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Showing 1 - 200 of 3043 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 20, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 18, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 83, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 23, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 27, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 332, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 211, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 9, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 23, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
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Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
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Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 3)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 8, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 129, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 25, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
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Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 24, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 4)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 41, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 40, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 47, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 25)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 35, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 5)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 60)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 2, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 345, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 7, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 15)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 309, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 8, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 405, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 38, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 53, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 6)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, SJR: 0.776, h-index: 35)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 7, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 48, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 45, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 38, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 16, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 24, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 33, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 46, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 191, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 54, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 3)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 23, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 26, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 34, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 55, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 10)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 38, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 162, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 157, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (Followers: 1, SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
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Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

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Journal Cover Alcohol
  [SJR: 0.922]   [H-I: 66]   [9 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0741-8329
   Published by Elsevier Homepage  [3043 journals]
  • Binge alcohol consumption 18 h after induction of sepsis in a
           mouse model causes rapid overgrowth of bacteria, a cytokine storm, and
           decreased survival
    • Authors: Minny Bhatty; Wei Tan; Maria Basco; Stephen Pruett; Bindu Nanduri
      Pages: 9 - 17
      Abstract: Publication date: September 2017
      Source:Alcohol, Volume 63
      Author(s): Minny Bhatty, Wei Tan, Maria Basco, Stephen Pruett, Bindu Nanduri
      Alcohol abuse increases vulnerability to infections and infection-related mortality. In previous studies, we found that acute alcohol abuse in a binge-drinking model in mice decreased resistance to bacterial sepsis when alcohol was administered near the time of bacterial challenge. In the present study, we investigated the effects of alcohol administered later in the course of sepsis (18 h after injection of Escherichia coli). Our working hypothesis was that decreased production of cytokines caused by alcohol at this time would actually improve survival, because overproduction of pro-inflammatory mediators is thought to be the proximate cause of mortality in sepsis. Unexpectedly, administration of alcohol late in the course of sepsis led to a rapid increase in the number of viable bacteria in the peritoneal cavity. Significant increases in the concentrations of several cytokines and chemokines coincided with the increased number of bacteria in alcohol-treated mice and decreased survival time. These results demonstrated our working hypothesis to be incorrect, and reiterated the complexity of sepsis. Hypothermia is a consistent feature in this model of sepsis. In control mice (E. coli only), body temperature was near normal by 18 h or 21 h after administration of E. coli, but in mice treated with alcohol 18 h after E. coli, hypothermia was significant 3 h later and ultimately mortality was significantly increased. However, counteracting the hypothermic effect of alcohol by external warming of mice led to earlier mortality, demonstrating that hypothermia was not the major cause of mortality. These results, along with previous results from studies in which alcohol was given before initiation of sepsis, suggest that decreased cytokine and chemokine production may not be the key effect of alcohol that decreases resistance to sepsis. It seems more likely that suppression of mechanisms by which macrophages and neutrophils kill bacteria is critical, and this can occur even in the presence of high levels of cytokines and chemokines.

      PubDate: 2017-07-27T20:00:33Z
      DOI: 10.1016/j.alcohol.2016.11.007
      Issue No: Vol. 63 (2017)
  • A modified Timeline Followback assessment to capture alcohol exposure in
           pregnant women: Application in the Safe Passage Study
    • Authors: Kimberly Dukes; Tara Tripp; Marian Willinger; Hein Odendaal; Amy J. Elliott; Hannah C. Kinney; Fay Robinson; Julie M. Petersen; Cheryl Raffo; Dale Hereld; Coen Groenewald; Jyoti Angal; Gary Hankins; Larry Burd; William P. Fifer; Michael M. Myers; Howard J. Hoffman; Lisa Sullivan
      Abstract: Publication date: August 2017
      Source:Alcohol, Volume 62
      Author(s): Kimberly Dukes, Tara Tripp, Julie Petersen, Fay Robinson, Hein Odendaal, Amy Elliott, Marian Willinger, Dale Hereld, Cheryl Raffo, Hannah C. Kinney, Coen Groenewald, Jyoti Angal, Rebecca Young, Larry Burd
      Prenatal alcohol exposure (PAE) has been linked to poor pregnancy outcomes, yet there is no recognized standard for PAE assessment, and the specific effects of quantity, frequency, and timing remain largely unknown. The Safe Passage Study was designed to investigate the role of PAE in a continuum of poor peri- and postnatal outcomes. The objective of this manuscript is to describe the rationale for, and feasibility of, modifications to the traditional Timeline Followback (TLFB) for collecting PAE information in a large cohort of pregnant women. Participants from the Northern Plains region (in the United States) and Cape Town, South Africa, were followed prospectively using a modified 30-day TLFB interview, administered up to five times, to obtain detailed PAE information. Required modifications for our population included capturing information regarding sharing, type/brand, container size, and duration, in order to accurately record the amount of alcohol consumed. PAE status was defined for 99.9% of the 11,892 enrolled pregnancies at least once during pregnancy and for 92% across all trimesters. Of 53,823 drinks reported, 98% had all items necessary for standard drink computation. Sharing was reported for 74% of drinks in Cape Town, South Africa and for 10% in the Northern Plains. Compared to referent values from the traditional TLFB, 74% and 67% of drinks had different alcohol-by-volume and container size, respectively. Furthermore, a statistically significant difference was found between the number of containers reported and the number of standard drinks computed, using information from the modified TLFB. This is the first study of this size to wholly encompass all of these changes into a single measure in order to more accurately calculate daily consumption and assess patterns over time. The methods used to collect PAE information and create alcohol exposure measures likely increased the accuracy of standard drinks reported and could be generalized to other populations.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.03.001
