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Showing 1 - 200 of 3089 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 7)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 25, SJR: 1.402, h-index: 51)
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Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 363, SJR: 0.726, h-index: 43)
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Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 133, SJR: 5.2, h-index: 222)
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Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
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Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
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Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
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Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 331, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 8, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 417, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
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Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 40, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 55, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
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Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 46, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 49, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 48, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 40, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 9, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 46, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 199, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 59, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 25, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 35, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
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Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 12)
Anales de Cirugia Vascular     Full-text available via subscription  
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Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 167, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
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Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
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Angiologia e Cirurgia Vascular     Open Access  

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Journal Cover Alcohol
  [SJR: 0.922]   [H-I: 66]   [11 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0741-8329
   Published by Elsevier Homepage  [3049 journals]
  • Increased risk of peripheral arterial disease in patients with alcohol
           intoxication: A population-based retrospective cohort study
    • Authors: Jin-Yuan Huang; Wei-Kung Chen; Cheng-Li Lin; Ching-Yuan Lai; Chia-Hung Kao; Tse-Yen Yang
      Pages: 25 - 30
      Abstract: Publication date: December 2017
      Source:Alcohol, Volume 65
      Author(s): Jin-Yuan Huang, Wei-Kung Chen, Cheng-Li Lin, Ching-Yuan Lai, Chia-Hung Kao, Tse-Yen Yang
      Previous studies have reported that light-to-moderate drinkers have a lower risk of peripheral arterial disease (PAD) than abstainers, and that heavy drinking increases the risk of PAD. However, reports of the effects of severe alcohol drinking on PAD are lacking within a population-based cohort. Alcohol intoxication is typically considered a medical emergency at clinics in Taiwan and is commonly attributed to excessive alcohol use. The present study aimed to investigate the association between alcohol intoxication and PAD risk. We conducted a retrospective, population-based, health insurance cohort study consisting of 56,544 adult patients with alcohol intoxication between January 1, 2000 and December 31, 2009, using claims data from the National Health Insurance Research Database (NHIRD) of Taiwan. This database included a control cohort of 226,176 residents without alcohol intoxication. The patients were age- and gender-matched. The incidence rate of PAD, after data regarding alcohol intoxication were obtained, was 12.8 per 10,000 person-years, and the adjusted hazard ratio (aHR) of PAD was 3.80 (95% confidence interval [CI] = 3.35–4.32, p < 0.05). The log-rank test showed that patients with alcohol intoxication had a considerably higher PAD cumulative incidence rate than those without alcohol intoxication. Alcohol intoxication was significantly associated with an increased risk of PAD in men (hazard ratio [HR] = 3.77, 95% CI = 3.30–4.31) and women (HR = 4.26, 95% CI = 2.60–6.97). The aHRs of PAD risk were 7.64 (95% CI = 4.39–13.3), 4.51 (95% CI = 3.83–5.29), and 2.16 (95% CI = 1.69–2.77) for patients with alcohol intoxication compared to participants of the control group aged <35 years, 35–64 years, and ≥65 years, respectively. The individuals with alcohol intoxication and without any comorbidities had a 3.77-fold increased risk of PAD in comparison to that of the control cohorts (HR = 3.77, 95% CI = 3.30–4.30). The aHR of PAD in patients with alcohol intoxication was 4.53 (95% CI = 2.51–8.16) in comparison to the control cohort, which consisted of patients with at least one existing comorbidity. Alcohol intoxication, along with the severe complications of excessive alcohol use, should be considered as major risk factors of PAD in the setting of a medical emergency. Further research needs to be performed to evaluate the quantitative effect of alcohol use on PAD.

      PubDate: 2017-11-11T12:34:57Z
      DOI: 10.1016/j.alcohol.2017.06.003
      Issue No: Vol. 65 (2017)
  • Acute ethanol intoxication suppresses pentraxin 3 expression in a mouse
           sepsis model involving cecal ligation and puncture
    • Authors: Shogo Kasuda; Risa Kudo; Katsuya Yuui; Yoshihiko Sakurai; Katsuhiko Hatake
      Pages: 1 - 9
      Abstract: Publication date: November 2017
      Source:Alcohol, Volume 64
      Author(s): Shogo Kasuda, Risa Kudo, Katsuya Yuui, Yoshihiko Sakurai, Katsuhiko Hatake
      Acute ethanol intoxication impairs immunological reactions and increases the risk of sepsis; however, the underlying mechanism remains unclear. Pentraxin (PTX) 3 is a humoral pattern recognition receptor whose levels rapidly increase in response to inflammation. PTX3 production is triggered by tumor necrosis factor (TNF)-α and is mediated by c-Jun N-terminal kinase (JNK). As PTX3 exerts protective effects against sepsis as well as acute lung injury, we investigated whether acute ethanol exposure exacerbates sepsis by altering PTX3 expression. Sepsis was induced in C57/BL6 mice by cecal ligation and puncture (CLP) after ethanol/saline administration. Survival rates were significantly lower in ethanol-treated than in saline-treated mice. Increased vascular permeability and attenuation of PTX3 expression were observed in the lungs of ethanol-treated mice 4 h after CLP. Concomitant with a delayed increase of plasma TNF-α in ethanol-treated mice, plasma PTX3 was also suppressed in the early phase of sepsis. Although TNF-α level in ethanol-treated mice exceeded that in saline-treated mice 16 h after CLP, PTX3 levels were still suppressed in the former group. JNK phosphorylation in lung tissue was suppressed in both groups 4 and 16 h after CLP. Furthermore, JNK phosphorylation in ethanol-treated human umbilical vein endothelial cells was suppressed even in the presence of exogenous TNF-α, resulting in inhibition of PTX3 mRNA and protein expression. Our results suggest that ethanol suppresses de novo PTX3 synthesis via two mechanisms – i.e., suppression of TNF-α production and inhibition of JNK phosphorylation. PTX3 suppression may therefore contribute to exacerbation of sepsis in acute ethanol intoxication.
      Graphical abstract image

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.04.003
      Issue No: Vol. 64 (2017)
  • Altered functional connectivity during spatial working memory in children
           with heavy prenatal alcohol exposure
    • Authors: M. Alejandra Infante; Eileen M. Moore; Amanda Bischoff-Grethe; Susan F. Tapert; Sarah N. Mattson; Edward P. Riley
      Pages: 11 - 21
      Abstract: Publication date: November 2017
      Source:Alcohol, Volume 64
      Author(s): M. Alejandra Infante, Eileen M. Moore, Amanda Bischoff-Grethe, Susan F. Tapert, Sarah N. Mattson, Edward P. Riley
      Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and controls (CON group; n = 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.05.002
      Issue No: Vol. 64 (2017)
  • Both alcoholic and nonalcoholic steatohepatitis association with
           cardiovascular risk and liver fibrosis
    • Authors: D. Brizuela-Alcántara; B.A. Sánchez-Jiménez; M.H. Ramos-Ostos; L.F. Alva-López; M. Uribe-Esquivel; N.C. Chávez-Tapia
      Abstract: Publication date: Available online 15 November 2017
      Author(s): D. Brizuela-Alcántara, B.A. Sánchez-Jiménez, M.H. Ramos-Ostos, L.F. Alva-López, M. Uribe-Esquivel, N.C. Chávez-Tapia
      Background Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Mortality in NAFLD is mainly related to cardiovascular disease (CVD) and cancer. NAFLD and its association with both CVD and liver risk has been well evaluated, but the association of NAFLD and alcohol, known as both alcoholic and nonalcoholic steatohepatitis (BASH) remain uncertain. The objective of this study was to assess the influence of alcohol and obesity in the development of liver and cardiovascular risk. Methods This is a case-control study that included patients from a regular check-up. Alcohol consumption was evaluated with MAST, AUDIT and CAGE. Cardiovascular risk was evaluated using Framingham score, and liver fibrosis with APRI and NAFDL-score. Patients were classified in five groups: healthy patients, steatosis with obesity, steatosis with alcoholism, BASH, and idiopathic steatosis. Results A total of 414 patients were included. BASH group represents 16% of patients, and showed a greater proportion of patients with high cardiovascular risk with 17% (P=0.001), and liver fibrosis with 9% according APRI-score (P=0.10). A multivariate logistic regression showed that alcohol consumption >140g/week (OR 2.546, 95% CI 1.11-5.81, P=0.003) and BMI >25kg/m2 (OR 12.64, 95% CI 1.66-96.20, P=0.001) were related to high cardiovascular risk. Liver fibrosis according APRI was only related to alcohol consumption >140g/week (OR 2.74, 95% CI 1-7.48, P=0.03). Conclusions BASH remains an area not well explored, and of great implication given the increasing number of patients affected. We observed an additive effect of both etiologies in the development of high cardiovascular and liver risk.

