Pilot test of twelve-step linkage for alcohol abusing women in leaving jail

More than a million U.S. women are detained in jails each year; many have alcohol use disorders (AUD). AUD intervention with pretrial jail detainees presents a logistical challenge due to limited jail stays and lack of resources for post release treatment. The availability, no-cost entry, and promise of anonymity of Alcoholics Anonymous (AA) make it a highly accessible resource for underserved populations. However, the outreach of AA volunteers into jails (as opposed to prisons) has been limited, and incarcerated women are unlikely to seek out strangers for help after release.

This study pilot tested an enhanced referral approach introducing a twelve-step volunteer to a woman in jail who would attend a meeting with her after release.
Methods: Participants were 14 unsentenced female pretrial jail detainees with AUD. Intervention consisted of introducing participants detained in jail to female AA volunteers who could accompany them to an AA meeting after release. Assessments took place at baseline and one month after release. This uncontrolled pilot study evaluated the feasibility and acceptability of this enhanced referral approach. We also report pre-post alcohol use, drug use, alcohol problems, and AA attendance.

 Enhanced referral was feasible and acceptable. Many (57%) of the 14 participants who met with AA volunteers in jail were in contact with those volunteers after release from jail. Participants had significantly fewer drinking days, heavy drinking days, alcohol problems, and drug-using days during the post-release follow-up than they did before jail detention.

Providing linkage between women in jail and female AA volunteers who can accompany them to post-release a meeting is achievable, and may be a disseminable and low-cost method to improve alcohol outcomes in this vulnerable population.

 

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Request Reprint E-Mail:   Jennifer_Johnson@brown.edu

Dissociable Effects of Kappa-Opioid Receptor Activation on Impulsive Phenotypes in Wistar Rats

The kappa-opioid receptor (KOR) is the primary target for the endogenous opioid peptide dynorphin (DYN) and KORs reside within brain circuitry underlying the complex integration of information related to different behavioral domains such as motivation, negative affect and decision-making.

Alterations in extended amygdala dynorphins (DYN) and kappa-opioid receptor (KOR) function following chronic alcohol exposure have been shown to mediate escalated alcohol self-administration during acute withdrawal. In addition to excessive alcohol consumption and increased negative affect, other symptoms of alcohol dependence include compromised impulse control.

Given that DYN and KOR expression are dysregulated within prefrontal brain circuitry associated with decision-making and impulse control in alcohol-dependent humans and rodents and have been shown to modify multiple neurotransmitter systems associated with impulse control disorders, we hypothesized that KOR activation could contribute to impulsive phenotypes.

To test this hypothesis, separate cohorts of male Wistar rats were trained in one of two animal models of impulsivity: delay discounting (DD) or stop-signal reaction time (SSRT) tasks and once stable responding was observed, received intracerebroventricular infusions of the KOR agonist U50,488 (0-50 μg) according to a within-subject dosing regimen.

The results demonstrated a dissociable effect of U50 488 on impulsive phenotypes related to intolerance to delay or response inhibition with selective effects in the SSRT. Furthermore, the pro-impulsive effects of KOR activation were rescued by pretreatment with the KOR antagonist nor-binaltorphimine (norBNI). Therefore, KOR activation was shown to induce an impulsive phenotype that was norBNI-sensitive.

Dysregulation of impulsive behavior by increased DYN/ KOR activity could serve to increase vulnerability for the initiation, or perpetuate existing patterns of excessive alcohol abuse and can enhance the probability of relapse in dependent individuals. Furthermore, KOR-mediated impulsivity has implications for numerous neuropsychiatric disorders.



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Rerquest Reprint E-Mail:     b_walker@wsu.edu

Baseline Research for Action: Adolescent Alcohol Consumption in Los Palacios Municipality, Cuba

In Cuba, alcohol is an important contributor to morbidity,ortality and social problems. The foundation of Cuba’s universal primary health care coverage, family doctor-and-nurse offices play a critical role in prevention, early detection and treatment of alcohol abuse.

Los Palacios Municipality of the westernmost province of Pinar del Río, Cuba, is a socially complex, periurban area where alcohol abuse and alcoholism have been identified as important health problems. Adolescents constitute a population at high risk for alcohol abuse because of their receptivity to social influences, but the precise extent of the problem is unknown.

