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Concept: Alcoholism

399

Research on a possible causal association between alcohol consumption and risk of prostate cancer is inconclusive. Recent studies on associations between alcohol consumption and other health outcomes suggest these are influenced by drinker misclassification errors and other study quality characteristics. The influence of these factors on estimates of the relationship between alcohol consumption and prostate cancer has not been previously investigated.

Concepts: Alcohol, Epidemiology, Cancer, Metastasis, Prostate cancer, Alcoholism, Beer, Vodka

335

Alcoholic beverages are widely consumed. Depression, the most prevalent mental disorder worldwide, has been related to alcohol intake. We aimed to prospectively assess the association between alcohol intake and incident depression using repeated measurements of alcohol intake.

Concepts: Alcohol, Ethanol, Alcoholism, Mental disorder, Schizophrenia, Wine, Alcoholic beverage, Distilled beverage

296

High levels of alcohol consumption and increases in heavy episodic drinking (binge drinking) are a growing public concern, due to their association with increased risk of personal and societal harm. Alcohol consumption has been shown to be sensitive to factors such as price and availability. The aim of this study was to explore the influence of glass shape on the rate of consumption of alcoholic and non-alcoholic beverages.

Concepts: Alcohol, Alcoholism, Alcohol abuse, Alcoholic beverage, Beer, Drinking culture, Binge drinking, Kefir

202

Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol.

Concepts: Alcoholism, Following, English-language films, Learning, Facilitation, Task, Intoxication, Alcohol intoxication

171

BACKGROUND: Alcohol misuse amongst young people is a serious concern. The need for effective prevention is clear, yet there appear to be few evidenced-based programs that prevent alcohol misuse and none that target both high and low-risk youth. The CAP study addresses this gap by evaluating the efficacy of an integrated approach to alcohol misuse prevention, which combines the effective universal internet-based Climate Schools program with the effective selective personality-targeted Preventure program. This article describes the development and protocol of the CAP study which aims to prevent alcohol misuse and related harms in Australian adolescents. METHODS: A cluster randomized controlled trial (RCT) is being conducted with Year 8 students aged 13 to 14-years-old from 27 secondary schools in New South Wales and Victoria, Australia. Blocked randomisation was used to assign schools to one of four groups; Climate Schools only, Preventure only, CAP (Climate Schools and Preventure), or Control (alcohol, drug and health education as usual).The primary outcomes of the trial will be the uptake and harmful use of alcohol and alcohol related harms. Secondary outcomes will include alcohol and cannabis, related knowledge cannabis related harms, intentions to use and uptake of alcohol and other drugs, and mental health symptomatology. All participants will complete assessments on five occasions; baseline; immediately post intervention, and at 12, 24 and 36 months post baseline. DISCUSSION: This study protocol presents the design and current implementation of a cluster RCT to evaluate the efficacy of the CAP study; an integrated universal and selective approach to prevent alcohol use and related harms among adolescents. Compared to students who receive the stand-alone universal Climate Schools program or alcohol and drug education as usual (Controls), we expect the students who receive the CAP intervention to have significantly less uptake of alcohol use, a reduction in average alcohol consumption, a reduction in frequency of binge drinking, and a reduction in alcohol related harms.Trial registrationThis trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12612000026820.

Concepts: Pharmacology, Clinical trial, Randomized controlled trial, Alcoholism, Alcohol abuse, High school, Drinking culture, Binge drinking

169

The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/-) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/-) and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors.

Concepts: Alcoholism, Nicotine, Enzyme inhibitor, Neurotransmitter, Inhibitor, Dopamine, Norepinephrine, Cocaine

