Alcohol - The myth of cardiovascular protection.

BACKGROUND & AIMS: To investigate potential biases that exist in available epidemiological evidence resulting in negative associations or underestimation of cardiovascular (CV) risk associated with alcohol consumption. METHODS: UK Biobank involved baseline data collection from 22 assessment centres across the United Kingdom. The cohort consisted of 333 259 alcohol consumers and 21 710 never drinkers. Participants were followed up for a median 6.9 years capturing incident fatal and non-fatal CV events, ischemic heart disease and cerebrovascular disease. Alcohol intake was reported as grams/week. RESULTS: Using never drinkers as reference, alcohol from all drink types combined (hazard ratios ranging between 0.61 and 0.74), beer/cider (0.70-0.80) and spirits combined, and all wines combined (0.66-0.77) associated with a reduced risk for all outcome measures (all CV events, ischaemic heart disease, cerebrovascular disease). In continuous analysis, alcohol captured from all drink types combined (hazard ratio, 1.08, 95% confidence interval, 1.01-1.14), and beer/cider and spirits combined (1.24, 1.17-1.31) associated with an increased risk for overall CV events, however hazard ratios were stronger for beer/cider and spirits (P < 0.0001). Wine associated with a reduced risk for overall CV events (0.92, 0.86-0.98) and ischemic heart disease (0.75, 0.67-0.84). This negative relationship with overall CV events was lost after excluding ischemic heart disease events (1.00, 0.93-1.08), while the positive association of alcohol captured from beer/cider and spirits remained significant (1.30, 1.22-1.40). This positive association with overall CV events was present even when consuming less than 14 units per week. CONCLUSIONS: Avoiding potential biases prevents underestimation of cardiovascular risk and indicates that consuming up to 14 units per week also associated with increased CV risk in the general population.

Gender Equality, Drinking Cultures and Second-Hand Harms from Alcohol in the 50 US States.

BACKGROUND: Gender inequality and cultures of binge drinking may increase the risk of second-hand harms from alcohol. METHODS: Using the 2014-2015 National Alcohol Survey and 2015 National Alcohol's Harm to Others Survey (N = 7792), we examine associations of state-level gender equality measures (contraceptive access, abortion rights, women's economic equality) and binge drinking cultures (rates of men's and women's binge drinking) with individual-level indicators of second-hand harms by drinking strangers and partners/spouses. RESULTS: In main effects models, only male binge drinking was associated with greater odds of harms from drinking strangers. There were significant interactions of gender equality with male binge drinking: High male binge drinking rates were more strongly associated with stranger-perpetrated harms in states low on contraceptive access or abortion rights compared to states high on these measures. Conversely, male binge drinking was more strongly associated with spouse/partner-perpetrated second-hand harms in states with more economic equality, compared to states lower on this measure. CONCLUSIONS: Detrimental effects of high male binge drinking rates may be modified by gender equality. Targeted interventions may reduce alcohol-related harms experienced by women in states with high rates of male binge drinking. Restrictions in access to contraception and abortion may exacerbate harms due to men's drinking.

Binge Drinking's Effects on the Body.

Studies have focused on the effects of chronic alcohol consumption and the mechanisms of tissue injury underlying alcoholic hepatitis and cirrhosis, with less focus on the pathophysiological consequences of binge alcohol consumption. Alcohol binge drinking prevalence continues to rise, particularly among individuals ages 18 to 24. However, it is also frequent in individuals ages 65 and older. High blood alcohol levels achieved with this pattern of alcohol consumption are of particular concern, as alcohol can permeate to virtually all tissues in the body, resulting in significant alterations in organ function, which leads to multisystemic pathophysiological consequences. In addition to the pattern, amount, and frequency of alcohol consumption, additional factors, including the type of alcoholic beverage, may contribute differentially to the risk for alcohol-induced tissue injury. Preclinical and translational research strategies are needed to enhance our understanding of the effects of binge alcohol drinking, particularly for individuals with a history of chronic alcohol consumption. Identification of underlying pathophysiological processes responsible for tissue and organ injury can lead to development of preventive or therapeutic interventions to reduce the health care burden associated with binge alcohol drinking.

Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance.

