Reduce Alcohol Intake Research Articles

Preconception Health Attitudes and Behaviours of Women: A Qualitative Investigation.

The preconception period is a critical window in which maternal health can profoundly affect both individual and intergenerational health. Despite its importance, little information about women’s preconception health attitudes, behaviours and information preferences exists, yet these details are vital to inform targeted health communication. Semi-structured interviews were conducted to explore women’s attitudes to preconception health (areas of importance, support sources, enablers and barriers), behaviours (information seeking and health actions taken) and information preferences. Interviews were transcribed, coded and thematically analysed. Fifteen women participated (n = 7 preconception, n = 7 pregnant and n = 1 postpartum). Women perceived optimising lifestyle behaviours including a healthy diet, regular physical activity, reducing alcohol intake and pre-pregnancy vitamin supplementation as important preconception health actions to adopt. Few women acknowledged the importance of formal preconception health checks and screening with health professionals. Barriers to achieving health behaviour change included anxiety, stress and challenges obtaining reputable information. Participants reported a lack of preconception information about supplementation requirements, safe foods and exercise recommendations. Information preferences included the internet or their general practitioner. Whilst women predominantly prioritised optimising diet and physical activity prior to pregnancy, there appeared to be limited awareness of preconception health checks and screening, highlighting a need for broader awareness of overall preconception health and wellbeing.

Activation of glycine receptors in the lateral habenula rescues anxiety- and depression-like behaviors associated with alcohol withdrawal and reduces alcohol intake in rats

The lateral habenula (LHb) is activated by a range of aversive states including those related to alcohol withdrawal and has glycine receptors (GlyRs), a sensitive target of alcohol. However, whether GlyRs in the LHb contribute to alcohol-related behaviors is unknown. Here, we report that rats experiencing withdrawal from chronic alcohol consumption showed higher anxiety and sensitivity to stress compared to their alcohol-naïve counterparts. Intra-LHb injection of glycine attenuated these aberrant behaviors and reduced alcohol intake upon alcohol re-access. Glycine's effect was blocked by strychnine, a GlyR antagonist, indicating that it was mediated by strychnine-sensitive GlyRs. Conversely, intra-LHb strychnine elicited anxiety- and depression-like behaviors in Naïve rats but not in withdrawal rats. Additionally, both the frequency and the amplitude of the spontaneous IPSCs were lower in LHb neurons in slices of withdrawal rats compared to naïve rats. Also, there were sporadic strychnine-sensitive synaptic events in some LHb neurons. Bath perfusion of strychnine induced a depolarizing inward current and increased action potential firings in LHb neurons. By contrast, bath perfusion of glycine or sarcosine, a glycine transporter subtype 1 inhibitor, inhibited LHb activity. Collectively, these data reveal that LHb neurons are under the tonic glycine inhibition both in physiological and pathological conditions. Activation of GlyRs reverses LHb hyperactivity, alleviates aberrant behaviors, and reduces alcohol intake, thus highlighting the GlyRs in the LHb as a potential therapeutic target for alcohol-use disorders.

Knowledge, attitudes and preventive practices of primary health care professionals towards alcohol use: A national, cross-sectional study.

IntroductionPrimary care (PC) professionals' knowledge about alcohol use has been identified as one of the barriers PC providers face in their clinic. Both PC professionals’ level of training and attitude are crucial in the clinical practice regarding alcohol use.ObjectiveTo evaluate the knowledge, attitude, and preventive practices of Spanish PC physicians and nurses towards alcohol use.DesignAn observational, descriptive, cross-sectional, multi-center study.MethodologyLocation: PC centers of the Spanish National Health System (NHS). Participants: PC physicians and nurses selected randomly from health care centers, and by sending an e-mail to semFYC and SEMERGEN members. Healthcare providers completed an online survey on knowledge, attitude, and follow-up recommendations for reducing alcohol intake. A descriptive, bivariate, and multivariate statistical analysis was conducted (p<0.05).ResultsParticipants: 1,760 healthcare providers completed the survey (75.6% [95% CI 73.5–77.6] family physicians; 11.4% [95% CI 9.9–12.9] medical residents; and 12.5% [95% CI 10.9–14.1] nurses), with a mean age of 44.7 (SD 11.24, range: 26–64, 95% CI: 47.2–48.2). Knowledge was higher in family physicians (p<0.001), older professionals (Spearman's r = 0.11, p<0.001), and resident trainers (p<0.001). The PC professional most likely to provide advice for reducing alcohol use was: a nurse (p <0.001), female (p = 0.010), between 46 and 55 years old (p <0.001).ConclusionsPC providers’ knowledge and preventive practices regarding alcohol use are scarce, hence specific training strategies to increase their knowledge and improve their attitude and skills with regard to this health problem should be considered a healthcare policy priority.