This paper reports baseline findings from a survey and direct observation of alcohol consumption in the catchment area of a primary care center, conducted to inform planning for an educational intervention.

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Alternative CHRNB4 3'-UTRs Mediate the Allelic Effects of SNP rs1948 on Gene Expression.

Common genetic factors strongly contribute to both nicotine, the main addictive component of tobacco, and alcohol use. Several lines of evidence suggest nicotinic acetylcholine receptors as common sites of action for nicotine and alcohol. Specifically, rs1948, a single-nucleotide polymorphism (SNP) located in the CHRNB4 3′-untranslated region (UTR), has been associated to early age of initiation for both alcohol and tobacco use.

To determine the allelic effects of rs1948 on gene expression, two rs1948-containing sequences of different lengths corresponding to the CHRNB4 3′-UTR were cloned into pGL3-promoter luciferase reporter vectors.

Data obtained showed that the allelic effects of SNP rs1948 on luciferase expression are mediated by the length and species of transcripts generated. In addition, it was found that miR-3157 increased the overall luciferase expression while miR-138, a microRNA known to play a role in neuroadaptation to drug abuse, decreased luciferase expression when compared to basal conditions.

These findings demonstrate the importance of SNP rs1948 on the regulation of CHRNB4 expression and provide the first evidence of CHRNB4 down-regulation by miR-138.


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Effects of a Persistent Binge Drinking Pattern of Alcohol Consumption in Young People: A Follow-Up Study Using Event-Related Potentials

The objective of this study was to examine brain activity related to visual attention processes in youths who had maintained a binge drinking (BD) pattern of alcohol consumption for >2 years.

The participants were 57 university students (26 binge drinkers: BDs) with no personal or family history of alcoholism or psychopathological disorders in first-degree relatives. Event-related potentials (ERPs) were recorded while participants performed a visual oddball task (twice within a 2-year interval). The latency and amplitude of the P3b component of the ERPs were analysed.                   

The P3b amplitude was larger in young BDs than in aged-matched controls at both evaluation times, and the difference was more pronounced after 2 years of maintenance of a BD pattern of consumption. The larger P3b amplitude was associated with an earlier onset of regular drinking and with a greater quantity and intensity of consumption.
These findings suggest that young BDs exhibit anomalies in neural activity involved in attentional/working memory processes, which increase after 2 years of maintenance of BD. This anomalous neural activity may reflect underlying dysfunctions in neurophysiological mechanisms as well as the recruitment of additional attentional/working memory resources to enable the binge drinkers to perform the task adequately.


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Request Reprint E-Mail:   eduardo.lopez@usc.es

Breath Alcohol Estimation Training: Behavioral Effects and Predictors of Success

Breath alcohol concentration (BrAC) estimation training has been effective in increasing estimation accuracy in social drinkers. Predictors of estimation accuracy may identify populations to target for training, yet potential predictors typically are not evaluated. In addition, the therapeutic efficacy of estimation training as a preventive strategy for problematic drinking is unknown.

Forty-six social drinkers with a recent binge history were randomly assigned to an intervention or control group (n = 23 per group). In each of three sessions (pretraining, training, testing), participants consumed alcohol (0.32, 0.24, 0.16 and 0.08 g/kg, in random order) every 30 min (total dose: 0.8 g/kg). Participants provided five BrAC estimates within 3 h of alcohol administration. The intervention group, but not control group, received internal and external training. During testing, participants provided BrAC estimates, but received no feedback. Participants returned for two follow-up visits to complete self-report measures.

BrAC estimation training improved intervention group estimation accuracy within the laboratory. Together, training, low trait anxiety and low risk expectancy predicted high testing accuracy. There were no significant group differences in subsequent alcohol consumption, behavior under the influence or risk expectancy regarding potentially hazardous behaviors.
BrAC estimation training is effective in the laboratory but may not translate into naturalistic settings.


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Request Reprint E-Mail:     aliguori@wakehealth.edu

Alcohol consumption in adolescence and early adult life: What are the consequences? CLOSER event presentations

This month an event took place exploring 'Alcohol consumption in adolescence and early adult life: What are the consequences?'. It was organised by the Cohorts and Longitudinal Studies Enhancement Resources (CLOSER), a consortium of the UK’s leading birth cohort and longitudinal studies.  > > > >  Read More

Gender differences in reactivity to alcohol cues in binge drinkers: A preliminary assessment of event-related potentials

Binge drinking is associated with functional brain abnormalities similar to those observed in alcoholics and can be viewed as a first step towards alcohol dependence. Adult men are twice as likely as women to develop alcoholism.

