Alcohol Markers Research Articles

Mental Manifestations and Biomarkers of Alcohol Consumption.

The purpose of this study is to examine healthcare usage, morbidities, and alcohol consumption monitoring in patients before a diagnosis of mental manifestations to assist in the early identification of individuals at risk. Biological markers of alcoholism are separated into two groups: those biological variables that highlight with great confidence and validate the presence of a predisposition to alcoholism, also called trait markers, or those that highlight alcohol consumption, called markers of alcoholism ("status markers"). Biomarkers are the true "gold standard" for the diagnosis of alcoholism. They are valuable for tracking evolution and progress during biological and psychological therapy and for highlighting relapse. This review compiles the existing data from research on healthcare utilization, comorbidities, and alcohol consumption monitoring in patients before a diagnosis of mental manifestations to aid in the early identification of individuals at risk. This documentary study took place over three to four months by searching for terms on the Science Direct platform, PubMed, Web of Science, and Google Scholar such as alcoholism, alcohol use disorders, alcohol abuse, and biomarkers. Studies reporting on the development, characteristics, and utilization of blood biomarkers for alcohol consumption were included in the search. The initial search included a number of 11.019 articles that contained the keywords biomarkers and alcohol. Finally, a total of 50 research articles were considered. I am involved in clinical studies, meta-analyses, reviews, and case studies regarding alcohol consumption detection, as well as potential alcohol markers.

Is there a relationship between abuse of alcohol and illicit drugs seen in hair results?

Combined use of alcohol and illicit drugs is a serious health and social problem. In this study, it was examined, whether a relationship between alcohol and drug abuse can be ascertained by comparison of alcohol marker and drug concentrations in hair. In the frame of a social support system for families with parental abuse of illicit drugs, hair samples were analyzed between 2011 and 2022 for methadone, heroin (6-acetylmorphine), cocaine, amphetamine, ecstasy (MDMA), cannabinoids (THC), and the alcohol markers ethyl glucuronide (EtG) and ethyl palmitate (EtPa). For 1314 hair samples from adolescent and adult family members, the hair results show a prevalence of combined occasional or regular drug use and social or abusive alcohol use of 41%-60% except heroin (35%). The drug concentrations were statistically compared in the three categories of abstinence or moderate drinking, social drinking, and alcohol abuse. For the most frequently detected drug cocaine (n = 703), a significant increase of the concentrations with rising alcohol consumption was found. The frequent detection of cocaethylene proved the preferred simultaneous intake of both substances. For THC (n = 489), no significant difference between the alcohol consumer groups was seen. Concerning the less frequently detected methadone (n = 89), 6-acetylmorphine (n = 92), amphetamine (n = 123), and MDMA (n = 105), no clear trend between drug and alcohol marker results was determined. It is concluded that the evaluation of hair results is an appropriate way to study the extent of combined drug-alcohol consumption and complements other studies based on acquisition of consumption data by interview or questionnaire.

Hoe waarheidsgetrouw zijn verklaringen over middelengebruik in het rijgeschiktheidsonderzoek?

How truthful are statements about substance use in the fitness to drive examination? In Belgium, the court can order a fitness to drive examination on indication. One is not fit to drive if there has been excessive alcohol and/or drug use in the past 6 months. Chronic excessive alcohol use corresponds to an average consumption of ≥ 6 units per day or ≥ 42 units per week over several months. Toxicologically, 30 pg/mg ethylglucuronide (direct alcohol marker) in scalp hair strongly suggests this. For drugs, it is sufficient to demonstrate this substance in one of the samples. The anamnesis and toxicology were compared with a McNemar test. The sensitivity, specificity and positive/negative predictive value of the anamnesis as a diagnostic test were calculated. People are more likely to be unfit to drive based on the toxicological analysis than based on the anamnesis (respectively 60% versus 40%). The greatest discrepancy is seen regarding alcohol consumption. In addition, toxicologically more cases of drug use were detected. This study shows that statements regarding alcohol and drug use within the fitness to drive examination are not reliable.

Storage stability of phosphatidylethanol homologues in whole blood and dried blood spots of nonalcoholics at different temperatures over 60 days.