Drinking Levels and Profiles of Alcohol Addicted Rats Predict Response to Nalmefene.

Background: Pharmacotherapeutic options supporting the treatment of alcohol dependence are recommended and available but underutilized, partly due to questions about efficacy. Nalmefene, a μ-opioid receptor antagonist and partial kappa receptor agonist, is recommended for reduction of alcohol consumption, but evidence about its effectiveness has been equivocal; identifying factors which predict response will help optimize treatment.Methods: The alcohol deprivation effect paradigm is a tightly controlled procedure comprising repeated deprivation and reintroduction phases, leading to increased preference for alcohol; reintroduction approximates relapse. Using a digital drinkometer system measuring high-resolution drinking behavior, we examined the effects of nalmefene on relapse drinking behavior in alcohol addicted rats. We also tested whether drinking behavior in the relapse phase prior to nalmefene administration predicted treatment response. We further examined whether longitudinal drinking behavior and locomotor activity predicted treatment response.Results: Our results showed that nalmefene (0.3 mg/kg) reduced relapse-like consumption significantly (∼20%) compared to vehicle on the first 2 days of alcohol reintroduction. Examining the first 6 h of a preceded treatment-free relapse episode revealed drinking patterns clustering the rats into responders (reduction of >40%, n = 17) and non-responders (reduction of <40%, n = 7) to subsequent nalmefene treatment. During the first 6 h of the preceding relapse phase, responders consumed more alcohol than non-responders; the amount of alcohol consumed during each drinking approach was larger but frequency of drinking did not differ. Longitudinal drinking behavior and locomotor activity did not significantly predict response.Conclusion: Our results suggest that nalmefene reduces alcohol intake during a relapse-like situation but effectiveness can differ greatly at the individual level. However, who responds may be informed by examining drinking profiles and rats that show high drinking levels prior to treatment are more likely to respond to nalmefene.

Sex differences in the effect of bupropion and naltrexone combination on alcohol drinking in mice

A fixed dose combination of bupropion (BPP) and naltrexone (NTX), Contrave®, is an FDA approved pharmacotherapy for the treatment of obesity. A recent study found that combining BPP with low-dose NTX reduced alcohol drinking in alcohol-preferring male rats. To explore potential pharmacological effects of the BPP + NTX combination on alcohol drinking, both male and female C57Bl/6J mice were tested on one-week drinking-in-the dark (DID) and three-week intermittent access (IA) models. Neuronal proopiomelanocortin (POMC) enhancer knockout (nPE−/−) mice with hypothalamic-specific deficiency of POMC, and its bioactive peptides melanocyte stimulating hormone and beta-endorphin, were used as a genetic control for the effects of the BPP + NTX. A single administration of BPP + NTX (10 mg/kg + 1 mg/kg) decreased alcohol intake after DID in C57Bl/6J males, but not females. Also in C57Bl/6J males, BPP + NTX reduced intake of the caloric reinforcer sucrose, but not the non-caloric reinforcer saccharin. In contrast, BPP + NTX had no effect on alcohol DID in nPE−/− males. Pretreatment with the selective melanocortin 4 receptor (MC4R) antagonist HS014 reversed the anti-dipsogenic effect of BPP + NTX on alcohol DID in C57Bl/6J males. In the 3-week chronic IA model, single or repeated administrations for four days of BPP + NTX reduced alcohol intake and preference in C57Bl/6J males only. The behavioral measures observed in C57Bl/6J mice provide clear evidence that BPP + NTX profoundly reduced alcohol drinking in males, but the doses tested were not effective in females. Furthermore, our results suggest a hypothalamic POMC/MC4R-dependent mechanism for the observed BPP + NTX effects on alcohol drinking in male mice.

