Biomarkers of the alcohol hangover state: Ethyl glucuronide (EtG) and ethyl sulfate (EtS).

INTRODUCTION: The aim of this study was to investigate the usefulness of ethyl glucuronide (EtG) and ethyl sulfate (EtS) as biomarkers of the hangover state. METHODS: Thirty-sixhealthy social drinkers participated in this study, being of naturalistic design. Eighteen participants experience regular hangovers (the hangover group), whereas the other 18 claim to not experience a hangover (the hangover-immune group). On a control day (alcohol-free) day and a post-alcohol day, urine EtG and EtS concentrations were determined and hangover severity assessed. RESULTS: Urinary EtG and EtS concentrations were significantly increased on post-alcohol day compared to the control day (p = .0001). Both EtG and EtS concentrations did not significantly correlate with the overall hangover score, nor with the estimated peak blood alcohol concentrations and number of alcoholic drinks. EtG correlated significantly only with the individual hangover symptom "headache" (p = .033; r = .403). No significant correlations were found with the EtG to EtS ratio. EtG and EtS concentrations significantly correlated with urine ethanol concentrations. CONCLUSIONS: Although urine EtG and EtS concentration did not significantly correlate to estimated peak blood alcohol concentrations or the number of alcoholic drinks consumed, a significant correlation was found with urine ethanol concentration. However, urine EtG and EtS concentrations did not significantly correlate with overall hangover severity.

Global metabolic profiling for the study of alcohol-related disorders.

Alcohol-related disorders are multifaceted since ethanol can induce profound metabolic perturbations when taken in excess. Global metabolic profiling strategies may aid the understanding of ethanol-related effects by shedding light on these metabolic changes and potentially revealing unknown mechanisms of ethanol toxicity. Here an overview of studies designed to explore the effects of alcohol (ethanol) consumption using holistic metabolite profiling approaches (metabonomics/metabolomics) is presented, demonstrating the potential of this methodology. The analytical technologies used (NMR, GC-MS and LC-MS), have been applied to the profiling of serum, plasma, urine and tissues, obtained from animal models or humans, after exposure to alcohol. From the metabolic profiling data of a range of biological samples, a number of endogenous metabolites have been proposed as potential ethanol consumption-related biomarkers. The biomarkers suggested by these studies, and the biochemical insights that they provide for understanding the effects of ethanol mechanisms of toxicity, are discussed.

An evaluation of the DRI-ETG EIA method for the determination of ethyl glucuronide concentrations in clinical and post-mortem urine.

A commercial enzyme immunoassay for the qualitative and semi-quantitative measurement of ethyl glucuronide (EtG) in urine was evaluated. Post-mortem (n=800), and clinical urine (n=200) samples were assayed using a Hitachi 902 analyzer. The determined concentrations were compared with those obtained using a previously published liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of EtG and ethyl sulfate. Using a cut-off of 0.5 µg/ml and LC-MS/MS limit of reporting of 0.1 µg/ml, there was a sensitivity of 60.8% and a specificity of 100% for clinical samples. For post-mortem samples, sensitivity and specificity were 82.4% and 97.1%, respectively. When reducing the cut-off to 0.1 µg/ml, the sensitivity and specificity were 83.3% and 100% for clinical samples whereas for post-mortem samples the sensitivity and specificity were 90.3 % and 88.3 %, respectively. The best trade-offs between sensitivity and specificity for LC-MS/MS limits of reporting of 0.5 and 0.1 µg/ml were achieved when using immunoassay cut-offs of 0.3 and 0.092 µg/ml, respectively. There was good correlation between quantitative results obtained by both methods but analysis of samples by LC-MS/MS gave higher concentrations than by enzyme immunoassay (EIA), with a statistically significant proportional bias (P<0.0001, Deming regression) for both sample types. The immunoassay is reliable for the qualitative and semi-quantitative presumptive detection of ethyl glucuronide in urine.

Clinical application of ethyl glucuronide testing in the U.S. Army.

This study examined the clinical characteristics of ethyl glucuronide testing among service members referred to a military substance abuse program. The authors analyzed 1,852 urine specimens from 328 service members collected over a two year period. Among all participants, approximately one-fifth (n = 45/262, 17.2%) produced a positive ethyl glucuronide result at the initial assessment. Nearly two-thirds (n = 29/45, 64%) of the service members who initially tested positive had at least one additional positive specimen during the next five sequential tests. A statistically significant decline (p = 0.017) in ethyl glucuronide levels occurred with serial testing over time. The authors suggest that ethyl glucuronide testing can join with other risk mitigation strategies to help reduce alcohol-related adverse incidents.

Alcohol and unnatural deaths in the West of Ireland: a 5-year review.

AIM: To investigate the prevalence of alcohol in unnatural deaths in the West of Ireland between 2003 and 2007. METHODS: The reports of 1669 postmortem examinations carried out at Galway University Hospitals were reviewed; 379 non-homicidal unnatural deaths were eligible for the study. Alcohol levels were measured in blood and/or urine in 311 cases. For each case, gender, age, cause of death and toxicology results were recorded. RESULTS: Alcohol was detected in 162 out of 311 cases (52%); 133 (82%) cases were men and 29 (18%) were women. Alcohol levels >150 mg/100 ml were found in 99 cases (61%), most commonly in 18-49-year-olds (n=74; 75%). Road traffic crashes (RTCs) (n=38; 23%), drownings (n=38; 23%) and hangings (n=25; 15%) were common unnatural deaths associated with alcohol. The majority of RTC deaths involved the driver (n=27; 71%). The alcohol level was higher than the legal driving limit of 80 mg/100 ml in 82% (n=22) and >150 mg/100 ml in 59% (n=16) of these. Mortality of passengers (n=6; 16%) and pedestrians (n=5; 13%) was less common. CONCLUSIONS: Alcohol remains a major contributor to unnatural deaths in the West of Ireland, particularly with respect to mortality in young people. Young men are especially vulnerable. Deaths in RTCs and by drowning and hanging are commonly associated with alcohol. Many driver fatalities involve alcohol levels far above legal limits. Alcohol measurement in all unnatural deaths would facilitate more accurate determination of its role.

Procedures for transportation workplace drug and alcohol testing programs. Final rule.

The Department of Transportation is amending certain provisions of its drug and alcohol testing procedures to change instructions to collectors, laboratories, medical review officers, and employers regarding adulterated, substituted, diluted, and invalid urine specimen results. These changes are intended to create consistency with specimen validity requirements established by the U.S. Department of Health and Human Services and to clarify and integrate some measures taken in two of our own Interim Final Rules. This Final Rule makes specimen validity testing mandatory within the regulated transportation industries.

Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers, but have not been widely implemented in community drug abuse treatment settings. OBJECTIVE: To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment settings. DESIGN: Random assignment to usual care with (n = 198) or without (n = 190) abstinence incentives during a 12-week trial. SETTING: Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States. PARTICIPANTS: Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years. INTERVENTION: Participants submitting stimulant- and alcohol-negative samples earned draws for a chance to win prizes; the number of draws earned increased with continuous abstinence time. MAIN OUTCOME MEASURES: Total number of stimulant- and alcohol-negative samples provided, percentage of stimulant- and alcohol-negative samples provided, longest duration of abstinence, retention, and counseling attendance. RESULTS: Submission of stimulant- and alcohol-negative samples was twice as likely for incentive as for usual care group participants (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times more likely, respectively, for incentive vs usual care participants. Groups did not differ on study retention or counseling attendance. The average cost of prizes was 120 dollars per participant. CONCLUSION: An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics.