Explore the vast range of titles available.

In most studies, the alcohol marker phosphatidylethanol (PEth) was used to differentiate social drinking from alcohol abuse. This study investigates PEth’s potential in abstinence monitoring by performing a drinking study to assess the detection window of PEth after ingesting a defined amount of alcohol. After 2 weeks of abstinence, 16 volunteers ingested a single dose of alcohol, leading to an estimated blood alcohol concentration (BAC) of 1 g/kg. In the week after drinking, blood and urine samples were taken daily; in the second week, samples were taken every other day. PEth 16:0/18:1 and 16:0/18:2 were analyzed in blood by online-SPE-LC-MS/MS. Ethyl glucuronide and ethyl sulfate were determined in urine for abstinence monitoring. Prior to start of drinking, PEth 16:0/18:1 exceeded 30 ng/mL in blood samples of five volunteers despite the requested abstinence period. Positive PEth values resulted from drinking events prior to this abstinence period. After the start of drinking, maximum BACs were reached after 2 h with a mean of 0.80 ± 0.13 g/kg (range: 0.61–1.11 g/kg). PEth 16:0/18:1 increased within 8 h to maximum concentrations (mean: 88.8 ± 47.0 ng/mL, range: 37.2–208 ng/mL). After this event, PEth was detectable for 3 to 12 days with a mean half-life time of approximately 3 days. PEth has a potential in abstinence monitoring, since PEth could be detected for up to 12 days after a single drinking event. Further investigations are necessary, to establish cut-off levels for PEth as diagnostic marker for the determination of drinking habits like abstinence, social drinking, or risky alcohol consumption.

Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1·31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. Log e CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log e CRP concentration (three-fold higher) were 1·63 (95% CI 1·51–1·76) when initially adjusted for age and sex only, and 1·37 (1·27–1·48) when adjusted further for conventional risk factors; 1·44 (1·32–1·57) and 1·27 (1·15–1·40) for ischaemic stroke; 1·71 (1·53–1·91) and 1·55 (1·37–1·76) for vascular mortality; and 1·55 (1·41–1·69) and 1·54 (1·40–1·68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1·23 (1·07–1·42) for coronary heart disease; 1·32 (1·18–1·49) for ischaemic stroke; 1·34 (1·18–1·52) for vascular mortality; and 1·34 (1·20–1·50) for non-vascular mortality. CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.

Objective To systematically review interventional studies of the effects of alcohol consumption on 21 biological markers associated with risk of coronary heart disease in adults without known cardiovascular disease.Design Systematic review and meta-analysis.Data sources Medline (1950 to October 2009) and Embase (1980 to October 2009) without limits.Study selection Two reviewers independently selected studies that examined adults without known cardiovascular disease and that compared fasting levels of specific biological markers associated with coronary heart disease after alcohol use with those after a period of no alcohol use (controls). 4690 articles were screened for eligibility, the full texts of 124 studies reviewed, and 63 relevant articles selected.Results Of 63 eligible studies, 44 on 13 biomarkers were meta-analysed in fixed or random effects models. Quality was assessed by sensitivity analysis of studies grouped by design. Analyses were stratified by type of beverage (wine, beer, spirits). Alcohol significantly increased levels of high density lipoprotein cholesterol (pooled mean difference 0.094 mmol/L, 95% confidence interval 0.064 to 0.123), apolipoprotein A1 (0.101 g/L, 0.073 to 0.129), and adiponectin (0.56 mg/L, 0.39 to 0.72). Alcohol showed a dose-response relation with high density lipoprotein cholesterol (test for trend P=0.013). Alcohol decreased fibrinogen levels (−0.20 g/L, −0.29 to −0.11) but did not affect triglyceride levels. Results were similar for crossover and before and after studies, and across beverage types.Conclusions Favourable changes in several cardiovascular biomarkers (higher levels of high density lipoprotein cholesterol and adiponectin and lower levels of fibrinogen) provide indirect pathophysiological support for a protective effect of moderate alcohol use on coronary heart disease.

