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Alcoholism and alcohol abuse represent a significant medical and societal problem, and have been thoroughly investigated in humans as well as using animal models. A less well understood aspect of alcohol related disorders is the possible effect of this drug on offspring whose parents were exposed prior to conception. The zebrafish has been successfully employed in alcohol research, however, the effect of exposing the parents to alcohol before fertilization of the eggs on offspring has not been demonstrated in this species. In this proof of concept study, we attempt to address this hiatus. We exposed both adult male and female zebrafish to 0.0% (control) or 0.5% (vol/vol) alcohol chronically for 7 days, subsequently bred the fish within their respective treatment group, collected the fertilized eggs, allowed them to develop, and tested the behavior of free-swimming offspring at their age of 7-9 days post-fertilization. We conducted the analysis in two genetically distinct quasi-inbred strains of zebrafish, AB and TL. Although gross morphology and general activity of the fish appeared unaffected, we found significant behavioral alterations in offspring of alcohol exposed parents compared to offspring of control parents in both strains. These alterations included robustly increased duration and reduced frequency of immobility, increased turn angle, and increased intra-individual variance of turn angle in offspring of alcohol exposed parents in both strains. The mechanisms underlying these behavioral effects or whether the effects are due to exposure of the father, the mother, or both to alcohol are unknown. Nevertheless, our results now set the stage for future studies with zebrafish that will address these questions.

AbstractThe serotonin (5‐HT) system has been implicated in the pathophysiology of alcohol (ethanol; EtOH) use disorders. Lorcaserin, a 5‐HT2C receptor agonist, attenuates drug self‐administration in animal models. We investigated the effects of lorcaserin on EtOH intake using the drinking‐in‐the‐dark (DID) procedure, an animal model of binge‐like drinking. We compared the effects of lorcaserin to those of the Food and Drug Administration (FDA)‐approved drug naltrexone and examined the effects of combining lorcaserin and naltrexone. To examine whether effects were specific for EtOH, we examined the effects of lorcaserin and naltrexone, administered alone and in combination, on saccharin intake. Adult male C57BL/6J mice received EtOH access (20% v/v) for 2 h in the home‐cage during the first 3 days of the DID procedure, beginning 3 h into the dark cycle. On day 4, mice were injected with lorcaserin, naltrexone, or a combination of lorcaserin and naltrexone prior to a 4‐h EtOH access. Intake was measured at 2 and 4 h. Lorcaserin reduced EtOH intake in a dose‐dependent fashion over the 2‐ and 4‐h measurement periods. Naltrexone also reduced EtOH intake when administered alone, with dose‐dependent effects being more pronounced over 2 h rather than the full 4‐h session. Combining lorcaserin and naltrexone reduced binge‐like EtOH drinking to a greater extent than either drug alone. A similar pattern of results was obtained for saccharin intake. These results suggest that lorcaserin and naltrexone can have additive effects on binge‐like EtOH drinking. They also support continued research into the therapeutic potential of lorcaserin for alcohol use disorders.

Zebrafish have become a popular animal model for behavioural pharmacology due to their small size, rapid development, and amenability to high throughput behavioural drug screens. Furthermore, water-soluble compounds can be administered via immersion of the fish in the drug solution, which provides a non-invasive drug delivery method. Numerous studies have demonstrated stimulant effects of alcohol. Diazepam and caffeine, on the other hand have been found to have inhibitory effect on locomotor activity in zebrafish. However, the time-dependent changes induced by these psychoactive drugs are rarely reported, and potential drug interactions have not been examined in zebrafish, despite the translational relevance of this question. In the current study, we examine time- and dose-dependent changes in zebrafish following exposure to caffeine, diazepam, and ethanol quantifying four different behavioural parameters over a 30min recording session. We subsequently analyze potential drug-drug interactions by co-administering the three drugs in different combinations. Our time-course and dose-response analyses for each of the three drugs represent so far the most detailed studies available serving as a foundation for future psychopharmacology experiments with zebrafish. Furthermore, we report significant interactions between the three drugs corroborating findings obtained with rodent models as well as in humans, providing translational relevance for the zebrafish model.