Opposing roles of Sigma‐1 and Sigma‐2 receptors in heavy alcohol drinking and associated mechanical allodynia in mice

Alcohol Use Disorder (AUD) is a serious and complex neuropsychiatric disorder characterized by excessive alcohol intake, inability to control consumption, and the emergence of a negative emotional state in the absence of alcohol. While the role of the Sigma‐1 receptor (Sig‐1R) in animal models of AUD has been demonstrated, the role of Sigma‐2 receptor/Transmembrane Protein 97 (Sig‐2R/TMEM97), which has recently been cloned, is still unclear. Using an intermittent access, 2‐bottle choice paradigm, the effects of the Sig‐2R/TMEM97 modulator JVW‐1034 (0–30 mg/kg, i.p.) on ethanol drinking in male C57Bl/6J mice were assessed. Sucrose intake was used to control for non‐specific effects of the drug on an alternate reinforcer in a separate study, and locomotor intake was also assessed. In addition, using an automated von Frey filament test, the effects of JVW‐1034 on mechanical sensitivity in alcohol drinking mice was tested during withdrawal. The effects of the Sig‐2R modulator were compared to those of BD‐1063 (0–30 mg/kg, i.p.), a preferential Sig‐1R antagonist. Results showed that JVW‐1034 reduced alcohol intake and preference in this model, without affecting water intake. Sucrose intake was not affected by the drug, suggesting selectivity of the effect for alcohol. JVW‐1034 also blocked the mechanical allodynia induced by chronic alcohol drinking without affecting sensitivity in control mice. Lastly, JVW‐1034 did not affect locomotor activity in either group. BD‐1063 had a very similar profile. These data suggest that Sig‐1R and Sig‐2R play opposite roles in the regulation of alcohol drinking and associated allodynia and hyperalgesia, and lay the foundation for more extensive studies examining the involvement of the Sig‐2R/TMEM97 system in AUD.Support or Funding InformationR01‐AA024439This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Therapeutic Potential of G‐protein‐Biased Kratom‐Derived and Synthetic Carfentanil‐Amide Opioids for Alcohol Use Disorder

Mitragyna speciosa, also known as kratom, is a plant containing opioidergic alkaloids and is currently being used to self‐medicate chronic pain, opioid dependence, and is also used as a heroin substitute. Kratom, though unscheduled, may be less dangerous when compared to prescription opioids due to the preferential interaction of kratom alkaloids with G‐proteins instead of beta‐arrestin proteins. We hypothesized that kratom alkaloids and synthetic opioids with similar biased pharmacology can be used to treat alcohol use disorder. We completed in vitro pharmacological characterization for two kratom strain extracts, four kratom alkaloids (mitragynine, 7‐hydroxymitragynine, paynantheine, and speciogynine), and a series of synthetic carefentanil‐amide opioids by determining their ability to interact selectively with G‐proteins instead of beta‐arrestin at the mu, delta and kappa opioid receptors. In addition, in C57BL/6 mice we assessed if kratom (alkaloids) and opioids were capable of reducing alcohol use and determined if the alkaloids had rewarding properties. We found that kratom alkaloids are strongly biased towards the G‐protein pathway at all three opioid receptors. More specifically, we found the delta opioid receptor plays an important role in the mechanism of action as interpreted from reduced efficacy in knockout mice. MP102, one of the synthesized carfentanilamide opioids, displayed a pharmacological profile similar to the kratom alkaloids but with preference for delta opioid receptors, and also reduced alcohol intake and likewise produced less significant place preference than morphine. Our findings demonstrate that kratom use can decrease alcohol use, but its use still carries substantial risk. The development of further delta‐opioid‐selective synthetic opioids may provide an avenue for alcohol use treatment that does not produce strong rewards.Support or Funding InformationRMvR support: NIH grants AA025368, AA026949, AA026675, DA045897, a NARSAD young investigator award from The Brain and Behavior Research Foundation, the Purdue Institute for Drug Discovery and the Dept. of Med.Chem. and Molecular Pharmacology. SM support: NIH grants DA045884, DA046487, AA026949 and W81XWH‐17‐1‐0256 &amp; start‐up funds from the Center for Clinical Pharmacology in St. Louis. Funded in part through NIH/NCI Cancer Center Support Grant P30. CA008748.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fenofibrate -a PPARα agonist- increases alcohol dehydrogenase levels in the liver: implications for its possible use as an ethanol-aversive drug.

