Recognizing Alcohol-related neurodevelopment disorder (ARND) in Primary Health Care of Children

Initiative of the

Diagnostics Issues Work Group, Interagency Coordinating Committee on
Fetal Alcohol Spectrum Disorders (ICCFASD)

Sponsored by the

Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders (ICCFASD);
National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH);
Centers for Disease Control and Prevention (CDC); and
American Academy of Pediatrics (AAP)

The goal of this consensus development-style conference is to determine whether sufficient evidence exists to encourage screening and diagnosis (or referral for diagnosis) of ARND in pediatric practice and other primary care settings. ICCFASD, NIAAA, CDC, and AAP have assembled a panel of 13 unbiased critical thinkers who are knowledgeable about neurodevelopmental problems. Clinical and research experts on fetal alcohol spectrum disorders will present relevant evidence to the panel on October 31 and November 1, 2011. On the morning of November 2, 2011, the panel will announce recommendations based on the presented testimony. ICCFASD intends to post recommendations and the proceedings of the conference on the ICCFASD Web page in December 2011, http://www.niaaa.nih.gov/AboutNIAAA/Interagency/Pages/default.aspx.

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Statement from the European Expert Conference: Medical and Economic Disadvantages of Using Alcohol (MEDUSA

Poznan, 11‐12 October 2011

The participants acknowledge the scientific evidence and the results presented at conference. In the European Union, harmful and hazardous alcohol consumption is the second most significant risk factor for ill‐health and premature death. Harmful use of alcohol is a major public health concern. Comprehensive and effective alcohol policies are therefore crucial both at national, regional and EU levels. > > > > Read More

European action plan to reduce the harmful use of alcohol 2012–2020

The five main objectives of the plan build on previous European plans, and align with the WHO global strategy on alcohol, to:

- raise awareness of the magnitude and nature of the health, social and economic burdens due to alcohol;
- strengthen and disseminate the knowledge base;
- enhance capacity to manage and treat alcohol-related disorders;
- increase mobilization of resources for concerted action; and
- improve surveillance and advocacy.

The plan highlights ten action points, each presented with following strategies and options for action:

- leadership, awareness and commitment
- health services’ response
- community and workplace action
- drink–driving policies and countermeasures
- availability of alcohol
- pricing policies
- marketing of alcoholic beverages
- reducing the negative consequences of drinking and alcohol intoxication
- reducing the public health impact of illicit alcohol and informally produced
- monitoring and surveillance

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Exessive Alcohol Consumption is a key to chronic poverty in Uganda

Exessive Alcohol Consumption is a key ‘’driver and maintainer’’ of chronic poverty in Uganda. The reason why excessive consumption of alchole has become a new frontier for chronic poverty in Uganda is that, the discussion on excessive alcohol consumpion in the country has for long been in the back –seat of what is consired to be ‘’ personal choices.’’

This mentality has hindered attempts to bring the issue into the public domain and the frontline of public policy because; Policy makers and the gereral populace in the country have deliberately refised to acknowledge that Uganda has an alcohol problem.

In recent times, a lot has been reported in research reports, the Ugandan media and other development circles about Ugandas’ position in alchol consuming nations including South Africa, Nigeria, Tanzania, Zambia, Burundi, and Ghana among others. It should be remembered that in 2004 Global status report on Alcohol according to World Health Organisation (WHO); with a per capita consumption of 19.47 litters per adult (age 15 years and above), Uganda held the first position in the world out of 185 countris in consumption of pure alcohol.

Since 2002, documented evidence from the world Health Organisation (WHO) and the Ministry of finance have highlighted excessive alcohol consumption as one of the key drivers and maintainers of poverty especially in the rural countryside.

This is further evidenced by a recent research (2011) conducted by one of the local NGOs where too much drinking defined the social lives of people in Northern Uganda such as Oyam district. > > > > Read More

Does marketing communication impact on the volume and patterns of consumption of alcoholic beverages, especially by young people? - a review of longit

The European Alcohol and Health Forum requested scientific advice from the Science Group on the impact of marketing communication on the volume and patterns of consumption of alcoholic beverages, especially by young people.

The opinion of the Science Group noted that marketing communications are just one aspect of determinants of alcohol consumption and alcohol-related harm, and that it can be difficult to isolate the impact of one aspect from another.

