking and 52 (16%) quit. In fully adjusted models, Physical Component Scale scores (beta 6.47, 95% confidence interval 3.73 to 9.21.

Persistent moderate drinkers had a trend toward less angina (relative risk 0.65, 95% confidence interval 0.39 to 1.10, p = 0.11), fewer rehospitalizations (hazard ratio 0.79, 95% confidence interval 0.44 to 1.41, p = 0.42), lower 3-year mortality (relative risk 0.75, 95% confidence interval 0.23 to 2.51, p = 0.64), and better disease-specific quality of life (Seattle Angina Questionnaire Quality of Life, beta 3.88, 95% confidence interval −0.79 to 8.55, p = 0.10) and mental health (Mental Component Scale, beta 0.83, 95% confidence interval −1.62 to 3.27, p = 0.51) than quitters.

In conclusion, these data suggest that there are no adverse effects for moderate drinkers to continue consuming alcohol and that they may have better physical functioning compared to those who quit drinking after an AMI.

Read Full Abstract

Request Reprint E-Mail: jhokeefe@cc-pc.com


________________________________________________________

Use (and Misuse) of the Responsible Drinking Message in Public Health and Alcohol Advertising: A Review

The objective is to present a comparative analysis examining the alcohol industry’s and scholarly researchers’ use of the concept "responsible drinking."

Electronic databases associated with health, education, sociology, psychology, and medicine were the date sources. Results were limited to English, peer-reviewed articles and commentaries specifically addressing "responsible drinking." Search descriptors included responsible, responsibility, drinking, alcohol, brewer, and campaign. Eighteen articles constituted the final sample.
The matrix method was utilized to organize and abstract pertinent information.

Misunderstanding stemming from the inconsistency and counterintuitive nature of brewer-sponsored "responsible drinking" campaigns is further compounded by researchers’ use of the term and concept of "responsible drinking" in their scholarly reports.

In articulating the definition of "responsible drinking," researchers employ subjective notions and personal ideas, thus not differentiating the construct’s meaning from the one acquired in brewer-sponsored campaigns. Researchers are consistently inconsistent when identifying specific health measures that promote and/or contradict responsible alcohol consumption.

To evade the subjective notions of researchers and restrictive impressions attached by the alcohol industry, the manner in which individuals interpret, perceive, and practice responsible drinking must be systematically explored and examined using theoretically based constructs.


Read Full Abstract

Request Reprinrt E-Mail: aebarry@purdue.edu


______________________________________________________

DUI Offenders Delay License Reinstatement: A Problem?

We examined the extent to which driving under the influence (DUI) offenders delay reinstatement, the reasons for that delay, and the relationship of the delay to recidivism. Analyzed were the driving records of 40 million drivers (3 million convicted of DUI) from 7 of the largest states spanning 7 to 14 years. License suspension effectively reduces, but does not eliminate, impaired driving. Apparently, many feel they can avoid apprehension for unlicensed driving; the limited research to date suggests that up to 75% of convicted offenders continue to drive and up to 84% delay reinstatement for 3 or more years.

ANOVA and regression procedures were used to determine the relationship of prior driving record and sentence length to the DUI offender's delay in reinstatement. Meta-analysis was used to summarize results across the 7 states and survival analysis to determine the effect of the delay on recidivism.

Forty-two percent of first offenders and 55% of multiple offenders convicted for DUI delay reinstatement for more than a year. For a third of the offenders, there were no records of their having reinstated within 5 years of becoming eligible. Both factors—more than one prior offense and the length of suspension imposed—were related to delay in reinstatement. Offenders who delayed reinstatement were more likely to recidivate both while they delayed before reinstating and after they reinstated.

DUI offenders who delay reinstatement after they become eligible are high-risk drivers. Offenders who reinstate, however, have lower recidivism rates than those who do not. This suggests that encouraging reinstatement but with continued controls, as some states have provided through laws requiring interlocks as a condition of reinstatement, may be effective if they do not motivate extended delays.