      Issue No: Vol. 62 (2017)
  • Genome-wide profiling of differentially spliced mRNAs in human fetal
           cortical tissue exposed to alcohol
    • Authors: Yuka Imamura Kawasawa; Shahid Mohammad; Alexander I. Son; Hiroki Morizono; Aiesha Basha; Anna C. Salzberg; Masaaki Torii; Kazue Hashimoto-Torii
      Pages: 1 - 9
      Abstract: Publication date: August 2017
      Source:Alcohol, Volume 62
      Author(s): Yuka Imamura Kawasawa, Shahid Mohammad, Alexander I. Son, Hiroki Morizono, Aiesha Basha, Anna C. Salzberg, Masaaki Torii, Kazue Hashimoto-Torii
      Excessive alcohol consumption results in significant changes in gene expression and isoforms due to altered mRNA splicing. As such, an intriguing possibility is that disturbances in alternative splicing are involved in key pathological pathways triggered by alcohol exposure. However, no resources have been available to systematically analyze this possibility at a genome-wide scale. Here, we performed RNA sequencing of human fetal cortical slices that were obtained at the late first trimester and exposed to ethanol or control medium. We report 382 events that were identified as changes affecting the ratio of splicing isoforms in the ethanol-exposed fetal human cortex. Additionally, previously unreported novel isoforms of several genes were also identified. These results provide a broad perspective on the post-transcriptional regulatory network underlying ethanol-induced pathogenesis in the developing human cortex.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.05.001
      Issue No: Vol. 62 (2017)
  • A prospective cohort study examining the effectiveness of baclofen in the
           maintenance of abstinence in alcohol use disorder patients attending a
           joint liver and alcohol treatment clinic
    • Authors: Lynn Owens; Andrew Thompson; Abi Rose; Ian Gilmore; Munir Pirmohamed; Paul Richardson
      Pages: 11 - 15
      Abstract: Publication date: August 2017
      Source:Alcohol, Volume 62
      Author(s): Lynn Owens, Andrew Thompson, Abi Rose, Ian Gilmore, Munir Pirmohamed, Paul Richardson
      Objective Alcohol-related liver disease (ARLD) is the leading cause of alcohol-related mortality in the UK. Helping patients with ARLD to stop drinking is an important treatment goal. The aim of this study is to explore baclofen's utility in maintaining abstinence. Methods – a prospective cohort study Patients with ARLD were commenced on baclofen; the dose was titrated according to tolerability and response up to 30 mg three times daily. Severity of physical dependence and biochemical markers of liver injury were assessed at baseline, 3 months, and 12 months. Results Length of follow-up differed. Of 219 patients in the original cohort, 186 and 113 were evaluated at 3 months and 12 months, respectively. Loss to follow-up was due to death, baclofen non-adherence, and failure to attend appointments. Comparison of baseline and 1-year biochemical markers showed significant reductions in GGT (median change = 82.0; 95% CI = −149.0 to −40.0; p < 0.0005), ALT (−10.5; 95% CI = −16.5 to −5.0; p = 0.001), and bilirubin (−4.5; 95% CI = −7.0 to −2.0; p < 0.001). The proportion of eligible patients reporting complete abstinence at 3 and 12 months was 55% and 53%, respectively. A significant reduction in alcohol consumption and Severity of Alcohol Dependence Questionnaire score was observed at both follow-up time points. Conclusion Adherence to the baclofen was good, and it had a positive impact on measures of alcohol consumption. A limitation of our study is its observational nature. Further randomized studies alongside investigation of dosing strategies are required.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.12.005
      Issue No: Vol. 62 (2017)
  • Increased expression of M1 and M2 phenotypic markers in isolated microglia
           after four-day binge alcohol exposure in male rats
    • Authors: Hui Peng; Chelsea R. Geil Nickell; Kevin Y. Chen; Justin A. McClain; Kimberly Nixon
      Pages: 29 - 40
      Abstract: Publication date: August 2017
      Source:Alcohol, Volume 62
      Author(s): Hui Peng, Chelsea R. Geil Nickell, Kevin Y. Chen, Justin A. McClain, Kimberly Nixon
      Microglia activation and neuroinflammation are common features of neurodegenerative conditions, including alcohol use disorders (AUDs). When activated, microglia span a continuum of diverse phenotypes ranging from classically activated, pro-inflammatory (M1) microglia/macrophages to alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying microglia phenotypes is critical for understanding the role of microglia in the pathogenesis of AUDs. Therefore, male rats were gavaged with 25% (w/v) ethanol or isocaloric control diet every 8 h for 4 days and sacrificed at 0, 2, 4, and 7 days after alcohol exposure (e.g., T0, T2, etc.). Microglia were isolated from hippocampus and entorhinal cortices by Percoll density gradient centrifugation. Cells were labeled with microglia surface antigens and analyzed by flow cytometry. Consistent with prior studies, isolated cells yielded a highly enriched population of brain macrophages/microglia (>95% pure), evidenced by staining for the macrophage/microglia antigen CD11b. Polarization states of CD11b+CD45low microglia were evaluated by expression of M1 surface markers, major histocompatibility complex (MHC) II, CD32, CD86, and M2 surface marker, CD206 (mannose receptor). Ethanol-treated animals begin to show increased expression of M1 and M2 markers at T0 (p = n.s.), with significant changes at the T2 time point. At T2, expression of M1 markers, MHC-II, CD86, and CD32 were increased (p < 0.05) in hippocampus and entorhinal cortices, while M2 marker, CD206, was increased significantly only in entorhinal cortices (p < 0.05). All effects resolved to control levels by T4. In summary, four-day binge alcohol exposure produces a transient increase in both M1 (MHC-II, CD32, and CD86) and M2 (CD206) populations of microglia isolated from the entorhinal cortex and hippocampus. Thus, these findings that both pro-inflammatory and potentially beneficial, recovery-promoting microglia phenotypes can be observed after a damaging exposure of alcohol are critically important to our understanding of the role of microglia in the pathogenesis of AUDs.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.02.175
      Issue No: Vol. 62 (2017)
  • Efficient determination of six fatty acid ethyl ethers in human whole
           blood by gas chromatography-mass spectrometry
    • Authors: Jiaolun Li; Xinyu Zhang; Zebin Lin; Zhibin Huang; Yulan Rao
      Pages: 41 - 47
      Abstract: Publication date: August 2017
      Source:Alcohol, Volume 62
      Author(s): Jiaolun Li, Xinyu Zhang, Zebin Lin, Zhibin Huang, Yulan Rao
      Fatty acid ethyl esters (FAEEs) have been widely studied as specific markers of ethanol intake and mediators of ethanol-induced diseases. In the present study, a simple and rapid gas chromatography-mass spectrometry (GC-MS) method was established for the qualitative and quantitative analysis of six fatty acid ethyl esters (FAEEs), including ethyl myristate, ethyl palmitate, ethyl stearate, ethyl oleate, ethyl linoleate, and ethyl arachidonate, in human whole blood. FAEEs were extracted from 200 μL of human whole blood by a modified liquid-liquid extraction, and the hexane layer was injected directly into GC-MS with ethyl heptadecanoate as the internal standard. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 5–50 ng/mL and 15–200 ng/mL, respectively. Linearity ranged up to 10 μg/mL with r2 higher than 0.998. Accuracy was in the range of 90.3–109.7%, while intra-day and inter-day precision were 0.7–9.3% and 3.4–12.5%, respectively. This method was then applied to 38 real samples from forensic cases. Differences in the most common FAEEs between Chinese and Western subjects were discussed. The relationship of FAEE concentrations with age and gender was also investigated.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.02.359
      Issue No: Vol. 62 (2017)
  • Effects of acute alcohol intoxication on executive functions controlling
           self-regulated behavior
    • Authors: Suzanne Spinola; Stephen A. Maisto; Corey N. White; Tani Huddleson
      Pages: 1 - 8
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): Suzanne Spinola, Stephen A. Maisto, Corey N. White, Tani Huddleson
      Alcohol consumption may lead to deficits in the executive functions that govern self-regulation. These deficits could lead to risk-taking behaviors; therefore, it is important to determine the magnitude of these deficits on executive functioning. The purpose of this experiment was to investigate the acute effects of alcohol on three of the executive functions that are hypothesized to affect self-regulation, which are inhibition, set shifting, and working memory, using a mixed-methods study design. The participants were 75 moderate or heavy drinkers between the ages of 21 and 35 who were randomized into one of three beverage conditions (control, placebo, or 0.65-g alcohol dose/kg body weight). Performance on working memory, set shifting, and inhibition were measured pre- and post-beverage consumption. The results showed only a significant interaction in the working memory data, as there was an increase in performance post-beverage relative to pre-beverage for the control participants as compared to the alcohol and placebo participants. It was concluded that the dose of alcohol (BAC = 0.063%) given to moderate to heavy drinkers was not sufficient to cause significant impairment in the executive functions tested. The results were further discussed and methodological concerns were considered, such as the low BAC achieved, practice effects, and insensitivity of tasks.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.02.177
      Issue No: Vol. 61 (2017)
  • Quantifying the contribution of alcohol to cardiomyopathy: A systematic
    • Authors: Jürgen Rehm; Omer Syed Muhammad Hasan; Sameer Imtiaz; Maria Neufeld
      Pages: 9 - 15
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): Jürgen Rehm, Omer Syed Muhammad Hasan, Sameer Imtiaz, Maria Neufeld
      Alcohol has a direct toxic impact on the heart, and while there is an ICD code for alcoholic cardiomyopathy, the burden of alcohol-attributable cardiomyopathy is not clear. For the usual estimation of this burden via population-attributable fractions, one would need to determine the risk relationships, i.e., average risk associated with different dimensions of alcohol exposure. The most important among these risk relationships is the dose-response relationship with different levels of average alcohol consumption. To establish risk relationships, we systematically searched for all studies on dose-response relationships, directly and indirectly, via reviews. The results did not permit computation of pooled estimates through meta-analyses. There were clear indications that heavy drinking (≥80 g per day) over several years was linked to high risk of cardiomyopathy, with greater lifetime exposure of alcohol linked to higher risks. Some studies indicated potential effects of patterns of drinking as well. As such, the global quantification of alcohol-attributable cardiomyopathy will have to rely on other methods than those used conventionally.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.011
      Issue No: Vol. 61 (2017)
  • Working memory over a six-year period in young binge drinkers
    • Authors: C. Carbia; F. Cadaveira; E. López-Caneda; F. Caamaño-Isorna; S. Rodríguez Holguín; M. Corral
      Pages: 17 - 23
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): C. Carbia, F. Cadaveira, E. López-Caneda, F. Caamaño-Isorna, S. Rodríguez Holguín, M. Corral
      Adolescence and early adulthood are periods of particular vulnerability to the neurotoxic effects of alcohol. Young people with alcohol-use disorders display deficits in working memory (WM). This function is supported by the prefrontal cortex, a late-maturing brain region. However, little is known about the progression of cognitive dysfunctions associated with a binge-drinking (BD) pattern of alcohol consumption among non-clinical adolescents. The objective of this study was to analyze the relationship between BD trajectory and WM in university students. An initial sample of 155 male and female first-year university students was followed prospectively over 6 years. The participants were classified as stable non-BDs, stable BDs, and ex-BDs, according to the third item of the Alcohol Use Disorders Identification Test (AUDIT). WM was assessed using the Self-Ordered Pointing Task. Generalized linear mixed models were applied. The results showed that stable BDs committed more total perseverative errors and showed a lower WM span in the difficult blocks than stable non-BDs. Difficulties in WM span showed some improvement, whereas perseveration errors remained constant throughout the follow-ups in the stable BDs. There were no significant differences between ex-BDs and non-BDs. In conclusion, stable BD is associated with WM deficits, particularly perseverations and low WM span in demanding trials, when compensatory mechanisms may no longer be successful. The partial improvement in WM span may support the notion of a neuromaturational delay, whereas the temporal stability of perseveration deficits may reflect either neurotoxic effects of alcohol or premorbid characteristics. Abandoning the BD pattern of alcohol consumption may lead to partial recovery.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.013
      Issue No: Vol. 61 (2017)
  • Effects of moderate alcohol consumption on gene expression related to
           colonic inflammation and antioxidant enzymes in rats
    • Authors: DawnKylee S. Klarich; Jerrold Penprase; Patricia Cintora; Octavio Medrano; Danielle Erwin; Susan M. Brasser; Mee Young Hong
      Pages: 25 - 31
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): DawnKylee S. Klarich, Jerrold Penprase, Patricia Cintora, Octavio Medrano, Danielle Erwin, Susan M. Brasser, Mee Young Hong
      Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some studies have reported that moderate alcohol consumption may not contribute additional risk for developing colorectal cancer while others suggest that moderate alcohol consumption provides a protective effect that reduces colorectal cancer risk. The purpose of this study was to determine the effects of moderate voluntary alcohol (20% ethanol) intake on alternate days for 3 months in outbred Wistar rats on risk factors associated with colorectal cancer development. Colonic gene expression of cyclooxygenase-2, RelA, 8-oxoguanine DNA glycosylase 1, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase M1, and aldehyde dehydrogenase 2 were determined. Blood alcohol content, liver function enzyme activities, and 8-oxo-deoxyguanosine DNA adducts were also assessed. Alcohol-treated rats were found to have significantly lower 8-oxo-deoxyguanosine levels in blood, a marker of DNA damage. Alanine aminotransferase and lactate dehydrogenase were both significantly lower in the alcohol group. Moderate alcohol significantly decreased cyclooxygenase-2 gene expression, an inflammatory marker associated with colorectal cancer risk. The alcohol group had significantly increased glutathione-S-transferase M1 expression, an antioxidant enzyme that helps detoxify carcinogens, such as acetaldehyde, and significantly increased aldehyde dehydrogenase 2 expression, which allows for greater acetaldehyde clearance. Increased expression of glutathione-S-transferase M1 and aldehyde dehydrogenase 2 likely contributed to reduce mucosal damage that is caused by acetaldehyde accumulation. These results indicate that moderate alcohol may reduce the risk for colorectal cancer development, which was evidenced by reduced inflammation activity and lower DNA damage after alcohol exposure.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.02.179