The opinion also noted that a total marketing strategy includes not only marketing communication and promotional activities, but also product development, pricing, physical availability, and market segmentation and
targeting, factors not considered in the available published studies.


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Flash Report European Alcohol and Health Forum Plenary Meeting of 19 October 2011

The 9th Plenary meeting of the European Alcohol and Health Forum took place on 19 October 2011, focussing on alcohol and youth, and alcohol in the workplace.


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ALCOHOL, WORK AND PRODUCTIVITY

The Science Group of the European Alcohol and Health Forum has made a report on alcohol, work and productivity.

Reducing the negative impact of alcohol on the workplace is one of five priorities picked out in the EU strategy to support Member States in reducing alcohol related harm.



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South East Alcohol Innovation Programme

An independent evaluation of the South East Alcohol Innovation Programme (SEAIP), which ran from 2009 to 2011, found that all ten of the projects scrutinised could succeed anywhere in the country. It concluded that:

•Five of the projects identified significant cost savings, with the potential if extended to save the NHS and local authorities millions of pounds

•Five of the projects reported reduced hospital admissions among their client groups

•Three of the projects have been taken up as NHS Quality, Innovation, Productivity and Prevention (QIPP) initiatives, indicating their high potential to demonstrate innovation and increase quality and productivity. A further three of the projects are continuing.

The SEAIP was funded by the Government Office for the South East (GOSE) and managed by the Centre for Public Innovation (CPI). In its first year, it gave £146,000 to 26 projects to test a variety of innovative approaches to reduce the harm caused by alcohol misuse.

The five most successful models were then tested again the next year, with ten projects awarded a total of £118,750 to emulate their ideas. These were evaluated independently between May and August 2011, with the results published in October 2011. Although a formal health economic appraisal was not possible the evaluation indicates significant potential savings could be made using this approach.

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Substance misuse in Wales 2010-11

This report summarises Substance Misuse Statistics for Wales, 2010-11. It has been compiled by Welsh Government in collaboration with NHS Wales Informatics Service (NWIS) and Public Health Wales.

1.1. Part 1 includes statistics from the Welsh National Database for Substance Misuse. The profile of referrals during 2010-11 to substance misuse treatment services is described as well as treatment service activity between 2007-08 and 2010-11.

1.2. Part 2 provides additional substance misuse related information currently available from routinely published sources in Wales to support and add to the information gained through the Welsh National Database for Substance Misuse. Evidence is drawn from a number of data sources including information from the hospital admission data (Patient Episode Database Wales (PEDW)), Office for National Statistics (ONS) information, Home Office and Education data. Key points are summarised on page 54.

1.3. The database guidance and information about the Welsh Government’s Substance Misuse policy and key performance indicators can be obtained at http:/new.wales.gov.uk/substancemisuse


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Atypical Antipsychotic Drugs and Ethanol Withdrawal Syndrome: A Review

Alcoholism and psychosis are known to have common neurochemical substrates. The aim of this review is to assess the reports involved in the effects of some atypical antipsychotic agents on the signs of ethanol withdrawal syndrome (EWS) in rats. Thus, both effectiveness of these drugs in ethanol withdrawal and the association between the drug effects and the signs have been investigated here on the same animal model.

Adult Wistar rats were used as subjects. Ethanol was given to rats by modified liquid diet technique for inducing ethanol dependence. Clozapine, olanzapine, risperidone, quetiapine and ziprasidone were the drugs tested. Effects of these drugs on the signs of ethanol withdrawal such as locomotor hyperactivity, stereotyped behavior, tremor, wet dog shakes, tail-stiffness, abnormal posture and gait, agitation and audiogenic seizures were evaluated for the first 6 h of ethanol withdrawal.

Although some beneficial effects of all the drugs on ethanol withdrawal signs were observed, olanzapine precipitated abnormal posture and gait in the animals. Effectiveness rank of the used atypical antipsychotics was as follows: risperidone = quetiapine > ziprasidone > klozapine > olanzapine.

Our results suggest that risperidone and quetiapine seem to be potent and pharmacologically more active agents on EWS in rats. Thus, these drugs may be beneficial in treatment of EWS in patients with alcoholism. Ziprasidone and clozapine also seem to be useful drugs in treatment of ethanol withdrawal.



