Alcoholism, clinical and experimental research最新文献

{"title":"Discriminative Stimulus Effects and Metabolism of Ethanol in Rhesus Monkeys.","authors":"Daicia C Allen, Kathleen A Grant","doi":"10.1111/acer.14142","DOIUrl":"10.1111/acer.14142","url":null,"abstract":"<p><strong>Background: </strong>Animal models are an essential feature of drug and pharmacotherapy development for treating alcohol use disorders (AUDs). The rhesus macaque is a robust animal model for many aspects of AUDs particularly in exploiting individual differences in oral self-administration of ethanol (EtOH), endocrine orchestration of stress response, and menstrual cycle characteristics. However, the clearance rates of EtOH have not been reported in this species, and the GABA_A and N-methyl-D-aspartate (NMDA) receptor involvement in EtOH's discriminative stimulus effects has not been fully characterized.</p><p><strong>Methods: </strong>EtOH clearance rates following 2 doses of EtOH on separate days (0.5 and 1.0 g/kg, i.g.) were determined in 8 young adult male rhesus macaques. The EtOH was given by nasogastric gavage, and repeated blood samples were taken over 5 hours without sedation. Next, all subjects were trained on a 2-choice 1.0 g/kg EtOH (i.g.) versus water discrimination with a 60-minutes pretreatment period to capture peak blood EtOH concentration (BEC). Substitution testing was conducted with GABA_A ligands pentobarbital (i.g. and i.m.) and midazolam (i.g.), as well as NMDA antagonist MK-801 (i.m.).</p><p><strong>Results: </strong>Peak BECs were 34 and 87 mg/dl for 0.5 and 1.0 g/kg doses, respectively, and occurred at 66 and 87 minutes following gavage. All GABA_A and NMDA ligands tested resulted in responding on the EtOH-appropriate lever with the potency ranking of MK-801 (ED₅₀ : 0.017 mg/kg) > midazolam (ED₅₀ : 1.6 mg/kg) > pentobarbital (ED₅₀ : 3.7 mg/kg) > EtOH (ED₅₀ : 700 mg/kg, or 0.7 g/kg) in these subjects.</p><p><strong>Conclusions: </strong>These results suggest that the compound discriminative stimulus effects of EtOH are highly consistent across species, providing further support for the rhesus macaque as strong model for pharmacotherapy development for AUD.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"43 9","pages":"1909-1917"},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721990/pdf/nihms-1038079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37363402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergent Evidence From Humans and Drosophila melanogaster Implicates the Transcription Factor MEF2B/Mef2 in Alcohol Sensitivity.","authors":"Rebecca E Schmitt, Brandon C Shell, Kristen M Lee, Keith L Shelton, Laura D Mathies, Alexis C Edwards, Mike Grotewiel","doi":"10.1111/acer.14138","DOIUrl":"10.1111/acer.14138","url":null,"abstract":"<p><strong>Background: </strong>Self-Rating of the Effects of Alcohol (SRE) measures level of response to ethanol (EtOH) in humans. Interestingly, there is a positive relationship between the SRE and risk for abusing alcohol, suggesting mechanistic connections between SRE and alcohol abuse.</p><p><strong>Methods: </strong>To identify candidate genes with a role in SRE and alcohol-related behavior more generally, we coupled human genetic analyses with studies in Drosophila melanogaster. We first performed a gene-based analysis of Genomewide association studies (GWAS) summary statistics for SRE in the Avon Longitudinal Study of Parents and Children sample. Based on prior findings in humans, orthology to fly genes, and the availability of genetic reagents, we selected a subset of these genes for studies on EtOH behavior in Drosophila.</p><p><strong>Results: </strong>We found 37 genes with nominal associations in our SRE GWAS. We explored the role of 6 orthologous genes in Drosophila EtOH sedation and rapid tolerance. We found that the transcription factor Mef2 is required for normal EtOH sedation in flies. Pan-neuronal expression of 2 independent Mef2 RNAi transgenes significantly reduced Mef2 expression and made flies resistant to EtOH sedation. Additionally, flies with multiple independent mutant alleles of Mef2 were also resistant to EtOH sedation, confirming a role for Mef2 in this behavior. Altered expression of Mef2 did not change EtOH rapid tolerance or cause a net change in internal EtOH concentrations.</p><p><strong>Conclusions: </strong>Our studies indicate that MEF2B influences SRE in humans and that Mef2 impacts EtOH sedation in Drosophila.