Alcohol is a leading risk factor for disease burden. We examined longitudinal trends in sex and age-specific alcohol consumption among middle-aged and older subjects who had participated in the population-based Trøndelag Health Study (HUNT) in Norway since the 1990s. This study included 23,151 individuals aged ≥43 years when they participated in the HUNT2 Survey (1995-1997) and who also had participated in the HUNT3 Survey (2006-2008), and/or the HUNT4 Survey (2017-2019). We used self-reported data to examine trends and identify sex- and age-specific differences in abstinence from alcohol, current drinking, risky drinking (≥8 units of alcohol/week), and heavy episodic drinking (≥5 or ≥6 units of alcohol in one sitting at least monthly). Concentrations of the objective alcohol marker phosphatidylethanol (PEth) were available in subsamples from HUNT3 to HUNT4. The proportion of subjects with self-reported alcohol abstinence and with PEth concentrations <0.03 µmol/l increased from HUNT2 and/or HUNT3 to HUNT4, while heavy episodic drinking and PEth concentrations ≥0.03 µmol/l decreased from HUNT3 to HUNT4 in both sexes in most age groups, and more in men than in women. There was an increase in risky drinking from HUNT2 to HUNT4 in women and men aged 43-64 years in HUNT2. Men were more likely to consume alcohol than women measured with both self-report and with PEth in most age groups. Among those aged ≥65 years in HUNT2 a convergence between the sexes regarding abstinence and heavy episodic drinking was observed which was mostly caused by changes in men. Drinking patterns among middle-aged and older Norwegians have changed since the 1990s with a trend toward more abstinence and less heavy episodic drinking and PEth concentrations ≥0.03 µmol/l in both women and men with increasing age. There is a trend of more risky drinking with age among both sexes.

The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through “MeSH” and “free-text” protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and Ovid/Embase, combining the terms phosphatidylethanol and alcohol, provided 444 records, 58 of which fulfilled the inclusion criteria and were used to summarize the current evidence on the formation, distribution and degradation of PEth in human blood: (1), the presence and distribution of different PEth molecular species (2), the most diffused analytical methods devoted to PEth identification and quantization (3), the clinical efficiency of total PEth quantification as a marker of chronic excessive drinking (4), and the potential utility of this marker for identifying binge drinking behaviors (5). Twelve papers were included in the meta-analysis and the mean (M) and 95% confidence interval (CI) of total PEth concentrations in social drinkers (DAI ≤ 60 g/die; M = 0.288 µM; CI 0.208–0.367 µM) and heavy drinkers (DAI > 60 g/die; M = 3.897 µM; CI 2.404–5.391 µM) were calculated. The present analysis demonstrates a good clinical efficiency of PEth for detecting chronic heavy drinking.

Phosphatidylethanol (PEth) is a group of phospholipids formed in cell membranes following alcohol consumption by action of the enzyme phospholipase D (PLD). PEth measurement in whole blood samples is established as a specific alcohol biomarker with clinical and forensic applications. However, in blood specimens containing ethanol, formation of PEth may continue after sampling leading to falsely elevated concentrations. This study evaluated the use of dried blood spot (DBS) and microsampling specimens to avoid post-sampling formation of PEth. Filter paper cards and three commercial devices for volumetric microsampling of finger-pricked blood were assessed, using PEth-negative and PEth-positive whole blood fortified with 2 g/L ethanol. PEth (16:0/18:1) was measured by LC–MS/MS. Post-sampling formation of PEth occurred in wet blood and in the volumetric devices, but not filter paper cards, when stored at room temperature for 48 h. Addition of an inhibitor of PLD, sodium metavanadate (NaVO3), eliminated post-sampling formation during storage and drying. In conclusion, the present study confirmed previous observations that PEth can be formed in blood samples after collection, if the specimen contains ethanol. The results further demonstrated that post-sampling formation of PEth from ethanol also occurred with commercial devices for volumetric dried blood microsampling. In order for a PEth result not to be questioned, it is recommended to use a PLD inhibitor, whether venous blood is collected in a vacutainer tube or finger-pricked blood is obtained using devices for dried blood microsampling.