This study investigates (1) the presence of alcohol cue reactivity in bingers, a feature that has been proposed to underlie the emergence of alcohol dependence; and (2) a possible higher alcohol cue reactivity in men binge drinkers which could explain their higher risk for alcohol use disorders in adulthood.

The P3 component of the event-related potentials (ERPs) was recorded during a visual oddball task in which controls (n=27: 10 men and 17 women) and binge drinkers (n=29: 15 men and 14 women) had to detect infrequent deviant stimuli (related to alcohol or not) among frequent neutral stimuli.

Results showed that binge drinkers, compared to light drinkers, displayed increased P3 reactivity to alcohol related cues with a greater effect among men.

Our results suggest the phenomenon of alcohol cue reactivity to be a possible avenue by which a higher risk population, binge drinkers, and men in particular, are prone to develop problematic alcohol use.


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Request Reprint E-Mail:    geraldine.petit@chu-brugmann.be

Screening and Brief Interventions for Hazardous and Harmful Alcohol Use among University Students in South Africa: Results from a Randomized Controlled Trial

The aim of this study was to assess the effectiveness of Screening and Brief Intervention (SBI) for alcohol problems among university students in South Africa.

The study design for this efficacy study is a randomized controlled trial with 6- and 12-month follow-ups to examine the effects of a brief alcohol intervention to reduce alcohol use by hazardous and harmful drinkers in a university setting. The unit of randomization is the individual university student identified as a hazardous or harmful drinker attending public recruitment venues in a university campus. University students were screened for alcohol problems, and those identified as hazardous or harmful drinkers were randomized into an experimental or control group. The experimental group received one brief counseling session on alcohol risk reduction, while the control group received a health education leaflet.

Results indicate that of the 722 screened for alcohol and who agreed to participate in the trial 152 (21.1%) tested positive for the Alcohol Use Disorder Identification Test (AUDIT) (score 8 or more). Among the 147 (96.7%) university students who also attended the 12-month follow-up session, the intervention effect on the AUDIT score was −1.5, which was statistically significant (P = 0.009). Further, the depression scores marginally significantly decreased over time across treatment groups, while other substance use (tobacco and cannabis use), self-rated health status and Posttraumatic Stress Disorder (PTSD) scores did not change over time across treatment groups.

The study provides evidence of effective brief intervention by assistant nurses with hazardous and harmful drinkers in a university setting in South Africa. The short duration of the brief intervention makes it a realistic candidate for use in a university setting.


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A time series analysis of presentations to Queensland health facilities for alcohol-related conditions, following the increase in ‘alcopops’ tax

In response to concerns about the health consequences of high-risk drinking by young people, the Australian Government increased the tax on pre-mixed alcoholic beverages (‘alcopops’) favoured by this demographic. We measured changes in admissions for alcohol-related harm to health throughout Queensland, before and after the tax increase in April 2008. 
                   

We used data from the Queensland Trauma Register, Hospitals Admitted Patients Data Collection, and the Emergency Department Information System to calculate alcohol-related admission rates per 100,000 people, for 15 – 29 year-olds. We analysed data over 3 years (April 2006 – April 2009), using interrupted time-series analyses. This covered 2 years before, and 1 year after, the tax increase. We investigated both mental and behavioural consequences (via F10 codes), and intentional/unintentional injuries (S and T codes). 

                   

We fitted an auto-regressive integrated moving average (ARIMA) model, to test for any changes following the increased tax. There was no decrease in alcohol-related admissions in 15 – 29 year-olds. We found similar results for males and females, as well as definitions of alcohol-related harms that were narrow (F10 codes only) and broad (F10, S and T codes). 

                   

The increased tax on ‘alcopops’ was not associated with any reduction in hospital admissions for alcohol-related harms in Queensland 15 – 29 year-olds.