      Issue No: Vol. 61 (2017)
  • Impact of adolescent alcohol use across the lifespan: Long-lasting
           tolerance to high-dose alcohol coupled with potentiated spatial memory
           impairments to moderate-dose alcohol
    • Authors: Douglas B. Matthews; Adelle Novier; Jaime L. Diaz-Granados; Candice E. Van Skike; Laura Ornelas; G. Mittleman
      Pages: 33 - 42
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): Douglas B. Matthews, Adelle Novier, Jaime L. Diaz-Granados, Candice E. Van Skike, Laura Ornelas, G. Mittleman
      Understanding how alcohol exposure during adolescence affects aging is a critical but understudied area. In the present study, male rats were exposed to either alcohol or saline during adolescence, then tested every 4 months following either an ethanol or saline challenge; animals were tested until postnatal day (PD) 532. It was found that long-lasting tolerance to high-dose ethanol exists through the test period, as measured by loss of righting reflex, while tolerance to lower doses of ethanol is not found. In addition, alcohol exposure during adolescence facilitated spatial memory impairments to acute ethanol challenges later in life. The current work demonstrates that exposure to ethanol during adolescent development can produce long-lasting detrimental impairments.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.012
      Issue No: Vol. 61 (2017)
  • α6β2 nicotinic acetylcholine receptors influence locomotor activity and
           ethanol consumption
    • Authors: Helen M. Kamens; Colette Peck; Caitlin Garrity; Alex Gechlik; Brenita C. Jenkins; Akshat Rajan
      Pages: 43 - 49
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): Helen M. Kamens, Colette Peck, Caitlin Garrity, Alex Gechlik, Brenita C. Jenkins, Akshat Rajan
      Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have been implicated in ethanol behaviors. In particular, work in genetically engineered mice has demonstrated that α6-containing nAChRs are involved in ethanol consumption and sedation. A limitation of these studies is that the alteration in the receptor was present throughout development. The recently described α6β2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), now makes it possible to test for the involvement of these receptors using a pharmacological approach. The aim of this study was to examine the role of α6β2 nAChRs in ethanol behaviors using a pharmacological approach. Adolescent C57BL/6J mice were treated with bPiDI 30 min prior to testing the mice for binge-like ethanol consumption in the drinking-in-the-dark (DID) test, ethanol-induced motor incoordination using the balance beam, and ethanol-induced sedation using the Loss of Righting Reflex (LORR) paradigm. Adolescent animals were chosen because they express a high amount of α6 mRNA relative to adult animals. Control studies were also performed to determine the effect of bPiDI on locomotor activity and ethanol metabolism. Female mice treated with 20 mg/kg bPiDI had reduced locomotor activity compared to saline-treated animals during the first 30 min following an acute injection. Pretreatment with the α6β2 antagonist reduced adolescent ethanol consumption but also reduced saccharin consumption. No significant effects were observed on ethanol-induced ataxia, sedation, or metabolism. This study provides evidence that α6β2 nAChRs are involved in locomotor activity as well as ethanol and saccharin consumption in adolescent animals.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.02.178
      Issue No: Vol. 61 (2017)
  • Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral
           arteries via endocannabinoid receptors
    • Authors: Olga Seleverstov; Ana Tobiasz; J. Scott Jackson; Ryan Sullivan; Dejian Ma; J. Pierce Sullivan; Steven Davison; Yada Akkhawattanangkul; Danielle L. Tate; Terry Costello; Stacey Barnett; Wei Li; Giancarlo Mari; Alex M. Dopico; Anna N. Bukiya
      Pages: 51 - 61
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): Olga Seleverstov, Ana Tobiasz, J. Scott Jackson, Ryan Sullivan, Dejian Ma, J. Pierce Sullivan, Steven Davison, Yada Akkhawattanangkul, Danielle L. Tate, Terry Costello, Stacey Barnett, Wei Li, Giancarlo Mari, Alex M. Dopico, Anna N. Bukiya
      Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.014
      Issue No: Vol. 61 (2017)
  • Lobeline attenuates ethanol abstinence-induced depression-like behavior in
    • Authors: Monzurul Amin Roni; Shafiqur Rahman
      Pages: 63 - 70
      Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61
      Author(s): Monzurul Amin Roni, Shafiqur Rahman
      Evidence indicates that the brain nicotinic acetylcholine receptor (nAChRs) ligand lobeline reduces depression-like behaviors, ethanol drinking, and nicotine withdrawal-induced depression-like behaviors. The purpose of the present study was to determine the effects of lobeline on ethanol abstinence-induced depression-like behavior and associated neuroadaptive changes in mice. Adult C57BL/6J male mice were allowed to drink 10% ethanol for 4 weeks using a two-bottle choice procedure. Mice were tested after 24 h and 14 days of ethanol abstinence in a forced swim test (FST), a measure for depression-like behavior. Acute lobeline treatment (1 mg/kg) significantly reduced immobility time compared to controls after 24 h and 14 days of abstinence. In addition, abstinence from chronic ethanol exposure reduced serotonin levels in the hippocampus, which was reversed by acute lobeline treatment. Repeated lobeline treatment (1 mg/kg, once daily) for 14 days during ethanol abstinence also significantly reduced FST immobility in mice exposed to ethanol. Chronic ethanol exposure significantly reduced the number of 5-bromo 2′-deoxyuridine (BrdU)-positive cells in the dentate gyrus of the hippocampus, indicating decreased hippocampal cell proliferation. Abstinence from chronic ethanol exposure also decreased brain-derived neurotrophic factor (BDNF) in the dentate gyrus and CA3 region of the hippocampus. In contrast, repeated lobeline treatment significantly increased both BrdU- and BDNF-positive cells. Taken together, our results indicate that lobeline produced antidepressant-like effects, likely by targeting brain β2-containing nAChRs, serotonergic neurotransmission, and/or hippocampal cell proliferation. Therefore, lobeline may have therapeutic utility to treat alcohol abstinence-induced depression.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.015
      Issue No: Vol. 61 (2017)
  • DNA modifications in models of alcohol use disorders
    • Authors: Christopher T. Tulisiak; R. Adron Harris; Igor Ponomarev
      Pages: 19 - 30
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Christopher T. Tulisiak, R. Adron Harris, Igor Ponomarev
      Chronic alcohol use and abuse result in widespread changes to gene expression, some of which contribute to the development of alcohol-use disorders (AUD). Gene expression is controlled, in part, by a group of regulatory systems often referred to as epigenetic factors, which includes, among other mechanisms, chemical marks made on the histone proteins around which genomic DNA is wound to form chromatin, and on nucleotides of the DNA itself. In particular, alcohol has been shown to perturb the epigenetic machinery, leading to changes in gene expression and cellular functions characteristic of AUD and, ultimately, to altered behavior. DNA modifications in particular are seeing increasing research in the context of alcohol use and abuse. To date, studies of DNA modifications in AUD have primarily looked at global methylation profiles in human brain and blood, gene-specific methylation profiles in animal models, methylation changes associated with prenatal ethanol exposure, and the potential therapeutic abilities of DNA methyltransferase inhibitors. Future studies may be aimed at identifying changes to more recently discovered DNA modifications, utilizing new methods to discriminate methylation profiles between cell types, thus clarifying how alcohol influences the methylomes of cell-type populations and how this may affect downstream processes. These studies and more in-depth probing of DNA methylation will be key to determining whether DNA-level epigenetic regulation plays a causative role in AUD and can thus be targeted for treatment of the disorder.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.11.004