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"43 9","pages":"1872-1886"},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721962/pdf/nihms-1038089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37090786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol Effects on Colon Epithelium are Time-Dependent.","authors":"Faraz Bishehsari, Lijuan Zhang, Robin M Voigt, Natalie Maltby, Bita Semsarieh, Eyas Zorub, Maliha Shaikh, Sherry Wilber, Andrew R Armstrong, Seyed Sina Mirbagheri, Nailliw Z Preite, Peter Song, Alessia Stornetta, Silvia Balbo, Christopher B Forsyth, Ali Keshavarzian","doi":"10.1111/acer.14141","DOIUrl":"10.1111/acer.14141","url":null,"abstract":"<p><strong>Background: </strong>Alcohol intake increases the risk of developing colon cancer. Circadian disruption promotes alcohol's effect on colon carcinogenesis through unknown mechanisms. Alcohol's metabolites induce DNA damage, an early step in carcinogenesis. We assessed the effect of time of alcohol consumption on markers of tissue damage in the colonic epithelium.</p><p><strong>Methods: </strong>Mice were treated by alcohol or phosphate-buffered saline (PBS), at 4-hour intervals for 3 days, and their colons were analyzed for (i) proliferation (Ki67) and antiapoptosis (Bcl-2) markers, (ii) DNA damage (γ-H2AX), and (iii) the major acetaldehyde (AcH)-DNA adduct, N² -ethylidene-dG. To model circadian disruption, mice were shifted once weekly for 12 h and then were sacrificed at 4-hour intervals. Samples of mice with a dysfunctional molecular clock were analyzed. The dynamics of DNA damage repair from AcH treatment as well as role of xeroderma pigmentosum, complementation group A (XPA) in their repair were studied in vitro.</p><p><strong>Results: </strong>Proliferation and survival of colonic epithelium have daily rhythmicity. Alcohol induced colonic epithelium proliferation in a time-dependent manner, with a stronger effect during the light/rest period. Alcohol-associated DNA damage also occurred more when alcohol was given at light. Levels of DNA adduct did not vary by time, suggesting rather lower repair efficiency during the light versus dark. XPA gene expression, a key excision repair gene, was time-dependent, peaking at the beginning of the dark. XPA knockout colon epithelial cells were inefficient in repair of the DNA damage induced by alcohol's metabolite.</p><p><strong>Conclusions: </strong>Time of day of alcohol intake may be an important determinant of colon tissue damage and carcinogenicity.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"43 9","pages":"1898-1908"},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722020/pdf/nihms-1038080.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37363401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte-Neuron Lactate Shuttle in the Brain.","authors":"Daniel Lindberg,&nbsp;Ada Man Choi Ho,&nbsp;Lee Peyton,&nbsp;Doo-Sup Choi","doi":"10.1111/acer.14137","DOIUrl":"10.1111/acer.14137","url":null,"abstract":"<p><strong>Background: </strong>Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones.</p><p><strong>Methods: </strong>We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs.</p><p><strong>Results: </strong>Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs.</p><p><strong>Conclusion: </strong>CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"43 9","pages":"1838-1847"},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.14137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37367320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social and Situational Party Characteristics Associated With High-Intensity Alcohol Use Among Youth and Young Adults.","authors":"Melissa J Cox,&nbsp;Kathleen L Egan,&nbsp;Cynthia K Suerken,&nbsp;Beth A Reboussin,&nbsp;Eunyoung Y Song,&nbsp;Kimberly G Wagoner,&nbsp;Mark Wolfson","doi":"10.1111/acer.14143","DOIUrl":"https://doi.org/10.1111/acer.14143","url":null,"abstract":"<p><strong>Background: </strong>Rates of high-intensity drinking, which is alcohol consumption that exceeds standard heavy drinking levels, have increased in recent years and peak in young adulthood. To identify modifiable environmental targets for prevention of high-intensity drinking, we identified characteristics of parties attended by youth and young adults that were associated with high-intensity drinking and the consequences of this excessive form of drinking.