After ethanol consumption, disulfiram increases blood-acetaldehyde levels, generating an aversive reaction that deters alcohol drinking. Given the major secondary effects of disulfiram, finding other effective drugs to reduce alcohol consumption in individuals with alcohol-use-disorder is highly desirable. It has been reported that administering fenofibrate to high-drinking rats increases hepatic catalase levels and blood acetaldehyde after administering ethanol and a 60-70% inhibition of voluntary alcohol intake. This work evaluated whether fenofibrate has an additional effect on the activity of other ethanol-metabolizing enzymes, which could contribute to the high acetaldehyde levels generated upon administering ethanol. Male high-drinker rats were allowed to voluntary drink 10% ethanol or water for 2 months. Subsequently, fenofibrate (100 mg/kg/day) or vehicle was administered orally for 14 days. Then, alcohol dehydrogenase (ADH1) and aldehyde dehydrogenase (ALDH2) protein levels and enzymatic activities in the livers were quantified. Fenofibrate treatment produced a marked increase in ADH1 protein levels (396% ± 18%, p < 0.001) and enzymatic activity (425% ± 25%, p < 0.001). Fenofibrate did not result in differences in ALDH2 activity or in ALDH2 protein levels. The studies show that treatment with fenofibrate not only increased the activity of catalase in the liver of alcohol-drinking rats, as reported earlier, but also increased the levels and enzymatic activity of ADH1, while ALDH2 remained unchanged. The increases in ADH1 contribute to explaining the remarkable effect of fenofibrate in raising blood levels of acetaldehyde in ethanol-consuming animals, in which a marked reduction of alcohol intake is recorded.

The impact of reducing alcohol consumption in Australia: An estimate of the proportion of potentially avoidable cancers 2013-2037.

The International Agency for Research on Cancer first concluded that alcohol causes cancer in humans in 1988. The World Cancer Research Fund has declared that alcohol causes cancer of the oral cavity, pharynx, larynx, oesophagus (squamous cell carcinoma), female breast, colon, rectum, stomach and liver. It recommended that alcohol be avoided altogether to prevent cancer. We aimed to quantify the impact of reducing alcohol consumption on future cancer incidence in Australia. We used PREVENT 3.01 simulation modelling software to estimate the proportion of cancers that could potentially be prevented over a 25-year period under two hypothetical intervention scenarios and two latency periods (20 and 30 years). Under a scenario where alcohol consumption abruptly ceases, we estimated up to 4% of alcohol-related cancers could be avoided over a 25-year period (~49,500 cancers, depending on assumed latency). If the maximum consumption of all Australian adults was ≤20 g/day (~two Australian standard drinks), up to 2% of alcohol-related cancers could be avoided (~29,600 cancers). The maximum proportions were higher for men (6% for no alcohol consumption; 5% for ≤20 g/day) than women (3%; 1%). The proportion avoidable was highest for oesophageal squamous cell carcinoma (17% no alcohol consumption; 9% ≤20 g/day), followed by cancers of the oral cavity (12%; 5%) and pharynx (11%; 5%). The cancer sites with the highest numbers of potentially avoidable cases were colon in men (11,500; 9,900) and breast in women (14,400; 4,100). Successful interventions to reduce alcohol intake could lead to significant reductions in cancer incidence.