      Issue No: Vol. 60 (2017)
  • Emerging roles for ncRNAs in alcohol use disorders
    • Authors: R. Dayne Mayfield
      Pages: 31 - 39
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): R. Dayne Mayfield
      Chronic alcohol exposure produces widespread neuroadaptations and alterations in gene expression in human alcoholics and animal models. Technological advances in the past decade have increasingly highlighted the role of non-protein-coding RNAs (ncRNAs) in the regulation of gene expression and function. These recently characterized molecules were discovered to mediate diverse processes in the central nervous system, from normal development and physiology to regulation of disease, including alcoholism and other psychiatric disorders. This review will investigate the recent studies in human alcoholics and rodent models that have profiled different classes of ncRNAs and their dynamic alcohol-dependent regulation in brain.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.004
      Issue No: Vol. 60 (2017)
  • Long-term alterations to DNA methylation as a biomarker of prenatal
           alcohol exposure: From mouse models to human children with fetal alcohol
           spectrum disorders
    • Authors: Benjamin I. Laufer; Eric J. Chater-Diehl; Joachim Kapalanga; Shiva M. Singh
      Pages: 67 - 75
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Benjamin I. Laufer, Eric J. Chater-Diehl, Joachim Kapalanga, Shiva M. Singh
      Rodent models of Fetal Alcohol Spectrum Disorders (FASD) have revealed that prenatal alcohol exposure (PAE) results in differential DNA cytosine methylation in the developing brain. The resulting genome-wide methylation changes are enriched in genes with neurodevelopmental functions. The profile of differential methylation is dynamic and present in some form for life. The methylation changes are transmitted across subsequent mitotic divisions, where they are maintained and further modified over time. More recent follow up has identified a profile of the differential methylation in the buccal swabs of young children born with FASD. While distinct from the profile observed in brain tissue from rodent models, there are similarities. These include changes in genes belonging to a number of neurodevelopmental and behavioral pathways. Specifically, there is increased methylation at the clustered protocadherin genes and deregulation of genomically imprinted genes, even though no single gene is affected in all patients studied to date. These novel results suggest further development of a methylation based strategy could enable early and accurate diagnostics and therapeutics, which have remained a challenge in FASD research. There are two aspects of this challenge that must be addressed in the immediate future: First, the long-term differential methylomics observed in rodent models must be functionally confirmed. Second, the similarities in differential methylation must be further established in humans at a methylomic level and overcome a number of technical limitations. While a cure for FASD is challenging, there is an opportunity for the development of early diagnostics and attenuations towards a higher quality of life.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.11.009
      Issue No: Vol. 60 (2017)
  • Prefrontal cortex expression of chromatin modifier genes in male WSP and
           WSR mice changes across ethanol dependence, withdrawal, and abstinence
    • Authors: Joel G. Hashimoto; David P. Gavin; Kristine M. Wiren; John C. Crabbe; Marina Guizzetti
      Pages: 83 - 94
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Joel G. Hashimoto, David P. Gavin, Kristine M. Wiren, John C. Crabbe, Marina Guizzetti
      Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.010
      Issue No: Vol. 60 (2017)
  • Genome-wide analysis of the nucleus accumbens identifies DNA methylation
           signals differentiating low/binge from heavy alcohol drinking
    • Authors: Rita Cervera-Juanes; Larry J. Wilhelm; Byung Park; Kathleen A. Grant; Betsy Ferguson
      Pages: 103 - 113
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Rita Cervera-Juanes, Larry J. Wilhelm, Byung Park, Kathleen A. Grant, Betsy Ferguson
      Alcohol-use disorders encompass a range of drinking levels and behaviors, including low, binge, and heavy drinking. In this regard, investigating the neural state of individuals who chronically self-administer lower doses of alcohol may provide insight into mechanisms that prevent the escalation of alcohol use. DNA methylation is one of the epigenetic mechanisms that stabilizes adaptations in gene expression and has been associated with alcohol use. Thus, we investigated DNA methylation, gene expression, and the predicted neural effects in the nucleus accumbens core (NAcc) of male rhesus macaques categorized as “low” or “binge” drinkers, compared to “alcohol-naïve” and “heavy” drinkers based on drinking patterns during a 12-month alcohol self-administration protocol. Using genome-wide CpG-rich region enrichment and bisulfite sequencing, the methylation levels of 2.6 million CpGs were compared between alcohol-naïve (AN), low/binge (L/BD), and heavy/very heavy (H/VHD) drinking subjects (n = 24). Through regional clustering analysis, we identified nine significant differential methylation regions (DMRs) that specifically distinguished ANs and L/BDs, and then compared those DMRs among H/VHDs. The DMRs mapped to genes encoding ion channels, receptors, cell adhesion molecules, and cAMP, NF-κβ and Wnt signaling pathway proteins. Two of the DMRs, linked to PDE10A and PKD2L2, were also differentially methylated in H/VHDs, suggesting an alcohol-dose independent effect. However, two other DMRs, linked to the CCBE1 and FZD5 genes, had L/BD methylation levels that significantly differed from both ANs and H/VHDs. The remaining five DMRs also differentiated L/BDs and ANs. However, H/VHDs methylation levels were not distinguishable from either of the two groups. Functional validation of two DMRs, linked to FZD5 and PDE10A, support their role in regulating gene expression and exon usage, respectively. In summary, the findings demonstrate that L/BD is associated with unique DNA methylation signatures in the primate NAcc, and that the methylation signatures identify synaptic genes that may play a role in preventing the escalation of alcohol use.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.11.003
      Issue No: Vol. 60 (2017)
  • Disconnect between alcohol-induced alterations in chromatin structure and
           gene transcription in a mouse embryonic stem cell model of exposure
    • Authors: Kylee J. Veazey; Haiqing Wang; Yudhishtar S. Bedi; William M. Skiles; Richard Cheng-An Chang; Michael C. Golding
      Pages: 121 - 133
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Kylee J. Veazey, Haiqing Wang, Yudhishtar S. Bedi, William M. Skiles, Richard Cheng-An Chang, Michael C. Golding
      Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the ‘histone code’ induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program. To address this question, we examined the impact of ethanol exposure in mouse embryonic stem cells cultured under 2i conditions, where the transcriptional program is rigidly enforced through the use of small molecule inhibitors. We find that ethanol-induced changes in post-translational histone modifications are dose-dependent, unique to the chromatin modification under investigation, and that the extent and direction of the change differ between the period of exposure and the recovery phase. Similar to in vivo models, we find post-translational modifications affecting histone 3 lysine 9 are the most profoundly impacted, with the signature of exposure persisting long after alcohol has been removed. These changes in chromatin structure associate with dose-dependent alterations in the levels of transcripts encoding Dnmt1, Uhrf1, Tet1, Tet2, Tet3, and Polycomb complex members Eed and Ezh2. However, in this model, ethanol-induced changes to the chromatin template do not consistently associate with changes in gene transcription, impede the process of differentiation, or affect the acquisition of monoallelic patterns of expression for the imprinted gene Igf2R. These findings question the inferred universal relevance of epigenetic changes induced by drugs of abuse and suggest that changes in chromatin structure cannot unequivocally explain dysgenesis in isolation.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.007