147

The aim of the present study was to evaluate the effect of 15% alcohol dependence on ligature-induced alveolar bone loss and TNF- secretion in Wistar rats. Thirty-three male Wistar rats aged 45-60 days (mean weight=253 g) were randomly allocated test or control groups. Test group (n=18) received 15% alcohol as liquid intake and control group (n=15) received water during the experimental period. TNF-α was analyzed by ELISA assay in 11 animals per group. After 14 days of alcohol/water intake, alcohol dependency was assessed and silk ligatures were placed around the left second upper molars. Ligature presence and body weight were checked weekly. After 40 days, animals were sacrificed and the maxillae were defleshed for morphometric analysis using standardized images. All animals in the test group displayed signs of alcohol dependency at day 14. No statistically significant differences in final body weight (334.83±21.38 vs. 322.48±30.65 g, p=0.20) were observed between groups. In relation to alveolar bone loss, no statistically significant difference was observed among test and control groups both for ligated teeth (0.76±0.06 vs. 0.74±0.10 mm, p=0.60) and unligated teeth (0.41±0.16 vs. 0.35±0.05 mm, p=0.22). The TNF-α secretion also did not display statistically significant differences between test and control groups (10.78±1.84 vs. 12.13±2.11 pg/mL, p=0.12). It may be concluded that 15% alcohol dependency was not capable to alter alveolar bone loss and TNF-α secretion in Wistar rats.

Concepts: Controlling for a variable, Scientific control, Scientific method, Statistics, Statistical significance, Alcoholism, ELISA, Teeth

91

Excessive drinking accounted for approximately 4,300 deaths each year among persons aged <21 years during 2006-2010,* and underage drinking cost the United States $24.3 billion in 2010 (1). CDC analyzed data from the national Youth Risk Behavior Survey (YRBS) for the years 1991-2015 to examine trends in drinking by U.S. high school students, and from the 2015 YRBS to assess the usual source of alcohol consumed(†) and binge drinking intensity (i.e., the average number of drinks consumed per binge drinking occasion).(§) During 1991-2007, the prevalence of current drinking(¶) among high school students declined significantly, from 50.8% (1991) to 44.7% (2007), and then significantly declined to 32.8% in 2015. The prevalence of binge drinking** increased from 31.3% in 1991 to 31.5% in 1999, and then significantly declined to 17.7% in 2015. Most high school students who drank were binge drinkers (57.8%), and 43.8% of binge drinkers consumed eight or more drinks in a row. Despite progress, current drinking and binge drinking are common among high school students, and many students who binge drink do so at high intensity (i.e., eight or more drinks in a row). Widespread use of evidence-based strategies for preventing excessive drinking (e.g., increasing alcohol taxes, regulating alcohol outlet density, and having commercial host liability laws) could help reduce underage drinking and related harms.(††).

Concepts: Alcoholism, Alcohol abuse, Beer, Drinking culture, Binge drinking, Drink, Get Your Sexy Back

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Background: This study predicts the implications of under-reporting of alcohol consumption in England for alcohol consumption above Government drinking thresholds. Methods: Two nationally representative samples of private households in England were used: General LiFestyle survey (GLF) and Health Survey for England (HSE) 2008. Participants were 9608 adults with self-reported alcohol consumption on heaviest drinking day in the last week (HSE) and 12 490 adults with self-reported average weekly alcohol consumption (GLF). Alcohol consumption in both surveys was revised to account for under-reporting in three hypothetical scenarios. The prevalence of drinking more than UK Government guidelines of 21/14 (men/women) alcohol units a week, and 4/3 units per day, and the prevalence of binge drinking (>8/6 units) were investigated using logistic regression. Results: Among drinkers, mean weekly alcohol intake increases to 20.8 units and mean alcohol intake on heaviest drinking day in the last week increases to 10.6 units. Over one-third of adults are drinking above weekly guidelines and over three-quarters drank above daily limits on their heaviest drinking day in the last week. The revision changes some of the significant predictors of drinking above thresholds. In the revised scenario, women have similar odds to men of binge drinking and higher odds of drinking more than daily limits, compared with lower odds in the original survey. Conclusion: Revising alcohol consumption assuming equal under-reporting across the population does not have an equal effect on the proportion of adults drinking above weekly or daily thresholds. It is crucial that further research explores the population distribution of under-reporting.

Concepts: Demography, Alcoholism, Revision, Alcohol abuse, Wine, Beer, Drinking culture, Binge drinking

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Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

Concepts: Protein, Histone, Histone deacetylase, Alcoholism, Posttranslational modification, Nucleosome, Alcohol abuse, Acetylation