Assessment of incidence and various demographic risk factors of traumatic humeral shaft fractures in China

As a sub-study of the China National Fracture Study, this study aimed to better determine the incidence and risk factors of humeral shaft fracture in mainland China. We obtained all the data on humeral shaft fracture from the China National Fracture Study reported in 2017. Trained research teams personally interviewed all qualifying household members using a standardised questionnaire. A total of 512,187 (259649 boys and men, 252538 girls and women) questionnaires were collected and analysed from 112 neighbourhood communities and 223 administrative villages using stratified random sampling and the probability proportional to size method. The population-weighted incidence rate of humeral shaft fracture was 7.22 (95% confidence interval 4.90, 9.55) per 100,000 populations in 2014. Previous fracture history was an independent risk factor in adults of both sexes. Smoking was identified as an independent risk factor for humeral shaft fracture for men. Alcohol consumption and menstruation ceasing before the age of 46 years were considered as independent risk factors for women. Given the above data, specific public-health policies focusing on promoting a smoke-free environment and reducing alcohol intake should be encouraged. People who have had a fracture and women whose menstruation had ceased before the age of 46 should be vigilant against humeral shaft fracture.

Brain region specific glucagon-like peptide-1 receptors regulate alcohol-induced behaviors in rodents

Glucagon-like peptide 1 (GLP-1), an incretin hormone that reduces food intake, was recently established as a novel regulator of alcohol-mediated behaviors. Clinically available analogues pass freely into the brain, but the mechanisms underlying GLP-1-modulated alcohol reward remains largely unclear. GLP-1 receptors (GLP-1R) are expressed throughout the nuclei of importance for acute and chronic effects of alcohol, such as the laterodorsal tegmental area (LDTg), the ventral tegmental area (VTA) and the nucleus accumbens (NAc). We therefore evaluated the effects of bilateral infusion of the GLP-1R agonist exendin-4 (Ex4) into NAc shell, anterior (aVTA), posterior (pVTA) or LDTg on the acute alcohol-induced locomotor stimulation and memory of alcohol reward in the conditioned place preference (CPP) model in mice, as well as on alcohol intake in rats consuming high amounts of alcohol for 12 weeks. Ex4 into the NAc shell blocks alcohol-induced locomotor stimulation and memory of alcohol reward as well as decreases alcohol intake. The GLP-1R expression in NAc is elevated in high compared to low alcohol-consuming rats. On the contrary, GLP-1R activation in the aVTA does not modulate alcohol-induced behaviors. Ex4 into the pVTA prevents alcohol-induced locomotor simulation, but does neither modulate CPP-dependent alcohol memory nor alcohol intake. Intra-LDTg-Ex4 attenuates alcohol-induced locomotor stimulation and reduces alcohol intake, but does not affect memory of alcohol reward. Collectively, these data provide additional knowledge of the functional role of GLP-1R in reward-related areas for alcohol-mediated behaviors and further support GLP-1R as a potential treatment target for alcohol use disorder.

Probenecid Reduces Alcohol Drinking in Rodents. Is Pannexin1 a Novel Therapeutic Target for Alcohol Use Disorder?

The development of novel and more effective medications for alcohol use disorder (AUD) is an important unmet medical need. Drug repositioning or repurposing is an appealing strategy to bring new therapies to the clinic because it greatly reduces the overall costs of drug development and expedites the availability of treatments to those who need them. Probenecid, p-(di-n-propylsulfamyl)-benzoic acid, is a drug used clinically to treat hyperuricemia and gout due to its activity as an inhibitor of the kidneys' organic anion transporter that reclaims uric acid from urine. Probenecid also inhibits pannexin1 channels that are involved in purinergic neurotransmission and inflammation, which have been implicated in alcohol's effects and motivation for alcohol. Therefore, we tested the effects of probenecid on alcohol intake in rodents. We tested the effects of probenecid on operant oral alcohol self-administration in alcohol-dependent rats during acute withdrawal as well as in nondependent rats and in the drinking-in-the-dark (DID) paradigm of binge-like drinking in mice. Probenecid reduced alcohol intake in both dependent and nondependent rats and in the DID paradigm in mice without affecting water or saccharin intake, indicating that probenecid's effect was selective for alcohol and not the result of a general reduction in reward. These results raise the possibility that pannexin1 is a novel therapeutic target for the treatment of AUD. The clinical use of probenecid has been found to be generally safe, suggesting that it can be a candidate for drug repositioning for the treatment of AUD.