      Issue No: Vol. 60 (2017)
  • The BAF (BRG1/BRM-Associated Factor) chromatin-remodeling complex exhibits
           ethanol sensitivity in fetal neural progenitor cells and regulates
           transcription at the miR-9-2 encoding gene locus
    • Authors: Sasha G. Burrowes; Nihal A. Salem; Alexander M. Tseng; Sridevi Balaraman; Marisa R. Pinson; Cadianna Garcia; Rajesh C. Miranda
      Pages: 149 - 158
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Sasha G. Burrowes, Nihal A. Salem, Alexander M. Tseng, Sridevi Balaraman, Marisa R. Pinson, Cadianna Garcia, Rajesh C. Miranda
      Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs. Therefore, we assessed the role of the BAF (BRG1/BRM-Associated Factor) complex, which disassembles nucleosomes to facilitate access to chromatin, as an epigenetic mediator of ethanol's effects on miR-9. Chromatin immunoprecipitation and DNAse I-hypersensitivity analyses showed that the BAF complex was associated with both transcriptionally accessible and heterochromatic regions of the miR-9-2 locus, and that disintegration of the BAF complex by combined knockdown of BAF170 and BAF155 resulted in a significant decrease in miR-9. We hypothesized that ethanol exposure would result in loss of BAF-complex function at the miR-9-2 locus. However, ethanol exposure significantly increased mRNA transcripts for maturation-associated BAF-complex members BAF170, SS18, ARID2, BAF60a, BRM/BAF190b, and BAF53b. Ethanol also significantly increased BAF-complex binding within an intron containing a CpG island and in the terminal exon encoding precursor (pre)-miR-9-2. These data suggest that the BAF complex may adaptively respond to ethanol exposure to protect against a complete loss of miR-9-2 in fetal NSCs. Chromatin remodeling factors may adapt to the presence of a teratogen, to maintain transcription of critical miRNA regulatory pathways.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.003
      Issue No: Vol. 60 (2017)
  • Postnatal choline supplementation selectively attenuates hippocampal
           microRNA alterations associated with developmental alcohol exposure
    • Authors: Sridevi Balaraman; Nirelia M. Idrus; Rajesh C. Miranda; Jennifer D. Thomas
      Pages: 159 - 167
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Sridevi Balaraman, Nirelia M. Idrus, Rajesh C. Miranda, Jennifer D. Thomas
      Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4–9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by ethanol. These findings have important implications for the mechanisms by which choline may serve as a potential treatment for FASD.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.12.006
      Issue No: Vol. 60 (2017)
  • Paternal preconception alcohol exposure imparts intergenerational
    • Authors: Gregory R. Rompala; Andrey Finegersh; Michelle Slater; Gregg E. Homanics
      Pages: 169 - 177
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Gregory R. Rompala, Andrey Finegersh, Michelle Slater, Gregg E. Homanics
      While alcohol use disorder (AUD) is a highly heritable condition, the basis of AUD in families with a history of alcoholism is difficult to explain by genetic variation alone. Emerging evidence suggests that parental experience prior to conception can affect inheritance of complex behaviors in offspring via non-genomic (epigenetic) mechanisms. For instance, male C57BL/6J (B6) mice exposed to chronic intermittent vapor ethanol (CIE) prior to mating with Strain 129S1/SvImJ ethanol-naïve females produce male offspring with reduced ethanol-drinking preference, increased ethanol sensitivity, and increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). In the present study, we tested the hypothesis that these intergenerational effects of paternal CIE are reproducible in male offspring on an inbred B6 background. To this end, B6 males were exposed to 6 weeks of CIE (or room air as a control) before mating with ethanol-naïve B6 females to produce ethanol (E)-sired and control (C)-sired male and female offspring. We observed a sex-specific effect, as E-sired males exhibited decreased two-bottle free-choice ethanol-drinking preference, increased sensitivity to the anxiolytic effects of ethanol, and increased VTA BDNF expression; no differences were observed in female offspring. These findings confirm and extend our previous results by demonstrating that the effects of paternal preconception ethanol are reproducible using genetically identical, inbred B6 animals.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.11.001
      Issue No: Vol. 60 (2017)
  • Adolescent binge-pattern alcohol exposure alters genome-wide DNA
    • Authors: AnnaDorothea Asimes; Audrey Torcaso; Elena Pinceti; Chun K. Kim; Nancy J. Zeleznik-Le; Toni R. Pak
      Pages: 179 - 189
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): AnnaDorothea Asimes, Audrey Torcaso, Elena Pinceti, Chun K. Kim, Nancy J. Zeleznik-Le, Toni R. Pak
      Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37–44) and late (PND 67–74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2016.10.010
      Issue No: Vol. 60 (2017)
  • Strain-specific programming of prenatal ethanol exposure across
    • Authors: Daniel O. Popoola; Michael E. Nizhnikov; Nicole M. Cameron
      Pages: 191 - 199
      Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60
      Author(s): Daniel O. Popoola, Michael E. Nizhnikov, Nicole M. Cameron
      Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17–20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague-Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits' expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE did not alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits' expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.01.002
      Issue No: Vol. 60 (2017)
  • Instructions to Authors
    • Abstract: Publication date: August 2017
      Source:Alcohol, Volume 62

      PubDate: 2017-07-27T20:00:33Z
  • Isolation stress and chronic mild stress induced immobility in the
           defensive burying behavior and a transient increased ethanol intake in
           Wistar rats
    • Authors: Priscila Vázquez-León; Lucía Martínez-Mota; Lucía Quevedo-Corona; Abraham Miranda-Páez
      Abstract: Publication date: Available online 21 July 2017
      Author(s): Priscila Vázquez-León, Lucía Martínez-Mota, Lucía Quevedo-Corona, Abraham Miranda-Páez
      Stress can be experienced with or without adverse effects, of which anxiety and depression are two of the most important due to the frequent comorbidity with alcohol abuse in humans. Historically, stress has been considered a cause of drug use, particularly alcohol abuse due to its anxiolytic effects. In the present work we exposed male Wistar rats to two different stress conditions: single housing (social isolation, SI), and chronic mild stress (CMS). We compared both stressed groups to group-housed rats and rats without CMS (GH) to allow the determination of a clear behavioral response profile related to their respective endocrine stress response and alcohol intake pattern. We found that SI and CMS, to a greater extent, induced short-lasting increased sucrose consumption, a transient increase in serum corticosterone level, high latency/immobility, and low burying behavior in the defensive burying behavior (DBB) test, and a transient increase in alcohol intake. Thus, the main conclusion was that stress caused by both SI and CMS induced immobility in the DBB test and, subsequently, induced a transient increased voluntary ethanol intake in Wistar rats with a free-choice home-cage drinking paradigm.

