Effects Of Intoxication Research Articles

Morphofunctional State and Circadian Rhythms of the Liver of Female Rats under the Influence of Chronic Alcohol Intoxication and Constant Lighting

A separate and combined effect of constant illumination and chronic alcohol intoxication (CAI) on diurnal dynamics of micromorphometric parameters of hepatocytes in female Wistar rats and p53, Ki-67, PER2, BMAL1, and ADH5 expression in these cells were studied. The increase in apoptotic activity and proliferation in all animals under the action of chronodestructors is shown. All experimental animals showed a decrease in BMAL1 expression and increase in PER2 expression; ADH5 is overexpressed under the influence of ethanol. Circadian rhythms (CRs) of BMAL1, PER2, p53, and Ki-67 expression persist in all groups, except combined action of chronodestructors, and ADH5 CRs persist in all groups—thus, these rhythms in females are quite stable. CRs of the hepatocyte nuclei area are preserved in all the studied groups, although they undergo a significant shift. At the same time, the CRs of the hepatocyte area are destroyed under the action of light, both independently and in combination with CAI, and the CR of the nuclear-cytoplasmic ratio (NCR) is destroyed by exposure to CAI. It can be assumed that CRs of the hepatocyte area are significantly affected by dark deprivation and NCR rhythm is sensitive to ethanol consumption, while the stability of studied genes’ expression rhythms at separate influences of studied chronodestructors is maintained by yet unknown adaptation mechanisms. It is necessary to note that, according to our previous studies of male rats, rat females show significantly greater stability of the studied CRs.

Effects of aquatic heavy metal intoxication on the level of hematocrit and hemoglobin in fishes: A review

Environmental pollution caused due to the presence of heavy metals has become a great concern as it has an adverse effect on almost all types of ecosystem. In this sense, these pollutants have a tendency to pollute the aquatic ecosystem, thus badly affecting the health of aquatic organisms. As a result, toxicological studies believe them to be the most harmful pollutants in the aquatic environment. Among all the aquatic organisms, fish—being a chief organism in this system—become the easiest victim of these pollutants. Heavy metals enter fish bodies through the alimentary system by consumption of polluted food, or through the gills, and skin. They are finally delivered by the bloodstream to the organs and tissues where they accumulate after absorption. Ultimately, in this way heavy metals make their way into humans through the food chain. The fluctuations in the hematological values may serve as an initial indicator of the toxicant’s impact on fish health. It has been observed that when pollutants impact the quality of the aquatic medium, the first consequence is apparent in the form of physiological changes in fish, which are reflected in one or more hematological parameters, such as hemoglobin, hematocrit, red blood cell count, white blood cell count, etc. As a result of these alterations, fish become weak, anemic, and more susceptible to diseases. Over the past several decades, a vast number of studies have been reported on the qualitative and quantitative variations in hematological parameters due to the presence of heavy metal intoxication. Heavy metal contamination of water resources not only degrades the water quality but also negatively impacts the quality of food in the form of fish proteins. Therefore, this article sheds light on the effects of heavy metals on hemoglobin and hematocrit of fish hematology and calls for more attention to the protection and preservation of aquatic ecosystems, particularly those contaminated with heavy metals.

Effects of alcohol on sleep and nocturnal heart rate: Relationships to intoxication and morning-after effects.

Alcohol consumption produces feelings of well-being and stimulation, but also impairs psychomotor performance, disturbs cardiovascular function and sleep, and can disrupt next-day mood and behavior. A deeper understanding of how the acute effects of alcohol relate to its sleep and morning-after effects is needed to minimize harm resulting from its use. This study examined relationships between the effects of a high dose of alcohol on subjective and psychomotor measures, nocturnal heart rate, sleep quality, and morning-after mood and behavior. We hypothesized that alcohol would produce disturbances in cardiovascular and sleep regulation during the night, which would predict morning-after mood and behavioral performance. Thirty-one men and women participated in two overnight laboratory visits during which they consumed either alcohol (1.0g/kg for men, 0.85 g/kg for women) or placebo (randomized, crossover design). They consumed the beverage from 8 to 9pm, and remained in the laboratory overnight for polysomnographic sleep recording. Subjective and behavioral measures were obtained during consumption and at 7-8am the morning after. Alcohol increased both negative and positive arousal, urge to drink and sedation, and it impaired performance on behavioral tasks. During sleep, alcohol produced expected tachycardia and detriments in sleep quality including decreased total sleep time, sleep efficiency, and altered sleep architecture. Only modest effects on mood or performance were detected the following morning. The acute sedative-like effects of alcohol were related to increases in N2 sleep, but not to other disruptions in sleep or nocturnal heart rate, and neither sleep impairments nor nocturnal heart rate were related to mood or task performance the morning after. The effects of alcohol on sleep and nocturnal heart rate were not strongly related to either its acute or morning-after effects. These findings do not provide strong support for the idea that alcohol-induced sleep disruptions underlie morning-after effects.