The authors show that optogenetic inhibition of inputs from medial prefrontal cortex (mPFC) or insula to the nucleus accumbens core (NAcore) inhibits aversion-resistant alcohol intake. Alcohol-drinking rats showed increased hyperpolarization-active NMDARs at mPFC and insula inputs to NAcore medium spiny neurons. Knocking down these receptors in the NAcore inhibited aversion-resistant alcohol intake. Compulsive drinking despite serious adverse medical, social and economic consequences is a characteristic of alcohol use disorders in humans. Although frontal cortical areas have been implicated in alcohol use disorders, little is known about the molecular mechanisms and pathways that sustain aversion-resistant intake. Here, we show that nucleus accumbens core (NAcore) NMDA-type glutamate receptors and medial prefrontal (mPFC) and insula glutamatergic inputs to the NAcore are necessary for aversion-resistant alcohol consumption in rats. Aversion-resistant intake was associated with a new type of NMDA receptor adaptation, in which hyperpolarization-active NMDA receptors were present at mPFC and insula but not amygdalar inputs in the NAcore. Accordingly, inhibition of Grin2c NMDA receptor subunits in the NAcore reduced aversion-resistant alcohol intake. None of these manipulations altered intake when alcohol was not paired with an aversive consequence. Our results identify a mechanism by which hyperpolarization-active NMDA receptors under mPFC- and insula-to-NAcore inputs sustain aversion-resistant alcohol intake.

IntroductionDespite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change.MethodWe conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates.ResultsWe analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (−0.019 (95% CI: −0.021 to –0.017) mg/dL). Beer had the largest association with SU (−0.036 (95% CI: −0.039 to –0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with −0.056 mg/dL (95% CI: −0.068 to –0.043) decrease in SU; the association became larger in hyperuricemic participants (−0.110 mg/dL (95% CI: −0.154 to –0.066) for alcohol discontinuation from a mean of 1.0 drinks/day).ConclusionsThis study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

The objective of this study was to identify the prevalence and correlates of phosphatidylethanol (PEth) levels suggestive of unhealthy alcohol use among women living with and without HIV who self-reported no or low-risk drinking. We analyzed data from a cross-sectional study among women enrolled in the San Francisco Bay Area site of the Women’s Interagency HIV Study (WIHS). Between October 2017 and March 2018, PEth was tested from dried blood spots in 192 women enrolled in the San Francisco site of the WIHS. Using multivariable logistic regression, we identified the correlates of PEth levels suggestive of unhealthy alcohol use ( > 50 ng/ml) among the 168 women who reported no or low-risk drinking ( < 7 drinks per week) in the past six months, while controlling for age in years and race/ethnicity. Among the 168 women in the analysis sample, the median age was 55; 51% identified as Black/African American, 47% were living with HIV and 28% had PEth levels ≥50 ng/ml which are suggestive of unhealthy alcohol use. Factors independently associated with PEth levels ≥50 ng/ml in adjusted models were: identifying as Black/African American (adjusted odds ratio [aOR] = 8.34, 95% CI = 2.06–33.72), having an alanine transaminase to aspartate aminotransferase ratio > 1 (aOR = 3.10, 95% CI = 1.18–8.13), higher high-density lipoprotein levels (aOR = 1.31 per 10 mg/dL increase, 95% CI = 1.01–1.70), and consuming a greater number of drinks per week in the past six months (aOR = 1.40, 95% CI = 1.10–1.78). Nearly a third of women in this study had PEth levels suggestive of unhealthy alcohol use and potentially under-reported their use. To optimize alcohol related health care, there is a need to consider approaches to improve ascertainment of unhealthy alcohol use, especially among Black/African American women and those living with liver disease, so that interventions can be initiated.

Mendelian randomisation studies from Asia suggest detrimental influences of alcohol on cardiovascular risk factors, but such associations are observed mainly in men. The absence of associations of genetic variants (e.g. rs671 in ALDH2 ) with such risk factors in women – who drank little in these populations – provides evidence that the observations are not due to genetic pleiotropy. Here, we present a Mendelian randomisation study in a South Korean population (3,365 men and 3,787 women) that 1) provides robust evidence that alcohol consumption adversely affects several cardiovascular disease risk factors, including blood pressure, waist to hip ratio, fasting blood glucose and triglyceride levels. Alcohol also increases HDL cholesterol and lowers LDL cholesterol. Our study also 2) replicates sex differences in associations which suggests pleiotropy does not underlie the associations, 3) provides further evidence that association is not due to pleiotropy by showing null effects in male non-drinkers and 4) illustrates a way to measure population-level association where alcohol intake is stratified by sex. In conclusion, population-level instrumental variable estimation (utilizing interaction of rs671 in ALDH2 and sex as an instrument) strengthens causal inference regarding the largely adverse influence of alcohol intake on cardiovascular health in an Asian population.