      PubDate: 2017-11-18T13:37:19Z
      DOI: 10.1016/j.alcohol.2017.11.004
  • Instructions to Authors
    • Abstract: Publication date: December 2017
      Source:Alcohol, Volume 65

      PubDate: 2017-11-11T12:34:57Z
  • Enhanced sensitivity to socially facilitating and anxiolytic effects of
           ethanol in adolescent Sprague Dawley rats following acute prenatal ethanol
    • Authors: Sandra M. Mooney; Elena I. Varlinskaya
      Abstract: Publication date: Available online 6 November 2017
      Author(s): Sandra M. Mooney, Elena I. Varlinskaya
      Emerging evidence suggests that deficits in social functioning and social anxiety are associated with adolescent alcohol use. Our previous research has shown that acute exposure to a high dose of ethanol on gestational day (G) 12 produces social alterations in adolescent Sprague-Dawley rats. The present study assessed whether these social alterations can affect sensitivity to acute ethanol challenge during adolescence. Pregnant females were exposed intraperitoneally (i.p.) to ethanol (2.5 g/kg followed by 1.25 g/kg in 2 hr) or saline on G12, and their male and female offspring were tested on postnatal day (P) 42. Rats were challenged i.p. with one of four ethanol doses (0, 0.5, 0.75, and 1.0 g/kg), and their social behavior was assessed in a modified social interaction test. Social alterations associated with prenatal ethanol exposure and indexed via decreases of social investigation, social preference, and play fighting were evident in males and females challenged with the 0 g/kg ethanol dose. Acute ethanol increased social investigation, social preference, and play fighting in animals prenatally exposed to ethanol. In contrast, rats prenatally exposed to saline, showing no social facilitation, demonstrated significant ethanol-induced (0.75 and 1.0 g/kg) decreases in social behavior. Given that late adolescents demonstrating social alterations induced by prenatal ethanol exposure become sensitive to the socially anxiolytic as well as socially facilitating effects of acute ethanol, it is possible that the attractiveness of ethanol to these adolescents may be based on its ability to alleviate anxiety under social circumstances and facilitate interactions with peers.

      PubDate: 2017-11-11T12:34:57Z
      DOI: 10.1016/j.alcohol.2017.11.002
  • Prevention of Alcohol-Induced DNA Damage by a Proprietary
           Glycyrrhizin/D-Mannitol Product: A Randomized, Placebo-Controlled,
           Cross-over Human Study
    • Authors: Harsha Chigurupati; Biswajit Auddy; Manish Biyani; Shrabana Chakrabarti; Sidney J. Stohs
      Abstract: Publication date: Available online 6 November 2017
      Author(s): Harsha Chigurupati, Biswajit Auddy, Manish Biyani, Shrabana Chakrabarti, Sidney J. Stohs
      Objectives The purpose of the present study was to evaluate the ability of a proprietary combination of glycyrrhizin and D-mannitol to protect against oxidative damage to DNA associated with acute alcohol consumption by human subjects in a randomized, placebo-controlled cross-over designed study. Excessive alcohol consumption is associated with numerous diseases. Alcohol has been shown to generate reactive oxygen species that can result in DNA damage, leading to genetic and epigenetic changes. Methods A total of 25 subjects (13 male and 12 female) were enrolled. Alcohol intake in the form of vodka (40 % ethanol) was adjusted based on 1.275 grams of 100 % ethanol/kg body weight for men and 1.020 grams/kg body weight for women which was consumed with and without the study product. Blood samples were drawn at two hours after alcohol consumption, lymphocytes were isolated, and subjected to DNA comet electrophoresis on a blinded basis. Results Acute alcohol consumption increased lymphocyte DNA damage by approximately 8.36 %. Co-consumption of the glycyrrhizin/D-mannitol study product with alcohol reduced DNA damage to baseline levels. No adverse effects were associated with use of the study product, and no differences were observed in blood alcohol concentrations in the presence or absence of the study product in males and females. Conclusions Acute alcohol ingestion resulted in measurable increases in DNA damage which were prevented by the addition of the proprietary glycyrrhizin/D-mannitol (NTX®) study product to the alcohol, suggesting that the tissue damaging effects of alcohol consumption can be ameliorated.

      PubDate: 2017-11-11T12:34:57Z
      DOI: 10.1016/j.alcohol.2017.11.001
  • Proceedings of the 2017 Annual Meeting of the Fetal Alcohol Spectrum
           Disorders Study Group
    • Authors: Jeffrey R. Wozniak; Anna Y. Klintsova; Derek A. Hamilton; Sandra M. Mooney
      Abstract: Publication date: Available online 1 November 2017
      Author(s): Jeffrey R. Wozniak, Anna Y. Klintsova, Derek A. Hamilton, Sandra M. Mooney
      The 2017 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was entitled “Prenatal alcohol exposure in the context of multiple factors affecting brain development.” The theme was reflected in the interactions between members of the Teratology Society and the FASDSG this year. The first keynote speaker, Elaine Faustman, Ph.D., was a liaison between the societies and spoke about systems biology and the multiple genetic and environmental influences on development. The second keynote speaker, Rebecca Knickmeyer, Ph.D., discussed population neuroscience and multiple influences on brain development. The conference presented updates from three government agencies and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by Dr. John Hannigan, Ph.D., the recipient of the 2017 Henry Rosett award for career-long contributions to the field.

      PubDate: 2017-11-05T06:42:36Z
      DOI: 10.1016/j.alcohol.2017.10.007
  • Borderline personality disorder symptoms in treatment-naïve actively
           drinking alcoholics
    • Authors: George Fein (; Mathew Price (; Valerie A. Cardenas (
      Abstract: Publication date: Available online 31 October 2017
      Author(s): George Fein (, Mathew Price (, Valerie A. Cardenas (
      Borderline personality disorder (BPD) is often a complicating comorbid factor in alcohol use disorders and substance use disorders. Previous work showed that abstinent alcoholics endorsed lifetime and current symptoms of most all BPD criteria at much higher rates than controls, with much higher symptom counts for short-term abstinent alcoholic (STAA) women than men, consistent with such symptoms negatively impacting female alcoholics’ ability to maintain abstinence. Because prior work has also shown that treatment naïve alcoholics (TNA) are not just treated alcoholics observed earlier in their alcohol dependence, but are a different population with potentially lower psychiatric comorbidity, in this study we compared BPD symptom criteria between TNA samples of comparable age to the control and STAA samples, including both men and women and individuals dependent on alcohol only or with lifetime dependence on both alcohol and drugs. BPD symptoms were obtained using the SCID-II, and endorsed symptoms were classified as current or lifetime. Logistic regression analyses were used to test for effects of group, sex, presence of a lifetime drug dependence diagnosis, and their interactions for lifetime and current symptom endorsement for each BPD criteria. Groups were compared pairwise (TNA vs. NSAC, and STAA vs. TNA). The effect of a lifetime drug dependence diagnosis was not significant for any BPD symptom variable, consistent with the alcohol groups’ BPD symptoms being unaffected by the presence of a comorbid drug dependence. The primary result presented here is that TNA women have borderline symptomatology more similar to that of treated STAA than to NSAC, while TNA men have borderline symptomatology more similar to NSAC than to STAA. A visual examination of co-occurring BPD symptoms showed that while more BPD symptoms are likely to be present in TNA and STAA vs. NSAC, there is no grouping of criteria (i.e., symptom cluster) that is characteristic of TNA or STAA.

      PubDate: 2017-11-05T06:42:36Z
      DOI: 10.1016/j.alcohol.2017.10.005
  • Genome-wide profiling of differentially spliced mRNAs in human fetal
           cortical tissue exposed to alcohol
    • Authors: Yuka Imamura Kawasawa; Shahid Mohammad; Alexander I. Son; Hiroki Morizono; Aiesha Basha; Anna C. Salzberg; Masaaki Torii; Kazue Hashimoto-Torii
      Abstract: Publication date: Available online 31 October 2017
      Author(s): Yuka Imamura Kawasawa, Shahid Mohammad, Alexander I. Son, Hiroki Morizono, Aiesha Basha, Anna C. Salzberg, Masaaki Torii, Kazue Hashimoto-Torii
      Excessive alcohol consumption results in significant changes in gene expression and isoforms due to altered mRNA splicing. As such, an intriguing possibility is that disturbances in alternative splicing are involved in key pathological pathways triggered by alcohol exposure. However, no resources have been available to systematically analyze this possibility at a genome-wide scale. Here, we performed RNA sequencing of human fetal cortical slices that were obtained at the late first trimester and exposed to ethanol or in control medium. We report 382 events that were identified as changes affecting the ratio of splicing isoforms in the ethanol-exposed fetal human cortex. Additionally, previously unreported novel isoforms of several genes were also identified. These results provide a broad perspective on the post-transcriptional regulatory network underlying ethanol-induced pathogenesis in the developing human cortex.

      PubDate: 2017-11-05T06:42:36Z
      DOI: 10.1016/j.alcohol.2017.03.007
  • Involvement of neuronal nitric oxide synthase in cross-sensitization
           between chronic unpredictable stress and ethanol in adolescent and adult
    • Authors: Jaqueline Borges Santos-Rocha; Mariana Rae; Ana Maria Aristimunho Teixeira; Simone Aparecida Teixeira; Carolina Demarchi Munhoz; Marcelo Nicolas Muscará; Tania Marcourakis; Karen K. Szumlinski; Rosana Camarini
      Abstract: Publication date: Available online 31 October 2017
      Author(s): Jaqueline Borges Santos-Rocha, Mariana Rae, Ana Maria Aristimunho Teixeira, Simone Aparecida Teixeira, Carolina Demarchi Munhoz, Marcelo Nicolas Muscará, Tania Marcourakis, Karen K. Szumlinski, Rosana Camarini
      The peculiar neurochemical profile of the adolescent brain render it differently susceptible to several stimuli, including stress and/or drug exposure. Among several stress mediators, nitric oxide (NO) has a role in stress responses. We have demonstrated that adolescent mice are less sensitive to ethanol-induced sensitization than adults. The present study investigated whether chronic unpredictable stress (CUS) induces behavioral sensitization to ethanol in adolescent and adult Swiss mice and the influence of Ca2+-dependent nitric oxide synthase (NOS) activity in the phenomenon. Adolescent and adult mice were exposed to repeated 1.8 g/kg ethanol or CUS and challenged with saline or ethanol. A neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7NI), was administered along with ethanol and CUS to test its effects on behavioral sensitization. Both adolescent and adult mice displayed cross-sensitization between CUS and ethanol in adult mice, with adolescents showing lower degree of sensitization than adults. nNOS inhibition by 7NI reduced both ethanol sensitization and cross-sensitization. All age-differences in the Ca2+-dependent NOS activity in the hippocampus and prefrontal cortex were in the direction of greater activity in adults than in adolescents. Adolescents showed lower sensitivity to cross-sensitization between CUS and ethanol and NO system seems to have a pivotal role in ethanol-induced behavioral sensitization and cross-sensitization in both adolescent and adult mice.