Phosphatidylethanol (PEth) has recently become a popular direct alcohol marker for evaluating drinking behavior. This study aimed at gaining further information on the long-term stability of five PEth homologues (16:0/18:1, 16:0/18:2, 16:0/20:4, 18:0/18:1, 18:0/18:2) in whole blood (WB) and dried blood spots (DBS) stored at -80°C, 4°C, and room temperature (18°C) over a period of 60 days. Venous blood was taken from 10 volunteers (five females and five males, aged 21-40 years) with a moderate drinking behavior and a negative breath alcohol test at the time of collection. 100 μL aliquots of WB were prepared in addition to 20 μL DBS samples. The initial PEth concentrations were determined on the day of the blood collection. On days 1, 3, 5, 7, 11, 17, 40, and 60, DBS were analyzed in triplicate by means of LC-MS/MS. On these days, WB aliquots having been stored until that time were used to create further DBS in triplicate, which were subsequently stored at 18°C and analyzed in a single batch after day 60. All homologues, except PEth 16:0/20:4, were stable at -80°C in DBS and WB for 60 days. The initial PEth 16:0/18:1 concentrations remained stable in both DBS and WB in all but one volunteer's specimen at 4 and 18°C. Apart from this exception, simultaneously detected PEth homologues 16:0/18:2, 18:0/18:1, and 18:0/18:2 remained stable over at least 40 days in DBS. Nevertheless, the storage time between sample collection and analysis should be kept as short as possible if an ethanol-free sample cannot be ensured.

Analytical description of adolescent binge drinking patients

BackgroundBinge drinking is a widespread health compromising behavior among adolescents and young adults, leading to significant health problems, injuries and mortality. However, data on alcohol consumption is often unreliable, as it is mainly based on self-reporting surveys. In this five-year study (2014–2019) at the University Children’s Hospital Zurich, we analyzed blood samples from adolescent binge drinking patients to investigate blood alcohol concentrations (BACs), co-ingestion of drugs, assess compliance between self-reported and measured substance use, and test for genetic components of innate alcohol tolerance. Furthermore, hair analysis was performed to retrospectively access drug exposure and to evaluate the potential of hair analysis to assess binge drinking.MethodsIn a prospective, single-center study, patients with alcohol intoxications aged 16 years and younger were included. Blood and hair samples were analyzed by sensitive liquid chromatography – tandem mass spectrometry drug analysis. HTTLPR genotyping was performed with PCR and fragment analysis.ResultsAmong 72 cases, 72 blood and 13 hair samples were analyzed. BACs ranged from 0.08–3.20‰ (mean 1.63‰, median 1.60‰), while a mean concentration of 3.64 pg/mg hair (median 3.0 pg/mg) of the alcohol marker ethyl glucuronide (EtG) was detected in eleven hair samples, providing no evidence of chronic excessive drinking. In 47% of the cases, co-ingested drugs were qualitatively detected next to ethanol, but only 9% of the detected drugs had blood concentrations classified as pharmacologically active. Cannabis consumption (22%) and stimulant intake (16%) were the most frequently observed drugs. Compliance between patients’ statements and measured substances matched well. Although we investigated the genetic contribution to innate alcohol tolerance via the 5-HTTLPR polymorphism, the diverse genetic background of the cohort and small sample size did not allow any conclusions to be drawn.ConclusionAlmost half of our binge drinking patients tested positive for other substances, primarily cannabis. We anticipate that our study enhances understanding of consumption behavior of young people and encourage continued efforts to address the harmful effects of binge drinking and co-occurring substance use.

A preliminary investigation of salivary α-amylase as a novel biomarker of subjective response to alcohol: A brief report.

Alcohol misuse represents a universal public health concern that spans multiple demographics. As such, understanding shared, biological indicators of alcohol-related risk is vital to implementing targeted prevention and intervention efforts. Self-report measures of subjective response to alcohol (SR) capture both psychological and pharmacological effects of alcohol and robustly predict patterns of alcohol use, negative consequences, and the development of alcohol use disorders. Importantly, several biological markers of alcohol's sedating effects, including cortisol, have been identified and complement subjective response assessments. However, biological markers of alcohol's stimulating effects are less understood. Studies have implicated alcohol-induced changes in heart rate as a viable marker, but heart rate measurements are susceptible to measurement error. Salivary α-amylase, a reliable indicator of sympathetic nervous system activation, represents a promising alternative biomarker of alcohol-induced stimulation. Using data from a large, placebo-controlled alcohol administration study (N = 448), the present study examined the extent to which α-amylase is a viable marker of alcohol-induced stimulation. To test this, a measurement model was estimated in which baseline and ascending limb subjective stimulation latent variables were created using two validated measures of subjective response. Ascending self-reports of stimulation and levels of α-amylase were then regressed onto beverage conditions and allowed to correlate with each other. Findings indicated that α-amylase is sensitive to acute alcohol consumption and is positively, but not statistically reliably, related to the ascending limb stimulant SR. Future studies should consider including salivary α-amylase as a noninvasive physiological indicator of alcohol's stimulating effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Factors associated with higher alcohol concentrations in emergency department presentations: PACE study.

The health impact from alcohol is of recognised concern, from acute intoxication as well as increased risk of chronic health issues over time. Identifying factors associated with higher alcohol consumption when presenting to the emergency department (ED) will inform public health policy and enable more targeted health care and appropriate referrals. Secondary testing of blood samples collected during routine clinical care of 1160 ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, for 10 days between 22 January and 1 February 2021. Alcohol was measured by blood ethanol (intake in recent hours) and phosphatidylethanol (PEth; intake over 2-4 weeks). Zero-inflated negative binomial regression was used to identify demographic and clinical factors associated with higher alcohol concentrations. Males were found to have 83% higher blood ethanol and 32% higher PEth concentrations than females (adjusted rate ratio [ARR] 1.83, 95% confidence interval [CI] 1.37-2.45 and ARR 1.32, 95% CI 1.04-1.68, respectively). Blood ethanol concentrations were 3.4 times higher for those 18-44 years, compared to those aged 65+ (ARR 3.40, 95% CI 2.40-4.82) whereas PEth concentrations were found to be the highest in those aged 45-64 years, being 70% higher than those aged 65+ (ARR 1.70, 95% CI 1.19-2.44). Patients brought in involuntarily had eight-times higher blood ethanol concentrations than those who self-attended. This study used two alcohol markers to identify factors associated with higher alcohol concentrations in emergency presentations. The findings demonstrate how these biomarkers can provide informative data for public health responses and monitoring of alcohol use trends.

Comparison of two methods for the extraction of ethylglucuronide from hair.

The aim was the comparison between the Society of Hair Testing (SoHT) consensus for the use of alcohol markers which powdering hair for the extraction of ethylglucuronide (EtG) in water and extraction using the patented M3 Reagent Test kit on cut hair. Hair samples were cut into small segments and washed twice with methanol and diethyl ether. The SoHT-Consensus entails the extraction of pulverised hair in water. This is obtained by incubation of 25 mg of hair at room temperature overnight and 2 h sonication, even if the overnight incubation is not mandatory. The M3 method entails incubation of 25 mg of cut hair with the M3-Reagent at 100°C for 60 min. After centrifugation, the supernatant is injected into a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples (191) were collected in the APSS laboratory in Trento, Italy, between 2021 and 2022. The limit of quantification (LOQ) was set at 5pg/mg for the pulverised and M3-Reagent methods. Assays showed good linearity above the range of LOQ-300 pg/mg. Precision (within 20%) values were also obtained using both methods. In the Passing-Bablock linear regression, the final regression curve between M3 (y) and the pulverising method (x) showed good agreement; the Bland-Altman analysis did not show any significant bias between the two methods. The M3-Reagent method, due to cut hair use, is easy to perform, saves time and allows for a smaller sample quantity loss with use of nondisposable grinding jars for the ball mill to obtain the extraction of EtG.

Formation of phosphatidylethanol and ethylglucuronide after low to moderate alcohol consumption in volunteers with a previous three-week alcohol abstinence.

Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography-tandem mass spectrometry. Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3ng/mL) and urine (≥100ng/mL) upon 20-21h after alcohol administration. By combining both a lower cutoff of 10ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%.

Old and New Biomarkers of Alcohol Abuse: Narrative Review.

