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Publisher: Elsevier   (Total: 3184 journals)

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Showing 1 - 200 of 3184 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 37, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 26, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 100, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 40, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 6)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 434, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 28, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 308, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 18, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 11, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 184, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 12, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 17, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 29, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 11, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 33, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 29, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 20, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 13)
Advances in Digestive Medicine     Open Access   (Followers: 12)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 29, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 51, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 66, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 21, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 10, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 7, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 24)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 3, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 9, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 12, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 8, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 24)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 5)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 18, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 18)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 6)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 66)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 1, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 6)
Advances in Space Research     Full-text available via subscription   (Followers: 420, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 37, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 53, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 382, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 472, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 45, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 7, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 11)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 10, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 54, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 58, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 63, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 46, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 12)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 37, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 29, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 36, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 50)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 249, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 66, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 32, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 66, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 24, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 208, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 25, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 218, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 6, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)

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Similar Journals
Journal Cover
Journal Prestige (SJR): 1.153
Citation Impact (citeScore): 3
Number of Followers: 12  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0741-8329
Published by Elsevier Homepage  [3184 journals]
  • Evoked K-complexes and Altered Interaction Between the Central and
           Autonomic Nervous Systems during Sleep in Alcohol Use Disorder
    • Abstract: Publication date: Available online 17 September 2019Source: AlcoholAuthor(s): Adrian R. Willoughby, Massimiliano de Zambotti, Fiona C. Baker, Ian M. Colrain There is evidence for impairment in both central nervous system (CNS) and autonomic nervous system (ANS) function with prolonged alcohol use. While these impairments persist into abstinence, partial recovery of function has been demonstrated in both systems during sleep. To investigate potential ANS dysfunction associated with cortical CNS responses (impairment in CNS-ANS coupling), we assessed phasic heart rate (HR) fluctuation associated with tones that did and those that did not elicit a K-complex (KC) during stable N2 non-rapid eye movement (NREM) sleep in a group of 16 recently abstinent alcohol use disorder (AUD) patients (41.6±8.5 years) and a group of 13 sex- and age-matched control participants (46.6±9.3 years). Electroencephalogram (EEG) and electrocardiogram (ECG) were recorded throughout the night. Alcohol consumption questionnaires were also administered to the AUD patients. AUD had elevated HR compared to controls at baseline prior to tone presentation. The HR fluctuation associated with KCs elicited by tone presentation was significantly smaller in amplitude, and tended to be delayed in time, in the AUD group compared with the control group, and the subsequent deceleration was also smaller in AUD. In both groups the increase in HR was larger and occurred earlier when KCs were produced than when they were not and there was no difference in the magnitude of the KC effect between groups. Phasic HR changes associated with KCs elicited by tones are impaired in AUD participants, reflecting ANS dysfunction possibly caused by an alteration of cardiac vagal trafficking. However, only the timing of the HR response was found to relate to estimated lifetime alcohol consumption in AUD. The clinical meaning and implications of these novel findings need to be determined.
  • Association between alcohol consumption and hypertension in Chinese
           adults: findings from the CHNS
    • Abstract: Publication date: Available online 13 September 2019Source: AlcoholAuthor(s): Fanfan Zhao, Qingqing Liu, Yuanjie Li, Xiaojie Feng, Hong Chang, Jun Lyu ObjectivesTo obtain information about alcohol consumption (henceforth “drinking”) among Chinese adults from 1991 to 2011, and to explore the association between drinking behavior and hypertension.MethodsAccording to the longitudinal data obtained in the China Health and Nutrition Survey (1991–2011), 50013 records of 12577 adults were selected by applying eligibility criteria. Chi-test was employed to explore the association between drinking and hypertension, by considering the frequency of drinking, daily alcohol intake, alcohol type, and the prevalence of hypertension. A multilevel logistic regression model was used to analyze the longitudinal association between drinking frequency and the prevalence of hypertension.ResultsThe prevalence of hypertension was higher in participants with a high drinking frequency than those with a low drinking frequency among both males and females (P
  • Consequences Of Alcohol Use, And Its Association With Psychological
           Distress, Sensitivity To Emotional Contagion And Age Of Onset Of Alcohol
           Use, In Uruguayan Youth With Or Without College Degree
    • Abstract: Publication date: Available online 11 September 2019Source: AlcoholAuthor(s): Paul Ruiz, Angelina Pilatti, Ricardo M. Pautassi Psychological distress can promote alcohol consumption during emerging adulthood. Still unknown is, however, how predisposition to emotional contagion alters psychological distress, and how these phenomena are affected by level of education. The present study analyzed the effect of psychological distress, age of first contact with alcohol (early, late), and predisposition to emotional contagion on alcohol-induced negative consequences and on the volume of alcohol consumed during the last year. We also described alcohol-use behaviors as a function of sex, maximum level of education and age of first contact with alcohol, in 1505 youth from Uruguay (18-30 years). A survey measured alcohol use (Alcohol Use Disorders Identification Test and ad-hoc questionnaire), negative consequences of alcohol use [young adult alcohol consequences questionnaire (YAACQ)], psychological distress (Kessler scale) and proclivity to emotional contagion (Doherty Emotional contagion scale). The patterns of alcohol use were greater in men vs. women and in those featuring an early age of first alcohol use, yet similar in college and non-college graduates. Early drinkers had greater levels of psychological distress than late-onset drinkers. There was a significant bivariate and multiple correlation between psychological distress and the number of negative consequences of alcohol experienced during the last year, which remained significant even after controlling for total volume of alcohol consumed. Significant associations emerged between YAACQ scores and frequency of heavy episodic or binge drinking, and between psychological distress and emotional contagion, but not between emotional contagion and any of the remaining variables. Psychological distress was not significantly correlated with heavy episodic or binge drinking. The study indicates that, during adolescence and youth, psychological distress is associated with experiencing negative consequences of alcohol consumption. The study also suggested that greater levels of psychological distress may underlie the facilitating effect of an early age of drinking onset upon alcohol drinking patterns.
  • Inhibitory Influence of Agmatine in Ethanol Withdrawal-Induced Depression
           in Rats: Behavioral and Neurochemical Evidences
    • Abstract: Publication date: Available online 11 September 2019Source: AlcoholAuthor(s): Niyamat Chimthanawala, Shruti Patil, Rishabh Agrawal, Nandkishor R. Kotagale, Milind J. Umekar, Brijesh G. Taksande Although ethanol withdrawal depression is one of the prominent reasons for its reinstatement and dependence, its neurochemical basis is not clearly understood. Present study investigated the role of agmatinergic system in ethanol withdrawal-induced depression using forced swim test (FST) in rats. Chronic exposure of animals to ethanol for 21 days and its abrupt withdrawal produced depression like behavior as evidenced by increased immobility time in FST, compared to the pair-fed control animals. The ethanol withdrawal-induced depression was significantly attenuated by agmatine (20-40 μg/rat, i.c.v.), moxonidine (50 μg/rat, i.c.v.), 2-BFI (20 μg/rat, i.c.v.), L-arginine (80 μg/rat, i.c.v.), amino-guanidine (25 μg/rat, i.c.v.) and arcaine (50 μg/rat, i.c.v.) by their once daily administration during the withdrawal phase (Day 21, 22 and 23). The antidepressant effect of agmatine in ethanol withdrawn rats was potentiated by imidazoline receptor I1 agonist, moxonidine (25 μg/rat, i.c.v.) and imidazoline receptor I2 agonist 2-BFI (10 μg/rat, i.c.v.) at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan (10 μg/rat, i.c.v.) and imidazoline receptor I2 antagonist, idazoxan (4 μg/rat, i.c.v.). In addition, agmatine levels were significantly reduced in brain samples of ethanol withdrawn rats as compared to the pair-fed control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in ethanol withdrawal-induced depression. The data projects agmatine as a potential therapeutic target for the alcohol withdrawal-induced depression.
  • Alcohol-induced lipid dysregulation impairs glycolytic responses to LPS in
           alveolar macrophages
    • Abstract: Publication date: Available online 6 September 2019Source: AlcoholAuthor(s): William S. Slovinsky, Hoora Shaghaghi, Rachel Para, Freddy Romero, Ross Summer Several conditions are marked by increased susceptibility to, and enhanced severity of, bacterial infections. Alcohol use disorder, one of these conditions, is known to predispose to bacterial pneumonia by suppressing the lung’s innate immune system, and more specifically by disrupting critical alveolar macrophage (AM) functions. Recently, we established that chronic ethanol consumption also perturbs surfactant lipid homeostasis in the lung and that elevated concentrations of free fatty acids contribute to blocking essential AM functions, such as agonist-induced cytokine expression. In this study, we extend these observations by showing that elevated free fatty acid levels impair metabolic responses to lipopolysaccharide (LPS) in AMs. In particular, we show that the glycolytic reprogramming characteristic of LPS-stimulated AMs is blunted by the saturated fatty acid palmitate, whereas oleate, an unsaturated fatty acid, or ethanol alone, had no effect on this adaptive metabolic response. Additionally, we found that elevated concentrations of palmitate induced mitochondrial oxidative stress and that glycolytic reprogramming and cytokine production to LPS could be partially restored in AMs by either pharmacologically blocking palmitate entry into mitochondria or administering a mitochondrial specific antioxidant. Taken together, these findings suggest that alcohol and elevated levels of saturated fatty acids conspire to impair pulmonary innate immunity by altering metabolic responses in AMs. Additionally, our findings suggest that targeting the mechanisms involved in fatty acid metabolism can restore pulmonary immunity and limit bacterial pneumonia in individuals with alcohol use disorder.
  • Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH)
           compared to Non-alcoholic Steatohepatitis (NASH) and normal controls
    • Abstract: Publication date: Available online 5 September 2019Source: AlcoholAuthor(s): Jiajie G. Lu, Askalu Iyasu, Barbara French, Brittany Tillman, Samuel W. French, Samuel W. French, M.D Previously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). We conducted immunofluorescence studies of expression of MHCII, the binding partner of CD4, on patient liver biopsies of AH, NASH, and normal controls. In cases of alcoholic hepatitis, there was prominent sinusoidal expression of MHC II; In NASH biopsies there was comparatively lower expression of MHC II, but still more than control tissue. Immunohistochemical stain for CD4 showed CD4 positive lymphocytes closely associated with hepatocytes in AH biopsies. Furthermore, expression levels of the multifunctional cytokine IL-1α was higher in AH compared to NASH and control biopsies. These results underlie the more severe nature of alcoholic hepatitis and underscore the autoimmune mechanisms involved in the liver damage found in alcoholic hepatitis.
  • Home-detoxification and relapse prevention for alcohol dependence in low
           resource settings: an exploratory study from Goa, India.