      PubDate: 2017-11-05T06:42:36Z
      DOI: 10.1016/j.alcohol.2017.10.004
  • Summary of the 2017 Alcohol and Immunology Research Interest Group (AIRIG)
    • Authors: Holly J. Hulsebus; Brenda J. Curtis; Patricia E. Molina; Majid Afshar; Lisbeth A. Boule; Niya Morris; Ali Keshavarzian; Jay K. Kolls; Samantha M. Yeligar; Michael E. Price; Todd A. Wyatt; Mashkoor A. Choudhry; Elizabeth J. Kovacs
      Abstract: Publication date: Available online 31 October 2017
      Author(s): Holly J. Hulsebus, Brenda J. Curtis, Patricia E. Molina, Majid Afshar, Lisbeth A. Boule, Niya Morris, Ali Keshavarzian, Jay K. Kolls, Samantha M. Yeligar, Michael E. Price, Todd A. Wyatt, Mashkoor A. Choudhry, Elizabeth J. Kovacs
      On June 24, 2017, the 22nd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite conference during the annual Research Society on Alcoholism (RSA) Scientific Meeting in Denver, CO. The 2017 meeting focused broadly on mechanisms that link alcohol to tissue injury and inflammation, and how this research can be translated to improve human health. Two plenary sessions comprised the meeting, which first explored the association between alcohol and trauma/tissue injury, and finished with a discussion of alcohol and mucosal inflammation. The presentations encompassed diverse areas of alcohol research, from effects on the brain, to airway and pulmonary systems, to gut barrier disruption. The discussions also thoughtfully highlighted how current laboratory and clinical research can be used to prevent or treat alcohol-related morbidity and mortality.

      PubDate: 2017-11-05T06:42:36Z
      DOI: 10.1016/j.alcohol.2017.10.006
  • Yawning elicited by intravenous ethanol in rhesus monkeys with experience
           self-administering cocaine and ethanol: involvement of dopamine D3
    • Authors: Paul W. Czoty; William S. John; Amy Hauck Newman; Michael A. Nader
      Abstract: Publication date: Available online 17 October 2017
      Author(s): Paul W. Czoty, William S. John, Amy Hauck Newman, Michael A. Nader
      Characterization of the effects of long-term alcohol consumption on the brain would be aided by the development of behavioral assays that are relatively easy to implement in animal models of alcohol use disorders. Assessing unconditioned behaviors such as drug-elicited yawning in models that permit long-term alcohol ingestion may be a valuable complement to more invasive and costly procedures. The present studies investigated previous unexpected findings of ethanol-induced yawning in nonhuman primates. Subjects were adult male rhesus monkeys (n=8), all of which had experience self-administering intravenous cocaine for several years. One group also had experience consuming 2.0 g/kg ethanol over one hour per day, 5 days per week, for 6.8-12.0 months. All monkeys received saline or ethanol (0.25-1.0 g/kg) infused intravenously over 10 minutes and the number of yawns elicited during the infusion was counted. A second experiment in the ethanol-experienced monkeys examined whether ethanol-induced yawning could be blocked by PG01037 (1.0, 3.0 mg/kg, i.v.), a selective antagonist at dopamine D3 receptors (D3R). Ethanol significantly and dose-dependently increased yawns in the ethanol-experienced, but not ethanol-naïve animals. In the ethanol-experienced monkeys, this effect of ethanol was blocked by the D3R antagonist. The pharmacology of yawning is complex and a good deal of model development remains to be performed to characterize the potential involvement of other neurotransmitter systems. Nonetheless, drug-elicited yawning may be a useful unconditioned behavioral assay to assess the effects of long-term alcohol consumption in established nonhuman primate models.

      PubDate: 2017-10-21T11:47:54Z
      DOI: 10.1016/j.alcohol.2017.10.003
  • Role of Corticotropin Releasing Factor Binding Protein in the stress
           system: a strange case of Dr. Jekyll and Mr. Hyde in the stress
    • Authors: Carolina L. Haass-Koffler
      Abstract: Publication date: Available online 13 October 2017
      Author(s): Carolina L. Haass-Koffler
      The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP). Extensive literature suggests a role of CRF in alcohol use disorder (AUD). Less is known on the specific role, if any, of CRFBP in AUD. In this review, we summarize recent interdisciplinary efforts towards identifying the contribution of CRFBP in mediating CRF activation. The role of CRFBP in alcohol-related behaviors has been evaluated with the ultimate goal of designing effective novel therapeutic strategies for AUD. A series of in vitro, in vivo, ex vivo and genetic studies presented here provide initial evidence that CRFBP may possess both inhibitory and excitatory roles and support the original hypothesis that it represents a novel pharmacological target for the treatment of AUD. This report summarizes the proceedings of one of the talks at the Young Investigator Award symposium at the Alcoholism and Stress: A Framework for Future Treatment Strategies Conference, Volterra, Italy.

      PubDate: 2017-10-14T02:28:20Z
      DOI: 10.1016/j.alcohol.2017.10.001
  • Age as a factor in stress and alcohol interactions: A critical role for
           the Kappa Opioid System
    • Authors: Marvin Rafael Diaz; Kathryn Renee Przybysz; Siara K. Rouzer
      Abstract: Publication date: Available online 12 October 2017
      Author(s): Marvin Rafael Diaz, Kathryn Renee Przybysz, Siara K. Rouzer
      The endogenous kappa opioid system has primarily been shown to be involved with a state of dysphoria and aversion. Stress and exposure to drugs of abuse, particularly alcohol, can produce similar states of unease and anxiety, implicating the kappa opioid system as a target of stress and alcohol. Numerous behavioral studies have demonstrated reduced sensitivity to manipulations of the kappa opioid system in early-life relative to adulthood, and recent reports have shown that the kappa opioid system is functionally different across ontogeny. Given the global rise in early-life stress and alcohol consumption, understanding how the kappa opioid system responds and adapts to stress and/or alcohol exposure differently in early-life and adulthood is imperative. Therefore, the objective of this review is to highlight and discuss studies examining the impact of early-life stress and/or alcohol on the kappa opioid system, with focus on the documented neuroadaptations that may contribute to future vulnerability to stress and/or increase the risk of relapse. We first provide a brief summary of the importance of studying the effects of stress and alcohol during early-life (prenatal, neonatal/juvenile, and adolescence). We then discuss the literature on the effects of stress or alcohol during early-life and adulthood on the kappa opioid system. Finally, we discuss the few studies that have shown interactions between stress and alcohol on the kappa opioid system and provide some discussion about the need for studies investigating the development of the kappa opioid system.

      PubDate: 2017-10-14T02:28:20Z
      DOI: 10.1016/j.alcohol.2017.10.002
  • Association between alcoholism and the gene encoding endocannabinoid
           synthesizing enzyme Diacylglycerol Lipase Alpha in Japanese population
    • Authors: Hiroki Ishiguro; Susumu Higuchi; Tadao Arinami; Emmanuel S. Onaivi
      Abstract: Publication date: Available online 12 October 2017
      Author(s): Hiroki Ishiguro, Susumu Higuchi, Tadao Arinami, Emmanuel S. Onaivi
      The endocannabinoid system has been recognized to be involved in neuropsychiatric diseases. 2-Arachidonoyl glycerol (2-AG) is one of the two main endocannabinoids, and their regulation could play roles in the disorders under the environmental influence. This study investigated an involvement of Diacylglycerol Lipase Alpha (DAGLA) that is a 2-AG biosynthesizing enzyme in the pathogenesis of alcoholism. We investigated a possible association between alcoholism and single nucleotide polymorphisms (SNPs) of the human DAGLA gene in Japanese population. To find out any environmental influences on Dagla function in animal study, the Dagla gene expression in the brain from stressed model mice was analyzed. The SNPs, including missense polymorphism Pro899Leu, in the DAGLA gene showed associations with alcoholism in Japanese. The Dagla expression in mice was found to be modulated by chronic mild stress and by acquisition of alcohol preference. Our findings indicated the involvement of DAGLA in alcoholism, possibly by its genetic dysfunction and also by influence of stress.