The harmful use of alcohol is responsible for 5.1% of the global burden of disease, and the early detection of alcohol problems may prevent its development and progression. Therefore, the aim of the study is to review traditional and new biomarkers associated with alcohol use. The nature and practical application and limitations of alcohol biomarkers in the diagnosis and monitoring of drinking are reviewed. Despite the limited specificity and sensitivity in alcohol drinking detection, traditional biomarkers are useful in clinical practice, and new generations of biomarkers, e.g., proteomic markers, are in need of further investigation. Traditional biomarkers are broadly available and cost-efficient, providing valuable data on the complications of drinking and prognosis, as well as on concurrent conditions affected by drinking. The most important challenge in the future will be to translate methodically advanced methods of detecting alcohol markers into simpler and cheaper methods. Larger population studies are also needed to test the usefulness of these potential markers of alcohol use.

Comparison of patterns of drug levels in head and body hair for medico-legal and workplace testing.

This paper presents concentration ranges and positivity rates for the common drugs, alcohol markers, new psychoactive substances (NPS) and anabolic steroids tested in head hair (n =138,352) and body hair (n= 9532) on samples of hair from medico-legal (n =112,033) and workplace (n =35,851) sectors tested in our laboratory. Statistically significant higher levels were found more often in the various types of body hair when compared with head hair, but fewer cases exhibited lower levels. For example, statistically significant higher levels were detected in leg hair for cannabinol, THC, methadone and EtG and in beard hair for THC, THC-COOH and 6-acetylmorphine. In contrast, significantly lower levels were detected in axilla hair for cannabinol, THC and for EDDP, but median levels of mephedrone and DHEA were higher. Overall, higher medium levels were detected in head hair samples tested in the UK when compared with those previously published for samples tested in Germany, indicating geographical differences in drug consumption. Recommendations are, firstly, that hair testing laboratories use the results of their own compiled previous positive results for guidance when interpreting hair testing results and, secondly, that laboratories periodically share and combine their accumulated data with other testing laboratories. The latter could be used to establish reference ranges associated with specific technical procedures which would improve interlaboratory comparability and improve laboratory testing services when interpreting hair testing results.

Serum Carbohydrate Deficient Transferrin: A Sensitive Marker in Diagnosing Alcohol Abuse

Introduction: Alcohol is a psychoactive substance with dependence producing properties and the burden of disease and death related to alcohol consumption remains significant in most countries. Early detection and proper medication with counselling can restore the alcoholics to normalcy. There is a need for a specific assay procedure to detect alcoholics early, so that proper therapy can be instituted. The traditional biomarkers in liver function test (LFT) are more frequently used for diagnosing alcohol abuse but they have variable and limited sensitivity and specificity. Carbohydrate Deficient Transferrin (CDT) can be considered as a more sensitive and specific marker for diagnosing alcohol abuse. The aim of this study is to determine % CDT in alcoholics and compare it with other alcohol markers in respect with sensitivity and specificity. The results of the study will be helpful in assessment of the alcohol dependence patients and therefore in their early detection and management. Materials and Methods: This is a hospital based comparative cross-sectional study carried out in Dharan. A total of 40 cases of alcohol abuse with ≥2 score in CAGE questionnaire and matched 40 subjects with no history of alcohol intake were enrolled in the study. Informed written consent and ethical approval were taken. Result: Serum %CDT has the highest diagnostic efficacy followed by serum gamma glutamyl transferase (GGT), Aspartate Transaminase (AST), Alanine Transaminase (ALT), AST/AL, and ALP as a biomarker for diagnosing alcohol abuse. Serum %CDT has the highest sensitivity with 97.5% and specificity of 73% at a cut off value of 3.5% compared to serum GGT with the sensitivity and specificity of 87% and 73%, respectively at a cut off value of 33.5 U/L. Conclusion: Serum %CDT is a better marker both in terms of sensitivity and specificity compared to other conventional markers and thus can be used as a tool to early diagnose the alcoholic cases and monitor the therapy and for early identification of the relapses in alcoholics during treatment.

Predictive risk markers in alcoholism.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.