PURPOSE: There are still concerns regarding occupational exposure to hepatotoxic DMF. This study was designed to evaluate possible liver damaging effects of DMF under current workplace conditions in synthetic fibres industries. METHODS: Among other laboratory parameters, liver function parameters (alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase), the mean corpuscular erythrocyte volume (MCV) and carbohydrate-deficient transferrin (CDT) of the workforce of two companies present at the days of study were investigated. Internal exposure to DMF was assessed via three different biomarkers [sum of N-methylformamide and N-hydroxymethyl-N-methylformamide, N-acetyl-S-(N-carbamoyl)cysteine (AMCC) and 3-methyl-5-isopropylhydantoin (MIH)]. Alcohol consumption was assessed by means of direct ethanol metabolites (ethylglucuronide and ethylsulfate). RESULTS: None of the tested liver enzyme activities showed a positive association with any of the three exposure markers, nor did CDT and MCV. CDT was negatively associated with AMCC and the ALP activity negatively with all three exposure markers. Changes in liver function are seen mainly in conjunction with ethanol consumption but also with increasing body weight and age. MCV was associated with smoking. Almost half of the workers stated to experience alcohol flush reaction. CONCLUSION: The present study indicates that long-term exposure to DMF, which was specified by median urinary AMCC levels of 4.84 mg/g creatinine and DMF haemoglobin adduct levels of 60.5 nmol/MIH/g globin, respectively, does not result in any adverse liver effects. In contrast, these DMF exposure levels still elicit certain alcohol intolerance reactions.

Discussing alcohol and cancer with patients: Knowledge and practices of general practitioners in New South Wales and South Australia.

BACKGROUND: Alcohol is associated with several cancers; however, the Australian community has low awareness of the link between alcohol consumption and cancer. Little information exists regarding when and why general practitioners (GPs) discuss alcohol with patients. OBJECTIVE: The objective of this article is to explore GPs' attitudes and practices when discussing alcohol with patients. This includes awareness of alcohol recommendations and evidence of the alcohol-cancer link, and discussion around barriers and enablers to encouraging patients' alcohol behaviour change. RESULTS: GPs did not routinely ask patients about their alcohol consumption or advise on drinking recommendations. Many had a broad understanding of alcohol as a cancer risk factor, but knowledge of the causal mechanisms and current evidence was limited. DISCUSSION: GPs are trusted health advisers. Providing them with up-to-date evidence on the alcohol-cancer link and drinking recommendations may encourage routine patient screening of alcohol consumption and delivery of simple education on the harms of long-term drinking.

Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

Associations between alcohol use expectancies and drinking problems among French soldiers.

AIMS: The aim of the study was to evaluate which alcohol use expectancies could predict harmful use in the French Army to explore some hypotheses concerning socialising or coping effects. METHODS: A cross-sectional survey, using self-administered questionnaires, was conducted in two Army units in 2011 (n = 249). Hazardous alcohol use and dependence were screened using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol expectancies were measured with the Alcohol Effects Questionnaire (AEFQ). A cluster analysis was performed to identify AEFQ dimensions in our sample. Relationships between AUDIT and AEFQ were explored using multinomial logistic regression. RESULTS: According to AUDIT, 46.6% of soldiers used alcohol without hazard, 26.1% had hazardous use without dependence and 18.1% had use with dependence. The AEFQ had an adequate internal coherence with a 0.78 α coefficient. The scales identified by the cluster analysis in our sample fitted those retained in the originally validated AEFQ, with a correspondence ranging from 60% to 100%. In multivariate analysis, the scale "Social and physical pleasure" was associated with increasing hazardous use and subjects who scored higher on "Global positive" and "Social and physical pleasure" scales were more at risk of dependence. CONCLUSION: The present study, in line with previous research in terms of importance of alcohol use disorders among military personnel, found that alcohol use expectancies are associated with alcohol misuse among soldiers. This could suggest underlying coping mechanisms towards stress that have to be further explored.

Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring.

BACKGROUND: Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined whether any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol-exposed male rats during the adult period. METHODS: Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed [AF]), or pair-fed with isocaloric liquid diet (PF) or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostates of these animals were processed for determination of biochemical changes and histopathologies. RESULTS: Prostates of noncarcinogen treated animals that were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatal alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol (EtOH)-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia (PIN) primarily in the ventral prostate, whereas control animals showed only low-grade PIN. Prenatally EtOH-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. CONCLUSIONS: These results suggest for the first time that prenatal EtOH exposures induce histophysiological changes in the prostate as well as it increases the susceptibility of the prostate to develop neoplasia during adulthood.

An imbalance between VEGF and endostatin underlies impaired angiogenesis in gastric mucosa of aging rats.