Integration of Biblical and Pastoral Approaches in Dealing with Alcohol and Drug Abuse in the Presbyterian Churches of Kenya

Global statistics show persistence of alcohol and drug abuse despite the programmes religious organisations have come up with aimed at mitigating alcohol and drug abuse. This study analyzed the Biblical and pastoral approaches used by Presbyterian Churches (PCEA) in addressing the problem of alcohol and drug abuse. Multistage Cluster sampling technique was used to select three PCEA regions from the five regions. The study had a total sample of 144 respondents who were the Parish ministers. A descriptive survey research design was used to obtain qualitative data. Instrument for data collection was structured interview schedule. Data collected from the Parish ministers was analyzed qualitatively. The study established that the Presbyterian churches integrated both Biblical and pastoral approaches in mitigating alcohol and drug abuse. Majority of the parish ministers indicated that they used sermons as a pastoral intervention for alcohol and drug abuse among the youth in the Presbyterian churches. Other pastoral interventions included pastoral counseling, open discussions on alcohol and drugs and praying for the addicts. Parish ministers also indicated that they used the Bible to warn against the use of alcohol and more specifically its intoxicating effect and this justifies why the church should get involved in the lives of those abusing alcohol and drugs so as to help them get out of the bondage. The Bible commends self-control with regard to alcohol. Parish ministers used Bible verses to explain that the Bible forbids participating for the sake of personal pleasure, in practices that hinder moral judgment or weaken self-control. The findings of this study will help the clergy to address problem of alcohol and drug abuse in the society and particularly among the youth as this segment of the population is vital for church and societal development.

Modulation of type 1 cannabinoid receptor activity by cannabinoid by-products from Cannabis sativa and non-cannabis phytomolecules.

Cannabis sativa contains more than 120 cannabinoids and 400 terpene compounds (i.e., phytomolecules) present in varying amounts. Cannabis is increasingly available for legal medicinal and non-medicinal use globally, and with increased access comes the need for a more comprehensive understanding of the pharmacology of phytomolecules. The main transducer of the intoxicating effects of Cannabis is the type 1 cannabinoid receptor (CB1R). ∆9-tetrahydrocannabinolic acid (∆9-THCa) is often the most abundant cannabinoid present in many cultivars of Cannabis. Decarboxylation converts ∆9-THCa to ∆9-THC, which is a CB1R partial agonist. Understanding the complex interplay of phytomolecules—often referred to as “the entourage effect”—has become a recent and major line of inquiry in cannabinoid research. Additionally, this interest is extending to other non-Cannabis phytomolecules, as the diversity of available Cannabis products grows. Here, we chose to focus on whether 10 phytomolecules (∆8-THC, ∆6a,10a-THC, 11-OH-∆9-THC, cannabinol, curcumin, epigallocatechin gallate, olivetol, palmitoylethanolamide, piperine, and quercetin) alter CB1R-dependent signaling with or without a co-treatment of ∆9-THC. Phytomolecules were screened for their binding to CB1R, inhibition of forskolin-stimulated cAMP accumulation, and βarrestin2 recruitment in Chinese hamster ovary cells stably expressing human CB1R. Select compounds were assessed further for cataleptic, hypothermic, and anti-nociceptive effects on male mice. Our data revealed partial agonist activity for the cannabinoids tested, as well as modulation of ∆9-THC-dependent binding and signaling properties of phytomolecules in vitro and in vivo. These data represent a first step in understanding the complex pharmacology of Cannabis- and non-Cannabis-derived phytomolecules at CB1R and determining whether these interactions may affect the physiological outcomes, adverse effects, and abuse liabilities associated with the use of these compounds.