      PubDate: 2017-10-14T02:28:20Z
      DOI: 10.1016/j.alcohol.2017.09.005
  • Correlations of Blood Alcohol Concentrations (BACs), Breath Alcohol
           Concentrations (BrACs) and Psychomotor Evaluations in a Clinically
           Monitored Study of Alcohol Intake in Brazil
    • Authors: Ana Paula; Drummond-Lage Rodrigo Gomes Freitas Gabriel Cruz Luigi Perillo
      Abstract: Publication date: Available online 7 October 2017
      Author(s): Ana Paula Drummond-Lage, Rodrigo Gomes de Freitas, Gabriel Cruz, Luigi Perillo, Marco Antonio Paiva, Alberto Julius Alves Wainstein
      Background Policies that establish maximum blood alcohol concentrations (BACs) or breath alcohol concentration (BrACs) for drivers while driving can reduce traffic accidents by approximately 20%. In Brazil, the National Transit Council (CONTRAN) considers positive BAC and/or BrAC tests or signs of psychomotor capacity alterations as evaluated by a police authority to be an administrative infraction or even a crime. The observed clinical symptoms of alcohol intoxication based on a subject’s appearance may not necessarily reflect the quantified BAC and/or BrAC. This study compared the clinical symptoms identified by a medical authority (M) and a non-medical authority (NM) with BAC and BrAC measurements. Methods Brazilian health volunteers (n=15) drank ethanol (40%v/v) and, at scheduled times, the subjects underwent blood draws for BAC analysis, were tested for BrAC analysis, and underwent psychomotor alteration assessments performed by M and NM. Results Concentration-time profiles of the BACs and BrACs of the volunteer subjects were generated. The BAC values reached a peak at 60’ and subsequently decreased with time. The average BrAC values decreased with time since ingestion. During the evaluations, M was able to identify a lack of static equilibrium until 240’ and a lack of dynamic equilibrium until 120’. A lack of upper limb motor coordination was observed until 90’, and a lack of coordination in the lower limbs was observed only during the first hour. Regarding the tests performed by NM, the signs related to the subjects’ appearances were observed more frequently until 60’. The other analyzed symptoms were not identified. Naturally, the signs reported by both M and NM disappeared with time. Conclusion The evaluations of psychomotor changes performed by Brazilians M were superior to those performed by NM. However, independent of the examiner, at the alcohol concentrations reached in this study, the psychomotor alteration evaluations were ineffective compared with the BAC and BrAC results.

      PubDate: 2017-10-08T01:27:26Z
  • Regional Dysregulation of Taurine and Related Amino Acids in the Fetal Rat
           Brain Following Gestational Alcohol Exposure
    • Authors: Raine Lunde-Young; Katie Davis-Anderson; Vishal Naik; Matthew Nemec; Guoyao Wu; Jayanth Ramadoss
      Abstract: Publication date: Available online 30 September 2017
      Author(s): Raine Lunde-Young, Katie Davis-Anderson, Vishal Naik, Matthew Nemec, Guoyao Wu, Jayanth Ramadoss
      The fetal brain exhibits exquisite alcohol-induced regional neuronal vulnerability. A candidate mechanism for alcohol-mediated brain deficits is disruption of amino acid (AA) bioavailability. AAs are vitally important for proper neurodevelopment, as they comprise the most abundant neurotransmitters in the brain and act as neurotransmitter precursors, nitric oxide donors, antioxidants, and neurotrophic factors, which induce synaptogenesis, neuronal proliferation, and migration. We hypothesized that gestational alcohol alters brain AA concentrations, disrupts AAs associated with neuropathogenesis, and that alterations are region-specific. We assigned pregnant Sprague-Dawley rats to either a pair-fed control or a binge alcohol treatment group on gestational day (GD) 4. Alcohol animals acclimatized via a once daily orogastric gavage of a 4.5 g/kg alcohol dose from GD 5-10, and progressed to a 6 g/kg alcohol dose from GD 11-20. Pair-fed animals received isocaloric maltose dextrin (once daily; GD 5-20). Fetal cerebral cortex, cerebellum, and hippocampus were collected on GD 21. Following collection, Fluorometric High Performance Liquid Chromatography (HPLC) involving pre-column derivatization with o-phthaldialdehyde quantified regional content of 22 AAs. Chronic binge alcohol administration to pregnant dams regionally altered AA concentrations in all three structures, with the cerebral cortex exhibiting least vulnerability and the hippocampus exhibiting maximal vulnerability. We conjecture that the AA imbalances observed in this study are critically implicated in pathological and compensatory processes occurring in the brain in response to gestational alcohol exposure.

      PubDate: 2017-10-08T01:27:26Z
      DOI: 10.1016/j.alcohol.2017.07.010
  • Reduced expression of purinergic P2X4 receptors increases voluntary
           ethanol intake IN C57BL/6J mice
    • Authors: Sheraz Khoja; Nhat Huynh; Liana Asatryan; Michael W. Jakowec; Daryl L. Davies
      Abstract: Publication date: Available online 30 September 2017
      Author(s): Sheraz Khoja, Nhat Huynh, Liana Asatryan, Michael W. Jakowec, Daryl L. Davies
      Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ionotropic receptors that are gated by adenosine-5’-triphosphate (ATP). Accumulating evidence indicates that P2X4Rs play an important role in regulation of ethanol intake. At the molecular level, ethanol’s inhibitory effects on P2X4Rs are antagonized by ivermectin (IVM), in part; via action on P2X4Rs. Behaviorally, male mice deficient in p2rx4 gene [P2X4R knockout (KO)] have been shown to exhibit a transient increase in ethanol intake over a period of 4 days as demonstrated by social and binge drinking paradigms. Furthermore, IVM reduced ethanol consumption in male and female rodents, whereas, male P2X4R KO mice were less sensitive to anti-alcohol effects of IVM compared to wildtype (WT), further supporting a role for P2X4Rs as targets of IVM’s action. The current investigation extends testing the hypothesis that P2X4Rs play a role in regulation of ethanol intake. First, we tested the response of P2X4R KO mice to ethanol for a period of 5 weeks. Second, to gain insights into the changes in ethanol intake, we employed a lentivirus-shRNA (LV-shRNA) methodology to selectively knockdown P2X4R expression in the nucleus accumbens (NAc) core in male C57BL/6J mice. In agreement with our previous study, male P2X4R KO mice exhibited higher ethanol intake than WT mice. Additionally, reduced expression of P2X4Rs in NAc core significantly increased ethanol intake and preference. Collectively, the findings support the hypothesis that P2X4Rs play a role in regulation of ethanol intake and that P2X4Rs represent a novel drug target for treatment of alcohol use disorder.

      PubDate: 2017-10-08T01:27:26Z
      DOI: 10.1016/j.alcohol.2017.09.004
  • Instructions to Authors
    • Abstract: Publication date: November 2017
      Source:Alcohol, Volume 64