</p><p><strong>Methods: </strong>Data are from 15- to 20-year-old participants in an online survey (n = 2,442; 55.4% female, 74.8% White) who resided in 24 communities across 7 states that were a part of a community randomized intervention trial to reduce the incidence and consequences of underage drinking parties. We used multinomial logistic regression to predict level of drinking by 6 party characteristics (size, location, age and gender composition, supervision, others' drinking behavior), and to predict 6 consequences (hangover, not remember event, passed out, punished by parents, broke something/got in fight, and sex against will) from level of drinking. We tested study hypotheses in 2 models, one that used a single binge drinking threshold (below binge vs. at or above binge level) and one that additionally used a high-intensity drinking level (below binge, 1 to 2 times binge, 2+ times binge level).</p><p><strong>Results: </strong>We found that larger party size and a mostly male composition were unique predictors of high-intensity drinking when compared to those who consumed 1 to 2 times the binge drinking level. Odds of passing out, not remembering the drinking event, breaking/damaging property, or getting in a fight were more than double for high-intensity drinkers compared to standard binge level drinkers.</p><p><strong>Conclusions: </strong>Results from this study indicate there are unique precursors and consequences of high-intensity alcohol consumption among youth and young adults. These environmental factors associated with high-risk drinking contexts can be used to develop prevention strategies to mitigate the harms associated with excessive alcohol consumption.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"43 9","pages":"1957-1966"},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.14143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Drinking and Cortical Thickness in Younger Adult Drinkers: Findings From the Human Connectome Project.","authors":"Vanessa L Morris, Max M Owens, Sabrina K Syan, Tashia D Petker, Lawrence H Sweet, Assaf Oshri, James MacKillop, Michael Amlung","doi":"10.1111/acer.14147","DOIUrl":"10.1111/acer.14147","url":null,"abstract":"<p><strong>Background: </strong>Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences.</p><p><strong>Methods: </strong>This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; M_age  = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting).</p><p><strong>Results: </strong>Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men.</p><p><strong>Conclusions: </strong>This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":" ","pages":"1918-1927"},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721970/pdf/nihms-1040196.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40451511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized Clinical Trial Examining Cognitive Behavioral Therapy for Individuals With a First-Time DUI Offense.","authors":"K. Osilla, S. Paddock, Colleen M. McCullough, Lisa Jonsson, K. Watkins","doi":"10.1111/acer.14161","DOIUrl":"https://doi.org/10.1111/acer.14161","url":null,"abstract":"BACKGROUND\u0000Driving under the influence (DUI) programs are a unique setting to reduce disparities in treatment access to those who may not otherwise access treatment. Providing evidence-based therapy in these programs may help prevent DUI recidivism.\u0000\u0000\u0000METHODS\u0000We conducted a randomized clinical trial of 312 participants enrolled in 1 of 3 DUI programs in California. Participants were 21 and older with a first-time DUI offense who screened positive for at-risk drinking in the past year. Participants were randomly assigned to a 12-session manualized cognitive behavioral therapy (CBT) or usual care (UC) group and then surveyed 4 and 10 months later. We conducted intent-to-treat analyses to test the hypothesis that participants receiving CBT would report reduced impaired driving, alcohol consumption (drinks per week, abstinence, and binge drinking), and alcohol-related negative consequences. We also explored whether race/ethnicity and gender moderated CBT findings.