Gastric mucosa of aging individuals exhibits increased susceptibility to injury and delayed healing. Our previous studies in young rats showed that healing of mucosal injury depends on and is critically dependent on VEGF and angiogenesis. Since angiogenesis in aging gastric mucosa has not been examined before, in this study we examined the extent to which angiogenesis is impaired in gastric mucosa of aging vs. young rats and determined the underlying mechanisms with a focus on mucosal expression of VEGF (proangiogenic factor) and endostatin (antiangiogenic factor). Aging rats had significantly impaired gastric angiogenesis by ~12-fold, 5-fold, 4-fold, and 3-fold, respectively (vs. young rats; all P < 0.001) at 24, 48, 72, and 120 h following ethanol-induced gastric injury and reduced and delayed healing of mucosal erosions. In gastric mucosa of aging (vs. young) rats at baseline, VEGF expression was significantly reduced, whereas endostatin levels were significantly increased (P < 0.05 and P < 0.01, respectively). In contrast to young rats, gastric mucosal VEGF levels did not increase following ethanol-induced injury in aging rats. MMP-9 enzyme activity was significantly higher in gastric mucosa of aging vs. young rats both at baseline (2.7-fold) and 24 h (3.8-fold) after ethanol injury (both P < 0.001). Since endostatin is generated from collagen XVIII by MMP-9, this finding can explain the mechanism of increased endostatin expression in aging gastric mucosa. The above findings demonstrate that reduced VEGF and increased endostatin result in the impaired angiogenesis and delayed injury healing in gastric mucosa of aging rats.

Stopping insulin and achieving a good metabolic control in a heavy drinker five months after stopping alcohol.

In this case study, we describe a 25 year-old male who showed the symptoms of diabetes after a period of heavy drinking. (HbA1c=13%). Treatment was started with 120 units of insulin. After stopping alcohol consumption and taking an appropriate diet, insulin was tapered down. Five months after the start of treatment, insulin was stopped (HbA1c=5%). The results showed that he was in a good metabolic control after 18 months (HbA1c=5.9%).

Shortened telomeres in individuals with abuse in alcohol consumption.

Alcohol abuse leads to earlier onset of aging-related diseases, including cancer at multiple sites. Shorter telomere length (TL) in peripheral blood leucocytes (PBLs), a marker of biological aging, has been associated with alcohol-related cancer risks. Whether alcohol abusers exhibit accelerated biological aging, as reflected in PBL-TL, has never been examined. To investigated the effect of alcohol abuse on PBL-TL and its interaction with alcohol metabolic genotypes, we examined 200 drunk-driving traffic offenders diagnosed as alcohol abusers as per the Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR] and enrolled in a probation program, and 257 social drinkers (controls). We assessed alcohol intake using self-reported drink-units/day and conventional alcohol abuse biomarkers (serum γ-glutamyltrasferase [GGT] and mean corpuscular volume of erythrocytes [MCV]). We used multivariable models to compute TL geometric means (GM) adjusted for age, smoking, BMI, diet, job at elevated risk of accident, genotoxic exposures. TL was nearly halved in alcohol abusers compared with controls (GMs 0.42 vs. 0.87 relative T/S ratio; p<0.0001) and decreased in relation with increasing drink-units/day (p-trend=0.003). Individuals drinking >4 drink-units/day had substantially shorter TL than those drinking ≤4 drink-units/day (GMs 0.48 vs. 0.61 T/S, p=0.002). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be abusers (p=0.008), reported higher drink-units/day (p=0.0003), and exhibited shorter TL (p<0.0001). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with TL. The decrease in PBL-TL modulated by the alcohol metabolic genotype ADH1B*1/*1 may represent a novel mechanism potentially related to alcohol carcinogenesis in alcohol abusers.

Can intensive use of alcohol-based hand rubs lead to passive alcoholization?

Hand disinfection with alcohols-based hand rubs (ABHRs) are known to be the most effective measure to prevent nosocomial infections in healthcare. ABHRs contain on average 70% by weight of one or more alcohols. During the hand rubbing procedure, users are exposed to these alcohols not only through dermal contact, but also via inhalation, due to the physical and chemical properties of alcohols volatilizing from alcoholic solutions or gels into the air. Ethanol ingestion is well known to increase risks of several diseases (affecting the pancreas, liver, cardiovascular system…), but there is a lack of knowledge about the effects of exposure to other alcohols (including n- or isopropanol) via inhalation and dermal contact, despite the worldwide use of ABHRs. This work aims at discussing possible health effects related to unintentional alcoholization (via inhalation and dermal contact) from professional ABHR usage to suggest the need for more research in this area (but not to question the value of ABHRs). Based upon an average of 30 hand rubbings per healthcare professional per day, it can be assumed that a healthcare worker may be exposed to a maximum 5,500 mg/m(3) per work shift, five times above the recommended occupational time weighted average limit. Thus, in order to answer the question posed in the title, studies on spatial and temporal variability of alcohol emission from ABHRs in real world situations and studies on certain high risk individuals are needed.