Dietary crude protein concentrations and L-carnitine inclusions interactively influence performance parameters of grower broiler chickens offered sorghum-based diets

This study investigated the effects of dietary crude protein (CP) and L-carnitine on the performance of broiler chickens offered sorghum-based diets. In a 3 x 3 factorial array of CP concentrations (220, 190, 160 g/kg) and L-carnitine inclusions (0, 75, 150 mg/kg), dietary treatments were offered to 324 off-sex, male Ross 308 broiler chickens from 7 to 33 days post-hatch. Treatment interactions (P < 0.001) were observed for growth performance parameters with 75 and 150 mg/kg L-carnitine inclusions in 160 g/kg CP diets increasing weight gain by up to 15.9 % (1593 versus 1374 g/bird), feed intake by up to 12.4 % (2492 versus 2218 g/bird) and improved FCR by up to 3.16 % (1.564 versus 1.615). In contrast, L-carnitine inclusions in 230 and 190 g/kg CP diets had negligible impacts on growth performance. Reducing dietary CP compromised growth performance and increased relative abdominal fat-pad weights by 44.1 % (11.44 versus 7.94 g/kg) as main effects but L-carnitine did not influence fat-pad weights. The possibility that growth performance responses observed in birds offered 160 g/kg CP diets may be attributed to L-carnitine counteracting the effects of NH3 intoxication which is given consideration because it has been established that L-carnitine is protective against (NH3) toxicity. Reducing dietary CP significantly increased jejunal and ileal digestibility coefficients of the majority of amino acids; whereas, L-carnitine had negative effects. Also, L-carnitine significantly depressed free plasma concentrations of 13 amino acids but increased concentrations of lysine, methionine, valine and glutamine. The possibility that L-carnitine was competing with amino acids for intestinal uptakes is discussed.

The Roles of Emotion Regulation, Alcohol Consumption, and Women’s Condom Request Style in Men’s Coercive Condom Use Resistance Intentions

ABSTRACT Condom use resistance (CUR) remains a significant problem, and many men employ coercive CUR strategies to avoid using condoms with partners who do not consent to unprotected sex. To assess the decision-making process underlying men’s coercive CUR, the present study administered alcohol to assess the effects of alcohol intoxication, condom request style, and emotion regulation (ER) strategies (i.e., cognitive reappraisal, expressive suppression) on intentions to use coercive CUR to have unprotected sex during a hypothetical sexual scenario. Sexually active, male social drinkers (N = 297) were randomly assigned to either consume alcohol or remain sober, and to project themselves into a hypothetical sexual scenario during which they received either indirect, direct, or insistent condom requests. Results showed that, although cognitive reappraisal had no relationship with coercive CUR or unprotected sex intentions, expressive suppression’s relationship with intentions to have unprotected sex was mediated by coercive CUR and moderated by alcohol intoxication and condom request. Specifically, suppression was positively associated with coercive CUR among sober individuals who received an indirect condom request only. Such results suggest that sober men with suppressive tendencies may use coercive CUR to regulate negative emotions, such as frustration at not being able to have unprotected sex.

Development and initial validation of a reliable German self-report measure to assess acute cannabis intoxication-effects (CanTox-17).

ObjectivesBoth positive and negative including psychotic‐like cannabis intoxication effects are well‐established. Yet, consequences for consumption patterns, addictive behavior or psychotic developments are poorly researched in general, in Germany not at all. Thus, objective was to develop the first German‐language questionnaire operationalizing acute cannabis intoxication effects, based on the original “Cannabis Experience Questionnaire” (CEQ).MethodsAfter expert translation of the CEQ, items related to acute intoxication effects were presented to a sample of 537 cannabis users. Four‐ and five‐factorial solutions of explorative factor analysis with a randomly split sub‐sample 1 were cross‐validated by confirmatory factor analysis on sub‐sample 2.ResultsAfter content review of factors and analysis of external validity, a 17 item four‐factorial model was approved. Factors are (1) “paranoia/dysphoria”, (2) “confusion/disorientation”, (3) “euphoria/creativity”, (4) “psychosis‐like/loss of reality”. Model fit is satisfactory (RMSEA = 0.058, SRMR = 0.065, CFI = 0.929, TLI = 0.914). Correlations with corresponding external measures support construct validity.ConclusionsThe present questionnaire is a time‐efficient, valid and reliable instrument. Thus, predictors of different cannabis intoxication effects can be analysed for the first time in German‐speaking area, as well as their significance for substance use or psychosis risk.