      PubDate: 2017-09-30T00:11:54Z
  • Effects of Group II Metabotropic Glutamate Receptor Modulation on Ethanol-
           and Sucrose-Seeking and Consumption in the Rat
    • Authors: Kyle A. Windisch; Cristine L. Czachowski
      Abstract: Publication date: Available online 23 September 2017
      Author(s): Kyle A. Windisch, Cristine L. Czachowski
      Rationale Previous studies suggest that group II metabotropic glutamate receptors (mGluR2/3) are involved in regulating ethanol seeking and consumption. Objective The mGluR2/3 agonist LY379268 (LY37) and selective mGluR2 positive allosteric modulator biphenyl-indanone A (BINA) were used to investigate the relative contribution of mGlu2 and mGlu3 receptors on ethanol and sucrose seeking and consumption. A microinjection study was then performed to examine the role of nucleus accumbens (NAc) core mGluR2/3 on ethanol-seeking. Methods For the systemic experiments, separate groups of male Wistar rats [LY37 (0-2.0 mg/kg); BINA (0-20 mg/kg)] were trained to complete a response requirement (RR) resulting in access to 10% ethanol or 2% sucrose (in separate groups) for a 20-minute drinking period. Animals then underwent consummatory testing (weekly drug injections with RR1) followed by appetitive testing (weekly drug injections followed by extinction session). A separate group of male Wistar rats was surgically implanted with bilateral guide cannulae directed towards the NAc core and had weekly microinjections followed by an extinction session. Results Systemic administration of the mGluR2/3 agonist LY37 significantly reduced ethanol- and sucrose-seeking. The same treatment also reduced sucrose consumption and body weight (24-hours post injection). Systemic administration of the selective mGluR2 PAM BINA, however, had no effect on either seeking or consumption of ethanol or sucrose. Intra-accumbens core LY37 significantly reduced ethanol-seeking. Conclusions: These findings suggest that systemic mGluR2/3 agonism, but not allosteric modulation of mGluR2, reduces reinforcer seeking. In particular, NAc core group II mGluR may be involved in regulating ethanol-seeking.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.011
  • First description and evaluation of SNPS in the ADH and ALDH genes in a
           population sample of alcoholics in the Central-West Region of Brazil
    • Authors: Thallita Monteiro Teixeira; Hugo Delleon da Silva; Rebeca Mota Gouvea; Paulo Eduardo Martins Ribolla; Diego Peres Alonso; Alessandro Arruda Alves; Daniela Melo e Silva; Rosane Garcia Collevatti; Lucilene Arilho Bicudo; Nádia Aparecida Bérgamo; Elisângela de Paula Silveira-Lacerda
      Abstract: Publication date: Available online 23 September 2017
      Author(s): Thallita Monteiro Teixeira, Hugo Delleon da Silva, Rebeca Mota Gouvea, Paulo Eduardo Martins Ribolla, Diego Peres Alonso, Alessandro Arruda Alves, Daniela Melo e Silva, Rosane Garcia Collevatti, Lucilene Arilho Bicudo, Nádia Aparecida Bérgamo, Elisângela de Paula Silveira-Lacerda
      Worldwide, there are different studies that reported to association of alcohol dependence with different types of Single Nucleotide Polymorphisms (SNPs) in the genes ALDH and ADH. In Brazil, there is little information about the occurrence of these SNPs in the alcohol dependence population and an absence of studies characterizing the population in the Central-West Region of Brazil. Actually, in Brazil, there are more than four million of alcohol dependents and despite the major health hazards by alcohol dependence, information on its consumption and consequences are not as well understood. Therefore, it is extremely important, the characterization of these SNPs for the better understanding of the alcohol dependence as genetic disease in a Brazilian population and that, unlike other studies in different countries shows an intensive racial miscegenation. We evaluated presence of SNPs in the ADH (ADH1B, ADH1C and ADH4) and ALDH (ALDH2) genes in alcohol users of Goiânia, State of Goiás–Brazil, and then we established a possible relationship with alcohol dependence, by allelic and genotypic study. This study was conducted with a population of alcohol dependents (n = 99) from Goiás Alcohol Dependence Recovery Center (GO CEREA) and Psychosocial Care Center for Alcohol and Drugs (CAPS AD), and with a population of non-alcohol dependents as control (n = 100). DNA was extracted from patient whole blood sample and the genotyping was performed using TaqMan® SNP genotyping assays. For characterization and evaluation of SNPs in the population, genotype frequency, allele frequency, haplotype frequency, Hardy-Weinberg Equilibrium and Linkage disequilibrium were analyzed. Statistical analyzes were calculated by GENEPOP 4.5 and Haploview software. The allele 1 was considered as "wild" (or *1) and allele 2 as mutant (or *2). Significant differences were found for ADH1B*, ADH4*2 and ALDH2*2 SNPs when the genotype and allele frequencies were analyzed. In addition, it was observed four haplotypes between ADH1B*2 and ADH1C*2, through of the Linkage disequilibrium analyze. The genetic variants may be associated with protection or alcohol dependence in the population studied.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.04.006
  • Evaluation of laboratory tests for cirrhosis and for alcohol use, in the
           context of alcoholic cirrhosis
    • Authors: John B. Whitfield; Steven Masson; Suthat Liangpunsakul; Jessica Hyman; Sebastian Mueller; Guruprasad Aithal; Florian Eyer; Dermot Gleeson; Andrew Thompson; Felix Stickel; Michael Soyka; Ann K. Daly; Heather J. Cordell; Tiebing Liang; Tatiana Foroud; Lawrence Lumeng; Munir Pirmohamed; Bertrand Nalpas; Camille Bence; Jean-Marc Jacquet; Alexandre Louvet; Romain Moirand; Pierre Nahon; Sylvie Naveau; Pascal Perney; Philippe Podevin; Paul S. Haber; Helmut K. Seitz; Christopher P. Day; Philippe Mathurin; Timothy M. Morgan; Devanshi Seth
      Abstract: Publication date: Available online 23 September 2017
      Author(s): John B. Whitfield, Steven Masson, Suthat Liangpunsakul, Jessica Hyman, Sebastian Mueller, Guruprasad Aithal, Florian Eyer, Dermot Gleeson, Andrew Thompson, Felix Stickel, Michael Soyka, Ann K. Daly, Heather J. Cordell, Tiebing Liang, Tatiana Foroud, Lawrence Lumeng, Munir Pirmohamed, Bertrand Nalpas, Camille Bence, Jean-Marc Jacquet, Alexandre Louvet, Romain Moirand, Pierre Nahon, Sylvie Naveau, Pascal Perney, Philippe Podevin, Paul S. Haber, Helmut K. Seitz, Christopher P. Day, Philippe Mathurin, Timothy M. Morgan, Devanshi Seth
      Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests’ ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with AUCs of 0.91 ± 0.01 and 0.88 ± 0.01 respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/l gave 90% specificity and 37% sensitivity; for GGT cut-off limits of 288 units/l in men and 138 units/l in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.006
  • Urinary bladder volume measured in Whole-body CT scans is a useful marker
           for alcohol intoxication
    • Authors: Denis Gümbel; Frank Schneidler; Matthias Frank; Britta Bockholdt; Peter Hinz; Matthias Napp; Romy Spitzmüller; Axel Ekkernkamp; Sönke Langner
      Abstract: Publication date: Available online 23 September 2017
      Author(s): Denis Gümbel, Frank Schneidler, Matthias Frank, Britta Bockholdt, Peter Hinz, Matthias Napp, Romy Spitzmüller, Axel Ekkernkamp, Sönke Langner
      Purpose of the study was to investigate whether a correlation between urinary bladder volume and blood alcohol concentration exists in a cohort of trauma patients treated in the emergency department. We further aimed to elucidate the usefulness of semi-automated 3D-Volumetry for urinary bladder volume calculation. Whole-body computer tomography scans of 831 individuals treated in the emergency department with suspected multiple injury were included. Manual 3D-CT-Volumetry of the urinary bladder was performed and the mechanism of injury, patient demographics, blood alcohol concentration, serum creatinine and haematocrit were retrospectively analysed. Semi-automated calculation of urinary bladder volume was performed in 30 patients. Statistical analysis included ROC-analysis to calculate cut-off values, sensitivity and specificity. Mann-Whitney test and Spearman’s correlation coefficient were used to detect significant correlations between urinary bladder volume and blood alcohol concentration. Manual 3D-CT-Volumetry showed maximum sensitivity and specificity with a cut-off value of 416.3 ml (sensitivity 50.9%; specificity 76.3%; AUC 0.678). With a cut-off value of 4.2 ml/μmol for creatinine quotient (quotient of serum creatinine and UBV) sensitivity was 64.2% (specificity 67.0%; AUC 0.681). Semi-automated 3D-CT-Volumetry resulted in lower measurement values also in patients with intraabdominal free fluid or intravesical contrast media. Positive blood alcohol concentration results correlate with urinary bladder volume. Semi-automated 3D-CT-Volumetry is a reliable method to quantify urinary bladder volume. A urinary volume above 416 ml seen on initial whole-body computer tomography must raise suspicion of alcohol intoxication. Creatinine quotient is an even more sensitive and specific parameter for the detection of alcohol intoxication.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.004
  • Alcohol withdrawal upregulates mRNA encoding for CaV2.1-α1 subunit in the
           rat inferior colliculus
    • Authors: Jamila Newton; Shubhankar Suman; Luli R. Akinfiresoye; Kamal Datta; David M. Lovinger; Prosper N’Gouemo
      Abstract: Publication date: Available online 23 September 2017
      Author(s): Jamila Newton, Shubhankar Suman, Luli R. Akinfiresoye, Kamal Datta, David M. Lovinger, Prosper N’Gouemo
      We previously reported increased current density through P-type voltage-gated Ca2+ channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased P-type channel current is currently unknown. Here, we probe changes in mRNA and protein expression of the pore-forming CaV2.1-α1 (P/Q-type) subunits in IC neurons during the course of alcohol withdrawal‒induced seizures (AWSs). Rats received three daily doses of ethanol or the vehicle every eight hours for four consecutive days. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV2.1-α1 subunits were measured. In separate experiments, rats were tested for acoustically evoked seizure susceptibility 3, 24, and 48 hours after alcohol withdrawal. AWSs were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours or in the control-treated rats. Compared to control-treated rats, the mRNA levels of the CaV2.1α1 subunit were increased 1.9-fold and 2.1-fold at 3 and 24 hours, respectively; change in mRNA expression was nonsignificant 3 and 48 hour following alcohol withdrawal. Western blot analyses revealed that protein levels of the CaV2.1-α1 subunits were not altered in IC neurons following alcohol withdrawal. We conclude that expression of the Cacna1a mRNA increased in before the onset of AWS susceptibility, suggesting that altered CaV2.1 channel expression may play a role in AWS pathogenesis.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.007
  • Impact of a brief intervention on reducing alcohol use and increasing
           alcohol treatment services utilization among alcohol- and drug-using adult
           emergency department patients
    • Authors: Roland C. Merchant; Justin Romanoff; Zihao Zhang; Tao Liu; Janette R. Baird
      Abstract: Publication date: Available online 23 September 2017
      Author(s): Roland C. Merchant, Justin Romanoff, Zihao Zhang, Tao Liu, Janette R. Baird
      Most previous brief intervention (BI) studies have focused on alcohol or drug use, instead of both substances. Our primary aim was to determine if an alcohol and drug use BI reduced alcohol use and increased alcohol treatment services utilization among adult emergency department (ED) patients. Our secondary aims were to assess when the greatest relative reductions in alcohol use occurred, and which patients (stratified by need for an alcohol use intervention) reduced their alcohol use the most. We studied a sub-sample of participants from a randomized, controlled trial of a BI vs. no BI whose responses to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) indicated a need for a BI for any drug use and who also reported alcohol use. Participants were stratified by their ASSIST alcohol subscore: (1) no BI needed, (2) a BI needed, or (3) an intensive intervention needed for alcohol use. Alcohol use and alcohol treatment services utilization were measured every three months for 12 months post-enrollment. Of these 833 participants, median age was 29 years-old, 46% were female; 55% were white/non-Hispanic, 27% black/non-Hispanic and 15% Hispanic. Although any alcohol use, alcohol use frequency, days of alcohol use, typical drinks consumed/day, and most drinks consumed/day decreased in both the BI and no BI arms, there were no differences between study arms. Few patients sought alcohol use treatment services in follow-up, and utilization also did not differ by study arm. Compared to baseline, alcohol use reduced the most during the first three months after enrollment, yet reduced little afterwards. Participants whose ASSIST alcohol subscores indicated a need for an intensive intervention generally had the greatest relative decreases in alcohol use. These results indicate that the BI used was not efficacious in reducing alcohol use among alcohol- and drug-using adult ED patients. There is a need to develop and test more robust interventions.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.003
  • The Effects of Working Memory Load and Attention Refocusing on Delay
           Discounting Rates in Alcohol Use Disorder with Comorbid Antisocial
           Personality Disorder
    • Authors: Rachel L. Gunn; Kyle R. Gerst; Allison J. Lake; Peter R. Finn
      Abstract: Publication date: Available online 23 September 2017
      Author(s): Rachel L. Gunn, Kyle R. Gerst, Allison J. Lake, Peter R. Finn
      Executive working memory capacity (eWMC) is central to adaptive decision-making. Research has revealed reduced eWMC and higher rates of impulsive decision-making in those with alcohol use disorders (AUDs: DSM-IV Alcohol Dependence of Alcohol Abuse) and antisocial psychopathology (AP). Recent work has shown that placing a load on working memory (WM) further increases impulsive decision-making on the delay discounting (DD) task in those with AUDs and AP. The current study examined the effects of an attention refocusing manipulation to offset the effects of this WM-load on DD rates in control subjects, those with AUDs without AP, and AUDs with AP (AUD-AP). Results revealed that (1) the AUD-AP group had higher DD rates (i.e., more impulsive decision-making) than the AUD group, followed by controls, and, (2) attention refocusing after a load is placed on WM was associated with lower DD rates compared to the load without refocusing in both AUD groups, but not controls. Results suggest that refocusing attention after a cognitive load may be an effective cognitive strategy for reducing the impulsivity-enhancing effects of cognitive load on decision-making in individuals with AUDs and AP.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.009
  • Hazardous alcohol use among patients with Schizophrenia and Depression
    • Authors: Mythily Subramaniam; Mithila Valli Mahesh; Chao Xu Peh; Junda Tan; Restria Fauziana; Pratika Satghare; Bhanu Gupta; Kandasami Gomathinayagam; Siow Ann Chong
      Abstract: Publication date: Available online 22 September 2017
      Author(s): Mythily Subramaniam, Mithila Valli Mahesh, Chao Xu Peh, Junda Tan, Restria Fauziana, Pratika Satghare, Bhanu Gupta, Kandasami Gomathinayagam, Siow Ann Chong
      Aims The current study aimed to (i) report the prevalence of hazardous alcohol use in an outpatient population among those with schizophrenia and depressive disorders, (ii) assess the sociodemographic and clinical correlates of hazardous alcohol use, (iii) examine the association of hazardous alcohol use with severity of depression and anxiety and smoking and (iv) assess the association of hazardous alcohol use with quality of life. Methods The study was conducted among 310 outpatients seeking treatment at a tertiary psychiatric institute with a diagnosis of either schizophrenia spectrum disorder or depressive disorder. Patients were assessed for hazardous alcohol use using the Alcohol Use Disorders Identification Test. Information on sociodemographic correlates, clinical history, severity of symptoms of depression and anxiety as well as quality of life was collected. Results The overall prevalence of hazardous alcohol use among the sample was 12.6%. The prevalence of hazardous alcohol use among patients with depression and schizophrenia was 18.8%, and 6.4% respectively. Compared to those who were students, patients who were gainfully employed or unemployed were more likely to engage in hazardous alcohol use (OR = 5.5 and 7.7 respectively). Patients with depression compared to those with schizophrenia (OR = 11.1) and those who were current smokers compared to those who had never smoked (OR = 14.5) were more likely to engage in hazardous alcohol use. Hazardous alcohol use was associated with lower quality of life (QOL) in the physical health domain (p = 0.002). Conclusion Given the significant prevalence of hazardous alcohol use in this population, routine screening for hazardous alcohol use and brief interventions could be an effective way of managing this comorbidity. There is a need to develop and evaluate culturally appropriate brief interventions based on patient preference in this setting.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.07.008
  • THC inhibits the expression of ethanol-induced locomotor sensitization in
    • Authors: Renato Filev; Douglas S. Engelke; Dartiu X. da Silveira; Luiz E. Mello; Jair G. Santos-Junior
      Abstract: Publication date: Available online 21 September 2017
      Author(s): Renato Filev, Douglas S. Engelke, Dartiu X. da Silveira, Luiz E. Mello, Jair G. Santos-Junior
      The motivational circuit activated by ethanol leads to behavioral changes that recruit the endocannabinoid system (ECS). Case reports and observational studies suggest that the use of Cannabis sp. mitigates problematic ethanol consumption in humans. Here, we verified the effects of the two main phytocannabinoid compounds of Cannabis sp., cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), in the expression of ethanol-induced locomotor sensitization in mice. Male adult DBA/2 mice were exposed to locomotor sensitization by daily intraperitoneal injections of ethanol (2.5 g/kg) for 12 days; control groups received saline. After the acquisition phase, animals were treated with cannabinoids: CBD (2.5 mg/kg); THC (2.5 mg/kg); CBD + THC (1:1 ratio), or vehicle for 4 days with no access to ethanol during this period. One day after the last cannabinoid injection, all animals were challenged with ethanol (2.0 g/kg) to evaluate the expression of the locomotor sensitization. Mice treated with THC alone or THC + CBD showed reduced expression of locomotor sensitization, compared to the vehicle control group. No effects were observed with CBD treatment alone. Our findings showing that phytocannabinoid treatment prevents the expression of behavioral sensitization in mice provide insight into the potential therapeutic use of phytocannabinoids in alcohol-related problems.