      PubDate: 2017-07-21T10:10:10Z
      DOI: 10.1016/j.alcohol.2017.03.005
  • P3b Amplitude is not reduced in abstinent alcoholics with a current MDD
    • Authors: George Fein; Valerie A. Cardenas
      Abstract: Publication date: Available online 18 July 2017
      Author(s): George Fein, Valerie A. Cardenas
      Background and Aims In two studies of long-term abstinent alcoholics (LTAAs), we found that about 17% had a current major depressive disorder (MDD). We tested the hypothesis that LTAAs with a current MDD diagnosis do not exhibit the reduced P3b event-related potential amplitude endophenotype for alcoholism. This is consistent with the majority of LTAAs with a current MDD having developed alcohol dependence via self-medication of their MDD rather than their alcohol dependence arising from the alcoholism endophenotype. We revisited the P3b data from the two LTAAs studies, comparing LTAAs with a current MDD vs. LTAAs without a current MDD to each other and to non-substance abusing controls (NSACs). In northern California, 48 LTAAs and 48 non-substance abusing controls were studied, while in Honolulu, 105 LTAAs and 77 NSACs were studied. A total of 26 LTAAs had a current MDD (10 in California and 16 in Honolulu). The difference in P3b amplitude and latency (measured in targets-standards) in a 3-condition visual oddball paradigm was compared to MDD diagnoses gathered using the computerized Diagnostic Interview Schedule. Across both study sites, LTAAs without a current MDD (either with no lifetime MDD or a lifetime, but not current MDD) had lower P3b amplitudes than NSACs. In contrast, P3b amplitudes in LTAAs with a current MDD did not differ from controls. We conclude that alcohol dependence in LTAAs with a current MDD did not derive from the alcoholism endophenotype. This group may not exhibit the externalizing diathesis characterized by impulsive, disinhibited behavior and may have developed alcohol dependence via excessive drinking in an attempt to self-medicate their MDD. These results have major implications for targeted treatments of alcoholism and comorbid MDD.

      PubDate: 2017-07-21T10:10:10Z
      DOI: 10.1016/j.alcohol.2017.03.004
  • A GABRA2 Polymorphism Improves a Model for Prediction of Drinking
    • Authors: Samuel Kuperman; Grace Chan; John Kramer; Leah Wetherill; Laura Acion; Howard J. Edenberg; Tatiana M. Foroud; John Nurnberger; Arpana Agrawal; Andrey Anokhin; Andrew Brooks; Victor Hesselbrock; Michie Hesselbrock; Marc Schuckit; Jay Tischfield; Xiangtao Liu
      Abstract: Publication date: Available online 28 June 2017
      Author(s): Samuel Kuperman, Grace Chan, John Kramer, Leah Wetherill, Laura Acion, Howard J. Edenberg, Tatiana M. Foroud, John Nurnberger, Arpana Agrawal, Andrey Anokhin, Andrew Brooks, Victor Hesselbrock, Michie Hesselbrock, Marc Schuckit, Jay Tischfield, Xiangtao Liu
      Background Survival analysis was used to explore the addition of a single nucleotide polymorphism (SNP) and covariates (sex, interview age, and ancestry) on a previously published model’s ability to predict onset of drinking. A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking. Methods A subsample of 674 adolescents (ages 14–17) participating in the Collaborative Study on the Genetics of Alcoholism (COGA) was examined using a previously derived Cox proportional hazards model containing: 1) number of non-drinking related conduct disorder (CD) symptoms, 2) membership in a high-risk alcohol-dependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach Youth Self Report (YSR) externalizing score, and 5) YSR social problems score. The above covariates along with the SNP variant of GABRA2, rs279871, were added to this model. Five new prototype models were examined. The most parsimonious model was chosen based on likelihood ratio tests and model fit statistics. Results The final model contained four of the five original predictors (YSR social problems score was no longer significant and hence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (two copies of the high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype were more likely to begin drinking than those without this genotype. Conclusions The joint effect of the gene (rs279871 TT genotype) and environment (MBFD) on adolescent alcohol initiation is additive, but not interactive, after controlling for behavior problems (CD and YSR externalizing score). This suggests that the impact of the high-risk TT genotype on the onset of drinking is affected by controlling for peer drinking and does not include genotype-by-environment interactions.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.03.003
  • Persistent Negative Effects of Alcohol Drinking on Aspects of
           Novelty-directed Behavior in Male Rhesus Macaques
    • Authors: Cassie M. Chandler; Meagan E. Follett; Nicholas J. Porter; Kevin Y. Liang; Eric J. Vallender; Gregory M. Miller; James K. Rowlett; Donna M. Platt
      Abstract: Publication date: Available online 23 June 2017
      Author(s): Cassie M. Chandler, Meagan E. Follett, Nicholas J. Porter, Kevin Y. Liang, Eric J. Vallender, Gregory M. Miller, James K. Rowlett, Donna M. Platt
      Humans with histories of prolonged heavy alcohol use exhibit poorer performance on cognitive tasks associated with problem solving, short-term memory, and visuospatial reasoning, even following the cessation of drinking, when compared with healthy controls. It is unclear, however, whether the cognitive problems are a consequence of alcohol exposure or a contributing factor to alcohol-use disorders. Here, we examined the relationship between performance on a novel object recognition (NOR) task and total alcohol consumption (TAC) in adult male rhesus macaques (n = 12; ETH group; trained to self-administer alcohol). NOR performance in this group was assessed prior to induction of alcohol drinking (“pre”) and, again, after a 1-year abstinence period (“post”) and was compared to the performance of a second group (n = 6; Control group), which was alcohol-naïve. In the NOR task, difficulty was manipulated across three phases by varying specific object features and/or by varying duration of access to objects. For each monkey, we measured aspects of novelty-related behavior including novelty detection, novelty reactivity, and perseverative behavior. TAC during induction and a “free” access period in which the monkey could choose between water and a 4% w/v ethanol solution also was determined. We found that performance deficits in the NOR task were a consequence of high total alcohol intake instead of a predictor of subsequent high intake. Poor NOR performance in drinkers with the highest intakes was characterized by increased perseverative behavior rather than an inability to detect or react to novelty. Finally, the observed deficits are long-lasting – persisting even after a year of abstinence. Given the prevalent and persistent nature of alcohol-induced cognitive deficits in patients in treatment settings, understanding the nature of the deficit and its neural basis could ultimately offer novel treatment approaches based on the reversal of alcohol-induced impairment.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.03.002