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Request Reprint E-Mail:    s.kisely@uq.edu.au


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Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood

Longitudinal analyses allow us to understand how genetic risk unfolds across development, in a way that is not possible with cross-sectional analyses of individuals at different ages. This has received little attention in genetic association analyses. In this study, we test for genetic effects of GABRA2, a gene previously associated with alcohol dependence, on trajectories of drunkenness from age 14 to 25.

We use data from 1070 individuals who participated in the prospective sample of the Collaborative Study on the Genetics of Alcoholism, in order to better understand the unfolding of genetic risk across development. Piecewise linear growth models were fit to model the influence of genotype on rate of increase in drunkenness from early adolescence to young adulthood (14–18 years), the change in drunkenness during the transition to adulthood (18–19 years) and the rate of change in drunkenness across young adulthood (≥ 19 years).

Variation in GABRA2 was associated with an increase in drunkenness that occurred at the transition between adolescence and adulthood. The genotypic effect was more pronounced in females.

These analyses illustrate the importance of longitudinal data to characterize how genetic effects unfold across development. The findings suggest that transitions across important developmental periods may alter the relative importance of genetic effects on patterns of alcohol use. The findings also suggest the importance of considering gender when evaluating genetic effects on drinking patterns in males and females.


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Request Reprint E-Mail:     ddick@vcu.edu

World Health Organization to tackle non-communicable disease

The 66th World Health Assembly opened in Geneva today. One of the main issues is how the increasing burden of non-communicable diseases (NCD) will be handled in the future. Referring to the difference between malaria and NCDs the Director General of WHO, Dr. Margaret Chan, in her opening speech stated that “Mosquitoes do not have front groups, and mosquitoes do not have lobbies.”   > > > >   Read More

Cohort Study of Risk Factors for Breast Cancer in Post Menopausal Women

The present study assessed more than 800 potential risk factors to identify new predictors of breast cancer and compare the independence and relative importance of established risk factors.

Data were collected by the Women's Health Initiative and included 147,202 women ages 50 to 79 who were enrolled from 1993 to 1998 and followed for 8 years. Analyses performed in 2011 and 2012 used the Cox proportional hazard regression to test the association between more than 800 baseline risk factors and incident breast cancer.

Baseline factors independently associated with subsequent breast cancer at the p<0 .001="" age="" and="" aspiration="" at="" biopsies="" births="" breast="" cancer="" decreasing="" digitalis="" estrogen="" family="" fewer="" greater="" history="" in="" level="" live="" menopause="" of="" order="" progestin="" significance="" statistical="" strong="" tenderness="" thyroid="" use="" weight="" were="">alcohol intake, white race, not restless, no vaginal dryness, relative with prostate cancer, colon polyps, smoking, no breast augmentation, and no osteoporosis. Risk factors previously reported that were not independently associated with breast cancer in the present study included socioeconomic status, months of breast feeding, age at first birth, adiposity measures, adult weight gain, timing of initiation of hormone therapy, and several dietary, psychological, and exercise variables. Family history was not found to alter the risk associated with other factors.

These results suggest that some risk factors not commonly studied may be important for breast cancer and some frequently cited risk factors may be relatively unimportant or secondary.


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Impaired odor identification in children with histories of heavy prenatal alcohol exposure

Prenatal alcohol exposure can lead to behavioral and cognitive impairments across multiple domains. Many of the brain regions impacted by prenatal alcohol exposure are also linked with olfactory processing, and odor identification deficits have been documented in certain neurological disorders associated with these brain regions.

As odor identification following prenatal alcohol exposure is not well studied, we compared odor identification in children with prenatal exposure to alcohol (AE) to typically developing controls (CON) (N = 16/group). It was hypothesized that children in the AE group would perform more poorly than children in the CON group on the San Diego Odor Identification Test, an identification test of 8 common household odorants.

Children exposed to alcohol during prenatal development were significantly impaired in olfactory identification (M = 5.95, SE = 0.37) compared to typically developing controls (M = 7.24, SE = 0.37).

These findings confirmed the hypothesis that prenatal exposure to alcohol is associated with odor identification deficits, and suggest that further research is warranted to identify the mechanisms underlying these deficits, the integrity of brain areas that are involved, and to determine whether olfactory performance might contribute to better identification of children at risk for behavioral and cognitive deficits.