      PubDate: 2017-09-23T23:26:19Z
      DOI: 10.1016/j.alcohol.2017.06.004
  • Progressive White Matter Atrophy with Altered Lipid Profiles is Partially
           Reversed by Short-Term Abstinence in an Experimental Model of
           Alcohol-Related Neurodegeneration
    • Authors: Emine B. Yalcin; Tory McLean; Ming Tong; Suzanne M. de la Monte
      Abstract: Publication date: Available online 15 September 2017
      Author(s): Emine B. Yalcin, Tory McLean, Ming Tong, Suzanne M. de la Monte
      Chronic ethanol exposure causes white matter (WM) atrophy and degeneration with major impairments in the structural integrity of myelin. Since myelin is composed of oligodendrocyte lipid-rich membranes, understanding the consequences and reversibility of alcohol-related oligodendrocyte dysfunction in relation to myelin structure could provide new insights into the pathogenesis of WM degeneration and potential strategies for treatment. Adult male Long Evans rats were pair-fed with isocaloric liquid diets containing 0% or 26% ethanol (caloric) for 3 or 8 weeks. During the last 2 weeks of feeding, the ethanol groups were binged with 2 g/kg of ethanol by intraperitoneal (i.p.) injection on Mondays, Wednesdays, and Fridays; controls were treated with i.p. saline. For recovery effects, at the 6-week time point, ethanol exposures were tapered over 2 days, and then discontinued, rendering the rats ethanol-free for 12 days. Anterior corpus callosum WM lipid ion profiles were analyzed using matrix-assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS) and correlated with histopathology. Ethanol exposures caused progressive atrophy and reductions in myelin staining intensity within the corpus callosum, whereas short-term recovery partially reversed those effects. MALDI-IMS demonstrated striking ethanol-associated alterations in WM lipid profiles characterized by reduced levels of phosphatidylinositols, phosphatidylserines, phosphatidylethanolamines, and sulfatides, and partial “normalization” of lipid expression with recovery. Ethanol exposure duration and recovery responses were further distinguished by heatmap hierarchical dendrogram and PCA plots. In conclusion, chronic+binge ethanol exposures caused progressive, partially reversible WM atrophy with myelin loss associated with reduced expression of WM phospholipids and sulfatides. The extent of WM lipid abnormalities suggests that ethanol broadly impairs molecular and biochemical functions regulating myelin synthesis, degradation, and maintenance in oligodendrocytes.

      PubDate: 2017-09-17T23:21:31Z
      DOI: 10.1016/j.alcohol.2017.05.008
  • Gene expression changes in the ventral hippocampus and medial prefrontal
           cortex of adolescent alcohol-preferring (P) rats following
           binge-like-alcohol drinking
    • Authors: Jeanette N. McClintick; William J. McBride; Richard L. Bell; Zheng-Ming Ding; Yunlong Liu; Xiaoling Xuei; Howard J. Edenberg
      Abstract: Publication date: Available online 14 September 2017
      Author(s): Jeanette N. McClintick, William J. McBride, Richard L. Bell, Zheng-Ming Ding, Yunlong Liu, Xiaoling Xuei, Howard J. Edenberg
      Binge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including decreased hippocampal and prefrontal cortex volume and defects in memory. We used RNA sequencing to assess the effects of adolescent binge drinking on gene expression in these regions. Male adolescent alcohol-preferring (P) rats were exposed to repeated binge drinking (three 1-hour sessions/d during the dark/cycle, 5 days/week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5 to 3 g/kg/session). Ethanol significantly altered the expression of 416 of 11,727 genes expressed in the ventral hippocampus. Genes and pathways involved in neurogenesis, long-term potentiation and axonal guidance were decreased, which could relate to the impaired memory function found in subjects with adolescent alcohol binge-like exposure. The decreased expression of myelin and cholesterol genes and apparent decrease in oligodendrocytes in P rats could result in decreased myelination. In the medial prefrontal cortex, 638 of 11,579 genes were altered; genes in cellular stress and inflammatory pathways were increased, as were genes involved in oxidative phosphorylation. Overall, the results of this study suggest that adolescent binge-like alcohol drinking may alter the development of the ventral hippocampus and medial prefrontal cortex and produce long-term consequences on learning and memory, and on control of impulsive behaviors.