    • Abstract: Publication date: Available online 29 August 2019Source: AlcoholAuthor(s): Abhijit Nadkarni, Richard Velleman, Urvita Bhatia, Godwin Fernandes, Ethel D’souza, Pratima Murthy Despite the increasing burden of alcohol dependence, treatment resources in low- and middle-income countries such as India, are concentrated in poorly accessible tertiary care facilities. The aim of our study was to examine the feasibility and acceptability of lay health worker delivered home-based packages of care for alcohol dependence. We conducted an uncontrolled treatment cohort with alcohol dependent adult males recruited in primary and secondary care. Lay health workers delivered home-detoxification and/or relapse prevention counselling. Process data was analysed using descriptive statistics. 11 men with alcohol dependence received home detoxification and relapse prevention counselling and 27 received only relapse prevention counselling. Of the 11 receiving home detoxification, one participant re-started drinking; all the rest safely completed the home detoxification. During detoxification, the pulse, blood pressure and temperature remained within the normal range and ataxia, dehydration, disorientation, sleep normalised over the course of the detoxification. Of the 38 who entered relapse prevention treatment, 15 (39.5%) completed treatment or had a planned discharge. The mean number of sessions was 2.4 (SD=1.3); those who had a planned discharge received on an average 3.7 (SD 0.5) sessions and those who dropped out received on an average 1.4 (SD 0.8) sessions. There was no significant change in daily alcohol consumption and percentage days of heavy drinking (PDHD) between baseline and follow-up in the whole cohort. The SIP score reduced significantly in the whole cohort (24.5 vs 15.0, p=0.002), and also when segregated by treatment settings, and type of treatment package received. With appropriate adaptations, our intervention warrants further research as it has the potential to bridge the significant treatment gap for alcohol dependence in low- and middle- income countries.
  • Correlations between subunits of GABAA and NMDA receptors after chronic
           alcohol treatment or withdrawal and the effect of taurine in the
           hippocampus of rats
    • Abstract: Publication date: Available online 29 August 2019Source: AlcoholAuthor(s): Alana Witt Hansen, Felipe Borges Almeida, Solange Bandiera, Rianne Remus Pulcinelli, Greice Caletti, Grasiela Agnes, Leonardo Fernandes de Paula, Natália Azuaga Nietiedt, Maurício Schüler Nin, Helena Maria Tannhauser Barros, Rosane Gomez Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This unbalance includes changes in GABA receptors – importantly in GABAA subtypes – and glutamate receptor – especially in NMDA subtypes. A better comprehension of the different roles of GABAAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2x/day, for 28 days. From day 29 to 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally, once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.
  • Disinhibited Personality, Incentives, Disincentives, and Drinking-Related
    • Abstract: Publication date: Available online 28 August 2019Source: AlcoholAuthor(s): Peter R. Finn, Lindsey Fisher, Haley Mayer, Polly Ingram, Lindy Howe, Emily Atkinson Disinhibited personality traits, such as impulsivity (IMP), excitement seeking (ES), and low harm avoidance (HA) are thought to reflect a basic vulnerability toward alcohol use disorder (AUD), however, the specific vulnerability mechanisms associated with each trait are not well understood and there are no studies of the association between disinhibited personality and drinking-related decisions. This study investigated individual differences in drinking-related decisions associated with each trait using a task that manipulated the effects of incentives and disincentives on decisions to attend and drink at different hypothetical drinking events in a sample of 430 young adults (237 men, 193 women, mean age 21.3 years) over 60% of whom had an AUD of varying severity. The results revealed each personality domain was differentially associated with different aspects of drinking decisions. Both IMP and low HA were associated with being more likely to decide to attend party events with moderate and high goal-related responsibility disincentives. We suggest that low HA is associated with reduced sensitivity to the negative consequences of not meeting a responsibility, while IMP is associated with increased discounting of future rewards (associated with meeting a responsibility) relative to the immediate reward of attending a party event. ES was associated with being more responsive to alcohol party incentives when making decisions about attending party events and deciding to drink more at events with the highest reward potential suggesting that ES is related to a reward sensitivity decision bias. IMP appears to be associated with stronger approach that results in decisions to consume more alcohol regardless of context. The results suggest specific mechanisms by which different domains of disinhibited personality affect actual drinking-related decisions.
  • The effects of social instability stress and subsequent ethanol
           consumption in adolescence on brain and behavioural development in male
    • Abstract: Publication date: Available online 26 August 2019Source: AlcoholAuthor(s): Marina L. Marcolin, Jennet L. Baumbach, Travis E. Hodges, Cheryl M. McCormick Excessive drinking in adolescence continues to be a problem, and almost a quarter of young Canadians have reported drinking five or more in one occasion in recent surveys. The consequences of such drinking may be more pronounced when commenced in adolescence, given the ongoing brain development during this period of life. Here, we investigated the consequences of three weeks intermittent access to ethanol in mid-adolescence to early adulthood in rats and the extent to which a stress history moderated the negative consequences of ethanol access. In experiment 1, male rats that underwent adolescent social instability stress (SS; daily 1 hr isolation + return to unfamiliar cage partner every day from PND 30-45) did not differ from control (CTL) rats in intake of 10% ethanol sweetened with 0.1% saccharin (access period; PND 47-66). Ethanol drinking reduced proteins relevant for synaptic plasticity (αCaMKII, βCaMKII and PSD-95) in the dorsal hippocampus, and in CTL rats only in the prefrontal cortex (αCaMKII and PSD 95), attenuating the difference between CTL and SS rats in the water-drinking group. In experiment 2, ethanol also attenuated the difference between SS and CTL rats in a social interaction test by reducing social interaction in SS rats; CTL rats, however, had a higher intake of ethanol than did SS rats during the access period. Ethanol drinking reduced baseline and fear recall recovery concentrations of corticosterone relative to those exposed only to water, although there was no effect of either ethanol or stress history on fear conditioning. Ethanol drinking did not influence intake after 9 days of withdrawal, however, ethanol-naïve SS rats drank more than did CTL rats when given a 24-hour access in adulthood. These results reveal a complex relationship between stress history and ethanol intake in adolescence on outcomes in adulthood.
  • Alcohol Use Disorders Identification Test (AUDIT): Validation of the
           Persian Version in an Iranian Population
    • Abstract: Publication date: Available online 15 August 2019Source: AlcoholAuthor(s): Hosein Rafiemanesh, Kamran Yazdani, Saharnaz Nedjat, Alireza Noroozi, John B. Saunders, Ramin Mojtabai, Afarin Rahimi-Movaghar Background and AimsIt is important to incorporate a screening test for unhealthy alcohol use into primary and other health care settings. The Alcohol Use Disorders Identification Test (AUDIT) is one of the most commonly used of such tests. The objectives of this study were to evaluate the psychometric properties of the Persian version of AUDIT, and to determine the best cut-off points for detection of hazardous drinking and alcohol use disorders.MethodsWe translated the AUDIT to Persian and assessed its face and content validity, reliability and criterion validity against the diagnosis of alcohol use disorders according to the International Classification of Diseases, 10th Revision (ICD-10) diagnostic guidelines, as assessed using the Composite International Diagnostic Interview (CIDI). We determined the best cut-off points for detection of hazardous use, harmful use, and dependence using receiver operating characteristic (ROC) curve analysis. Psychometric properties were assessed in a sample of 400 participants attending medium-term residential drug treatment centers located in Tehran, Iran.ResultsThe Persian AUDIT had high internal consistency (Cronbach’s alpha = 0.88), and test-retest reliability (intraclass correlation coefficient = 0.84). The questionnaire also had excellent face and content validity as well as criterion validity when compared with CIDI. The best cut-off points for alcohol dependence, harmful use, and hazardous use were 11 (sensitivity = 95.6, specificity = 80.4), 7 (sensitivity = 85.5, specificity = 84.2), and 5 (sensitivity = 87.6, specificity = 92.9), respectively.ConclusionsThe Persian version of the AUDIT has excellent psychometric properties as a screening tool for alcohol use disorders and hazardous alcohol use in settings in which alcohol use is common. Further research on the AUDIT in the general population and in primary health care settings is warranted.
  • Impact of acute ethanol exposure on body temperatures in aged, adult and
           adolescent male rats
    • Abstract: Publication date: Available online 10 August 2019Source: AlcoholAuthor(s): Meredith R. Watson, Kimberly James, Guy Mittleman, Douglas B. Matthews The United States population is continuing to increase in age and data suggest that by the year 2060 the population of people over the age of 65 will more than double, providing a potentially massive strain on healthcare systems. Research demonstrates individuals 65 and older continue to consume ethanol, often at high levels. However, preclinical animal models are still being developed to understand how ethanol might interact with the aged population. The current experiments investigated differential body temperature responses in aged rats compared to adult rats and adolescent rats. Aged (19 months of age), adult (70 days of age) or adolescent (30 days of age) male Sprague Dawley rats were administered 1.0 g/kg, 2.0 g/kg or 3.0 g/kg ethanol, i.p., in a balanced Latin square design. Prior to ethanol administration, a core body temperature via an anal probe was obtained, and then repeatedly determined every 60 minutes following ethanol exposure for a total of 360 minutes. In addition, a blood sample was obtained from a tail nick 60, 180 and 300 minutes following the ethanol injection to investigate the relationship of ethanol levels and body temperature in the same animals. Aged rats had significantly greater reductions in body temperature compared to either adult or adolescent rats following both the 2.0 g/kg and 3.0 g/kg ethanol injection. Additionally, adolescent rats cleared ethanol significantly faster than aged or adult animals. These experiments suggest body temperature regulation in aged rats might be more sensitive to acute ethanol compared to adult rats or adolescent rats. Future studies are needed to identify the neurobiological effects underlying the differential sensitivity in aged rats to ethanol.
  • Functional exercise capacity in inpatients with alcohol use disorder
           versus healthy controls: a pilot study
    • Abstract: Publication date: Available online 6 August 2019Source: AlcoholAuthor(s): Davy Vancampfort, Mats Hallgren, Hannelore Vandael, Michel Probst, Philip Van Hoof, Joseph Firth, Tine Van Damme The purpose of this study was to compare the functional exercise capacity of patients with alcohol use disorders (AUD) with an age-, gender- and body mass index (BMI)-matched healthy control group. Thirty patients (22♂, 40.4±10.5years, illness duration=9.7±9.3 years) and healthy control subjects (22♂, 40.2±10.7 years) participated. Participants performed a 6-minute walk test (6MWT) to assess their functional exercise capacity, were asked about musculoskeletal problems and dyspnea, executed a standing broad jump to assess the muscular strength and completed the International Physical Activity Questionnaire (IPAQ). Patients also filled in the Positive Affect and Negative Affect Schedule (PANAS) and Alcohol Use Disorders Identification Test (AUDIT). Our data show that patients with AUD walked a significantly shorter distance on the 6MWT (649.0±72.9 meters versus 724.4±89.0 meters, P=0.001). In patients with AUD the variance in standing broad jump score explained 43.6% of the variance in the 6MWT-score. The current study demonstrates that an impaired muscle strength is negatively associated with functional outcomes in patients with AUD. Exercise interventions should be investigated in order assess whether they can ameliorate muscle strength and daily life functioning of this vulnerable population.