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Request Reprint E-Mail:    cmurphy432000@yahoo.com

NIAAA Clinician's Guide Online Training

 




 

Contents
Clinician Support and Training

Free CME/CE Credits through Medscape® VIDEO CASES: Helping Patients Who Drink Too Much Interactive, engaging course with four 10-minute, realistic video cases

• The Guide
• Medications update (10/08)
• Online training for CME/CE credits
• Forms for downloading
• PowerPoint™ slide show
• Manuals from Project COMBINE
• Other publications for professionals

Patient Education

• Rethinking Drinking booklet and Web site
• Other publications for the public in English and Spanish

Alcohol News - 20/2013

 

 

 

Science Nordic (Sweden) - Sick Swedes keep on swigging

Even though alcohol consumption can delay a return to work, a new survey shows that Swedes like their liquor, particularly at sporting events, and even when they are on sick leave.

Read more

Addiction (Norway) - The collectivity of drinking cultures: is the theory applicable to African settings?

Skog's theory of collective drinking behaviour implies that countries with a strict informal social control of drinking alcohol would not exhibit ‘collective displacement’ of consumption (a linear association between population mean consumption and percentile values across the full range of the distribution), as do countries with less informal social control.

Read more

Postimees (Estonia) - Consumption of alcohol in Estonia did not change last year – study

The consumption of alcohol by residents of Estonia did not change in 2012 compared to the previous year, averaging 10.6 liters of pure alcohol per capita, it appears from the fresh alcohol market survey by the Estonian Institute of Economic Research (EKI).

Read more

Al-Arabiya (Egypt) - Egypt faces social pressure to end alcohol sales

Egypt’s liquor stores are under growing pressure to stop selling alcohol, they say, not from the country’s Islamist government, but from society itself.

Read more

Healio - Adolescents' first drink tied to alcohol-related problems in adulthood

Adolescents who have their first drink during puberty are more likely to develop frequent drinking habits later in life, results from a new study show.

Read more

Newstalk 106-108 fm (Ireland) - Irish Alcohol consumption drops by 20% in 12 years

The alcohol consumption in Ireland has fallen by 20% over 12 years, with the idea that all Irish people now drink to excess now believed to be far from the truth.

Read more

The Guardian (UK) - Parliament too alcohol fuelled, say MPs

One in four MPs thinks parliament, where the price of alcohol is subsidised, has an unhealthy drinking culture.

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EurActiv (EU) - EU's alcohol strategy needs further push, MEPs say

Europeans are the heaviest drinkers in the world and in some EU member states, such as Luxembourg and the Czech Republic, the alcohol consumption is 2.5 times more than what an average person in the world drinks. The Commission's new strategy on alcohol, to be published later this year, has to better address the issue of alcohol-related harm, MEPs say.

Read more

TIME (USA) - Safety Board Recommends Defining Legally Drunk With Lower Blood Alcohol Level

The government wants to drop the blood alcohol limit for being legally drunk in order to avoid drunk driving fatalities.

Read more

TIME (USA) - Task Force Recommends Screening All Adults for Alcohol Misuse

Questions about alcohol use should be a part of regular physical checkups, according to a panel of experts.

Read more

News-Medical.net - Alcohol advertising pre-disposes young people to have favorable attitudes toward drinking

The alcohol industry has developed and regulates its own guidelines regarding advertising. A new study has investigated the ability of panels to find consensus around code violations.

Read more

FRANCE 24 (Turkey) - Turkish parliament considers bill limiting alcohol sales

Turkey's parliament is reviewing a bill that would restrict alcohol sales, including banning purchases at educational, sports and health institutions. The bill has the beverage industry worried, including Diageo, owner of Turkey’s leading raki brand.

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Examiner.com (USA) - Study: Female college students abuse alcohol more than men

New research shows that female college student drinkers exceed National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for weekly drinking more frequently than their male counterparts.

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WSYM-TV - New Study Finds Alcohol Increases Risk of Breast Cancer

A lot of us unwind after a tough day with a drink, but sobering new research says just a few of those a week, could put some women's health at risk.

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Medical Daily - Mixing Excessive Alcohol And Smoking Can Make Your Brain Old Before Its Time

A new study found that heavy drinkers who smoke excessively develop problems with memory, thinking and problem solving skills earlier than those who do not.