Modulation of Gpr39, a G-protein coupled receptor associated with alcohol use in non-human primates, curbs ethanol intake in mice.

Alcohol use disorder (AUD) is a chronic condition with devastating health and socioeconomic effects. Still, pharmacotherapies to treat AUD are scarce. In a prior study aimed at identifying novel AUD therapeutic targets, we investigated the DNA methylome of the nucleus accumbens core (NAcc) of rhesus macaques after chronic alcohol use. The G-protein coupled receptor 39 (GPR39) gene was hypermethylated and its expression downregulated in heavy alcohol drinking macaques. GPR39 encodes a Zn2+-binding metabotropic receptor known to modulate excitatory and inhibitory neurotransmission, the balance of which is altered in AUD. These prior findings suggest that a GPR39 agonist would reduce alcohol intake. Using a drinking-in-the-dark two bottle choice (DID-2BC) model, we showed that an acute 7.5 mg/kg dose of the GPR39 agonist, TC-G 1008, reduced ethanol intake in mice without affecting total fluid intake, locomotor activity or saccharin preference. Furthermore, repeated doses of the agonist prevented ethanol escalation in an intermittent access 2BC paradigm (IA-2BC). This effect was reversible, as ethanol escalation followed agonist "washout". As observed during the DID-2BC study, a subsequent acute agonist challenge during the IA-2BC procedure reduced ethanol intake by ~47%. Finally, Gpr39 activation was associated with changes in Gpr39 and Bdnf expression, and in glutamate release in the NAcc. Together, our findings suggest that GPR39 is a promising target for the development ofprevention and treatment therapies for AUD.

Long-term pharmacotherapy aimed at maintaining abstinence or reducing alcohol intake in alcohol-dependent individuals. Guidelines from the Section of Pharmacotherapy of Polish Society for Research on Addictions (PTBU) and the Section of Psychopharmacology of Polish Psychiatric Association (PTP) – 2019 update

The article presents update of the 2013 Guidelines of the Pharmacotherapy Section of the Polish Society for Research on Addictions (PTBU) and the Psychopharmacology Section of the Polish Psychiatric Association (PTP) on long-term pharmacotherapy aimed at maintaining abstinence or reducing alcohol intake in adult alcohol-dependent patients. Apart from practical guidelines for long-term pharmacotherapy of alcohol dependence, the authors present the areas of uncertainty, which still require further studies and scientific debate.

Epidemiology of Hypopharyngeal Cancer.

Hypopharyngeal cancer is uncommon in the developed world; it is mostly diagnosed in men who smoke tobacco and consume excessive alcohol and uncommon in women. However, recent trends in the developed world show that there has been an annual increase in the percentage of women with hypopharyngeal cancer. In France, there has been a significant annual percentage change in the incidence of this form of cancer - a decrease in men and a greater increase in women since the 1980s. In the developing world, India, Taiwan and other countries, the incidence of hypopharyngeal cancer has increased in both men and women. These populations indulge widely in the social habit of tobacco usage at an earlier age, both smoking and chewing, excessive alcohol drinking, along with the chewing of the areca nut. Recent research has proven that areca nut alone is carcinogenic. The combination of tobacco and alcohol has a greater multiplicative impact on increasing the risk of cancer, while the involvement of areca nut remains to be proven. The World Health Organisation has commenced a Global Mission on the cessation of smoking and reduction of alcohol intake. The effect of this work has been credited with a reduction of hypopharyngeal and other head and neck cancers. While the younger aged should be the targeted population to avoid tobacco usage, the middle and older age of the population must be targeted for quitting smoking tobacco.