  • Chronic alcohol induced liver injury correlates with memory deficits: Role
           for neuroinflammation
    • Abstract: Publication date: Available online 6 August 2019Source: AlcoholAuthor(s): Jean A. King, Benjamin C. Nephew, Asmita Choudhury, Guillaume L. Poirier, Arlene Lim, Pranoti Mandrekar Alcohol use disorder (AUD) affects over 15 million adults over age 18 in the United States, with estimated costs of 220 billion dollars annually—mainly due to poor quality of life and lost productivity, which in turn is intricately linked to cognitive dysfunction. AUD induced neuroinflammation in the brain, notably the hippocampus, is likely to contribute to cognitive impairments. The neuroinflammatory mechanisms mediating the impact of chronic alcohol on the central nervous system, specifically cognition, require further study. We hypothesized that chronic alcohol consumption impairs memory and increases the inflammatory cytokines TNFα, IL6, MCP1, and IL1β in the hippocampus and prefrontal cortex regions in the brain. Using the chronic-binge Gao-NIAAA alcohol mouse model of liver disease, representative of the drinking pattern common to human alcoholics, we investigated behavioral and neuroinflammatory parameters. Our data show that chronic alcohol intake elevated peripheral and brain alcohol levels, induced serum alanine aminotransferase (ALT), a marker of liver injury, impaired memory and sensorimotor coordination, increased inflammatory gene expression in the hippocampus and prefrontal cortex. Interestingly, serum ALT and hippocampal IL6 correlated with memory impairment, suggesting an intrinsic relationship between neuroinflammation, cognitive decline, and liver disease. Overall, our results point to a likely liver-brain functional partnership and suggest that future strategies to alleviate hepatic and/or neuroinflammatory impacts of chronic AUD may result in improved cognitive outcomes.
  • Inverse association between habitual alcohol drinking and d-dimer in
           patients with type 2 diabetes mellitus
    • Abstract: Publication date: Available online 11 July 2019Source: AlcoholAuthor(s): Mikio Marumo, Kazumi Ekawa, Shigeyuki Ebara, Ichiro Wakabayashi Alcohol is known to inhibit blood coagulation. Patients with diabetes mellitus are prone to show hypercoagulability. However, it remains to be clarified whether and how habitual alcohol drinking affects coagulability in patients with diabetes. The purpose of this study was to determine the relationship between alcohol intake and d-dimer, a sensitive marker of blood coagulation, in patients with diabetes. We investigated the relationship between alcohol intake and d-dimer in plasma of 269 patients with type 2 diabetes by using analysis of covariance and logistic regression analysis after adjustment for age, gender, body mass index, hemoglobin A1c, and histories of smoking and anti-coagulation therapy. Log-transformed d-dimer and HDL cholesterol were significantly lower and higher, respectively, in regular drinkers than in nondrinkers, while there were no significant differences in log-transformed d-dimer and HDL cholesterol in occasional drinkers and nondrinkers. Odds ratios of regular drinkers vs. nondrinkers for high d-dimer (0.46 [0.21-0.98]) and low HDL cholesterol (0.20 [0.08-0.50]) were significantly lower than the reference level, while the odds ratios of occasional drinkers for high d-dimer (1.24 [0.41-3.73] and low HDL cholesterol (0.43 [0.15-1.25]) were not significantly different from the reference level. HDL cholesterol showed a significant inverse correlation with log-transformed d-dimer both in overall subjects and in nondrinkers. Regular drinking, but not occasional drinking, was associated with lower d-dimer levels, suggesting that habitual alcohol drinking suppresses hypercoagulability in patients with diabetes. There is an alcohol intake-independent inverse association between HDL cholesterol and d-dimer.
  • Introduction to a Special Issue on Wearable Alcohol Biosensors:
           Development, Use, and State of the Field
    • Abstract: Publication date: Available online 9 July 2019Source: AlcoholAuthor(s): M. Katherine Jung
  • Special Issue on Alcohol Biosensors: Development, Use, and State of the
           Field:Summary, Conclusions, and Future Directions
    • Abstract: Publication date: Available online 9 July 2019Source: AlcoholAuthor(s): Susan E. Luczak, Vijay A. Ramchandani
  • Young Adult Binge Drinkers Have Immunophenotypical Disarrangements In
           Peripheral Natural Killer Cells
    • Abstract: Publication date: Available online 29 June 2019Source: AlcoholAuthor(s): Adolfo Pérez-García, América Guadalupe Arroyo-Valerio, Mayra A. Bustos-Esquivel, Rosa M. Quispe-Siccha, José Luis Zaldívar-Fujigaki, Judith Pacheco-Yepez, David Kershenobich, Joselín Hernández-Ruiz Alcohol consumption is an issue of worldwide relevance and a national scale problem in Mexico. The consumption pattern of large amounts in weekends is rapidly increasing in young adults between 18-29 years. Despite various studies have focused on the noxious effect of alcohol in immunity, the changes in the immunoprofiles of peripheral blood cells have not been completely described. Natural Killer Cells (NKC) are lymphoid origin cells of the immune system that are responsible of defense against tumors among other functions. In homeostatic conditions, they have found to be in a state of “dynamic balance” between activation and inhibition stimuli, which if broken, may lead to immunosuppression or activation of cytotoxic mechanisms. In this study we evaluated the immunoprofile of peripheral NKC of 54 young adults, 29 of which were binge drinkers and 25 low risk (LR), as classified by validated tools. Drinking habits were assessed. Blood samples were collected to perform hematic biometry and liver enzyme tests. Peripheral NKC were identified by FACS, and stained for CCR2, CCR4, CCR5, CXCR4, CD 69, CD127, CD137, TLR4 and Granzyme B. The data were analyzed using the T-test and Mann– Whitney’s U-test for contrasts, and the effect size was obtained in order to evaluate the impact of each immunoprofile. The binge group showed increased expression of CCR5 and PD-1 in NKC respect to the LR, and decreased expression of TLR4, along with less CCR4+ cells. Moreover, the increase found in CCR5 and PD-1 expression was correlated to the number of drinks in last occasion. Our findings show that young binge drinkers have different immunoprofiles that could suggest an early status of immunosupression and trafficking of NKC to the liver, that could be related to the onset of primeval liver damage
  • Munc+13-1+heterozygosity+does+not+alter+Voluntary+ethanol+consumption+or+sensitivity+in+mice&rft.title=Alcohol&rft.issn=0741-8329&">Munc 13-1 heterozygosity does not alter Voluntary ethanol consumption or
           sensitivity in mice
    • Abstract: Publication date: Available online 29 June 2019Source: AlcoholAuthor(s): Jessica I. Wooden, Kyle Schuller, Gregg Roman, Joydip Das, J. Leigh Leasure The role of the munc 13-1 pre-synaptic protein in alcohol-related behaviors has been little-studied, despite being a known site of action for ethanol binding. Munc 13-1 is an active zone protein that plays a vital role in vesicle maturation and the release of neurotransmitter in excitatory neurons. Ethanol binds munc 13-1, decreasing its functionality. In Drosophila, loss of the homologous protein Dunc13 is associated with an increase in ethanol preference, and a resistance to sedation following ethanol exposure. The current study assessed the effects of munc 13-1 heterozygosity on ethanol sensitivity and consumption in mice, as well as on learning and anxiety-like behaviors, which can influence alcohol intake. Wild type and mutant mice underwent 6 cycles of drinking-in-the-dark (DID) as well as rotarod testing following ethanol injection, to probe for differences in ethanol consumption and sensitivity, respectively. We did not detect genotype-based differences in our measures of anxiety, spatial learning, ethanol consumption, or ethanol sensitivity. However, heterozygotes showed increased use of a spatial navigation strategy in a dual solution water maze, as opposed to a stimulus-response strategy. To summarize, although reduction of Dunc13 in flies produces clear effects on ethanol consumption and sensitivity, heterozygosity for munc 13-1 does not, potentially due to compensatory adaptation by other munc 13 isoforms.
  • Is burden of disease differentially linked to spirits' A systematic
           scoping review and implications for alcohol policy
    • Abstract: Publication date: Available online 29 June 2019Source: AlcoholAuthor(s): Jürgen Rehm, Omer S.M. Hasan Most epidemiological research on alcohol as a risk factor is based on the assumption that outcomes are linked to pattern and level of alcohol exposure where different beverages are converted into grams of ethanol. This review examines this basic assumption, that alcohol has the same impact, independent of beverage type. We conducted a systematic search on comparative research of beverage-specific alcohol exposure and consequences. Research was divided by methodology (survey, case-control, cohort, time-series analyses, interventional research). Overall, many studies showed higher risks for spirits compared to beer or wine; however, most research was not controlled adequately for confounders such as patterns of drinking. While there is no conclusive evidence for spirits being associated with more harm, given the same pattern and level of alcohol exposure, some evidence supports for certain outcomes such as injuries and poisonings a potential excess risk for spirits consumption due to rapid ethanol intake and intoxication. Accordingly, encouraging people to opt for beverages with lower alcohol content via taxation strategies has the potential to reduce alcohol-attributable harm. This does not necessarily involve switching beverage type, but also can achieved within the same beverage category, by shifting from higher to lower concentration beverages.
  • Active immunization against serum alcohol dehydrogenase normalizes brain
           dopamine metabolism disturbed during chronic alcohol consumption
    • Abstract: Publication date: Available online 28 June 2019Source: AlcoholAuthor(s): Nikita A. Mitkin, Petr K. Anokhin, Maria V. Belopolskaya, Olga Y. Frolova, Ekaterina A. Kushnir, Maxim L. Lovat, Vsevolod V. Pavshintsev Chronic ethanol consumption in high doses is associated with constitutively elevated activity of the serum alcohol dehydrogenase I (ADH I) isoform, which demonstrates a high affinity not only for ethanol but also for a number of bioamine metabolites. Such excessive ADH activity is probably associated with disruptions in the metabolism of neurotransmitters (dopamine, serotonin and norepinephrine) and subsequent long-term changes in the activity of their receptors. Ultimately, a stable depressive-like condition contributes to the development of patients' craving for ethanol intake, frequent disruptions during therapy, and low efficiency of treatment.We applied active immunization against ADH to investigate its efficiency in the reduction of excessive serum ADH activity and regulation of ethanol consumption by chronically ethanol-fed Wistar rats (15% ethanol, 4 months, free-choice method), and we analyzed its ability to influence the levels of bioamines in the brain. Immunization (2 injections, 2-week intervals) was performed using a combination of recombinant horse ADH isozyme as an antigen and 2% aluminum hydroxide-based adjuvant.The efficiency of immunization was demonstrated by the production of high titers of ADH-specific antibodies, which was consistent with the significantly reduced ADH activity in the serum of chronically ethanol-fed rats. On the 26th day after the first vaccine injection, we registered significantly lower levels of alcohol consumption compared to ethanol-fed control animals, and the difference reached 16% on the 49th day of the experiment. These observations were accompanied by data that showed reduced levels of ethanol preference in immunized rats. Chronic alcohol drinking led to a decrease in dopamine and DOPAL (a direct dopamine metabolite and a high-affinity ADH substrate) levels in the striatum, while immunization neutralized this effect. Additionally, we observed that inhibition of serum ADH activity caused a decrease in peak dopamine levels during acute alcohol intake in chronically ethanol-fed rats during ethanol withdrawal that was associated with reduced tyrosine hydroxylase activity in the striatum.The obtained data suggest a significant contribution of ADH to the changes in neurotransmitter systems during chronic alcohol consumption and makes available new prospects for developing innovative strategies for treatment of excessive alcohol intake.