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Tribune-Review (USA) - Hagel believes alcohol is ‘a very big factor’ in many of military’s sexual assault and harassment cases

Defense Secretary Chuck Hagel on Friday ordered the military to recertify all 25,000 people involved in programs designed to prevent and respond to sexual assault, an acknowledgement that assaults have escalated beyond the Pentagon's control.

Read more

MADD - Get the Facts on Privatized Alcohol Sales-MADD Canada Releases Newly-Updated Alcohol Policy Paper

MADD Canada is pleased to share its newly-updated alcohol policy paper, "Provincial Liquor Boards: Meeting the Best Interests of Canadians." The paper supports the role of provincial liquor boards and outlines the negative health and public safety impacts associated with privatized alcohol sales.

Read more

 

 

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Acute Alcohol Intoxication Characteristics in Children

To describe clinical, mental and physical signs in children with different severity acute alcohol intoxication (AAI) determined either by serum alcohol concentration (SAC) or by blood alcohol concentration (BAC) to study the diagnostic performance characteristics of clinical assessment and to establish the ratio of SAC:BAC in children.

Data were analysed from 256 children aged 8.4–17.9 years who were hospitalized at Estonia's two children's hospitals over a 3-year period. In each case, the on-call paediatrician completed a special form about the clinical, mental (consciousness, balance and speech) and physical (muscle tone, blood pressure, pulse and body temperature) signs of AAI. Blood samples were drawn for measurements of SAC and BAC. Diagnostic performance characteristics (sensitivity, specificity, efficiency) of the clinical assessments and the SAC:BAC ratio were calculated.

The most correctly described signs in children in different SAC groups were consciousness (r_s = 0.16) and speech (r_s = 0.13) (P < 0.0001). The severity of alteration of consciousness and degrees of disturbance in balance and speech were positively correlated with SAC (P < 0.001). The clinical judgment matched better with AAI determined by SAC rather than by BAC with the mean efficiency. The mean ratio between SAC and BAC was 1.19 ± 0.13 (P < 0.001) in children.

The level of consciousness is the leading sign in the clinical evaluation of children with AAI and correlates well with SAC. The severity of AAI judged by clinical assessment matched better with AAI severity stages determined by SAC than by BAC. For legal cases where BAC is required, the SAC:BAC ratio of 1.19:1 should be used in children regardless of their gender or age.    

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Request Reprint E-Mail:      mailis.tonisson@ut.ee   

Relationship Between Blood Alcohol Concentration and Observable Symptoms of Intoxication in Patients Presenting to an Emergency Department

Clinical and medico-legal decisions often require knowledge of alcohol impairment that is not necessarily revealed by an individual's appearance, and in turn, may not necessarily reflect level of blood alcohol. This study compares clinical signs and symptoms with measured and estimated blood alcohol concentrations (BACs).

Individuals (n = 384) perceived to be under the influence of alcohol at presentation to an emergency department were assessed by physicians and nurses for clinical features of alcohol intoxication (alcohol symptom checklist, ASC), who were asked to estimate the patient's BAC. Relation to measured BACs was assessed by correlation.

BACs ranged from 0 to 418 mg/100 ml. The correlation between the estimated BAC and measured BAC was r = 0.513. Measured BAC correlated with ASC r = 0.250. In subjects without a history of chronic drinking (n = 134) there was a better (P < 0.05) correlation with the ASC score (r = 0.363) versus measured BAC compared with that for chronic drinkers (r = 0.154). The positive predictive value of estimating BAC at or above a particular BAC cut-off decreased from 93.2% at 100 mg/100 ml to 37.7% at 300 mg/100 ml (P < 0.05).

Measured BAC does not correlate well with the outward physical signs of intoxication, especially for chronic drinkers. There is a need for further education on how tolerance masks clinical signs of intoxication for the chronic drinker. BACs should be measured especially in the obtunded where no history (symptoms) can be given by the patient.

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Request Reprint E-Mail:   apple004@umn.edu

Prevalence of Hepatitis C Virus Infection in Alcoholic Patients: Cohort Study and Systematic Review

Prevalence of chronic hepatitis C virus (HCV) infection among alcoholics is thought to be higher than in the general population, although prevalence rates reported are quite variable. Our study is aimed to analyze HCV prevalence in a cohort of alcoholics and to perform a systematic review on this topic.