Read Full Abstract

Request Reprint E-Mail: voas@pire.org

____________________________________________________________

Physical Health and Drinking Among Medical Inpatients With Unhealthy Alcohol Use: A Prospective Study

Unhealthy alcohol use is common in medical inpatients, and hospitalization has been hypothesized to serve as a "teachable moment" that could motivate patients to decrease drinking, but studies of hospital-based brief interventions have often not found decreases. Evaluating associations between physical health and subsequent drinking among medical inpatients with unhealthy alcohol use could inform refinement of hospital-based brief interventions by identifying an important foundation on which to build them.

We tested associations between poor physical health and drinking after hospitalization and whether associations varied by alcohol dependence status and readiness to change.

Participants were medical inpatients who screened positive for unhealthy alcohol use and consented to participate in a randomized trial of brief intervention (n = 341). Five measures of physical health were independent variables. Outcomes were abstinence and the number of heavy drinking days (HDDs) reported in the 30 days prior to interviews 3 months after hospitalization. Separate regression models were fit to evaluate each independent variable controlling for age, gender, randomization group, and baseline alcohol use. Interactions between each independent variable and alcohol dependence and readiness to change were tested. Stratified models were fit when significant interactions were identified.

Among all participants, measures of physical health were not significantly associated with either abstinence or number of HDDs at 3 months. Having an alcohol-attributable principal admitting diagnosis was significantly associated with fewer HDDs in patients who were nondependent [adjusted incidence rate ratio (aIRR) 0.10, 95% CI 0.03–0.32] or who had low alcohol problem perception (aIRR 0.36, 95% CI 0.13–0.99) at hospital admission. No significant association between alcohol-attributable principal admitting diagnosis and number of HDDs was identified for participants with alcohol dependence or high problem perception.

Among medical inpatients with nondependent unhealthy alcohol use and those who do not view their drinking as problematic, alcohol-attributable illness may catalyze decreased drinking. Brief interventions that highlight alcohol-related illness might be more successful.

Read Full Abstract

Request Reprint E-Mail: emily.williams3@va.gov

____________________________________________________________

Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases

There exists a substantial need to identify new neuropharmacological targets to treat alcohol-dependent individuals. Ghrelin represents a gut-brain peptide, initially discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R).

The existing literature clearly demonstrates that ghrelin affects appetite and food intake. Both animal and human studies provide evidence that ghrelin not only influences hunger but also has a role in the search for rewarding substances, such as alcohol.

Animal studies provide evidence that ghrelin stimulates the reward system, acting on specific brain reward nodes, and that ghrelin signaling is required for stimulation of the reward system by alcohol.

Human studies show that ethanol acutely affects ghrelin levels. Interestingly, human studies with alcohol-dependent individuals suggest that higher ghrelin levels are associated with higher self-reported measurements of alcohol craving.

Altogether, these findings suggest that the ghrelin system plays a role in alcohol dependence. Ghrelin antagonists (i.e., GHS-R1a antagonists and/or inverse agonists) might affect alcohol-seeking behavior, thus having therapeutic potential in alcohol use disorders.

Future laboratory and clinical studies testing this hypothesis are warranted.


Read Full Abstract

Request Reprint E-Mail: Lorenzo_Leggio@brown.edu


____________________________________________________

Maternal Alcohol Consumption during Pregnancy and Risk of Childhood Leukemia: Systematic Review and Meta-analysis

Leukemia is the most frequently occurring cancer in children. Although its etiology is largely unknown, leukemia is believed to result from an interaction between genetic and environmental factors. Among different potential risk factors, the possible role of maternal alcohol consumption during pregnancy has been questioned.

To assess the association between maternal alcohol consumption during pregnancy and childhood leukemia, a systematic review and meta-analysis of published studies was done.