  • Carbohydrate deficient transferrin (CDT) predicts heavy drinking in
           adolescents with alcohol dependence
    • Abstract: Publication date: Available online 21 June 2019Source: AlcoholAuthor(s): Deborah Deas, Natalie Johnson, Suzanne Thomas A biomarker that could indicate problematic drinking in adolescents and/or reflect changes in heavy drinking would be a valuable addition to prevention, treatment, and research efforts. Carbohydrate deficient transferrin (CDT) is a valid biomarker of heavy drinking in adults, however not well examined in adolescents. Adolescents with alcohol dependence (AD) (n=21; 9 females) and non-dependent controls (ND) (n=6; 3 females), ages 14-20, were interviewed to determine drinks per drinking day, peak number of drinks, and percent days heavy drinking (≥4 standard drinks/day). Blood samples from participants were assayed for percent of transferrin that was carbohydrate deficient (%CDT). Analyses compared groups on drinking and %CDT, examined the relationship between %CDT and indices of drinking, and provided preliminary estimates of the test validity of %CDT for heavy drinking in adolescents. Among adolescents with AD, %CDT was significantly and strongly correlated (r=.54) with percent heavy drinking days, and this relationship was consistent for both males and females. AD adolescents did not differ from ND on mean %CDT levels, despite significantly greater alcohol use. Indicators of test validity showed that %CDT had low sensitivity (33%) but adequate specificity (83%) for heavy drinking. Results provide proof of concept that %CDT is a potentially valuable tool to use in alcohol treatment and research in adolescents. Even if %CDT doesn’t discriminate between adolescents with and without alcohol dependence, it could be an effective monitoring tool to indicate changes over time in binge drinking. Improved %CDT measurement methods might enhance its utility.
  • Age-dependent impairment of metabotropic glutamate receptor 2-dependent
           long-term depression in the mouse striatum by chronic ethanol exposure
    • Abstract: Publication date: Available online 21 June 2019Source: AlcoholAuthor(s): Kari A. Johnson, Daniel J. Liput, Gregg E. Homanics, David M. Lovinger Chronic alcohol exposure is associated with increased reliance on behavioral strategies involving the dorsolateral striatum (DLS), including habitual or stimulus-response behaviors. Presynaptic G protein-coupled receptors (GPCRs) on cortical and thalamic inputs to the DLS inhibit glutamate release, and alcohol-induced disruption of presynaptic GPCR function represents a mechanism by which alcohol could disinhibit DLS neurons and thus bias towards use of DLS-dependent behaviors. Metabotropic glutamate receptor 2 (mGlu2) is a Gi/o-coupled GPCR that robustly modulates glutamate transmission in the DLS, inducing long-term depression (LTD) at both cortical and thalamic synapses. Loss of mGlu2 function has recently been associated with increased ethanol seeking and consumption, but the ability of alcohol to produce adaptations in mGlu2 function in the DLS has not been investigated. We exposed male C57Bl/6J mice to a two-week chronic intermittent ethanol (CIE) paradigm followed by a brief withdrawal period, then used whole-cell patch clamp recordings of glutamatergic transmission in the striatum to assess CIE effects on mGlu2-mediated synaptic plasticity. We report that CIE differentially disrupts mGlu2-mediated long-term depression in the DLS vs. dorsomedial striatum (DMS). Interestingly, CIE-induced impairment of mGlu2-LTD in the dorsolateral striatum is only observed when alcohol exposure occurs during adolescence. Incubation of striatal slices from CIE-exposed adolescent mice with a positive allosteric modulator of mGlu2 fully rescues mGlu2-LTD. In contrast to the two-week CIE paradigm, acute exposure of striatal slices to ethanol concentrations that mimic ethanol levels during CIE fails to disrupt mGlu2-LTD. We did not observe a reduction of mGlu2 mRNA or protein levels following CIE, suggesting that alcohol effects on mGlu2 occur at the functional level. Our findings contribute to growing evidence that adolescents are uniquely vulnerable to certain alcohol-induced neuroadaptations, and identify enhancement of mGlu2 activity as a strategy to reverse the effects of adolescent alcohol exposure on DLS physiology.
  • Influence of moderate beer consumption on human gut microbiota and its
           impact on fasting glucose and β-cell function
    • Abstract: Publication date: Available online 12 June 2019Source: AlcoholAuthor(s): Fernando Hernández-Quiroz, Khemlal Nirmalkar, Loan Edel Villalobos-Flores, Selvasankar Murugesan, Yair Cruz-Narváez, Enrique Rico-Arzate, Carlos Hoyo-Vadillo, Alejandra Chavez-Carbajal, María Luisa Pizano-Zárate, Jaime García-Mena Beer is a beverage consumed worldwide for thousands of years due to social, religious, and cultural reasons, it contains polyphenolic compounds as well as phenolic acids with a potential positive effect in human health. This study aimed to explore the impact of moderate beer consumption in human health and gut microbiota function. 355 mL of non-alcoholic beer (NAB) or alcoholic beer (AB) were consumed daily by the participants for 30 days in each study. Anthropometric measures, blood samples for biochemistry, and fecal samples for microbiota analysis were collected on day 1 and 30. Microbial diversity was characterized by high throughput sequencing of 16S rDNA libraries, and data were analyzed using QIIME pipeline. We found, NAB and AB, have effect on the composition of the gut microbiota favoring the proliferation of Bacteroidetes with respect to Firmicutes. No increase in weight, waist, and hip parameters was observed, and the liver and lipid profile values were not modified only for NAB. In addition, the consumption of NAB induced a decrease in fasting blood serum glucose and an increase in functional β cells, while, on the other hand, there was an increase in blood serum glucose and decreased in functional β cells with the consumption of AB. In general, beer consumption neither change anthropometric values, nor affected liver function and although the glucose values decreased with NAB or increased with AB, they remained within normal range. Our conclusion is that moderate consumption of NAB has a positive effect on human health by supplementation of biological active polyphenol and phenolic acids, and by enrichment of the gut microbiota diversity with beneficial bacteria; while the presence of alcohol in AB interferes with this effect in our study. More work should be made on this topic before more general conclusions are drawn.Graphical abstractGraphical abstract for this article
  • Psychometric properties of the Alcohol Use Disorder Identification Test
           (AUDIT) in adolescents and young adults from Suthern Mexico: Alcohol Use
           Disorder Identification Test (AUDIT) in young Mexicans
    • Abstract: Publication date: Available online 12 June 2019Source: AlcoholAuthor(s): Luz Anyela Morales Quintero, María de la Villa Moral Jiménez, José Luis Rojas-Solís, Carolina Bringas Molleda, Alejandro Soto Chilaca, Francisco Javier Rodríguez Díaz IntroductionAlcohol abuse is a worldwide health problem because of its association with high rates of morbidity, mortality and interpersonal conflicts. In Mexico, young people are the group most severely affected by high levels of alcohol intake. This study attempts to evaluate the psychometric characteristics of the Alcohol Use Disorders Identification Test (AUDIT) in the Mexican youth population since validation studies do not exist to date.Material and methodsAn opinion sampling method was used based on the inclusion criteria for the study and the accessibility of the sample. Participants’ ages ranged from 14 to 30, and 44.2% (N=854) were male and 55.8% (N=1078) female.ResultsThe psychometric guarantees of AUDIT have been confirmed, highlighting the value of Alpha Cronbach (.804) of the scale, and the validity of its internal structure through a confirmatory factor analysis which showed the validity of the model of the three factors (Risky use, Dependence symptoms and Harmful alcohol use). The results confirm a pattern of non-daily use, and concentrated, excess use on a single occasion. The existence of significant differences has also been confirmed in terms of the legal drinking age in some of the indicators used, and the risk of alcohol consumption increases with age.ConclusionsThe appropriate psychometric properties of AUDIT have been confirmed in the Mexican youth population. It shows a public health issue that requires the design of prevention programs that impact risk factors and promote protective factors.
  • Perceptions of alcohol use among injury patients and their family members
           in Tanzanian society
    • Abstract: Publication date: Available online 10 June 2019Source: AlcoholAuthor(s): Brian J. Meier, Deena El-Gabri, Mark Mvungi, Blandina T. Mmbaga, Joao Ricardo Nickenig Vissoci, Catherine A. Staton BackgroundAlcohol is one of the leading causes of death and disability worldwide. Rates of alcohol abuse in Moshi, Tanzania, are about 2.5 times higher than the Tanzanian average. We sought to qualitatively assess the perceptions of alcohol use among injury patients in Moshi, including availability, consumption patterns, abuse, and treatments.MethodsParticipants were Emergency Department injury patients, their families, and community advisory board members. Participants were included if they were ≥15 years of age, a patient or patient’s family member seeking care at the Kilimanjaro Christian Medical Center Emergency Department, Moshi, Tanzania, for an acute injury, clinically sober at the time of enrollment, medically stable, able to communicate in Swahili and consented to participate. Focus group discussions were audiotaped, transcribed, translated, and analyzed in parallel using an inductive thematic content analysis approach. Resultant themes were then reanalyzed to ensure internal homogeneity and external heterogeneity.ResultsFourteen focus group discussions, with a total of 15 participants (40 patients, 50 family members, 15 community advisory board members), were conducted. Major themes resulting from the analysis included: 15) Early/repeated exposure; 2) Moderate use as a social norm with positive attributes; 3) Complications of abuse are widely stigmatized; and 4) Limited knowledge of availability of treatment.ConclusionsOur findings suggest that, among our unique injury population and their families, despite the normalization of alcohol-related behaviors, there is strong stigma toward complications stemming from excess alcohol use. Overall, resources for alcohol treatment and cessation, although broadly desired, are unknown to the injury population.