Association between Change in Alcohol Consumption and Metabolic Syndrome: Analysis from the Health Examinees Study.

BackgroundThe association between change in alcohol intake and metabolic syndrome is unclear.MethodsThis retrospective cohort consisted of 41,368 males and females from the Health Examinees-GEM study. Participants were divided into non-drinkers (0.0 g/day), light drinkers (male: 0.1 to 19.9 g/day; female: 0.1 to 9.9 g/day), moderate drinkers (male: 20.0 to 39.9 g/day; female: 10.0 to 19.9 g/day), and heavy drinkers (male: ≥40.0 g/day; female: ≥20.0 g/day) for each of the initial and follow-up health examinations. Logistic regression analysis was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for developing metabolic syndrome according to the change in alcohol consumption between the initial and follow-up health examinations. Adjusted mean values for the change in waist circumference, fasting serum glucose (FSG), blood pressure, triglycerides, and high density lipoprotein cholesterol (HDL-C) levels were determined according to the change in alcohol consumption by linear regression analysis.ResultsCompared to persistent light drinkers, those who increased alcohol intake to heavy levels had elevated risk of metabolic syndrome (aOR, 1.45; 95% CI, 1.09 to 1.92). In contrast, heavy drinkers who became light drinkers had reduced risk of metabolic syndrome (aOR, 0.61; 95% CI, 0.44 to 0.84) compared to persistent heavy drinkers. Increased alcohol consumption was associated with elevated adjusted mean values for waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels (all P<0.05). Reduction in alcohol intake was associated with decreased waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels among initial heavy drinkers (all P<0.05).ConclusionHeavy drinkers who reduce alcohol consumption could benefit from reduced risk of metabolic syndrome.

Multiple infected ulcerative plaques in an alcohol addicted patient.

A 47-year-old male patient came to the Souza Araujo outpatient clinic of the Oswaldo Cruz Foundation, a reference center for treating leprosy, to confirm mycobacteriosis after living in close contact with a leprosy patient. The patient was emaciated, having lost 12 kg in 2 months, febrile and presented nystagmus. The patient had multiple erythematous-livedoid, hypoesthetic, ulcerated, and purulent wounds in light-exposed areas, which had appeared suddenly 2 months before admission and did not regress after amoxicillin therapy. The patient reported loss of sensitivity, paresthesia, and asthenia in the lower limbs. Adenomegaly and visceromegaly were not observed. The patient had an approximately 25-year history of alcoholism and smoking. The patient also reported having intermittent diarrhea. The patient was instructed to take 300 mg of niacinamide per day, ingest other B-complex vitamins, use amoxicillin-clavulanic acid to treat impetigo, reduce alcohol intake and improve nutrition. On the return visit one month later, the lesions and peripheral neuropathy had regressed significantly, although the patient had used B-complex formulations containing only 50 mg of niacinamide for financial reasons. Pellagra was described in eighteenth-century Europe by Gaspar Casal, related to poverty and low ingestion of animal products. It was a public health problem in the United States at the beginning of the last century, but pellagra is rare today and diagnosed particularly among individuals with alcohol abuse, taking some medications, with desorption syndromes and HIV. The classic triad of symptoms includes dermatitis, diarrhea and dementia. Scaly dermatitis is more common in areas exposed to sunlight.

Can Inhibitory Training Produce Reductions in Drinking? Evaluating the Influence of the Control Condition