As múltiplas faces do álcool: estudo de caso em uma unidade de transplante

Atualmente cresce o número de pessoas que fazem uso abusivo do álcool, acarretando uma série de prejuízos à saúde. O alcoolismo já é reconhecido como doença e um problema de saúde pública. Diante desta realidade, a Unidade de Transplante de Fígado do Hospital de Base atende às pessoas com diagnóstico e tratamento de doenças hepáticas agudas e crônicas ocasionadas pelo álcool e também outros fatores. O referido estudo tem o objetivo de demonstrar as múltiplas faces do álcool através da história de vida de um paciente que teve experiência com o uso abusivo da bebida. A pesquisa de caráter qualitativo embasou-se no método do estudo de caso, onde foi realizada entrevista composta por perguntas abertas e roteiro pré-estabelecido. De acordo com a conjuntura analisada, observamos que o contexto familiar foi a fonte de introdução do álcool na vida do paciente. As intoxicações agudas trouxeram riscos como acidentes de carro, incentivo para utilização de outras drogas, prejuízos financeiros, alterações comportamentais que implicaram em atritos e reorganização no âmbito familiar, através de mudança de papéis. O sujeito da pesquisa ressaltou o apoio de seus familiares durante o tratamento e apontou a extrema importância em acessar os direitos para a construção no sucesso da terapêutica; atividade essa desenvolvida pelo profissional do Serviço Social. Ademais, tais fatores culturais, físicos, emocionais e sociais resultam nas múltiplas faces do álcool, visto que a pessoa ao utilizar tal substância é atingida em toda sua integridade

Individual differences in acute alcohol impairment of inhibitory control predict ad libitum alcohol consumption.

RATIONALE: Research has begun to examine how acute cognitive impairment from alcohol could contribute to alcohol abuse. Specifically, alcohol-induced impairment of inhibitory control could compromise the drinker's ability to stop the self-administration of alcohol, increasing the risk of binge drinking. OBJECTIVE: The present study was designed to test this hypothesis by examining the relation between acute alcohol impairment of inhibitory control and alcohol consumption during a single drinking episode. MATERIALS AND METHODS: Twenty-six healthy adults performed a cued go/no-go task that measured inhibitory control. The study tested the degree to which their inhibitory control was impaired by a moderate dose of alcohol (0.65 g/kg) versus a placebo and the extent to which individual differences in this impairment predicted levels of alcohol consumption as assessed by ad lib drinking in the laboratory. RESULTS: In accord with the hypothesis, greater impairment of inhibitory control from alcohol was associated with increased ad lib consumption. CONCLUSION: Acute impairment of inhibitory control might be an important cognitive effect that contributes to abuse in addition to the positive rewarding effects of the drug.

Incidence of cardiovascular and cerebrovascular disease in Danish men and women with a prolonged heavy alcohol intake.

BACKGROUND: Several epidemiological studies have found U- or J-shaped relationships between alcohol intake and cardiovascular conditions. The influence of heavy drinking is, however, sparsely studied. The objective of the present study was to examine whether alcohol addicts have higher incidence rates of cardio- and cerebrovascular diseases than the population in general. METHODS: The cohort comprised 19,185 subjects (15,368 men and 3,817 women) who attended outpatient clinics for alcohol abusers within the Copenhagen Hospital Corporation (1954 to 1992). Incidence rates were standardized (SIR) according to sex, age and calendar time to compare subjects' cardio- and cerebrovascular incidence with that of the general population of Copenhagen. RESULTS: During the period 1977 to 2001 a total of 9,397 events of cardio- and cerebrovascular disease were observed. In both men and women, statistically significant higher incidence rates than would be expected in a standard population were observed for cardiovascular diseases (e.g., ischemic heart diseases, men: SIR = 1.76; 95% CI 1.69-1.83; women: SIR = 2.44; 95% CI 2.19-2.73) and cerebrovascular diseases (e.g., hemorrhagic stroke, men: SIR = 2.71; 95% CI 2.45-2.99; women: SIR = 2.77; 95% CI 2.18-3.48). CONCLUSIONS: The study indicates increased risks of cardio- and cerebrovascular diseases in subjects with an excessive alcohol intake.

Alcohol and pregnancy: the pivotal role of the obstetrician.

New draft alcohol guidelines for Australia state that, for pregnant women and women planning pregnancy, 'no drinking is the safest option'. One of the best known adverse effects of alcohol exposure on the fetus is the fetal alcohol syndrome. Others include alcohol-related birth defects, alcohol-related neurodevelopmental disorders and increased risks of miscarriage, stillbirth, intrauterine growth restriction, preterm birth and low birthweight. Over half of Australian women consume alcohol during pregnancy. Obstetricians have a pivotal role in advising women of the effects of alcohol on the fetus and reducing fetal exposure.