  • Lorazepam versus Chlordiazepoxide for the Treatment of Alcohol Withdrawal
           Syndrome and Prevention of Delirium Tremens in General Medicine Ward
    • Abstract: Publication date: Available online 6 June 2019Source: AlcoholAuthor(s): Katherine L. March, Jennifer D. Twilla, Anne B. Reaves, Timothy H. Self, Melissa M. Slayton, Jaclyn B. Bergeron, Sami A. Sakaan Alcohol withdrawal syndrome (AWS) is a serious complication of abrupt alcohol cessation. Severe AWS can develop into delirium tremens (DT), which is potentially life-threatening. Lorazepam (LOR) and chlordiazepoxide (CDE) are mainstays of therapy for AWS. Current literature lacks studies comparing outcomes between the two for patients who are not in a de-addiction ward specifically for withdrawal treatment. The primary objective of the study was to determine the incidence rate of DT between the groups. Of 2112 patients screened, 142 met inclusion criteria (LOR=74, CDE=68). Baseline characteristics were similar between groups. No significant difference in the primary outcome of DT development was observed (7% LOR, 9% CDE; p=0.76). No significant differences in cumulative doses of scheduled LOR or CDE were observed (LOR 14.6±8mg, CDE 15.4 ± 12; p=0.64). However, significant differences were found in the amount of as needed (PRN) LOR required for the two groups (LOR 3.2±4mg, CDE 6.6±13mg; p=0.03) and the amount of scheduled plus PRN LOR required (LOR 17.7±10mg, CDE 21.9±14mg; p=0.04). Doses are reported in LOR equivalents. There were no observed differences in duration of treatment (LOR 3.6±1.3 days, CDE 3.9±2.1 days; p=0.3) or length of stay (LOR 5.28±3.8 days, CDE 4.73±4.2 days p=0.4). No adverse events related to BZD were noted in either group. Hospital outcomes did not differ between the groups, but patients treated with CDE may require more adjuvant therapy to control symptoms of AWS. Both agents appear equally effective at preventing the development of DT in those patients admitted to general medicine wards.
  • Suppression of Voluntary Ethanol Intake in Mice under Constant Light and
           Constant Darkness
    • Abstract: Publication date: Available online 5 June 2019Source: AlcoholAuthor(s): Alan M. Rosenwasser, Walter D. McCulley, Matthew C. Hartmann, Michael C. Fixaris, John C. Crabbe Seasonal variations in photoperiod are associated with alterations in human mood and behavior. Similarly, manipulation of the environmental lighting regimen can exert pronounced effects on affective behavior in experimental animals. These observations may be due, in part, to light-induced alterations in circadian rhythms, but it seems likely that other, non-circadian factors also contribute. Several studies have shown that voluntary alcohol (ethanol) consumption can be affected by lighting conditions in rodents, suggesting that photoperiodic variation may account for seasonal and geographic patterns of human alcohol consumption. Nevertheless, the existing animal data are somewhat inconsistent, and little work in this area has been performed in mice. In the present study, we monitored circadian activity rhythms and voluntary ethanol consumption under standard 12:12 light-dark (LD) cycles, and in constant light (LL) and constant darkness (DD). Experiment 1 employed male C3H/He inbred mice, while Experiment 2 employed males and females from a genetically heterogeneous line (WSC). Relative to LD conditions, ethanol intake and ethanol preference were reduced under both LL and DD in both experiments. Because similar effects were seen in both LL and DD, neither circadian disruption nor a classical photoperiodic mechanism are likely to account fully for these findings. Instead, we suggest that the absence of circadian entrainment may function as a mild stressor, resulting in reduced ethanol consumption.
  • An LC-MS/MS method for comparing the stability of ethanol’s
           non-oxidative metabolites in dried blood spots during 90 days
    • Abstract: Publication date: Available online 5 June 2019Source: AlcoholAuthor(s): Hao Wang, Yi Zhang, Xinyu Zhang, Jiaolun Li, Zebin Lin, Zhibin Huang, Jing Chang, Yunfeng Zhang, Jingru Wang, Chengqiang Zhang, Yulan Rao Problems of stability were found for biomarkers of alcohol consumption, ethyl glucuronide (EtG), ethyl sulfate (EtS), phosphatidylethanols (PEths) and fatty acid ethyl esters (FAEEs) in whole blood. The purpose of this study was to establish a method for the determination of these 4 kinds of ethanol’s non-oxidative metabolites in dried blood spots (DBS) by liquid chromatography tandem mass spectrometry (LC-MS/MS), and to evaluate their stability. In this method, 50 μL of human blood was spotted on a filter paper for DBS analysis. Samples were extracted by methanol, reconstituted by 2-propanol and injected in the LC-MS/MS system. Limits of detection were among 0.5 – 50 ng/mL, deviations in accuracy and precision were all lower than 15% at three quality control levels. The stability of the 4 kinds of ethanol non-oxidative metabolites in DBS was investigated during a 90-day range under 3 temperatures, -20 °C, 4 °C and 25 °C. EtG and EtS showed a high level of stability in DBS in the 90-day range, regardless of the temperature. FAEEs was unstable in 3 days. PEths showed a stability within 15 days in postmortem DBS and 60 days in antemortem DBS respectively at all temperatures.
  • Risky Drinking Decisions: The Influence of Party Music and Alcohol Abuse
           in Young Adult Women
    • Abstract: Publication date: Available online 15 May 2019Source: AlcoholAuthor(s): Anastasia I. Nikoulina, Lindsay R. Arcurio, Peter R. Finn, Thomas W. Jame Music is a ubiquitous feature of young adults’ social drinking environments, yet no studies have assessed whether and how it impacts risky decisions to drink alcohol. Previous research on the influence of music on risky decisions is largely based around decision tasks with monetary incentives.MethodsTo assess the impact of music listening on risky drinking decisions, the current study used visual alcohol cues paired with hypothetical risky drinking scenarios (e.g. “You do not have a safe ride home,” for alcohol). Young adult women with a history of alcohol abuse (N = 34), and casual-drinking control women (N = 29), made hypothetical decisions about whether or not to drink alcohol, or eat food (an appetitive control condition), in risky contexts while personal “party music” (music chosen by participants for “going out”) and “home music” (music chosen for “staying in”) played in the background. The main dependent measure – likelihood of drinking – was reported on a 4-point scale where 1 corresponded to “very unlikely,” and 4 to “very likely.”ResultsListening to party music while making decisions increased the likelihood of making risky drinking decisions regardless of a history of alcohol abuse, while other personal music did not. Further, party music specifically increased the likelihood of risky drinking decisions relative to risky eating decisions. As expected, those with a history of alcohol abuse made more risky drinking decisions in general, regardless of the type of music heard.DiscussionThe results suggest that party music is an important feature of the drinking environment associated with increased risky decisions about drinking alcohol in young adult women, regardless of their history of alcohol abuse. The finding that music plays an important role in risky drinking decisions indicates that further investigation into the real-world drinking environments of young adults is crucial, as it will aid in the development of a more complete picture of risky drinking decisions in young adults.
  • School and town factors associated with risky alcohol consumption among
           Catalan adolescents
    • Abstract: Publication date: Available online 11 May 2019Source: AlcoholAuthor(s): Núria Obradors-Rial, Carles Ariza, Xavier Continente, Carles Muntaner Risky alcohol consumption among adolescents has health and social consequences. Evidence identifying the school context that determines alcohol consumption among rural and urban adolescents is lacking. This study aimed to describe the contextual school and town factors determining risky alcohol consumption among rural and urban 10th-grade adolescents (15-17 years old) from Catalonia (north-eastern Spain). The study had a cross-sectional design. Cluster sampling with the class as the sampling unit was used, and a total of 1,268 10th-grade adolescents from Catalonia nested in 26 high schools participated in the study. A computerized and self-administrated questionnaire was used to collect individual variables. Contextual variables were collected from the Catalan police registers, geocoded sources, and governmental internet databases and by aggregation of answers from the self-administrated questionnaire. The prevalence of risky alcohol consumption was calculated, and a multilevel Poisson regression analysis with robust variance was conducted with data from adolescents nested within high schools. The results show that risky alcohol consumption is higher among rural adolescents (59.3%) than among urban youth (51.1%) (p
  • Maternal Choline Supplementation Mitigates Alcohol-Induced Fetal
           Cranio-Facial Abnormalities Detected Using an Ultrasonographic Examination
           in A Sheep Model
    • Abstract: Publication date: Available online 10 May 2019Source: AlcoholAuthor(s): Onkar B. Sawant, Sharla M. Birch, Charles R. Goodlett, Timothy A. Cudd, Shannon E. Washburn Early detection of prenatal alcohol exposure is critical for designing and testing effectiveness of interventional therapeutics. Choline supplementation during and after prenatal alcohol exposure has shown promising benefits in improving outcomes in rodent models and clinical studies. A sheep model of first trimester-equivalent binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Pregnant sheep were randomly assigned to six groups: Saline+Placebo control, Saline+Choline, binge Alcohol+Placebo (light binging), binge Alcohol+Choline, Heavy binge Alcohol+Placebo (heavy binging) and Heavy binge Alcohol+Choline. Ewes received intravenous alcohol or saline on three consecutive days per week from gestational day (GD) 4 to 41 to mimic first trimester-equivalent weekend binge drinking paradigm. Choline (10 mg/kg in the daily food ration) was administered from GD 4 until term. On GD 76, 11 fetal ultrasonographic measurements were collected transabdominally. Heavy binge alcohol exposure reduced fetal Frontothalamic Distance (FTD), Mean Orbital Diameter (MOD) and Mean Lens Diameter (MLD) and increased Interorbital Distance (IOD) and Thalamic Width (TW). Maternal choline supplementation mitigated most of these alcohol-induced effects. Maternal choline supplementation also improved overall fetal femur and humerus bone lengths compared to their respective placebo groups. Taken together these results indicate a potential dose dependent effect that could impact the sensitivity of these ultrasonographic measures in predicting prenatal alcohol exposure. This is the first study in the sheep model to identify biomarkers of prenatal alcohol exposure in-utero with ultrasound and co-administration of maternal choline supplementation.
  • Operant, oral alcohol self-administration: Sex differences in Sardinian
           alcohol-preferring rats
    • Abstract: Publication date: Available online 26 April 2019Source: AlcoholAuthor(s): Irene Lorrai, Andrea Contini, Gian Luigi Gessa, Claudia Mugnaini, Federico Corelli, Giancarlo Colombo, Paola Maccioni Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost forty years, for high alcohol preference and consumption. sP rats have served as animal model for more than 120 published studies. With very few exceptions however, these studies have always employed male sP rats, and little is known on alcohol-related behaviors in female sP rats. The present study was designed to fill, at least in part, this gap. Accordingly, alcohol self-administration under the fixed ratio 4 schedule of reinforcement was compared among male, intact female, and ovariectomized female sP rats. Additionally, it was investigated whether (i) estrous cycle influenced alcohol self-administration and (ii) alcohol self-administration in the 3 sP rat groups differed in sensitivity to pharmacological manipulation. Lever-responding for alcohol was steadily higher in male than intact and ovariectomized female sP rats; conversely, because of large sex differences in rat body weight, estimated amount of self-administered alcohol (in g/kg) did not differ among the 3 sP rat groups or occasionally was higher in intact female than male and ovariectomized female sP rats. Blood alcohol levels deriving from self-administered alcohol (i) did not differ among the 3 sP rat groups and (ii) positively correlated with number of lever-responses for alcohol and estimated amount of self-administered alcohol. Treatment with the opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p.), and the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, i.g.), reduced alcohol self-administration with comparable potency and efficacy in the 3 sP rat groups. Impact of estrous cycle on alcohol self-administration was relatively modest, limited to a tendency toward a reduction in number of lever-responses for alcohol and estimated amount of self-administered alcohol in estrus and metestrus. Together, these results provide the first characterization of alcohol-seeking and -taking behavior in female sP rats.