A total of 396 alcoholic patients consecutively referred to our Alcoholism Unit were included. HCV infection status and other clinical variables were recorded for each patient. Variables associated with HCV infection were analyzed by means of logistic regression. Additionally, we performed a systematic review focused on previous studies on this topic.

Among our alcoholic patients, 14 of them (3.53%) had chronic HCV infection. Variables independently associated with HCV infection were female gender, injection drug use (IDU) and the presence of alcoholic liver disease (ALD). Twenty-four studies analyzing HCV prevalence in alcoholic patients were included in our systematic review, showing prevalence rates of HCV infection ranging from 2.1 to 51% and an average weighted prevalence of 16.32%.

In our series, the prevalence rate of chronic HCV infection among alcoholic patients is lower than previously reported, which is probably explained by the relatively low number of patients with ALD or IDU in our sample. Prevalence rates previously published are quite different and the presence of ALD and/or IDU can act as confounding factors for HCV prevalence among alcoholics.


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Request Reprint E-Mail:    mmarcos@usal.es

Effect of Transferrin Glycation on the Use of Carbohydrate-Deficient Transferrin as an Alcohol Biomarker

 


Measurement of an alcohol-induced shift in the serum transferrin glycosylation pattern, termed carbohydrate-deficient transferrin (CDT), is used as a biomarker for sustained high alcohol consumption. The present work examined whether non-enzymatic reaction of transferrin with glucose (glycation) might interfere with the use of CDT as an alcohol biomarker.

The blood specimens were leftover volumes from the routine sample pool. Plasma and serum were collected among samples submitted for hemoglobin A1c (HbA1c) and CDT testing. Quantification of individual transferrin glycoforms in percentage of total transferrin was performed by an HPLC candidate CDT reference method.

Incubating serum spiked with 20 or 200 mmol/l glucose caused time- and dose-dependent changes in the chromatographic profile of transferrin glycoforms, resulting in gradually wider peaks and reduced relative amounts of disialo- and trisialotransferrin. No similar chromatographic effects were seen in samples collected from diabetic patients with elevated HbA1c (>68 mmol/mol) values. These samples instead showed slightly higher mean %disialotransferrin levels (1.21%) compared with low HbA1c samples, pointing at a higher alcohol consumption level in the former group. Altogether ∼5% of the CDT values exceeded the cutoff. There was no significant difference in phosphatidylethanol (PEth) levels between the high and low HbA1c samples, but several (∼14%) showed elevated PEth concentrations.

Glycation of serum transferrin in vivo was indicated to differ from that in vitro, and suggested not to interfere with %CDT testing by the HPLC method. The results indicated that CDT and PEth are useful as objective, complementary alcohol biomarkers to identify risky drinking also in diabetic subjects.


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Request Reprint E-Mail:    anders.helander@ki.se

                 

A report into the effectiveness of civil commitment in the treatment of alcoholism, and its suitability for implementation the Northern Territory

Long-term harmful use of alcohol remains a large problem in the Northern Territory and a model of civil commitment for ‘problem drinkers’ has been proposed. This planned system has been strongly criticised on a number of ethical, moral and legal grounds.

This report explores existing evidence from studies on both civil and forensic mandatory rehabilitation, in order to evaluate if it would be an effective form of treatment for alcohol dependent persons, and appropriate to implement such a system in the Northern Territory.

The report concludes that given the lack of evidence for the effectiveness of civil commitment and the potentially significant impact upon the freedoms of individuals, families and the communities, it could be difficult to justify the
proposal.


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Characterization of Two Mutations, M287L and Q266I, in the α1 Glycine Receptor Subunit That Modify Sensitivity to Alcohols

Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels. Ethanol potentiates glycine activation of the GlyR, and putative binding sites for alcohol are located in the transmembrane (TM) domains between and within subunits.

To alter alcohol sensitivity of GlyR, we introduced two mutations in the GlyR α1 subunit, M287L (TM3) and Q266I (TM2). After expression in Xenopus laevis oocytes, both mutants showed a reduction in glycine sensitivity and glycine-induced maximal currents. Activation by taurine, another endogenous agonist, was almost abolished in the M287L GlyR. The ethanol potentiation of glycine currents was reduced in the M287L GlyR and eliminated in Q266I. Physiological levels of zinc (100 nM) potentiate glycine responses in wild-type GlyR and also enhance the ethanol potentiation of glycine responses. Although zinc potentiation of glycine responses was unchanged in both mutants, zinc enhancement of ethanol potentiation of glycine responses was absent in M287L GlyRs. The Q266I mutation decreased conductance but increased mean open time (effects not seen in M287L).