      PubDate: 2017-09-17T23:21:31Z
      DOI: 10.1016/j.alcohol.2017.09.002
  • QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall
           remodelling in excessive alcohol consumers: The SABPA study
    • Authors: Annemarie Wentzel; Leoné Malan; Jacobus D. Scheepers; Nicolaas T. Malan
      Abstract: Publication date: Available online 14 September 2017
      Author(s): Annemarie Wentzel, Leoné Malan, Jacobus D. Scheepers, Nicolaas T. Malan
      Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption – measured via ethnic specific gamma glutamyl transferase (γ-GT) cut-points – and markers of cardiac perfusion, electrical activity and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic gender cohort (N=405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT ≥ 19.5U/L and γ-GT ≥55U/L indicated excessive alcohol consumption in Caucasians and Africans respectively. Ambulatory 24h BP and-electrocardiograms (ECG), 12-lead ECG-left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP) and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile, mean 24h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol high and presented significant increases in NT-proBNP (p<0.001), QTc prolongation (p=0.008) and ischemic events (p=0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events and SBP, in the African high γ-GT group exclusively. High alcohol consumer’s presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.

      PubDate: 2017-09-17T23:21:31Z
      DOI: 10.1016/j.alcohol.2017.09.001
  • Alcohol-Naïve USVs Distinguish Male HAD-1 from LAD-1 Rat Strains
    • Authors: Nitish Mittal; Neha Thakore; James M. Reno; Richard L. Bell; W. Todd Maddox; Timothy Schallert; Christine L. Duvauchelle
      Abstract: Publication date: Available online 14 September 2017
      Author(s): Nitish Mittal, Neha Thakore, James M. Reno, Richard L. Bell, W. Todd Maddox, Timothy Schallert, Christine L. Duvauchelle
      Ultrasonic vocalizations (USVs) are mediated through specific dopaminergic and cholinergic neural pathways and serve as real-time measures of positive and negative emotional status in rodents. Although most USV studies focus primarily on USV counts, each USV possesses a number of characteristics shown to reflect activity in the associated neurotransmitter system. In the present study, we recorded spontaneously emitted USVs from alcohol-naïve high alcohol drinking (HAD-1) and low alcohol drinking (LAD-1) rats. Using our recently developed WAAVES algorithm we quantified four acoustic characteristics (mean frequency, duration, power and bandwidth) from each 22 – 28 kHz and 50 – 55 kHz frequency modulated (FM) USV. This rich USV representation allowed us to apply advanced statistical techniques to identify the USV acoustic characteristics that distinguished HAD-1 from LAD-1 rats. Linear mixed models (LMM) examined the predictability of each USV characteristic in isolation and linear discriminant analysis (LDA) and binomial logistic regression examined the predictability of linear combinations of the USV characteristics as a group. Results revealed significant differences in acoustic characteristics between HAD-1 and LAD-1 rats in both 22 – 28 kHz and 50 – 55 kHz FM USVs. In other words, these rats selectively bred for high- and low-alcohol consumption can be identified as HAD-1 or LAD-1 rats with high classification accuracy (approx. 92-100%) exclusively on the basis of their emitted 22-28 kHz and 50-55 kHz FM USV acoustic characteristics. In addition, acoustic characteristics of 22 – 28 kHz and 50 – 55 kHz FM USVs emitted by alcohol-naïve HAD-1 and LAD-1 rats significantly correlate with their future alcohol consumption. Our current findings provide novel evidence that USV acoustic characteristics can be used to discriminate between alcohol-naïve HAD-1 and LAD-1 rats, and may serve as biomarkers in rodents with a predisposition for, or against, excessive alcohol intake.

      PubDate: 2017-09-17T23:21:31Z
      DOI: 10.1016/j.alcohol.2017.09.003
  • Alcohol intake in two different mouse drinking models after recovery from
           the lipopolysaccharide-induced sickness reaction
    • Authors: Mira Lainiola; Anni-Maija Linden
      Abstract: Publication date: Available online 14 September 2017
      Author(s): Mira Lainiola, Anni-Maija Linden
      Neuroinflammation may play an important role in the development of alcohol addiction. Recent preclinical reports suggest that enhanced innate immune system signaling increases consumption of alcohol. Our aim was to study whether consequences of lipopolysaccharide (LPS)-induced sickness reaction increase long-term alcohol intake. Adult male C57BL/6J mice, housed in individually ventilated cages, were injected with LPS intraperitoneally (i.p.) and allowed to recover from an acute sickness reaction for 1 week before analysis of their alcohol intake in two different drinking models. Effects of LPS challenge were tested in a continuous two-bottle free choice test with increasing concentrations of alcohol and in a drinking in the dark (DID) binge model. In addition, the effect of repeatedly administered LPS during abstinence periods between binge drinking was analyzed in the DID model. In addition, the DID model was used to study the effects of the microglia inhibitor minocycline (50 mg/kg/day, 4 days) and purinergic P2X7 receptor antagonist Brilliant Blue G (75 mg/kg/day, 7 days) on alcohol intake. In contrast to previous findings, pretreatment with a 1-mg/kg dose of LPS did not significantly increase ethanol consumption in the continuous two-bottle choice test. As a novel finding, we report that increasing the LPS dose to 1.5 mg/kg reduced consumption of 18 and 21% (v/v) ethanol. In the DID model, pretreatment with LPS (0.2–1.5 mg/kg) did not significantly alter 15% or 20% ethanol consumption. Neither did repeated LPS injections affect binge alcohol drinking. Minocycline reduced alcohol, but also water, intake regardless of LPS pretreatment. No data on effects of P2X7 antagonists on alcohol consumption have been previously published; therefore, we report here that subchronic Brilliant Blue G had no effect on alcohol intake in the DID model. As a conclusion, further studies are needed to validate this LPS model of the interaction between immune system activation and alcohol consumption.

      PubDate: 2017-09-17T23:21:31Z
      DOI: 10.1016/j.alcohol.2017.06.002
  • An alcohol withdrawal test battery measuring multiple behavioral symptoms
           in mice
    • Authors: Pamela Metten; Jason P. Schlumbohm; Lawrence C. Huang; Gian D. Greenberg; Wyatt R. Hack; Stephanie E. Spence; John C. Crabbe
      Abstract: Publication date: Available online 6 September 2017
      Author(s): Pamela Metten, Jason P. Schlumbohm, Lawrence C. Huang, Gian D. Greenberg, Wyatt R. Hack, Stephanie E. Spence, John C. Crabbe
      Despite acceptance that risk for alcohol use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many seen in multiple species, and can be experienced over a wide-ranging time course. In the present 3 studies, we developed a battery of withdrawal tests examining behavioral symptoms from multiple domains that could be measured over time in mice. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing 8 inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hrs. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using some apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), straub tail, backward walking and reductions in activity, but not changes in thermal pain sensitivity, hyperreactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should be reflecting the influences of different constellations of genes.

      PubDate: 2017-09-11T23:17:54Z
      DOI: 10.1016/j.alcohol.2017.08.014
  • Evaluation of N-acetyltaurine as an ethanol marker in human blood
    • Authors: Marc Luginbühl; Stefan König; Stefan Schürch; Wolfgang Weinmann
      Abstract: Publication date: Available online 5 September 2017
      Author(s): Marc Luginbühl, Stefan König, Stefan Schürch, Wolfgang Weinmann
      To investigate the potential of N-acetyltaurine (NAcT) in blood as a biomarker for alcohol uptake, a previously published LC-MS/MS method for urine was modified to simultaneously detect NAcT and ethyl glucuronide (EtG). The method was applied in a drinking study and by analyzing 147 forensic case samples. In the drinking study, contrary to EtG, NAcT proved to be an endogenous substance, which was present at 22 ± 7 ng/mL (13–31 ng/mL) in the blood after 2 weeks of abstinence. A moderate increase in NAcT to 40 ± 10 ng/mL (27–57 ng/mL) was observed after drinking. Within 24 h, the NAcT concentrations declined to starting concentrations in seven out of eight subjects. Peak EtG concentrations (c̅max) of 445 ± 101 ng/mL (278–662 ng/mL) were reached. While EtG in blood can be used to detect alcohol consumption even if ethanol is already eliminated, some of the maximum NAcT concentrations after a single ethanol dose were in the range of endogenous levels detected prior to the start of drinking in other subjects. In the 147 blood samples, the following concentrations were found: blood alcohol concentration (BAC): 1.22 ± 0.95 g/kg (0–3.46 g/kg); NAcT: 37.8 ± 18.4 ng/mL (12.1–109 ng/mL); EtG: 1149 ± 1121 ng/mL (0–5950 ng/mL). ROC curve analysis for BAC thresholds at 0.8 and 1.6 g/kg were performed for EtG and NAcT. Due to the presence of endogenous NAcT levels resulting in a lower sensitivity and selectivity when compared to EtG, and due to a minor increase in concentration after alcohol uptake, the usefulness of NAcT as an alcohol biomarker in blood is very limited.
      Graphical abstract image