Twenty-one case-control studies were included in categorical and dose-response meta-analyses. No cohort study was identified. Analyses were conducted by type of leukemia, children's age at diagnosis, and type of alcoholic beverage and trimester of pregnancy at alcohol use. Alcohol intake during pregnancy (yes versus no) was statistically significantly associated with childhood acute myeloid leukemia (AML) [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.13-2.15] but not with acute lymphoblastic leukemia (OR, 1.10; 95% CI, 0.93-1.29). Heterogeneity between studies was observed. The OR of AML for an increase of a drink per week was 1.24 (95% CI, 0.94-1.64). The association of alcohol intake during pregnancy with AML was observed for cancers diagnosed at age 0 to 4 years (OR, 2.68; 95% CI, 1.85-3.89) in five studies without heterogeneity (I² ≤ 0.1%).

The results of case-control studies indicate that maternal alcohol consumption during pregnancy is associated with a significantly increased risk of AML in young children.

Avoidance of maternal alcohol drinking during pregnancy might contribute to a decrease in the risk of childhood AML.

Read Full Abstract

Request Reprint E-Mail: Paule.Martel@jouy.inra.fr

____________________________________________________________

A Differential Role for Neuropeptides in Acute and Chronic Adaptive Responses to Alcohol: Behavioural and Genetic Analysis in Caenorhabditis elegans P

Prolonged alcohol consumption in humans followed by abstinence precipitates a withdrawal syndrome consisting of anxiety, agitation and in severe cases, seizures. Withdrawal is relieved by a low dose of alcohol, a negative reinforcement that contributes to alcohol dependency. This phenomenon of ‘withdrawal relief’ provides evidence of an ethanol-induced adaptation which resets the balance of signalling in neural circuits.

We have used this as a criterion to distinguish between direct and indirect ethanol-induced adaptive behavioural responses in C. elegans with the goal of investigating the genetic basis of ethanol-induced neural plasticity.

The paradigm employs a ‘food race assay’ which tests sensorimotor performance of animals acutely and chronically treated with ethanol.

We describe a multifaceted C. elegans ‘withdrawal syndrome’. One feature, decrease reversal frequency is not relieved by a low dose of ethanol and most likely results from an indirect adaptation to ethanol caused by inhibition of feeding and a food-deprived behavioural state.

However another aspect, an aberrant behaviour consisting of spontaneous deep body bends, did show withdrawal relief and therefore we suggest this is the expression of ethanol-induced plasticity.

The potassium channel, slo-1, which is a candidate ethanol effector in C. elegans, is not required for the responses described here. However a mutant deficient in neuropeptides, egl-3, is resistant to withdrawal (although it still exhibits acute responses to ethanol). This dependence on neuropeptides does not involve the NPY-like receptor npr-1, previously implicated in C. elegans ethanol withdrawal. Therefore other neuropeptide pathways mediate this effect.

These data resonate with mammalian studies which report involvement of a number of neuropeptides in chronic responses to alcohol including corticotrophin-releasing-factor (CRF), opioids, tachykinins as well as NPY.

This suggests an evolutionarily conserved role for neuropeptides in ethanol-induced plasticity and opens the way for a genetic analysis of the effects of alcohol on a simple model system.


Read Full Article (PDF)


____________________________________________________

Use of Alcoholic Beverages and Other Psychoactive Substances Among Women in Turkey: Medical, Biological, and Social Consequences. A Pilot Study

This research was planned for determining the genitourinary health problems of alcohol and other psychoactive substance-dependent women.

This research was conducted using a descriptive method at the Alcohol-Substance Research, Treatment and Education Center (ASRTEC). The research sample comprised 126 women who presented at ASRTEC clinic between September 15, 2006 and March 15, 2007, and were diagnosed as being alcohol/drug dependent according to DSM-IV. The data were collected using an Addicted Women's Genitourinary Health Evaluation Form and the Arizona Sexual Experiences Scale.

In this study 37.3% of the women were alcohol dependent and 62.7% were substance dependent. It was determined that alcohol and other psychoactive substance-dependent women experience a high rate of genitourinary health problems, such as unprotected sexual intercourse with multiple partners, irregular menstrual cycles, sexual dysfunction, unwanted pregnancies, and abortions.

Read Full Abstract

Request Reprint E-Mail: umranoskay@yahoo.com


____________________________________________________