Effect of subchronic intoxication with thyram on the activity of antioxidant enzymes and the state of lipoperoxidation processes

AIM: This study aimed to investigate the effect of oxidative stress on the antioxidant defense system and state of lipid peroxidation of the body. MATERIAL AND METHODS: Modeling of oxidative stress was carried out on 240 rats by daily administration of thiram at a dose of 1/50 LD50 (8 mg/kg body weight) in the diet of rats for 4 weeks. The catalytic activity of superoxide dismutase and catalase and the concentration of malondialdehyde and diene conjugates were analyzed. RESULTS: The modeling of subchronic intoxication significantly decreased the activity of catalase and superoxide dismutase (p 0.05) and increased the concentration of malondialdehyde, diene conjugates in blood plasma, erythrocyte mass, and liver homogenate. After experimental subchronic intoxication, antioxidants such as vitamin E at a dose of 8.58 mg/kg and milk thistle extract at a dose of 13.74 mg/kg were used. Using such antioxidants within 30 days had significantly restored the activity of superoxide dismutase and catalase, and it also reduced the concentration of malondialdehyde and diene conjugates in all investigated body media. CONCLUSION: Fungicide intoxication with thiram affects redox homeostasis. In addition, the usage of vitamin E and milk thistle extract can restore the prooxidantantioxidant balance of the body.

Intoxication and pitch control in tonal and non-tonal language speakers

Alcohol intoxication is known to affect pitch variability in non-tonal languages. In this study, intoxication's effects on pitch were examined in tonal and non-tonal language speakers, in both their native language (L1; German, Korean, Mandarin) and nonnative language (L2; English). Intoxication significantly increased pitch variability in the German group (in L1 and L2), but not in the Korean or Mandarin groups (in L1 or L2), although there were individual differences. These results support the view that pitch control is related to the functional load of pitch and is an aspect of speech production that can be advantageously transferred across languages, overriding the expected effects of alcohol.

Understanding the Evidence for Medical Cannabinoids for the Treatment of Chronic Pain

This paper is an examination of the existing literature on the use of medical cannabinoids for the treatment of adults with chronic pain (CP). The use of medical cannabinoids in the treatment of CP has been a controversial topic due to societal associations with the recreational use of cannabis and the lack of information as to their analgesic effects. This paper analyzes trends in how medical cannabinoids perform as an analgesic treatment for adults with CP, especially in comparison to opioids. Additionally, this paper explores any secondary effects participants may experience as a result of treatment with medical cannabinoids. It will be shown that, while medical cannabinoids have the potential to reduce pain in those suffering from CP, there are numerous factors that must be considered before they become an acceptable treatment option. In addition, there is evidence that the analgesic effects of medical cannabinoids may be primarily due to their intoxicating effect rather than their interaction with neural pain pathways. This review of existing literature acts to guide future research on the use of medical cannabinoids for the treatment of CP.

Increase in Serum MMP-9 and TIMP-1 Concentrations during Alcohol Intoxication in Adolescents-A Preliminary Study.