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.05.007
  • Interactive effects of ethanol on ulcerative colitis and its associated
           testicular dysfunction in pubertal BALB/c mice
    • Authors: Isaac A. Adedara; Babajide O. Ajayi; Ifeoluwa O. Awogbindin; Ebenezer O. Farombi
      Abstract: Publication date: Available online 4 September 2017
      Author(s): Isaac A. Adedara, Babajide O. Ajayi, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi
      Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulfate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.06.001
  • Broad-spectrum protein kinase inhibition by the staurosporine analog
           KT-5720 reverses ethanol withdrawal-associated loss of NeuN/Fox-3
    • Authors: Anna R. Reynolds; Meredith A. Saunders; Jennifer N. Berry; Lynda J. Sharrett-Field; Sydney Winchester; Mark A. Prendergast
      Abstract: Publication date: Available online 30 August 2017
      Author(s): Anna R. Reynolds, Meredith A. Saunders, Jennifer N. Berry, Lynda J. Sharrett-Field, Sydney Winchester, Mark A. Prendergast
      Chronic, intermittent ethanol (CIE) exposure is known to produce neuroadaptive alterations in excitatory neurotransmission that contribute to the development of dependence. Although activation of protein kinases (e.g., cyclic AMP [cAMP]-dependent protein kinase) is implicated in the synaptic trafficking of these receptors following CIE exposure, the functional consequences of these effects are yet to be fully understood. The present study sought to delineate the influence of protein kinase in regulating cytotoxicity following CIE exposure, as well as to examine the relative roles of ethanol exposure and ethanol withdrawal (EWD) in promoting these effects. Rat hippocampal explants were exposed to a developmental model of CIE with or without co-application of broad-spectrum protein kinase inhibitor KT-5720 (1 μM) either during ethanol exposure or EWD. Hippocampal cytotoxicity was assessed via immunofluorescence (IF) of neuron-specific nuclear protein (NeuN) with thionine staining of Nissl bodies to confirm IF findings. Concomitant application of ethanol and KT-5720 restored the loss of NeuN/Fox-3 IF in pyramidal CA1 and granule DG cell layers produced by CIE, but there was no restoration in CA3. Application of KT-5720 during EWD failed to significantly alter levels of NeuN IF, implying that ethanol exposure activates protein kinases that, in part, mediate the effects of EWD. KT-5720 application during EWD also restored thionine staining in CA1, suggesting kinase regulation of both neurons and non-neuronal cells. These data demonstrate that CIE exposure alters protein kinase activity to promote ethanol withdrawal-associated loss of NeuN/Fox-3 and highlight the influence of kinase signaling on distinct cell types in the developing hippocampus.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.05.006
  • The new kisspeptin derivative – kissorphin (KSO) – attenuates acute
    • Authors: Ewa Gibula-Bruzda; Marta Marszalek-Grabska; Kinga Gawel; Roza Trzcinska; Jerzy Silberring; Jolanta H. Kotlinska
      Abstract: Publication date: Available online 24 August 2017
      Author(s): Ewa Gibula-Bruzda, Marta Marszalek-Grabska, Kinga Gawel, Roza Trzcinska, Jerzy Silberring, Jolanta H. Kotlinska
      Kissorphin (KSO) is a new peptide derived from kisspeptin-10. This peptide possesses neuropeptide FF (NPFF)-like biological activity in vitro; NPFF, in many cases, inhibits opioid and ethanol effects in rodents. Therefore, the current study explored the influence of KSO on acute ethanol- and morphine-induced hyperactivity, and on the development and expression of locomotor sensitization induced by these drugs. In the present study, sensitization to locomotor effects was induced by repeated exposure to ethanol (2.4 g/kg, intraperitoneally [i.p.], 1 × 4 days) or morphine (10 mg/kg, subcutaneously [s.c.], 1 × 7 days). We found that KSO (1–10 nmol/300 μL, intravenously [i.v.]) did not have an impact on locomotor activity of naïve mice. However, it reduced both acute ethanol- (10 nmol/300 μL) and morphine-induced hyperactivity (3 and 10 nmol/300 μL). Pretreatment of animals with KSO (10 nmol/300 μL), before every ethanol or morphine injection during development of sensitization or before the ethanol or morphine challenge, attenuated the development, as well as the expression of locomotor sensitization to both substances. Moreover, prior administration of the NPFF receptor antagonist RF9 (10 nmol/300 μL, i.v.) inhibited the ability of KSO (10 nmol/300 μL) to reduce the expression of ethanol and morphine sensitization. KSO given alone, at all used doses, did not influence the motor coordination measured via the rotarod test. The results from this study show that KSO effectively attenuated acute and repeated effects of ethanol and morphine. Thus, KSO possesses NPFF-like anti-opioid activity in these behavioral studies.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.04.005
  • Alcohol-use disorders and suicide: Results from a psychological autopsy
           study in Australia
    • Authors: Kairi Kõlves; Brian M. Draper; John Snowdon; Diego De Leo
      Abstract: Publication date: Available online 24 August 2017
      Author(s): Kairi Kõlves, Brian M. Draper, John Snowdon, Diego De Leo
      Introduction People who die by suicide have a higher risk of an alcohol-use disorder (AUD) at the time of death. The present study aims to compare 1) suicide cases with and without AUD, and 2) suicide and sudden-death controls with AUD. Methods The psychological autopsy method was utilized to investigate suicide and sudden death in Australia (QLD and NSW). Initial information was gathered from coroners’ offices. Potential informants were approached and semi-structured interviews were conducted. Univariate and multivariate logistic regression were applied. Results People with AUD who died by suicide were significantly more likely to have another substance-use disorder, history of suicide attempt, recent serious arguments with spouse/partner and other family members, been unfaithful to partner/spouse, be victims of a crime, and were less likely to be from a non-English speaking background. They were also younger and had higher levels of aggression compared to non-AUD suicides. AUD suicides were more likely to have mood disorders, previous suicide attempt, expressing hopelessness, higher scores in aggression towards self, romantic relationship breakup, and serious arguments with other family members than AUD sudden deaths. Aggressive behavior, having another substance-use disorder, and history of serious arguments with family members remained significant in the final model comparing suicides with and without AUD. Conclusion Our findings support that aggressive behavior, comorbidity with other psychiatric disorders as predisposing factors, and recent interpersonal conflicts such as breakup and family conflicts can trigger suicide in people with AUD. There is a need for proper diagnosis, risk assessment, and treatment in suicidal people with AUD.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.05.005
  • Effects of Binge Alcohol Exposure on Burkholderia thailandensis-Alveolar
           Macrophage Interaction
    • Authors: Victor Jimenez; Ryan Moreno; Emily Kaufman; Heidie Hornstra; Erik Settles; Bart J. Currie; Paul Keim; Fernando P. Monroy
      Abstract: Publication date: Available online 19 August 2017
      Author(s): Victor Jimenez, Ryan Moreno, Emily Kaufman, Heidie Hornstra, Erik Settles, Bart J. Currie, Paul Keim, Fernando P. Monroy
      Alcohol consumption has diverse and well-documented effects on the human immune system and its ability to defend against infective agents. One example is melioidosis, a disease caused by infection with Burkholderia pseudomallei, which is of public health importance in Southeast Asia and Northern Australia, with an expanding global distribution. While B. pseudomallei infections can occur in healthy humans, binge alcohol use is progressively being recognized as a major risk factor. Although binge alcohol consumption has been considered as a risk factor for the development of melioidosis, no experimental studies have investigated the outcomes of alcohol exposure on Burkholderia spp. infection. Therefore, we proposed the use of non-pathogenic B. thailandensis E264 as a useful BSL-1 model system to study the effects of binge alcohol exposure on bacteria and alveolar macrophage interactions. The MH-S alveolar macrophage (AMs) cell line was used to characterize innate immune responses to infection in vitro. Our results showed that alcohol exposure significantly suppressed the uptake and killing of B. thailandensis by AMs. Alveolar macrophages incubated in alcohol (0.08%) for 3 h prior to infection showed significantly lower bacterial uptake at 2 and 8 h post infection. Activated AMs with IFN-γ and pre and post-incubation in alcohol when exposed to B. thailandensis released lower nitric oxide (NO) concentrations, compared to activated AMs with IFN-γ from non-alcoholic controls. As a result, B. thailandensis survival and replication increased ∼2.5-fold compared to controls. The presence of alcohol (1%) also increased bacterial survival within AMs. Alcohol significantly decreased bacterial motility compared to non-alcoholic controls. Increased biofilm formation was observed at 3 and 6 h when bacteria were pre-incubated in (0.08%) alcohol. These results provide insights into binge alcohol consumption, a culturally prevalent risk factor, as a predisposing factor for melioidosis.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.04.004
  • Increased risk of pyogenic liver abscess in patients with alcohol
           intoxication: A population-based retrospective cohort study
    • Authors: Yao-Chien Wang; Kai-Wei Yang; Peter Tien-Ying Lee; Cheng-Li Lin; Geng-Wang Liaw; Dong-Zong Hung; Chia-Hung Kao; Wei-Kung Chen; Tse-Yen Yang
      Abstract: Publication date: Available online 18 August 2017
      Author(s): Yao-Chien Wang, Kai-Wei Yang, Peter Tien-Ying Lee, Cheng-Li Lin, Geng-Wang Liaw, Dong-Zong Hung, Chia-Hung Kao, Wei-Kung Chen, Tse-Yen Yang
      We designed a population-based retrospective cohort study to investigate the association between the event of alcohol intoxication and the risk of pyogenic liver abscess. The present study enrolled 245,076 patients with a history of alcohol intoxication from 2000 to 2010 and matched each of them with four comparison patients, with similar mean age and sex ratios. We determined the cumulative incidences and adjusted hazard ratios (aHRs) of liver abscess. A significant association was observed between alcohol intoxication and liver abscess. The incidence density rate of liver abscess was 3.47-fold greater in the alcohol intoxication (AI) cohort than in the non-AI cohort (12.2 vs. 3.43 per 10,000 person-years), with an adjusted HR (aHR) of 2.64 (95% CI = 2.26 to 3.08). This population-based study positively associated the event of alcohol intoxication with increased risk of liver abscess. Our findings warrant further large-scale and in-depth investigations in this area.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.05.003
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