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Request Reprint E-Mail: tuzbay@gata.edu.tr;

Universal Prevention is Associated with Lower Prevalence of Fetal Alcohol Spectrum Disorders in Northern Cape, South Africa: A Multicentre Before–Afte

Prevalence of fetal alcohol spectrum disorders (FASDs) is remarkably high in several provinces of South Africa; yet population-level knowledge of the harms of maternal drinking remains low. In two heavily affected areas, we assessed effectiveness of interventions to heighten awareness of these harms and to alter social norms about drinking in pregnancy.

FASD prevalence, maternal knowledge and drinking behaviours were investigated in two Northern Cape Province towns, before and after interventions which included highlighting FASD using local media and health promotion talks at health facilities. Independently, two dysmorphologists and a neuropsychometrist examined children at 9 and 18 months.

Pre-intervention maternal knowledge of alcohol harms was low and FASD prevalence 8.9% (72/809). Interventions reached high coverage and knowledge levels increased substantially. FASD prevalence was 5.7% post-intervention (43/751; P = 0.02); 0.73 lower odds, controlling for maternal age and ethnicity (95% confidence interval = 0.58–0.90). No change was detected in more severe FASD forms, but in the whole population, median dysmorphology scores reduced from 4 [inter-quartile range (IQR) = 2–7] to 3 (IQR = 1–6; P = 0.002).

This, the first prevention study using FASD outcomes, suggests that universal prevention might reduce FASD by ∼30% and have population-level effects. This supports intensifying universal interventions where knowledge of harms of maternal drinking is low. These efforts need to be accompanied by alcohol-dependence treatment to lower more severe FASD forms.

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Request Reprint E-Mail: matthew.chersich@wits.ac.za

Effect of Retirement on Alcohol Consumption: Longitudinal Evidence from the French Gazel Cohort Study

Little is known about the effect of retirement on alcohol consumption. The objectives were to examine changes in alcohol consumption following retirement, and whether these patterns differ by gender and socioeconomic status.

We assessed alcohol consumption annually from 5 years before to 5 years after retirement among
10,023 men and 2,361 women of the French Gazel study. Data were analyzed separately for men and women, using repeated-measures logistic regression analysis with generalized estimating equations. Five years prior to retirement, the prevalence of heavy drinking was about 16% among men, and not patterned by socioeconomic status. Among women, this
prevalence was 19.5% in managers, 14.7% in intermediate occupations, and 12.8% in clerical workers. Around retirement,the estimated prevalence of heavy drinking increased in both sexes. In men, this increase was 3.1 percentage points for managers, 3.2 in intermediate occupations, 4.6 in clerical workers, and 1.3 in manual workers. In women, this increase was
6.6 percentage points among managers, 4.3 in intermediate occupations, and 3.3 among clerical workers. In men the increase around retirement was followed by a decrease over the following four years, not significant among manual workers; among women such a decrease was also observed in the non-managerial occupations. It is difficult to assess the extent to which the results observed in this cohort would hold for other working populations, other conditions of
employment, or in other cultural settings. A plausible explanation for the increase in heavy drinking around retirement could be that increased leisure time after retirement provides more opportunities for drinking, and not having to work during the day after may decrease constraints on drinking.

Our findings of increased consumption around retirement suggest that information about negative effects of alcohol consumption should be included in pre-retirement planning programs.


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Global Actions October 27, 2011

Recent Highlights:
· ICAP has launched a series of Expert Interviews on our YouTube channel. Global Actions Country Manager Lanre Onigbogi spoke about recent activity in Nigeria.

Global Actions in Focus: Noncommercial Alcohol in Russia
Russia is a country of focus for Global Actions’ Noncommercial Alcohol initiative. For many years, unrecorded alcohol has comprised a large segment of the market in Russia. It includes home production of vodka (samogon) and illicit alcohol production for commercial purposes. Among the very poor and marginalized, consumption of surrogate alcohol has been a public health issue. There have been numerous efforts to ban or restrict the production and sale of noncommercial alcohol but today, Russians are still buying homemade samogon.

“There is a tradition in Eastern Europe of purchasing alcohol from individual suppliers,” said ICAP’s Senior Vice President Marjana Martinic. “Many of these relationships are still intact. In most cases, the producers of samogon rely on sales to supplement their incomes.”



Our studies show that people in Russia consume noncommercial alcohol for three main reasons: lower price when compared to legally produced drinks, round-the-clock availability, and a long tradition of home production. “As in other parts of the world, the consumption of unrecorded alcohol is driven by price,” said ICAP’s Science and Policy Analyst Guillermo Cantor. “Legally produced commercial vodka is often twice as expensive as illicit vodka.”