The endocannabinoid system is implicated in psychiatric disorders and drug dependence. Within this system, fatty acid amide hydrolase (FAAH) metabolizes endocannabinoids. Individuals with A-group genotypes (C/A or A/A) of a common FAAH variant (rs324420; C > A; Pro129Thr) have slower enzymatic activity compared to C-group individuals (C/C genotype). Slow FAAH activity is differentially associated with alcohol and nicotine use.Among European-ancestry participants in the NDIT study (n = 249-607), genotype associations with past-year binge drinking in young adults were estimated in logistic regression models. In adolescents, hazard ratios (HR) were estimated from Cox proportional hazards models to assess the FAAH genotype group association with time to drinking initiation and attaining drinking frequency outcomes. HR were also used to assess genotype effect on time to smoking initiation and attaining early smoking milestones (e.g., first inhalation, ICD-10 dependence).Compared to those in the C-group, those in the A-group had higher odds of binge drinking at ages 20 (Odds ratio (OR) = 2.16, 95 % CI 1.36-3.42) and 30 (OR = 1.61, 95 % CI 1.10-2.36). Time to initiation of drinking and daily drinking was faster in adolescents in the A-group (HR = 1.39, 95 % CI 1.09-1.77 and HR = 2.24, 95 % CI 1.05-4.76, respectively). Time to smoking initiation was faster in the A-group (HR = 1.20, 95 % CI 1.04-1.39); however, time to smoking milestones among adolescent smokers was not consistently different for the A- versus C-groups (HR = 0.43 to 1.13).Slow FAAH activity (A-group) was associated with greater risks for binge drinking, drinking initiation and escalation, and cigarette smoking initiation, but had little impact on the escalation in cigarette smoking behaviors.

Twenty patients withdrawing from alcohol who had reliable histories of previous alcohol-withdrawal seizures and thus were at high risk for a subsequent seizure were treated in hospital with oral diazepam loading: 20 mg of the drug was given every hour to a minimum total of 60 mg. None of the patients had a seizure during the stay in hospital. We believe that phenytoin prophylaxis is not necessary in these circumstances. However, if the patient is already taking phenytoin, this drug should not be abruptly discontinued in the withdrawal period in favour of diazepam loading.

Abstract Fuel poverty and cold housing constitute a significant public health problem. Energy efficiency interventions, such as facade retrofitting, address the problem from a structural and long-term perspective. Despite evidence of the health benefits of insulation, little is known about the political and social contexts that contribute to social inequalities in receiving and experiencing health benefits from these interventions. We used a realist review methodology to better understand the mechanisms that explain how and why variations across different social groups appear in receiving energy efficiency facade retrofitting interventions and in their impact on health determinants. We considered the four stages of the policy implementation framework: public policy approach; policy; receiving intervention and impact on health determinants. We found strong evidence that certain social groups (low-income, renters, elderly) suffering most from fuel poverty, experience more barriers for undertaking a building retrofitting (due to factors such as upfront costs, “presentism” thinking, split incentives, disruption and lack of control), and that some public policies on housing energy efficiency may exacerbate these inequalities. This can be avoided if such policies specifically aim at tackling fuel poverty or social inequities, are completely free to users, target the most affected groups and are adapted to their needs.

Alcohol consumption during pregnancy can lead to Fetal Alcohol Spectrum Disorder (FASD), and because maternal self-reports are often unreliable, biomarkers of alcohol use are sometimes necessary to accurately determine fetal risk. Ethyl glucuronide (EtG), a direct metabolite of ethanol, has been detected in the meconium of infants born to mothers who consumed excessive alcohol during pregnancy. It is still unknown whether EtG detected in meconium originated from maternal hepatic glucuronidation of ethanol followed by subsequent placental transfer. Therefore, the objective of this study was to determine if EtG crosses the human placenta.The transfer of EtG was measured using the ex vivo dual perfusion of an isolated human placental lobule. EtG (1 μg/mL) was added to the maternal circulation and samples were taken throughout the 1 h pre-experimental and 3 h experimental phases for measurement of EtG and markers of placental viability.After 3 h, the fetal-to-maternal ratio was 0.29 ± 0.02 and net maternal-to-fetal transfer was still occurring. Triplicate averages of EtG concentrations in perfused placental lobules ranged from 140 to 414 ng/g tissue. Placental validation markers were within normal ranges for all perfusions.The data show that EtG crosses the human placenta and primarily represents maternal exposure to alcohol.This information can help with the development of more thorough biomarker screens for alcohol use during pregnancy.

ABSTRACTAims  To review the concept of binge drinking as a measure of risky single occasion drinking (RSOD), to illustrate its differential impact on selected health outcomes and to identify research gaps.Methods  Narrative literature review with focus on conceptual and methodological differences, trajectories of RSOD and effects of RSOD on fetal outcomes, coronary heart disease (CHD) and injuries.Results  Effects ascribed commonly to RSOD may often be the effects of an undifferentiated mixture of risky single occasions and regular heavy volume drinking, constituted by frequent, successive RSOD. This leads to the problem that additional risks due to RSOD are mis‐specified and remain unidentified or underestimated in some cases, such as for injuries or CHD, but are probably overstated for some chronic consequences or for effects of maternal drinking on newborns.Conclusion  A stronger focus should be placed upon methods that can differentiate the effects of RSOD from those due to frequent occasions of heavy drinking that result in heavy volume drinking.

The health of whole populations within nations and globally and the implications of climate change are two of the most important challenges facing humanity in the 21st century. Both are components of a complex global crisis that must be acknowledged and addressed. Here we draw the attention of health professionals to some emerging threats and insights from key works of environmentalists in the hope that these may catalyze reflection on the broader challenges facing human health at a time of deep planetary malaise.