Training in an inhibitory control task has produced reductions in alcohol use among heavy drinkers. However, the longevity of effects remains unknown, and much research has used suboptimal control conditions. Here, we assess the effectiveness of "Beer-NoGo" inhibitory training to reduce consumption up to 4 weeks after training compared with a "Beer-Go" control task, an online version of the Brief Alcohol Intervention (BAI), and an Oddball control condition. Eighty-one regular drinkers were randomized into one of four training conditions. In the Beer-NoGo condition, participants responded to a letter superimposed on water-related images and refrained from responding to another letter superimposed on beer-related images. The mapping was reversed for the Beer-Go condition, whereas the Oddball control condition was presented with letters only and inhibition was not required. The last condition was an online BAI. Alcohol use was assessed using a bogus taste test and weekly alcohol consumption. Taste-test consumption was greater in the Beer-Go condition than in the Beer-NoGo, which did not differ from the Oddball and BAI conditions. All groups reduced alcohol intake during the study; however, in the first week the Beer-Go group reduced their drinking while the Beer-NoGo group increased. No group differences were apparent at the fourth week. The Beer-NoGo task did not produce effects beyond simple assessment on reducing alcohol use among regular drinkers. Previously reported training effects may be artifacts of the Beer-Go task as a suboptimal control. More robust forms of inhibitory training are necessary if a useful clinical adjunct for managing alcohol abuse is to be developed.

Aldehyde Dehydrogenase 2 Anti-Sense in the Ventral Tegmental Area Reduces Alcohol Drinking

Background: We have reported that aldehyde dehydrogenase 2 (ALDH2) inhibitors suppress alcohol seeking and drinking in rats even in the absence of alcohol and acetaldehyde. These behavioural changes suggest that ALDH2 in brain could be a target for ANS-6637 inhibition to suppress alcohol seeking and drinking. Here we ask whether ALDH2-RNA anti-sense administered directly into the Ventral Tegmental Area (VTA) also reduces alcohol drinking. Methods: A recombinant adenoviral vector expressing rat AGS3 and specific RNA antisense against ALDH2 was injected into the VTA of actively drinking alcohol-preferring (iP) rats in a 2-bottle choice study with 10% alcohol (v/v) and water. Controls received scrambled RNA. Alcohol consumption was assayed before and after adenoviral injection. Histology confirmed cannulae implantation. Results: ALDH2 antisense microinjected in the VTA of alcohol-drinking iP rats reduces alcohol intake when compared with baseline drinking prior to antisense microinjection. Controls are unaffected. Reduction occurs between days 5 and 12 post-ALDH2 antisense microinjection with maximal effects on days 7 and 9 (31% from baseline). Rats recover baseline alcohol intake values by day 16. Conclusions: The major finding is that ALDH2 antisense in the VTA appears to reduce alcohol drinking. Consistent with previous results suggesting that ALDH2 inhibitors might reduce drinking by acting in the brain, this observation with ALDH2 antisense suggests that ALDH2 in the VTA may be an important target for pharmacologic ALDH2 inhibitors.

Combined ∆9-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats.

Whereas co-use of alcohol and marijuana is prevalent in adolescents, the effects of such drug co-exposure on ingestive and cognitive behaviors remain largely unexplored. We hypothesized that co-exposure to alcohol and ∆9-tetrahydrocannabinol (THC), the main psychoactive constitute of marijuana, alters feeding behavior and cognition differently from either drug alone. Male rats received daily THC (3-20mg/kg/day) or oil vehicle through subcutaneous injection or consumption of a cookie with access to saccharin or saccharin-sweetened alcohol during adolescence (P30-45). Barnes maze and sucrose preference tests were applied to assess spatial memory and behavioral flexibility and abstinence-related anhedonia, respectively. Subcutaneous THC did not affect alcohol intake but dose-dependently increased acute (3h) chow intake and reduced weight gain. Moderate alcohol consumption reduced the acute hyperphagic effect of subcutaneous THC. By contrast, oral THC at a dose > 5mg/kg robustly reduced alcohol intake without affecting 3-h chow intake. At this dose, some rats stopped consuming the THC-laced cookies. Furthermore, oral THC reduced weight gain, and co-exposure to alcohol alleviated this effect. Chronic subcutaneous, but not oral, THC reduced sucrose intake during abstinence. Neither treatment impaired cognitive behaviors in the Barnes maze. Moderate alcohol and THC consumption can interact to elicit unique outcomes on ingestive behaviors and energy balance. Importantly, this study established a novel model of voluntary alcohol and THC consumption for studying mechanisms underlying the consequences of adolescent onset co-use of the two drugs.