  • Relation of plasma carnitine and aminotransferases to alcohol dose and
           time of dependence.
    • Abstract: Publication date: Available online 25 April 2019Source: AlcoholAuthor(s): Alina Kępka, Piotr Zwierz, Sylwia Chojnowska, Agnieszka Ochocińska, Ewa Skorupa, Marek Szczepański, Sławomir Dariusz Szajda, Napoleon Waszkiewicz BackgroundSerum aspartate and alanine aminotransferases (AST, ALT) and plasma carnitine are all indirect biomarkers of alcohol abuse. Carnitine transfers long chain fatty acids from cytoplasm to mitochondria for β-oxidation. The aim of the study was determination the relationship between daily alcohol intake, time of alcohol dependence, plasma carnitine and serum aminotransferases.Patients and methodswe studied 26 men addicted for 2-30 years, consuming ethanol 75-700 g/day (alcoholic group) and 17 healthy men (control group).ResultsIn alcoholics, compared to the controls, we found: a significant increase in serum: AST (p = 0.0014), ALT (p = 0.0071), AST/ALT ratio (p < 0.000); significantly lower plasma free carnitine (FC) (p = 0.0316) and total carnitine (TC) (p = 0.0349); a significant negative correlation between FC (r =-0.6200; R2 = 0.3844; p = 0.0007 ), TC (r = -0.4365; R2 = 0.1905; p = 0.0258) and time of alcohol dependence, suggesting carnitine as an indirect marker of alcohol abuse. We did not find any significant correlation between FC, TC and levels of alcohol or aminotransferase activity.ConclusionsIn the alcoholic group: an increase in serum activity of AST, ALT, AST/ALT ratio confirm liver injury; low plasma FC, TC may indicate on damage to mitochondrial β-oxidation caused by alcohol metabolites. The significantly higher plasma FC and TC in patients consuming the largest, compared to patients consuming smaller doses of alcohol, may be caused by: lowered carnitine demand of injured liver cells, decreased urinary carnitine excretion by impaired renal tubules, leakage carnitine to blood from damaged muscles by the higher amount of alcohol. The negative correlation between carnitine concentration and time of alcohol dependence may suggest the potential use of carnitine for treatment of alcohol abuse.
  • CUE-ALCOHOL associative learning in FEMALE RATS
    • Abstract: Publication date: Available online 17 April 2019Source: AlcoholAuthor(s): Roberto U. Cofresí, Marie-H. Monfils, Nadia Chaudhri, Rueben A. Gonzales, Hongjoo J. Lee The ability of environmental cues to trigger alcohol seeking behaviors is believed to facilitate problematic alcohol use. We previously showed that the development of this cue-evoked alcohol approach reflects cue-alcohol learning and memory in the adult male rat; however, we do not know whether the same is true for similarly aged female rats. Consequently, adult Long-Evans female rats were allowed to drink unsweetened alcohol in the homecage (MWF 24 hr two-bottle choice, 5 weeks) and subsequently split into two experimental groups: paired and unpaired. Groups were matched for ingested doses and alcohol bottle preference across the pre-conditioning homecage period. Both groups were trained in conditioning chambers using a Pavlovian procedure. For the paired group, the chamber houselight was illuminated to signal access to an alcohol sipper. Houselight onset was yoked for the unpaired group, but access to the alcohol sipper was scheduled to occur only during the intervening periods (in the absence of light). We found that in the paired, but not unpaired group, an alcohol approach reaction was conditioned to houselight illumination, and the level of cue-conditioned reactivity predicted drinking behavior within trials. Groups experienced equivalently low but non-negligible blood alcohol concentrations over the course of conditioning sessions. We conclude that cue-triggered alcohol seeking behavior in adult female rats reflects associative learning about the relationship between alcohol availability and houselight illumination.
  • The association between alcohol metabolism and genetic variants of ADH1A,
           SRPRB, and PGM1 in Korea
    • Abstract: Publication date: Available online 17 April 2019Source: AlcoholAuthor(s): Yoo Jeong Lee, Min-Gyu Yoo, Hyeon-Kyeong Kim, Han Byul Jang, Keon Jae Park, Hye-Ja Lee, Sung-Gon Kim, Sang Ick Park BackgroundExcessive alcohol consumption is a major public health problem in East Asian countries. Alcohol use leads to a cascade of problems including increased chances of risky behavior and wide range of negative health consequences from alcoholic liver disease to upper gastric and liver cancer. These alcohol effects are known to be influenced by ethnic variability and genetics.MethodsIn this study, subjects were administered a single dose of alcohol (0.6 g/kg for men or 0.4 g/kg for women) and blood alcohol and acetaldehyde concentration were measured 8 times over 5 h. To investigate genetically susceptible factors to alcohol metabolism, we selected single-nucleotide polymorphisms of genes identified by prior genetic association studies for alcohol metabolism, alcohol consumption, alcohol dependence, and related traits, and performed genotyping all subjects (n = 104).ResultsWe identified variations in the ADH1A, SRPRB, and PGM1 genes, which are directly associated with blood alcohol or acetaldehyde concentrations. Namely, the T-allele of SRPRB rs17376019 and C-allele of PGM1 rs4643 were associated with lower blood alcohol levels, while the ADH1 rs1229976 C- allele group exhibited markedly higher blood acetaldehyde levels than those of the ADH1 rs1229976 T-allele group.ConclusionThese results suggest that genetic variations in ADH1A, SRPRB, and PGM1 lead to variations in blood alcohol and acetaldehyde concentration after alcohol intake.
  • Cerebrolysin attenuates ethanol-induced spatial memory impairments through
           inhibition of hippocampal oxidative stress and apoptotic cell death in
    • Abstract: Publication date: Available online 11 April 2019Source: AlcoholAuthor(s): Ladan Vaghef, Fereshteh Farajdokht, Marjan Erfani, Alireza Majdi, Saeed Sadigh-Eteghad, Pouran Karimi, Siamak Sandoghchian Shotorbani, Manouchehr Seyedi Vafaee, Javad Mahmoudi The present study investigates the potential neuroprotective effect of cerebrolysin (CBL), a combination of neurotrophic factors, on the cognitive and biochemical alterations induced by chronic ethanol administration in rats. The animals were divided into 5 groups as follows: Control, ethanol (4 g/kg, for 30 days) plus normal saline (Ethanol + NS), ethanol plus CBL 1 ml/kg (Ethanol + CBL 1), ethanol plus CBL 2.5 ml/kg (Ethanol + CBL 2.5), and ethanol plus CBL 5 ml/kg (Ethanol + CBL 5). Morris water maze (MWM) test was performed to assess cognitive impairment. The status of the lipid peroxidation marker (MDA), antioxidant capacity as well as alterations of the apoptotic factors such as Bcl-2, BAX, and cleaved-caspase 9 and 3 were evaluated in the hippocampus. The results showed that CBL treatment not only normalized the increased MDA levels in the alcoholic rats and enhanced antioxidant defense but also reduced Bax/Bcl-2 ratio and cleaved-caspase 9 and 3 in the hippocampus. These results were parallel with improvement in the spatial memory performance in the MWM test. The findings of the present study provide evidence for the promising therapeutic effect of CBL in chronic ethanol consumption through counteracting oxidative stress and apoptosis markers.
  • The kisspeptin derivative - kissorphin reduces the acquisition, expression
    • Abstract: Publication date: Available online 11 April 2019Source: AlcoholAuthor(s): E. Gibula-Tarlowska, P. Grochecki, J. Silberring, J.H. Kotlinska Research has shown that opioids are involved in the rewarding effects of ethanol. Neuropeptyde FF (NPFF) has been described as an anti-opioid peptide because it, in many cases, inhibits opioid and ethanol effects in rodents. Kissorphin (KSO) is a new peptide derived from kisspeptin-10 with structural similarities to NPFF. This peptide possesses NPFF-like biological activity in vitro. The aim of the current study was to investigate whether a KSO (Tyr-Asn-Trp-Asn-Ser-Phe-NH2) influences the acquisition, expression and reinstatement of ethanol-induced conditioned place preference (EtOH-CPP) in rats. The EtOH-CPP was established (conditioning for 5 days) by intraperitoneal (i.p.) administration of EtOH (1 g/kg, 20%, w/v) using an unbiased procedure. After that, one group of rats were used in final post-conditioning testing (expression of CPP) and the other group received priming injection of EtOH after 10 days of extinction (reinstatement of CPP). Our experiments showed that KSO, given intravenously (i.v.) at the doses of 1, 3 and 10 nmol before every EtOH administration inhibited the acquisition, and given acutely before the post-conditioning test or before the priming dose of EtOH inhibited the expression and reinstatement of EtOH-CPP, respectively, in a dose-dependent manner. KSO given itself, neither induced place preference nor aversion and did not alter locomotor activity and coordination of rats. These results suggest that KSO can alter rewarding/motivational effects of EtOH. These data suggest this peptide possesses an anti-opioid character.
  • Acute Alcohol and Cognition: Remembering What It Causes Us to Forget
    • Abstract: Publication date: Available online 11 April 2019Source: AlcoholAuthor(s): Candice E. Van Skike, Charles Goodlett, Douglas B. Matthews Addiction has been conceptualized as a specific form of memory that appropriates typically adaptive neural mechanisms of learning to produce the progressive spiral of drug-seeking and drug-taking behavior, perpetuating the path to addiction through aberrant processes of drug-related learning and memory. From that perspective, to understand the development of alcohol use disorders it is critical to identify how a single exposure to alcohol enters into or alters the processes of learning and memory, so that involvement of and changes in neuroplasticity processes responsible for learning and memory can be identified early on. This review characterizes the effects produced by acute alcohol intoxication as a function of brain region and memory neurocircuitry. In general, exposure to ethanol doses that produce intoxicating effects causes consistent impairments in learning and memory processes mediated by specific brain circuitry, whereas lower doses either have no effect or produce a facilitation of memory under certain task conditions. Therefore, acute ethanol does not produce a global impairment of learning and memory, and can actually facilitate particular types of memory, perhaps particular types of memory that facilitate the development of excessive alcohol use. In addition, the effects on cognition are dependent on brain region, task demands, dose received, pharmacokinetics, and tolerance. Additionally, we explore the underlying alterations in neurophysiology produced by acute alcohol exposure that help to explain these changes in cognition and highlight future directions for research. Through understanding the impact acute alcohol intoxication has on cognition, the preliminary changes potentially causing a problematic addiction memory can better be identified.