Dried blood spot (DBS) for ethyl glucuronide (EtG) and ethyl sulfate (EtS) determination in blood with a new design of “volumetric” DBS filter paper card

Determination of EtG in blood can be performed from capillary blood with high sensitivity and detection limits of down to 1 ng/mL for EtG–and in addition to phosphatidyl ethanol (PEth) determination, EtG concentrations can be used for interpretation of consumption habits of patients in maintenance therapy. Sampling of capillary blood is a crucial preanalytical step–and different methods have been suggested for collection of a defined volume (VAMS, Capitainer, HemaXis, and capillaries for collection of samples). We used and validated a new volumetric capillary blood sampling card (DBSv cards, Protzek, Lörrach/Germany) which can be used either for self-sampling of dried blood spots (up to 4 times 20 microliter of blood) on filter paper with convenient handling by the patients or also in laboratory work. In contrast to standard DBS cards with printed circles on a filter paper, a newly designed card with a paper comb with four teeth per card, which allows a volumetric collection of 20 microlitres of blood per tooth, was used. Venous blood was pipetted on the teeth of DBSv cards, dried, and one paper tooth was ripped off and extracted by adding 490 microliter of methanol and 10 microliter of ISTD (400 ng/ml D5-EtG and 400 ng/ml D5-EtS). The samples were then vortexed for 5 minutes and centrifuged for 10 minutes. After transferring them into vials, the solutions were evaporated under a stream of nitrogen and reconstituted in 80 microliter of a water/0.1% formic acid. The samples were shaken and 10 μL were injected onto the LC column. A previously published LC-MS/MS method was adapted for a QTrap 5500 triple-quadrupole ion trap mass spectrometer (Sciex, Toronto, Canada) with an Acquity C18 HSS T3 column (Waters, Wexford, Ireland) and detection of EtG, D5-EtG, EtS and D5-EtS was performed according to forensic guidelines using one precursor and two product ions. Lower limits of quantification were 10 ng/mL for EtG and 20 ng/mL for EtS–with linear ranges of 10 to 5000 ng/mL for EtG and (50 to 2500 ng/mL for EtS. Traces of EtS were found in HPLC grade solvent, and a solvent selection between products of different manufacturers had to be performed. One brand methanol showed the lowest baseline level of EtS, which was in the range of 20 ng/mL. Thus, for determination of EtS, a lower limit of quantitation of 50 ng/mL was defined, whereas EtG could be quantified at concentrations above 10 ng/mL. A validation with spiked blood samples was performed. Samples from forensic cases and from drinking studies, where DBS were collected for the analysis of alcohol biomarkers (PEth and EtG/EtS) have been analyzed. The dried blood spot sample collection in laboratory or by self-sampling (of capillary blood) can be used to detect EtG and EtS at very low levels. The results show the potential of DBS analysis for alcohol markers EtG and EtS–which can be used for abstinence monitoring by very low limits of detection, especially for EtG, or for the detection of a recent alcohol consumption, when ethanol has already been eliminated from the body. A contamination of pure HPLC-grade solvent methanol was found for EtS determination, this has to be kept in mind, and needs further optimization for detection of EtS at lower concentrations in biological samples.

Possibility of falsely low levels of the alcohol marker phosphatidylethanol in patients with high alcohol consumption and hemolytic conditions

Although PEth is considered both a sensitive and specific marker of high alcohol intakes, false negative results are seen occasionally. Since the rate of PEth formation is a function of erythrocyte exposure to ethanol, short erythrocyte lifetime in hemolytic conditions may result in falsely lower or even negative PEth levels. Thus, our present study aimed to elucidate this hypothesis. PEth and CDT from 9893 serum and whole blood samples collected from 5746 patients were included along with markers of hemolysis (i.e. haptoglobin, HbA1c, reticulocytes, LD and Hb). Cases showing discrepancy between PEth and CDT, i.e. a low PEth value and a high CDT value, were considered to be possibly caused by falsely lowered PEth despite high alcohol consumption. These cases ( n = 233) were compared to the control group without PEth and CDT mismatch. The levels of haptoglobin were significantly lower in the cases showing low PEth and high CDT (estimate = −0.62, P = 0.002). The levels of HbA1c (estimate = −3.26, P = 0.001) and Hb (estimate = −0.507, P < 0.001) were also significantly lower in this group. These findings indicate hemolytic conditions in the low PEth/high CDT group. There were no significant differences for reticulocytes and LD concentrations between the low PEth/high CDT group and the control group. We also present a patient case with five samples illustrating the combination of low PEth and high CDT values combined with other findings indicative of hemolysis. These results indicate that PEth values could be falsely low in the presence of hemolytic conditions, although more research is needed to highlight this further. If high alcohol intake is suspected in the case of low PEth values, CDT should also be measured, and analysis of hemolytic biomarkers could be indicated.