Background: Alcohol consumption by adolescents is responsible for a number of adverse health and social outcomes. Despite the well-established effect of alcohol use on the development of alcoholic liver disease, the relationship between the pattern of alcohol consumption and liver fibrosis is still unclear. This study is a follow-up to work on liver damage from alcohol intoxication. The aim of our study was to explore the early effects of alcohol intoxication on liver fibrosis in adolescents. Methods: The prospective study included 57 adolescents aged 14–17 years admitted to the emergency department (ED) from February 2017 to June 2018 due to acute alcohol intoxication. Serum levels of amino terminal propeptide of type III procollagen (PIIINP), type IV collagen, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were determined by enzyme-linked immunosorbent assays. Results: There were significant differences in MMP-9 (p = 0.02) and TIMP-1 (p = 0.007) levels between the study and control groups. Liver parameters and selected markers of fibrosis were similar in groups in terms of blood alcohol concentrations (BAC). MMP-9 was positively correlated with alanine aminotransferase (ALT) (r = 0.38; p = 0.004) and total bilirubin (r = 0.39; p = 0.004). Positive significant correlations were also found between TIMP-1 and ALT (r = 0.47; p < 0.001), AST (r = 0.29; p = 0.03) and total bilirubin (r = 0.32; p = 0.02). In receiver operating characteristic (ROC) analysis, MMP-9 (AUC = 0.67, p = 0.02) and TIMP-1 (AUC = 0.69, p = 0.003) allowed for the differentiation of patients with and without alcohol intoxication. Conclusion: Our results show that even a single episode of alcohol intoxication in adolescents can lead to imbalance in markers of fibrosis.

Playing the Petrocene: Toxicity and Intoxication in Leigh Fondakowski’s Spill and Ella Hickson’s Oil

Abstract Ella Hickson’s Oil (2016) and Leigh Fondakowski’s Spill (2014) make palpable to their audiences what I call the Petrocene: the age in which human existence has become impossible to conceive without oil. Each play illuminates the pervasive presence of petroleum infrastructures in its own way: while Spill focuses on the specific and sensational crisis of the BP oil spill in the Gulf of Mexico in 2010, Oil presents a series of scenes which focus on two women (mother and daughter) who struggle to carve out their existence in various time periods and in the context of different fossil-energy regimes. Both plays succeed in unveiling not only the toxicity of extractive regimes necessary to fuel the Petrocene, but also the toxicity of the narratives that uphold extractive regimes and their attendant injustices. Moreover, both plays convey the intoxicating effects of oil, which appears as a near-magical substance that promises unfettered progress and access to the good life. Examining these plays in conjunction not only highlights the increasing presence of ecological concerns in dramatic pieces, but also illustrates the ways in which dramatic performance can distill enormous oil infrastructures into apprehensible worlds and thus create vital spaces for pondering the Petrocene.

Diisopropylfluorophosphate (DFP) volatizes and cross-contaminates wells in a common 96-well plate format used in zebrafish larvae toxicology studies

Diisopropylfluorophosphate (DFP) is an organophosphate (OP) that is commonly used as a surrogate of OP nerve agents to study the neurotoxic effects of acute OP intoxication. In preliminary studies, we discovered abnormally high incidence of deaths in DMSO control zebrafish larvae housed in the same 96-well plate as DFP-exposed larvae and hypothesized that DFP volatilizes and cross-contaminates wells when using static waterborne exposures. Survivability and acetylcholinesterase activity assays were indicative of the presence of DFP in the tissues of zebrafish ostensibly exposed to DMSO only. These findings are consistent with DFP cross-contamination, which raises concerns for the experimental design of studies evaluating the toxicity of volatile and semi-volatile substances in zebrafish using medium-to-high throughput approaches.

Educational/Professional Partnership in the Development of a Novel Strain of S‐11 Saccharomyces cerevisiae Brewing Yeast