  • Status of inflammation and alcohol use in a 6-month follow-up study of
           patients with major depressive disorder
    • Abstract: Publication date: Available online 12 February 2019Source: AlcoholAuthor(s): Mari Archer, Onni Niemelä, Kaisa Luoto, Johanna Kultti, Mari Hämäläinen, Eeva Moilanen, Antti Koivukangas, Esa Leinonen, Olli KampmanEditor highlights•The level of IL-8 decreases in depressed patients during 6 months of treatment.•The decrease of IL-8 level during treatment is independent of alcohol consumption.•YKL-40 level correlates with serum liver-derived enzymes, but not depressive symptoms. IntroductionThe studies on the relations between alcohol consumption, the status of inflammation and depression have produced conflicting results. In this study we followed patients with major depressive disorders by monitoring biomarkers of inflammation together with biomarkers of heavy alcohol use.MethodThe levels of IL-6 (interleukin-6), IL-8 (interleukin-8), hs-CRP (high sensitivity C-reactive protein), YKL-40 (also known as Chitinase-3-like protein 1 or CHI3L1) and biomarkers of alcohol consumption and liver status (GT, CDT, ALT, alkaline phosphatase) were measured at baseline and after 6 months of psychiatric treatment from 242 patients suffering from current major depressive disorder (MDD) with (n = 99) or without (n = 143) alcohol use disorder (AUD).ResultsAt baseline the patients with MDD + AUD showed higher levels of inflammatory biomarkers IL-6 (p < 0.001), hs-CRP (p < 0.01), YKL-40 (p < 0.05), and biomarkers of alcohol consumption, than the corresponding group of non-AUD patients. These differences disappeared during follow-up and recovery from depression. The level of IL-8 decreased significantly in both AUD (p < 0.05) and non-AUD (p < 0.05) patients. During follow-up, the biomarkers of alcohol consumption, GT and CDT, in AUD patients were found to decrease in parallel with serum YKL-40 levels.ConclusionsAlcohol consumption appears to modulate the status of inflammation in depressive patients. A more systematic use of biomarkers of inflammation together with biomarkers of alcohol consumption and liver status may prove to be of value in a more comprehensive assessment and treatment of patients with depression.
  • Alcohol consumption and cardiovascular health: A nationwide survey of
           Uruguayan cardiologists
    • Abstract: Publication date: Available online 12 February 2019Source: AlcoholAuthor(s): Alejandro Cuesta, Sohaib Haseeb, Federico Aquistapache, Pedro Grosso, Bryce Alexander, Wilma Hopman, Ricardo Lopez Santi, Adrian Baranchuk Background and aimsHeavy alcohol use is a risk factor for disease and mortality; however epidemiological findings have demonstrated protective effects of a light-to-moderate intake of alcohol on cardiovascular health. There are many misconceptions regarding appropriate levels of alcohol intake and the risks and benefits of consumption. We sought to examine physician attitudes and recommendations regarding alcohol intake in a cohort of Uruguayan cardiologists.MethodsA cross-sectional survey of 25 questions was distributed through the Uruguayan Society of Cardiology to attending cardiologists and advanced cardiology trainees.ResultsThere were 298 respondents; 237 were attending cardiologists and 61 were advanced cardiology trainees. In total, 34% of cardiologists viewed moderate alcohol intake to be beneficial for cardiovascular health, 27% believed only wine offered such benefits, 36% viewed any intake to be harmful, and 3% had other opinions. More than half (57%) self-reported their perceived knowledge to come from academic sources. Regarding knowledge of guidelines, only 42% were aware of the concept of ‘standard drink’ (SD). Cardiologists were not comfortable (on a Likert scale) converting SD into other metric units (1.92 ± 2.77). Cardiologists were not satisfied with their knowledge of drinking guidelines (2.42 ± 2.63); however, men were more comfortable than women (p=0.003). Cardiologists were generally comfortable in counseling patients regarding safe limits of consumption (5.46 ± 3.08, on a 0-10 scale).ConclusionsUruguayan cardiologists were not satisfied with their knowledge of drinking guidelines or understanding of the alcohol metric units. This study suggests a necessity to optimize educational resources for physicians.
  • Objective Continuous Monitoring of Alcohol Consumption for Three Months
           Among Alcohol Use Disorder Treatment Outpatients
    • Abstract: Publication date: Available online 31 January 2019Source: AlcoholAuthor(s): Sheila Alessi, Nancy Petry, Nancy Barnett BackgroundTransdermal alcohol sensing technology allows for objective continuous monitoring of alcohol use. The purpose of this study was to characterize alcohol consumption measured with this technology among alcohol use disorder treatment outpatients in two clinical trials.MethodsParticipants were community-based alcohol treatment outpatients in usual care (N = 63) during the first three years of studies that monitored drinking with the secure continuous remote alcohol monitor (SCRAMx®) ankle bracelet. Research visits for uploading SCRAMx data occurred every other week in Study 1 (n = 43) and once weekly in Study 2 (n = 20), for 3 months. Staff used timeline follow-back procedures to collect self-reports of drinking frequency and magnitude at each research visit.ResultsIn the 90 days before intake, 85.7% (n = 54) of participants reported consuming alcohol, and consumption occurred on a median (interquartile range) 35.7% (29.0%) of days. During the treatment period, per SCRAMx versus self-report, the percentage who drank was 92.1% (n = 58) versus 46.6% (n = 30), p = .03, and consumption occurred on 16.5% (36.5%) versus 0.0% (21.4%) of days, respectively, p < .001. Median longest duration of abstinence was 26.0 (25.0) versus 39.0 (58.0) days, respectively, p < .001. Breath alcohol concentration, estimated from SCRAMx data, ranged from 0.02-0.91 g/dL.ConclusionsThis is the first study to quantify alcohol consumption among alcohol treatment outpatients using transdermal sensor technology. Results indicate that most patients drank while in outpatient care. Issues to consider for future applications of this technology and implications for alcohol treatment are discussed.
  • Absence of compulsive drinking phenotype in adult male rats exposed to
           ethanol in a binge-like pattern during adolescence
    • Abstract: Publication date: Available online 18 January 2019Source: AlcoholAuthor(s): Todd B. Nentwig, E. Margaret Starr, L. Judson Chandler, Elizabeth J. Glover The abuse of alcohol during adolescence is widespread and represents a particular concern given that earlier age of drinking onset is associated with increased risk for the development of alcohol use disorders (AUDs). Despite this risk, it remains unclear whether binge-like adolescent alcohol exposure facilitates drinking despite aversive consequences, a characteristic common among individuals with AUDs. The present study examined voluntary alcohol consumption and aversion-resistant drinking in adult male Long-Evans rats that had undergone adolescent intermittent ethanol (AIE) exposure by vapor inhalation between post-natal days (PD) 28-44. Ethanol consumption during adulthood was examined using a two-bottle choice (2BC) intermittent access procedure. Rats were tested for aversion-resistant drinking using ethanol adulterated with quinine (10, 30, 100 mg/L) after two 7-week periods of 2BC drinking. After completion of the second test of aversion-resistant drinking, rats were trained to operantly self-administer ethanol. The results revealed that both air control (AIR) and AIE exposed rats exhibited similar ethanol intake and preference in the 2BC paradigm. After seven weeks of 2BC drinking, quinine adulteration significantly suppressed ethanol intake, but only at the highest concentration examined (100 mg/L). However, upon retesting after a total of 17 weeks of 2BC drinking, 30 mg/L quinine suppressed ethanol intake. Notably, AIR and AIE exposed rats were equally sensitive to quinine adulterated ethanol at both time-points. In addition, AIR and AIE exposed rats responded similarly during operant ethanol self-administration on both fixed and progressive ratio schedules of reinforcement. Finally, both AIR and AIE exposed rats exhibited similar preference for sucrose. The results of this study show that binge-like ethanol vapor exposure during adolescence does not alter voluntary ethanol consumption, motivation to operantly respond for ethanol, or promote aversion-resistant ethanol consumption in adulthood. These data, together with previous work reporting conflicting results across various rodent models of adolescent alcohol exposure, underscore the need to further explore the role that exposure to alcohol during adolescence has on the development of heavy and compulsive drinking phenotypes in adulthood.
  • Effects of Rat Strain and Method of Inducing Ethanol Drinking on
           Pavlovian-Instrumental-Transfer with Ethanol-Paired Conditioned Stimuli
    • Abstract: Publication date: Available online 11 January 2019Source: AlcoholAuthor(s): R.J. Lamb, Brett C. Ginsburg, Alexander Greig, Charles W. Schindler Ethanol-paired Conditioned Stimuli are widely thought to invigorate ethanol responding, and thus, precipitate relapse to drinking. However, preclinical studies investigating this issue using Pavlovian Instrumental Transfer (PIT) procedures have had mixed results, with some studies finding PIT while others did not. The studies failing to show PIT used Lewis rats and induced ethanol drinking using a post-prandial drinking procedure. The present experiments examined whether either of these two variables influenced the magnitude of PIT observed. In the first experiment, ethanol drinking in Lewis rats was induced using either sucrose fading or post-prandial drinking. In the second experiment, ethanol drinking was induced using post-prandial drinking in either Long-Evans Hooded or Lewis rats. In both experiments, rats were trained to respond for ethanol under a Random Interval schedule. Subsequently with the lever removed, 2-minute light presentations were paired with ethanol deliveries. Finally, with the lever returned, the effect of light presentations on responding was tested while responding was in extinction. Light presentations similarly affected responding in Lewis rats regardless of the method of drinking induction. Likewise, light presentations similarly affected responding in both Lewis and Long-Evans Hooded rats. Neither ethanol induction method nor rat strain affected the magnitude of PIT observed and thus, neither likely explains previous failures to observe PIT with ethanol-maintained behavior.