Evaluation of Alcohol Markers in Urine and Oral Fluid after Regular and Hard Kombucha Consumption.

Although kombucha is a popular fermented beverage, the presence of alcohol markers has not been well studied despite being potential indicators of unintentional impairment. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) were measured in oral fluid and urine collected after consumption of regular or hard kombucha. Participants drank within 20 min and provided all urine voids for 12 h, the first urine voids on days 2 and 3 and oral fluid specimens at fixed time points for 48 h. Screening employed liquid chromatography-tandem mass spectrometry (LC-MS-MS; EtS, 25 ng/mL cutoff [oral]; 100 ng/mL cutoff [urine]; EtG, 500 ng/mL cutoff [urine] and immunoassay (IA; EtG, 500 ng/mL cutoff [urine]). After consuming regular kombucha (n = 12 participants), EtS was not detected in oral fluid but both markers were detected by LC-MS-MS in urine specimens within the first five voids from 83% of participants with median (range) concentrations of 240 (100-3,700) ng/mL for EtS and 830 (530-2,200) ng/mL for EtG. Neither marker was positive by IA nor LC-MS-MS after day 1. After consuming hard kombucha (n = 7 participants), 2 (2.8%) of the 70 collected oral fluid specimens tested positive for EtS 3 h after consumption; however, 21 (30%) had EtS levels above the limit of detection (LOD, 10 ng/mL) after 0.5-8 h. Both markers were detected in urine specimens from all participants with median (range) concentrations of 3,381 (559-70,250) ng/mL for EtS and 763 (104-12,864) ng/mL For EtG. Urine specimens were negative for EtG and EtS by the end of the 48-hour study.

The neurobiological markers of acute alcohol's subjective effects in humans.

The ingestion of alcohol yields acute biphasic subjective effects: stimulation before sedation. Despite their predictive relevance to the development of alcohol use disorders (AUD), the neurobiological markers accounting for the biphasic effects of alcohol remain poorly understood in humans. Informed by converging lines of evidence, this study tested the hypothesis that alcohol ingestion acutely increases gamma-aminobutyric acid (GABA)-mediated inhibition, which would positively and negatively predict the feeling of stimulation and sedation, respectively. To do so, healthy participants (n = 20) ingested a single dose of 94% ABV alcohol (males: 1.0 ml/kg; females: 0.85 ml/kg) in a randomized placebo-controlled cross-over design. The alcohol's biphasic effects were assessed with the Brief-Biphasic Alcohol Effects Scale, and non-invasive neurobiological markers were measured with transcranial magnetic stimulation, before and every 30 min (up to 120 min) after the complete ingestion of the beverage. Results showed that acute alcohol ingestion selectively increased the duration of the cortical silent period (CSP) as compared to placebo, suggesting that alcohol increases non-specific GABAergic inhibition. Importantly, CSP duration positively and negatively predicted increases in the feeling of stimulation and sedation, respectively, suggesting that stimulation emerges as GABAergic inhibition increases and that sedation emerges as GABAergic inhibition returns to baseline values. Overall, these results suggest that modulations of GABAergic inhibition are central to the acute biphasic subjective effects of alcohol, providing a potential preventive target to curb the progression of at-risk individuals to AUD.