\u0000\u0000\u0000RESULTS\u0000Participants were 72.3% male and 51.7% Hispanic, with an average age of 33.2 (SD = 12.4). Relative to UC, participants receiving CBT had lower odds of driving after drinking at the 4- and 10-month follow-ups compared to participants receiving UC (odds ratio [OR] = 0.37, p = 0.032, and OR = 0.29, p = 0.065, respectively). This intervention effect was more pronounced for females at 10-month follow-up. The remaining 4 outcomes did not significantly differ between UC versus CBT at 4- and 10-month follow-ups. Participants in both UC and CBT reported significant within-group reductions in 2 of 5 outcomes, binge drinking and alcohol-related consequences, at 10-month follow-up (p < 0.001).\u0000\u0000\u0000CONCLUSIONS\u0000In the short-term, individuals receiving CBT reported significantly lower rates of repeated DUI than individuals receiving UC, which may suggest that learning cognitive behavioral strategies to prevent impaired driving may be useful in achieving short-term reductions in impaired driving.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"21 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2019-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78116244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic administration of the cyclin-dependent kinase inhibitor (S)-CR8 selectively reduces escalated ethanol intake in dependent rats.","authors":"S. P. Goulding, G. de Guglielmo, L. Carrette, O. George, C. Contet","doi":"10.1111/acer.14177","DOIUrl":"https://doi.org/10.1111/acer.14177","url":null,"abstract":"BACKGROUND\u0000Chronic exposure to ethanol and other drugs of abuse can alter the expression and activity of cyclin-dependent kinase 5 (CDK5) and its cofactor p35, but the functional implication of CDK5 signaling in the regulation of ethanol-related behaviors remains unknown. In the present study, we sought to determine whether CDK5 activity plays a role in the escalation of ethanol self-administration triggered by dependence.\u0000\u0000\u0000METHODS\u0000We tested the effect of systemically administered (S)-CR8, a non-selective CDK inhibitor, on operant responding for ethanol or saccharin, a highly palatable reinforcer, in adult male Wistar rats. Half of the rats were made ethanol-dependent via chronic intermittent ethanol inhalation (CIE). We then sought to identify a possible neuroanatomical locus for the behavioral effect of (S)-CR8 by quantifying protein levels of CDK5 and p35 in subregions of the extended amygdala and prefrontal cortex from ethanol-naïve, non-dependent, and dependent rats at the expected time of ethanol self-administration. We also analyzed the phosphorylation of four CDK5 substrates and of the CDK substrate consensus motif.\u0000\u0000\u0000RESULTS\u0000(S)-CR8 dose-dependently reduced ethanol self-administration in dependent rats. It had no effect on water or saccharin self-administration, nor in non-dependent rats. The abundance of CDK5 or p35 was not altered in any of the brain regions analyzed. In the bed nucleus of the stria terminalis, CDK5 abundance was negatively correlated with intoxication levels during ethanol vapor exposure but there was no effect of dependence on the phosphorylation ratio of CDK5 substrates. In contrast, ethanol dependence increased the phosphorylation of low-molecular weight CDK substrates in the basolateral amygdala.\u0000\u0000\u0000CONCLUSIONS\u0000The selective effect of (S)-CR8 on excessive ethanol intake has potential therapeutic value for the treatment of alcohol use disorders. Our data do not support the hypothesis that this effect would be mediated by the inhibition of upregulated CDK5 activity in the extended amygdala nor prefrontal cortex. However, increased activity of CDKs other than CDK5 in the basolateral amygdala may contribute to excessive ethanol consumption in alcohol dependence. Other (S)-CR8 targets may also be implicated. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"26 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2019-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81501510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic alcohol consumption, but not acute intoxication, decreases in vitro skeletal muscle contractile function.","authors":"K. Crowell, L. Laufenberg, C. Lang","doi":"10.1111/acer.14179","DOIUrl":"https://doi.org/10.1111/acer.14179","url":null,"abstract":"BACKGROUND\u0000Skeletal muscle myopathy accompanying chronic alcohol misuse results in part from a decrease in protein synthesis typically observed in type II-rich muscles that leads to muscle weakness. However, there are a paucity of studies investigating whether the alcohol-induced weakness is intrinsic to the muscle or results primarily from the loss of muscle mass. The present study determines whether acute alcohol (ethanol) intoxication or chronic alcohol consumption decreases the intrinsic contractile function of muscle.