  • Ethanol Activates Immune Response In Lymphoblastoid Cells
    • Abstract: Publication date: Available online 9 January 2019Source: AlcoholAuthor(s): Jeanette N. McClintick, Jay A. Tischfield, Li Deng, Manav Kapoor, Xiaoling Xuei, Howard J. Edenberg The short term effects of alcohol on gene expression in brain tissue cannot directly be studied in humans. Because neuroimmune signaling is altered by alcohol, immune cells are a logical, accessible choice to study and might provide biomarkers. RNAseq was used to study the effects of 48 h exposure to ethanol on lymphoblastoid cell lines (LCLs) from 21 alcoholics and 21 controls.Ethanol exposure resulted in differential expression of 4,577 of the 12,526 genes detectably expressed in the LCLs (FDR ≤ 0.05); 55% of these showed increased expression. Cells from alcoholics and controls responded similarly. The genes whose expression changed fell into many pathways. NFκB, neuroinflammation, IL-6, and dendritic cell maturation pathways were activated, consistent with increased signaling by NFκB, TNF, TGFβ, IL1, IL4, IL18, TLR4, and LPS. Signaling by Interferons A and B decreased, which may be responsible for a slightly blunted immune response compared to 24 h ethanol treatment. EIF2, phospholipase C and VEGF signaling were decreased.Baseline gene expression patterns were similar in LCLs from alcoholics and controls. At relaxed stringency (p
  • Effect of Nanoformulated Copper/Zinc Superoxide Dismutase on Chronic
           Ethanol-Induced Alterations in Liver and Adipose Tissue
    • Abstract: Publication date: Available online 3 January 2019Source: AlcoholAuthor(s): Gopalakrishnan Natarajan, Curtis Perriotte-Olson, Carol A. Casey, Terrence M. Donohue, Geoffrey A. Talmon, Edward N. Harris, Alexander V. Kabanov, Viswanathan Saraswathi BackgroundWe previously reported that nanoformulated copper/zinc superoxide dismutase (Nano) attenuates non-alcoholic fatty liver disease and adipose tissue (AT) inflammation in obese animals. Here, we sought to determine whether Nano treatment attenuates alcohol-associated liver disease (AALD) and AT inflammation in alcohol-fed mice.MethodsWe pre-treated E-47 cells (HepG2 cells that over-express CYP2E1) with native- or nano- SOD for 6 h, followed by treatment with ethanol and/or linoleic acid (LA), a free fatty acid. For in vivo studies, male C57BL/6 mice were fed the Lieber-DeCarli control or ethanol liquid diet for 4 wk. The mice received Nano once every two days during the last 2 wk of ethanol feeding.ResultsOur in vitro studies revealed that Nano pretreatment reduced LA+ethanol-induced oxidative stress in E-47 cells. Our in vivo experiments showed that ethanol-fed Nano-treated mice had 22% lower hepatic triglyceride levels than mice fed ethanol alone. Nano-treated ethanol-fed mice also had 2-fold lower levels of Cd68 and similarly-reduced levels of Ccl2 and Mmp12 mRNAs, than in untreated ethanol-fed mice. We also noted that ethanol feeding caused a remarkable increase in hepatic and/or plasma MCP-1 and CCR2 protein which was blunted in ethanol+Nano-treated animals. The hepatic content of SREBP-1c a transcription factor that promotes lipogenesis, was higher in ethanol-fed mice than controls but was attenuated in ethanol+Nano-treated animals. Further, livers of ethanol+Nano-treated mice had significantly higher levels of phosphorylated AMPK than both control and ethanol-fed mice. In AT, the level of Il6 mRNA a hepatoprotective cytokine, and that of Arg1, a marker of anti-inflammatory macrophages, were significantly increased in ethanol+Nano-treated mice compared with control mice.ConclusionOur data indicate that Nano treatment attenuates ethanol-induced steatohepatitis and this effect is associated with an apparent activation of AMPK signaling. Our data also suggest that Nano induces Arg1 and IL-6 expression in AT suggesting anti-inflammatory effects in this tissue.
  • Prenatal Ethanol Exposure Attenuates Sensitivity to The Aversive Effects
           of Ethanol in Adolescence and Increases Adult Preference For A 5% Ethanol
           Solution in Males, But Not Females
    • Abstract: Publication date: Available online 29 December 2018Source: AlcoholAuthor(s): Jonathan Kent Gore-Langton, Linda Patia Spear
  • Minocycline Attenuates Ethanol-induced Cell Death and Microglial
           Activation in the Developing Spinal Cord
    • Abstract: Publication date: Available online 7 December 2018Source: AlcoholAuthor(s): Zhenhua Ren, Xin Wang, Mei Xu, Jacqueline A. Frank, Jia Luo Developmental exposure to ethanol may cause fetal alcohol spectrum disorders (FASD), and immature central nervous system (CNS) is particularly vulnerable to ethanol. In addition to the developing brain, we previously showed that ethanol also caused neuroapoptosis, microglial activation, and neuroinflammation in the spinal cord. Minocycline is an antibiotic that inhibits microglial activation and alleviates neuroinflammation. We sought to determine whether minocycline could protect spinal cord neurons against ethanol-induced damage. In this study, we showed that minocycline significantly inhibited ethanol-induced caspase-3 activation, microglial activation, and the expression of pro-inflammatory cytokines in the developing spinal cord. Moreover, minocycline blocked ethanol-induced activation of glycogen synthase kinase 3 beta (GSK3β) a key regulator of microglial activation. Meanwhile, minocycline significantly restored ethanol-induced inhibition of protein kinase B (AKT), mammalian target of the rapamycin (mTOR), and ERK1/2 signaling pathways, which were important pro-survival signaling pathways for neurons. Together, minocycline may attenuate ethanol-induced damage to the developing spinal cord by inhibiting microglial activation/neuroinflammation and restoring the pro-survival signaling.
  • The α3β4 nicotinic acetylcholine receptor antagonist
           18-Methoxycoronaridine decreases binge-like ethanol consumption in adult
           C57BL/6J mice
    • Abstract: Publication date: Available online 26 November 2018Source: AlcoholAuthor(s): C.N. Miller, C. Ruggery, H.M. Kamens Binge alcohol drinking is a health burden in the United States which has an alarming economic impact. Unfortunately, medications available for alcohol abuse have low efficacy or adverse side effects creating a need to evaluate novel therapies. Growing research suggests that 18-Methoxycoronaridine (18-MC), an α3β4 nicotinic acetylcholine receptor (nAChR) antagonist, may be effective at reducing ethanol consumption. However, its effect on binge-like ethanol consumption and other alcohol behaviors have not been examined. The present study examined the effect of α3β4 nAChRs antagonism on basal locomotor activity in male and female C57BL/6J mice. Next we tested the effect of 18-MC on binge-like ethanol consumption, ethanol-induced sedation, and ethanol metabolism. Finally, we tested the effect of α3β4 nAChRs on saccharin consumption to ensure effects were specific for ethanol. We observed that 18-MC decreased binge-like ethanol consumption without altering saccharin consumption, the sedative effects of ethanol, or ethanol metabolism. 18-MC caused locomotor sedation in male C57BL/6J mice, but the effects were brief and likely do not contribute to differences in ethanol consumption. Our results support the involvement of the α3β4 nAChRs in binge-like ethanol intake and further work should explore the use of 18-MC for treatment of alcohol abuse disorders.
  • Assessment of Interleukin-6 Signaling Effects on Behavioral Changes
           Associated with Acute Alcohol Intoxication in adult male rats
    • Abstract: Publication date: Available online 22 November 2018Source: AlcoholAuthor(s): Thaddeus M. Barney, Andrew S. Vore, Anny Gano, Jamie E. Mondello, Terrence Deak Recent studies have demonstrated unique brain cytokine signatures associated with acute ethanol intoxication (increased IL-6) and withdrawal (increased IL-1β and TNFα). The purpose of the present studies was to examine the potential functional role of increased central interleukin-6 (IL-6). We utilized two tests of ethanol sensitivity to establish a potential role for IL-6 after high (3.5-4.0 g/kg i.p) or moderate (2.0 g/kg i.p) doses of ethanol: loss of righting reflex (LORR) and conditioned taste aversion (CTA), respectively. Briefly, guide cannula were implanted into the third ventricle of adult male Sprague-Dawley rats. In the first experiments, rats were infused with: 25, 50, 100, or 200 ng of IL-6; or 0.3, 3.0, or 9.0 μg of the JAK/STAT inhibitor AG490 30 min prior to a high dose ethanol challenge. Although sleep time was not affected by exogenous IL-6, infusion of AG490 increased latency to lose the righting reflex relative to vehicle infused rats. Next, we assessed whether IL-6 was sufficient to produce a CTA. Moderately water-deprived rats received i.c.v. infusions of 25, 50, or 100 ng IL-6 immediately after 60 min access to 5% sucrose solution. 48 hr later, rats were returned to the context and given 60 min access to sucrose solution. IL-6 infusion had no significant effect on sucrose intake when all rats were considered together. However, a median split revealed that low sucrose-consuming rats significantly increased their drinking on test day, an effect that was not seen in rats that received 50 or 100 ng of IL-6. In the last study, AG490 had no effect on ethanol-induced CTA (2 g/kg). Overall, these studies suggest that IL-6 had only a minor influence on ethanol-induced behavioral changes, yet phenotypic differences in sensitivity to IL-6 were apparent. These studies are among the first to examine a potential functional role for IL-6 in ethanol-related behaviors, and may have important implications for understanding the relationship between acute ethanol intoxication and its associated behavioral alterations.
  • Early life stress and voluntary alcohol consumption in relation to Maoa
           methylation in male rats
    • Abstract: Publication date: Available online 8 November 2018Source: AlcoholAuthor(s): Megha Bendre, Linnea Granholm, Ryan Drennan, Ann Meyer, Liying Yan, Kent W. Nilsson, Ingrid Nylander, Erika Comasco Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. The monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1–5, exons 5 and 6, together comprised of 107 CpGs, in a subgroup of rats. Pyrosequencing was used to analyse the methylation of ten candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interaction effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption and Maoa expression in reward-related brain regions.
  • Neonatal alcohol exposure augments voluntary ethanol intake in the absence
           of potentiated anxiety-like behavior induced by chronic intermittent
           ethanol vapor exposure
    • Abstract: Publication date: Available online 29 October 2018Source: AlcoholAuthor(s): K.E. Bosse, V.M. Chiu, S.C. Lloyd, A.C. Conti Individuals fetally exposed to alcohol have a disproportionate risk for developing lifetime alcohol dependence, an association that may be confounded by the presence of comorbid conditions, such as anxiety. Anxiety is also observed following fetal alcohol exposure and known to exacerbate ethanol consumption, highlighting the utility of animal models to assess this relationship. The present study evaluated the impact of third-trimester equivalent ethanol exposure on ethanol consumption and anxiety-like, marble burying behavior in adult, male C57BL/6 mice following exposure to chronic intermittent ethanol vapor, proposed to model dependence. Neonatal mice (P5 - 6, 2.5 - 3.0 g) were administered one injection of saline or ethanol (2.5 g/kg, s.c.). Pre-vapor marble burying and limited-access two-bottle choice ethanol intake (15% v/v, 2 h) were comparable in adults (8 weeks of age) across neonatal treatment groups. Five consecutive drinking sessions were repeated 72 h after each weekly ethanol vapor exposure procedure for a total of five vapor/drinking cycles. Consistent with prior research, an increase in voluntary ethanol drinking was observed in vapor-exposed, neonatal saline-treated mice throughout the study starting after the second vapor cycle compared to both air-exposed control groups. In neonatal ethanol-treated mice, this increase in ethanol intake and preference following vapor exposure was accelerated, being observed after the first vapor cycle, and observed at an augmented level compared to vapor, neonatal saline-treated mice and air controls for both neonatal conditions. Conversely, marble burying was enhanced equivalently in vapor-exposed mice from either neonatal treatment group relative to their respective air-exposed controls. These data recapitulate clinical observations of enhanced sensitivity for alcohol dependence following developmental alcohol exposure, which may reflect enhanced motivational drive rather than potentiated negative affect. The present model will facilitate the future exploration of mechanisms that underlie increased risk for alcohol use after early developmental exposure.
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