Dysregulation of the hypothalamic-pituitary-adrenal system in Tuvan alcoholics is associated with a high level of stress in comparison with ethnic Russian patients

IntroductionAlcoholization is considered as prolonged auto-aggression, low frustration tolerance, filling of the existential vacuum. In all cases, the use of a psychoactive substance that alters the state of consciousness is regarded as a way of escape from real life.ObjectivesThe study of clinically significant markers in alcoholism associated with the constitutional characteristics of craving for alcohol in people of different ethnicity is importance for the formation of new approaches to prevention and treatment.Methods68 Russian alcoholics and 67 Tuvans alcoholics only men and 20 healthy male were monitored. Clinical assessment of the condition of patients was carried out with the traditional clinical description. Enzyme-linked immunosorbent assay kits were used to determine serum hormone levels in patients and volunteers.ResultsDeeper shifts in the increase in ACTH and Cortisol levels were found in alcoholic Tuvinians compared with Russian patients, which is associated with a high risk of alcohol dependence and a highly progressive course of the disease. The index of the ratio Cortisol/ACTH (IR) in the blood of alcoholic patients of the Russian (IR - 10,36) and Tuvan (IR - 10,62) nationalities does not differ, but significantly (1.5 times) differs from the indicator in healthy individuals (IR - 15,12).ConclusionsThe background level of dysregulation of the hypothalamic-pituitary-adrenal axis in patients of Tuvan nationality is significantly more pronounced, however, the index of Cortisol/ACTH ratios (IR) in each ethnic group of patients is constant in this disease, which is characterized by a high level of stress.DisclosureNo significant relationships.

Set-up of a population-based model to verify alcohol abstinence via monitoring of the direct alcohol marker phosphatidylethanol 16:0/18:1.

Phosphatidylethanol 16:0/18:1 (PEth) is a biomarker for alcohol intake. It has a half-life of 7.9days. Chronic alcohol consumption causes high PEth values. It can take weeks before PEth values fall below the decision limit for 'alcohol abstinence'. Our aim was to validate whether alcohol abstinence can be determined based on two consecutive PEth results above the decision limit. Observational study. Belgium, February 2019. The study was linked to a social initiative in Belgium, 'Tournée Minérale'. Adults (aged > 18 years, n = 796) with varying drinking habits who self-reportedly refrained from alcohol consumption during the study. A validated liquid chromatography-tandem mass spectrometry method was used to quantify PEth in participants' dried blood samples, collected at three time-points via remote fingerprick-based self-sampling. A population-based algorithm to evaluate abstinence based on 95% prediction limits was developed by fitting a linear mixed-effect model to discern patterns in PEth elimination over time. It took intra- and inter-individual variability into consideration. The algorithm was included in a two-step decision tree, assessing whether (i) PEth values fell within the prediction interval and (ii) the slope between two PEth values was consistent with no alcohol consumption. Data for 74 participants reporting no alcohol intake during the study were used for validation. With a detection limit of 'four units spread over 14 days', the sensitivity and specificity of the decision tree was 89%. Claims of alcohol abstinence can be verified using a two-step decision tree for phosphatidylethanol 16:0/18:1 values, even when those values are above the limit for 'alcohol abstinence'.

Phosphatidylethanol in patients with liver diseases of different etiologies: Analysis of six homologues and comparison with other alcohol markers

Background and aimsPhosphatidylethanol (PEth) is a direct alcohol biomarker. Aim of the study was to evaluate the performance of six homologues of PEth in comparison to other alcohol markers in patients with liver diseases. MethodsThe study included 234 patients with liver disease, who gave statements about alcohol consumption during the three months prior to the doctor’s appointment. Ethylglucuronide in urine (uEtG) and in hair (hEtG) and carbohydrate-deficient transferrin (CDT) were analyzed in addition to PEth. ResultsOf all patients 47% stated to have drunk alcohol during the past three months. UEtG, hEtG and CDT showed a sensitivity of 29% and a specificity of 92% together for ingestion of at least two standard drinks (24 g) per week. With PEth 16:0/18:1 in addition, sensitivity increased to 59%. For consumption in the last week uEtG’s sensitivity and specificity was 28% and 100%, respectively. PEth’s was 75% and 93%. When looking at patients who consumed at least two standard drinks per week during the past three months and of which a hair sample could be obtained, hEtG’s sensitivity was 37% and specificity 90%. PEth had a sensitivity of 53% and specificity of 100%. Quotients of PEth 16:0/18:1 with 16:0/18:2, 16:0/20:4 and 18:0/18:2 were smaller when alcohol had been consumed more recently. ConclusionDespite the rather poor overall sensitivity of alcohol biomarkers in this study, PEth showed best sensitivity for all time periods of alcohol consumption.