\u0000\u0000\u0000METHODS\u0000Adult male mice were randomly assigned to the chronic alcohol group or given a binge dose of alcohol, and contractile characteristics of the extensor digitorum longus (EDL) determined in vitro.\u0000\u0000\u0000RESULTS\u0000The weight and physiological cross-sectional area (PCSA) of the EDL were decreased in alcohol-fed mice. Maximum twitch and tetanic tension were also reduced, and there was a downward shift of the absolute force-frequency curve in alcohol-fed mice. However, no alcohol-induced changes were noted when these contractile parameters were normalized for the lower PCSA. Alcohol-fed mice demonstrated greater fatigability, and alcohol-induced decreases in post-fatigue specific twitch and tetanic force were independent of a decreased PCSA. Furthermore, post-fatigue recovery of muscle force over time was reduced. While alcohol did not alter the content of high-energy phosphates or oxidative phosphorylation complexes I-V, it did reduce myosin heavy chain and troponin-T content. In contrast, contractile properties were not altered when examined 2 hours after binge alcohol.\u0000\u0000\u0000CONCLUSION\u0000These data demonstrate chronic alcohol consumption decreases isometric and tetanic tension development due to a reduction in muscle CSA, whereas the increased fatigability observed was independent of muscle mass. As none of the functional changes were produced by acute alcohol, which produced higher blood alcohol levels than chronic ingestion, our data suggest defects in intrinsic muscle contractility require sustained intake and appear independent of defects in basal energy production.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"26 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2019-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82813669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-Year Incidence of Hospital-Based Emergencies Related to Acute Recreational Intoxication in Minors.","authors":"A. Sanvisens, Irina Sanjeevan, P. Zuluaga, Adrià Túnez, A. de Francisco, E. Papaseit, L. García-Eroles, R. Muga","doi":"10.1111/acer.14166","DOIUrl":"https://doi.org/10.1111/acer.14166","url":null,"abstract":"BACKGROUND\u0000Alcohol or other drug (AOD) intoxication in minors is a public health challenge. We characterized underage patients admitted to an emergency department (ED) with acute, recreational AOD intoxication.\u0000\u0000\u0000METHODS\u0000We conducted a 5-year (2012 to 2016) analysis of minors admitted to the only hospital-based pediatric ED in an urban area. Episodes of AOD intoxication were selected using ICD-9-CM diagnostic codes. Sociodemographics, substance use and clinical characteristics, laboratory parameters, and discharge dispositions were collected through the revision of clinical charts.\u0000\u0000\u0000RESULTS\u0000A total of 266 admissions related to recreational AOD intoxication in 258 patients occurred during the study period. Among the 258 patients, 127 (49.2%) were men, median age 16 years [IQR: 15 to 17 years], and 234 (90.7%) of episodes were alcohol-related. At admission, 202/256 (78.9%) patients had a Glasgow Coma Scale ≥ 13 points, the median systolic and diastolic blood pressure was 109 mmHg (IQR: 101 to 118 mmHg) and 67 mmHg (IQR: 60 to 73 mmHg), respectively, and the median blood glucose level was 112 mg/dl (IQR: 99 to 127 mg/dl). Only 72/258 (27.9%) patients underwent urine screening (22/72 (30.5%) were positive for cannabis), and only 30/258 (11.6%) were tested for blood ethanol (median: 185 mg/dl, IQR: 163 to 240 mg/dl). There was a trend in admissions occurring early in the morning of weekend days, and 249 (96.5%) patients were discharged home the day of admission.\u0000\u0000\u0000CONCLUSIONS\u0000Though the severity of AOD intoxication seems to be mild to moderate, assessment of substance exposure is low and may underestimate polydrug use in underage populations.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":"77 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81187693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}