Vodka is clearly the drink of choice in Russia, with spirits making up 60% of pure alcohol consumption, beer at 30% and wine at 10%. “Vodka is the preferred beverage in Russia,” said Dr. Martinic. “The prevalent drinking pattern is heavy episodic drinking. Among many Russians, drunkenness is culturally acceptable.”

ICAP has partnered with the National Research Centre on Addictions to conduct case studies on the current state of noncommercial alcohol in Russia. A pilot study has been completed in Moscow region’s town of Klin and surrounding rural areas, where 24% of the population report consuming samogon, and 3.5% report consuming surrogates. ICAP plans to include other locations throughout Russia in Phase 2 of the Noncommercial Alcohol project.

Read more about Noncommercial Alcohol under ICAP’s Issues Briefings.

What’s Happening Next:

· Beijing, China, October 28: Global Actions China will meet with the China Alcoholic Drinks Industry Association (CADIA) and China Association of National Advertisers (CANA) to discuss self-regulation.

· Nairobi, Kenya: November 20-21, Global Actions noncommercial alcohol meeting with researchers, government, and industry from five countries in Africa (Uganda, Tanzania, Rwanda, Kenya, and Botswana).

News Release - Legacies of the legless

Students love alcohol. As long as there have been students there have been drunken students, staggering around campuses the world over as they experiment with levels of tolerance for the grape and grain. While their inexperience with intoxication often ends in tears, it was students’ enthusiastic embracing of all things alcoholic that led to the social drinking culture we know today.

In a talk for the Festival of Ideas, Dr Phil Withington, a lecturer in the History Faculty, will look at how the dramatic increase in university students during the education boom of the early 17^th century cemented much of the ritual and tradition that we are familiar with today, in pubs and clubs up and down the country.

“There’s an assumption among historians that drunkenness during early modernity became inappropriate for civil behaviour, and excessive consumption was the reserve of the common poor,” says Withington. “But there’s a huge amount of evidence that you needed to be affluent to indulge in vast quantities of alcohol, and the new wave of educated elite led the charge.” > > > > Read More

Policy Position Paper on Discrimination

OUR MISSION: Faces & Voices of Recovery is dedicated to organizing and mobilizing the over 20 million Americans in recovery from addiction to alcohol and other drugs, our families, friends and allies into recovery community organizations and networks, to promote the right and resources to recover through advocacy, education and demonstrating the power and proof of long-term recovery.

OUR POLICY POSITION ON DISCRIMINATION: People in or in need of recovery from addiction to alcohol and other drugs face myriad forms of discrimination. Discrimination creates barriers to our full participation in community life. Faces & Voices of Recovery strives to eliminate all policies and practices that discriminate against people and their impacted families based solely on their recovery status. > > > > Read More

Voices from the Field: The Social Construction of Alcohol Problems in Inner City Communities

This study examines the social construction of alcohol problems by activists involved in alcohol policy campaigns in inner-city neighborhoods in the 1990s. Nearly 200 informants were interviewed and asked to describe why they thought local neighborhoods mobilized around alcohol policy issues.

In contrast with other social movements that have emphasized individual alcohol problem or addiction experiences, informants in this study focused on the role of alcohol outlets and sales and marketing in contributing to various forms of social disorder, such as crime, violence, illicit drug use, public intoxication, and nuisances that were engulfing their neighborhoods.

These themes were interpreted in light of the social conditions faced by inner-city residents in the 1980s and 1990s, including the crack cocaine epidemic, the spectacular rise in youth violence, aggressive new alcoholic beverage marketing campaigns, and the increasing rates of poverty in dilapidated urban centers.



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Modulation by the GABAB receptor siRNA of ethanol-mediated PKA-α, CaMKII, and p-CREB intracellular signaling in prenatal rat hippocampal neurons

Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter γ-aminobutyric acid (GABA).

We studied modulation of the neurotransmitter receptor GABA_BR and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS.

ET increased GABA_B1R protein levels, but decreased protein kinase A-α (PKA-α), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5.

To elucidate GABA_B1R response to ethanol, we observed the effects of a GABA_BR agonist and antagonist in pharmacotherapy for ethanol abuse.

Baclofen increased GABA_BR, CaMKII and p-CREB levels, whereas phaclofen decreased GABA_BR, CaMKII and p-CREB levels except PKA-α.

Furthermore, when GABA_B1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET.

We speculate that stimulation of GABA_B1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.

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Neurocognitive deficits in male alcoholics: An ERP/sLORETA analysis of the N2 component in an equal probability Go/NoGo task

In alcoholism research, studies concerning time-locked electrophysiological aspects of response inhibition have concentrated mainly on the P3 component of the event-related potential (ERP).

The objective of the present study was to investigate the N2 component of the ERP to elucidate possible brain dysfunction related to the motor response and its inhibition using a Go/NoGo task in alcoholics.

The sample consisted of 78 abstinent alcoholic males and 58 healthy male controls. The N2 peak was compared across group and task conditions.

Alcoholics showed significantly reduced N2 peak amplitudes compared to normal controls for Go as well as NoGo task conditions. Control subjects showed significantly larger NoGo than Go N2 amplitudes at frontal regions, whereas alcoholics did not show any differences between task conditions at frontal regions. Standardized low resolution electromagnetic tomography analysis (sLORETA) indicated that alcoholics had significantly lower current density at the source than control subjects for the NoGo condition at bilateral anterior prefrontal regions, whereas the differences between groups during the Go trials were not statistically significant.

Furthermore, NoGo current density across both groups revealed significantly more activation in bilateral anterior cingulate cortical (ACC) areas, with the maximum activation in the right cingulate regions.

However, the magnitude of this difference was much less in alcoholics compared to control subjects.

These findings suggest that alcoholics may have deficits in effortful processing during the motor response and its inhibition, suggestive of possible frontal lobe dysfunction.

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Request Reprint E-Mail: akp@hbnl.downstate.edu

Spatio-temporal transcriptome of the human brain

Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete.

Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains.

We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time.

The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage.

We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression.

This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.



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Request Reprint E-Mail: nenad.sestan@yale.edu

The role of social isolation in ethanol effects on the preweanling rat

The present experiments investigated the effects of acute ethanol exposure on voluntary intake of 0.1% saccharin or water as well as behavioral and nociceptive reactivity in twelve–day-old (P12) rats exposed to differing levels of isolation.

The effects of ethanol emerged only during short-term social isolation (STSI) with different patterns observed in males and females and in pups exposed to saccharin or water.

The 0.5 g/kg ethanol dose selectively increased saccharin intake in females, decreased rearing activity in males and attenuated isolation-induced analgesia (IIA) in all water-exposed pups. Ingestion of saccharin decreased IIA, and the 0.5 g/kg ethanol dose further reduced IIA.

The 1.0 g/kg ethanol dose, administered either intragastrically or intraparentionally, also decreased IIA in P12 females, but not in P9 pups.

A significant correlation between voluntary saccharin intake and baseline nociceptive reactivity was revealed in saline injected animals, saccharin intake was inversely correlated with behavioral activation and latency of reaction to noxious heat after 0.5 g/kg ethanol in females.

The 0.5 g/kg ethanol dose did not affect plasma corticosterone (CORT) measured 5 hours after maternal separation or 20 minutes after ethanol injection. Female pups CORT level was inversely correlated with magnitude of IIA that accompanied the first episode of STSI (pretest isolation) 1.5 -2 hours before CORT measurement.

The present findings suggest that the anxiolytic properties of ethanol are responsible for enhancement of saccharin intake during STSI. Furthermore, differential reactivity of P12 males and females to STSI plays an important role in ethanol effects observed at this age.

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Request Reprint E-Mail: nspear@binghamton.edu

Press Release - Wayne State University receives $655,500 grant from NIH to develop a computer-delivered intervention for alcohol use among pregnant

A team of researchers at Wayne State University's Parent Health Lab in the School of Medicine have received a three-year grant to develop a computer-delivered intervention for pregnant women at risk for alcohol use, which can lead to lifelong negative effects on the fetus. Prenatal exposure to alcohol affects attentional, cognitive, social and behavioral functioning and is a major cause of mental retardation. Infants born to African American women are at increased risk of adverse effects.