Craft beers have revolutionized the beer industry. In 2018, the craft beer market made up 20% of the sales of beer in the United States, totaling over 26 billion dollars and experiencing significant growth during a period when many traditional breweries are reporting losses or shrinkage in their market values (Gaille, 2019). Survival in an increasingly competitive market is reliant on the ability to develop novel products that match the ever‐evolving tastes of consumers. I worked with the Three Roads Brewing Company of Farmville and Lynchburg, Virginia to meet this goal using molecular biology. My institution has a preexisting relationship with Three Roads Brewery, as my research advisor has been doing similar but less intensive projects to teach students about the fundamentals of genetic engineering. The Brewmaster uses a strain of baker’s yeast (Saccharomyces cerevisiae) called S‐11 to generate a French Saison beer, a highly carbonated pale ale. My research worked to modify the S‐11 strain to generate a French Saison beer that lacks fusel alcohols while still maintaining the complex flavor profile of the rest of the beer. Because fusel alcohols are “key contributors to the intoxicating effect [of alcohol products],” this request is very common in the brewing community (Xie 2018). By removing these fusel alcohols, the Brewmaster will have a product that he feels will be more enjoyable for his consumers to drink. During the fermentation process, fusel alcohols are produced through a process called the Ehrlich pathway, which is normally responsible for the catabolism of amino acids. There is a key divergence point within the Ehrlich pathway that is especially relevant to brewers during which the fusel aldehyde is either oxidized into a fusel alcohol or reduced into a fusel acid (Hazelwood, 2008). Using molecular genetics to disrupt key genes in this pathway, I eliminated relevant proteins, including ADH1, ADH2, ADH3, ADH4, ADH6, and AAD4 in this process to force reduction as opposed to oxidation, and thereby decrease the production of fusel alcohols. Two strains, S11‐ΔAAD4 and S11‐ΔADH4 produced fewer in fusel alcohols, a 104% and 87% decrease respectively. The Southside region of Virginia in which the brewery is located is one of the most historically disenfranchised regions of the state, and by generating a strain of yeast that better satisfies the needs of local businesses, my lab was able to make a tangible impact in the support of the long‐term high‐paying jobs generated by local businesses such as Three Roads Brewing Company.

The Relationship Between Circulating Endogenous Cannabinoids and the Effects of Smoked Cannabis.

Background: The endogenous cannabinoid system (ECS), including the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), plays an integral role in psychophysiological functions. Although frequent cannabis use is associated with adaptations in the ECS, the impact of acute smoked cannabis administration on circulating eCBs, and the relationship between cannabis effects and circulating eCBs are poorly understood. Methods: This study measured the plasma levels of AEA, 2-AG, and Δ-9-tetrahydrocannabinol (THC), subjective drug-effects ratings, and cardiovascular measures at baseline and 15-180 min after cannabis users (n=26) smoked 70% of a cannabis cigarette (5.6% THC). Results: Cannabis administration increased the ratings of intoxication, heart rate, and plasma THC levels relative to baseline. Although cannabis administration did not affect eCB levels relative to baseline, there was a significant positive correlation between baseline AEA levels and peak ratings of "High" and "Good Drug Effect." Further, baseline 2-AG levels negatively correlated with frequency of cannabis use (mean days/week) and with baseline THC metabolite levels. Conclusions: In a subset of heavy cannabis smokers: (1) more frequent cannabis use was associated with lower baseline 2-AG, and (2) those with lower AEA got less intoxicated after smoking cannabis. These findings contribute to a sparse literature on the interaction between endo- and phyto-cannabinoids. Future studies in participants with varied cannabis use patterns are needed to clarify the association between circulating eCBs and the abuse-related effects of cannabis, and to test whether baseline eCBs predict the intoxicating effects of cannabis and are a potential biomarker of cannabis tolerance.

From Ancient Hatei to Hubris Syndrome in SARS-CoV-2 Health Crisis Management.

COVID-19 pandemic has highlighted, in a very inflictive way, the need for less hubristic political leadership, revealing the menaces of arrogant decision making of those in power. Hubris Syndrome is associated with power and it is more likely to manifest itself the longer the person exercises power and the greater the power he exercises, while our modern times 'Hatei' (the goddess that blinded ancient leaders committing hubris) may be called positive illusion enhancement due to prolonged exposure to power. Hatei might also blurs the decision makers' vision through a hormonal pathway, since hormones seem to affect risk taking, as well as through serotonin, which is also involved in the regulation of decision making and processing punishment-related information, deficiencies of which could be relevant to Hubris Syndrome. Other findings may provide information regarding the neuro-anatomical 'location' of Hatei, since fronto-striatal and limbic-striatal dopaminergic pathways have been identified as important regulators of impulsive behaviors. Therefore we might consider choosing political leaders and state officials whose less illusionary character is more likely to become non-flammable against the fire of hubris, in periods of crisis like the current COVID-19 Pandemic. Especially in SARS-CoV-2 era we should bring whatever scientific data there may be to tackle the intoxicating effects of power, keeping also in mind that there are no anti-hubris medication and that it is unlikely to have this social construct improved via pharmacology. Before establishing constitutional procedures for the early diagnosis of hubris as well as for the subsequent constrain of our leaders' power, we should focus on the criteria by which we elect them and maybe include the pre-existence of depressive diathesis among those criteria, especially if we consider that those leaders might have to handle tough situations like the COVID-19 pandemic outbreak, that require increased empathy in decision making.

Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population.

A strong predictor for the development of alcohol use disorder (AUD) is altered sensitivity to the intoxicating effects of alcohol. Individual differences in the initial sensitivity to alcohol are controlled in part by genetic factors. Mice offer a powerful tool to elucidate the genetic basis of behavioral and physiological traits relevant to AUD, but conventional experimental crosses have only been able to identify large chromosomal regions rather than specific genes. Genetically diverse, highly recombinant mouse populations make it possible to observe a wider range of phenotypic variation, offer greater mapping precision, and thus increase the potential for efficient gene identification. We have taken advantage of the Diversity Outbred (DO) mouse population to identify and precisely map quantitative trait loci (QTL) associated with ethanol sensitivity. We phenotyped 798male J:DO mice for three measures of ethanol sensitivity: ataxia, hypothermia, and loss of the righting response. We used high-density MegaMUGA and GigaMUGA to obtain genotypes ranging from 77,808 to 143,259 SNPs. We also performed RNA sequencing in striatum to map expression QTLs and identify gene expression-trait correlations. We then applied a systems genetic strategy to identify narrow QTLs and construct the network of correlations that exists between DNA sequence, gene expression values, and ethanol-related phenotypes to prioritize our list of positional candidate genes. We observed large amounts of phenotypic variation with the DO population and identified suggestive and significant QTLs associated with ethanol sensitivity on chromosomes 1, 2, and 16. The implicated regions were narrow (4.5-6.9 Mb in size) and each QTL explained ~4-5% of the variance. Our results can be used to identify alleles that contribute to AUD in humans, elucidate causative biological mechanisms, or assist in the development of novel therapeutic interventions.

Changes in the Cardiotoxic Effects of Lead Intoxication in Rats Induced by Muscular Exercise.

Exposure to lead is associated with an increased risk of cardiovascular diseases. Outbred white male rats were injected with lead acetate intraperitoneally three times a week and/or were forced to run at a speed of 25 m/min for 10 min 5 days a week. We performed noninvasive recording of arterial pressure, electrocardiogram and breathing parameters, and assessed some biochemical characteristics. Electrophoresis in polyacrylamide gel was used to determine the ratio of myosin heavy chains. An in vitro motility assay was employed to measure the sliding velocity of regulated thin filaments on myosin. Isolated multicellular preparations of the right ventricle myocardium were used to study contractility in isometric and physiological modes of contraction. Exercise under lead intoxication normalized the level of calcium and activity of the angiotensin-converting enzyme in the blood serum, normalized the isoelectric line voltage and T-wave amplitude on the electrocardiogram, increased the level of creatine kinase-MB and reduced the inspiratory rate. Additionally, the maximum sliding velocity and the myosin heavy chain ratio were partly normalized. The effect of exercise under lead intoxication on myocardial contractility was found to be variable. In toto, muscular loading was found to attenuate the effects of lead intoxication, as judged by the indicators of the cardiovascular system.

Effects of Alcohol Intoxication on Sexual Decision-Making among Men Who Have Sex with Men (MSM): Alcohol's Influences on Self-Control Processes.

This experiment tested mechanisms linking alcohol intoxication and analogue determinants of condomless anal intercourse (CAI) in a sample of 257 men who have sex with men (MSM). The two mechanisms tested were implicit approach biases toward CAI stimuli and executive working memory. Participants were randomized to 3 conditions (water control, placebo, or alcohol) and following beverage administration completed a working memory task, an Approach Avoidance Task of sexual vs. condom stimuli, and two video role-play vignettes of high-risk sexual scenarios. Sexual arousal and CAI intentions were assessed by self-report, and behavioral skills and risk exposure were derived from participants' role-play behavior. Estimation of four path models showed that the hypothesized mechanisms were supported for the CAI intention outcome, but the findings for the skills and risk exposure outcome were mixed. Implications for development and enhancement of HIV prevention interventions were discussed.