Two lines of knockin mice bearing these mutations were developed. Survival of homozygous knockin mice was impaired, probably as a consequence of impaired glycinergic transmission. Glycine showed a decreased capacity for displacing strychnine binding in heterozygous knockin mice. Electrophysiology in isolated neurons of brain stem showed decreased glycine-mediated currents and decreased ethanol potentiation in homozygous knockin mice.

Molecular models of the wild-type and mutant GlyRs show a smaller water-filled cavity within the TM domains of the Q266I α1 subunit. The behavioral characterization of these knockin mice is presented in a companion article  (J Pharmacol Exp Ther 340:317–329, 2012).


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The Basic Property of Lys385 Is Important for Potentiation of the Human α1 Glycine Receptor by Ethanol

Ethanol alters the function of several members of the Cys-loop ligand-gated ion channel superfamily. Recent studies have shown that the sensitivity of the α1 glycine receptor (GlyR) to ethanol can be affected by the state of G protein activation mediated by the interaction of Gβγ with intracellular amino acids in the GlyR.

Here, we evaluated the physicochemical property of Lys385 that contributes to ethanol modulation by using mutagenesis, patch-clamp, and biochemical techniques.

A conserved substitution (K385R) did not affect either the apparent glycine EC₅₀ (40 ± 1 versus 41 ± 0.5 μM) or the ethanol-induced potentiation (53 ± 5 versus 46 ± 5%) of the human α1 GlyR. On the other hand, replacement of this residue with glutamic acid (K385E), an acidic amino acid, reduced the potentiation of the GlyR to 10 ± 1%. Furthermore, mutations with a hydrophobic leucine (K385L), a hydrogen bond donor glutamine (K385Q), or a neutral residue (K385A) also reduced ethanol modulation.

Finally, substitution by a large and hydrophobic residue (K385F) and deletion of 385 (Lys385_) reduced ethanol modulation to 10 ± 4 and 17 ± 0.4%, respectively.

Experiments using dynamic cysteine substitution with a methanethiosulfonate reagent and homology modeling indicate that the basic property and the position of Lys385, probably because of its interaction with Gβγ, is critical for ethanol potentiation of the receptor.


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The TM2 6′ Position of GABAA Receptors Mediates Alcohol Inhibition

Ionotropic GABA_A receptors (GABA_ARs), which mediate inhibitory neurotransmission in the central nervous system, are implicated in the behavioral effects of alcohol and alcoholism. Site-directed mutagenesis studies support the presence of discrete molecular sites involved in alcohol enhancement and, more recently, inhibition of GABA_ARs.

We used Xenopus laevis oocytes to investigate the 6′ position in the second transmembrane region of GABA_ARs as a site influencing alcohol inhibition. We asked whether modification of the 6′ position by substitution with larger residues or methanethiol labeling [using methyl methanethiosulfonate (MMTS)] of a substituted cysteine, reduced GABA action and/or blocked further inhibition by alcohols.

Labeling of the 6′ position in either α2 or β2 subunits reduced responses to GABA. In addition, methanol and ethanol potentiation increased after MMTS labeling or substitution with tryptophan or methionine, consistent with elimination of an inhibitory site for these alcohols. Specific alcohols, but not the anesthetic etomidate, competed with MMTS labeling at the 6′ position. We verified a role for the 6′ position in previously tested α2β2 as well as more physiologically relevant α2β2γ2s GABA_ARs.

Finally, we built a novel molecular model based on the invertebrate glutamate-gated chloride channel receptor, a GABA_AR homolog, revealing that the 6′ position residue faces the channel pore, and modification of this residue alters volume and polarity of the pore-facing cavity in this region.

These results indicate that the 6′ positions in both α2 and β2 GABA_AR subunits mediate inhibition by short-chain alcohols, which is consistent with the presence of multiple counteracting sites of action for alcohols on ligand-gated ion channels.


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