Screening, brief intervention, and referral for treatment ("SBIRT") approaches to alcohol use during pregnancy can be used by medical staff to identify and reduce alcohol use among pregnant women. SBIRT approaches are not often used, however, because of the amount of time, training, expertise and commitment required. Computer-delivered SBIRT approaches may offer an alternative approach through the use of consistent screening and evidence-based brief interventions at a lower cost, without requiring significant time of medical staff. > > > > Read More

Alcohol Concern calls for restrictions on alcohol advertising affecting children and young people

A survey of 2,300 young people published by Alcohol Concern said most respondents wanted more protection from alcohol advertising. Alcohol Concern said there is recognition of a need to protect under-18s from exposure to alcohol promotion, although children and young people as young as 11 are regularly exposed to alcohol advertising. > > > > Read More

New York Alcohol Policy Summit: Expanding Public Health Protection

In the United States today, much of the focus on alcohol problems is limited to the issues of underage drinking and drunk driving, with both narrowly defined in terms of the problem and the acceptable solutions. To expand this frame, several organizations including the New York Alcohol Policy Alliance (NYAPA), the New York State Public Health Association (NYSPHA), and the Council on Addiction of New York State (CANYS) met at the New York Alcohol Policy Summit in Syracuse October 6.

About 200 participants – including faith leaders, police officers, pediatric nurse practitioners, prevention educators, research scientists, coalition members, public health practitioners, policy analysts, university faculty, registered nurses, and suicide prevention advocates met to consider the health and social consequences of excessive alcohol consumption and to propose new policy approaches to reduce the adverse consequences of alcohol use in New York State. > > > > Read More

What place, if any, does information on putative cardioprotective effects of moderate alcohol use have in safer drinking guidelines?

The majority view among alcohol epidemiologists is that the lower coronary heart disease mortality observed in moderate drinkers is probably evidence for a protective effect of moderate drinking.

In this paper I critically discuss the debate about what type of information, if any, should be provided to the public about the putative coronary heart disease benefits of moderate alcohol use.

Most opposition to informing the public about these putative benefits is based on the fear that such advice will increase per capita alcohol consumption and therefore alcohol-related harm. It is unclear how well-based these concerns are. In the interim, the alcohol industry has communicated these putative benefits to the public.

There is a case for including some information on these putative benefits in specific safer drinking guidelines for middle-aged and older drinkers that: clearly conveys the remaining uncertainty about the benefits of moderate drinking, emphasises the conditional nature of any such benefits, and stresses the need to balance the potential benefits against the increased sensitivity of older adults to other adverse effects of alcohol, and the increased risk of interactions between alcohol and other medications used by older adults.

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Request Reprint E-Mail: w.hall@uq.edu.au

Biotransformation of ethanol to ethyl glucuronide in a rat model after a single high oral dosage

Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest that maximum blood EtG (BEtG) concentrations are reached between 3.5 and 5.5h after ethanol administration.

This study was undertaken to determine if the Sprague–Dawley (SD) rat biotransforms ethanol to EtG after a single high oral dose of ethanol.

SD rats (male, n=6) were gavaged with a single ethanol dose (4g/kg), and urine was collected for 3h in metabolic cages, followed by euthanization and collection of heart blood. Blood and urine were analyzed for ethanol and EtG by gas chromatography and enzyme immunoassay.

Blood and urine ethanol concentrations were 195±23 and 218±19mg/dL, whereas BEtG and urine EtG (UEtG) concentrations were 1,363±98ng equivalents/mL and 210±0.29mg equivalents/dL .

Sixty-six male SD rats were gavaged ethanol (4g/kg) and placed in metabolic cages to determine the extent and duration of ethanol to EtG biotransformation and urinary excretion. Blood and urine were collected up to 24h after administration for ethanol and EtG analysis.

Maximum blood ethanol, urine ethanol, and UEtG were reached within 4h, whereas maximum BEtG was reached 6h after administration. Maximum concentrations were blood ethanol, 213±20mg/dL; urine ethanol, 308±34mg/dL; BEtG, 2,683±145ng equivalents/mL; UEtG, 1.2±0.06mg equivalents/mL .

Areas under the concentration–time curve were blood ethanol, 1,578hmg/dL; urine ethanol, 3,096hmg/dL; BEtG, 18,284hng equivalents/mL; and UEtG, 850hmg equivalents/dL.

Blood ethanol and BEtG levels were reduced to below limits of detection (LODs) within 12 and 18h after ethanol administration. Urine ethanols were below LOD at 18h, but UEtG was still detectable at 24h after administration.

Our data prove that the SD rat biotransforms ethanol to EtG and excretes both in the urine and suggest that it is similar to that of the human.

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Request Reprint E-Mail: soccertre016@msn.com