  • Drinking and Smoking Patterns during Pregnancy: Development of Group-based
           Trajectories in the Safe Passage Study
    • Authors: Kimberly Dukes; Tara Tripp; Marian Willinger; Hein Odendaal; Amy J. Elliott; Hannah C. Kinney; Fay Robinson; Julie M. Petersen; Cheryl Raffo; Dale Hereld; Coen Groenewald; Jyoti Angal; Gary Hankins; Larry Burd; William P. Fifer; Michael M. Myers; Howard J. Hoffman; Lisa Sullivan
      Abstract: Publication date: Available online 15 June 2017
      Author(s): Kimberly Dukes, Tara Tripp, Marian Willinger, Hein Odendaal, Amy J. Elliott, Hannah C. Kinney, Fay Robinson, Julie M. Petersen, Cheryl Raffo, Dale Hereld, Coen Groenewald, Jyoti Angal, Gary Hankins, Larry Burd, William P. Fifer, Michael M. Myers, Howard J. Hoffman, Lisa Sullivan
      Precise identification of drinking and smoking patterns during pregnancy is crucial to better understand the risk to the fetus. The purpose of this manuscript is to describe the methodological approach used to define prenatal drinking and smoking trajectories from a large prospective pregnancy cohort, and to describe maternal characteristics associated with different exposure patterns. In the Safe Passage Study, detailed information regarding quantity, frequency, and timing of exposure was self-reported up to four times during pregnancy and at 1 month post-delivery. Exposure trajectories were developed using data from 11,692 pregnancies (9,912 women) where pregnancy outcome was known. Women were from three diverse populations: white (23%) and American Indian (17%) in the Northern Plains, US, and mixed ancestry (59%) in South Africa (other/not specified [1%]). Group-based trajectory modeling was used to identify 5 unique drinking trajectories (1 none/minimal, 2 quitting groups, 2 continuous groups) and 7 smoking trajectories (1 none/minimal, 2 quitting groups, 4 continuous groups). Women with pregnancies assigned to the low- or high-continuous drinking groups were less likely to have completed high school and were more likely to have enrolled in the study in the third trimester, be of mixed ancestry, or be depressed than those assigned to the none/minimal or quit-drinking groups. Results were similar when comparing continuous smokers to none/minimal and quit-smoking groups. Further, women classified as high- or low-continuous drinkers were more likely to smoke at moderate-, high-, and very high-continuous levels, as compared to women classified as non-drinkers and quitters. This is the first study of this size to utilize group-based trajectory modeling to identify unique prenatal drinking and smoking trajectories. These trajectories will be used in future analyses to determine which specific exposure patterns subsequently manifest as poor peri- and postnatal outcomes.

      PubDate: 2017-07-08T02:05:32Z
      DOI: 10.1016/j.alcohol.2017.03.001
  • Instructions to Authors
    • Abstract: Publication date: June 2017
      Source:Alcohol, Volume 61

      PubDate: 2017-07-08T02:05:32Z
  • Volterra Cover - Use the uploaded file after incoporating the changes. Use
           only Outside front cover
    • Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60

      PubDate: 2017-07-08T02:05:32Z
  • Title Page
    • Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60

      PubDate: 2017-07-08T02:05:32Z
  • TOC
    • Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60

      PubDate: 2017-07-08T02:05:32Z
  • Schedule
    • Abstract: Publication date: May 2017
      Source:Alcohol, Volume 60

      PubDate: 2017-07-08T02:05:32Z
  • Binge alcohol alters PNPLA3 levels in liver through epigenetic mechanism
           involving histone H3 acetylation
    • Authors: Ricardo J. Restrepo; Robert W. Lim; Ronald J. Korthuis; Shivendra D. Shukla
      Abstract: Publication date: Available online 12 March 2017
      Author(s): Ricardo J. Restrepo, Robert W. Lim, Ronald J. Korthuis, Shivendra D. Shukla
      The human PNPLA3 (patatin-like phospholipase domain-containing 3) gene codes for a protein which is highly expressed in adipose tissue and liver, and is implicated in lipid homeostasis. While PNPLA3 protein contains regions homologous to functional lipolytic proteins, the regulation of its tissue expression is reflective of lipogenic genes. A naturally occurring genetic variant of PNPLA3 in humans has been linked to increased susceptibility to alcoholic liver disease. We have examined the modulatory effect of alcohol on PNPLA3 protein and mRNA expression as well as the association of its gene promoter with acetylated histone H3K9 by chromatin immunoprecipitation (ChIP) assay in rat hepatocytes in vitro, and in vivo in mouse and rat models of acute binge, chronic, and chronic followed by acute binge ethanol administration. Protein expression of PNPLA3 was significantly increased by alcohol in all three models used. PNPLA3 mRNA also increased, albeit to a varying degree. ChIP assay using H3AcK9 antibody showed increased association with the promoter of PNPLA3 in hepatocytes and in mouse liver. This was less evident in rat livers in vivo except under chronic treatment. It is concluded for the first time that histone acetylation plays a role in the modulation of PNPLA3 levels in the liver exposed to binge ethanol both in vitro and in vivo.

      PubDate: 2017-03-12T22:40:46Z
      DOI: 10.1016/j.alcohol.2017.01.009
  • Mechanistic insights into epigenetic modulation of ethanol consumption
    • Authors: Igor Ponomarev; Claire E. Stelly; Hitoshi Morikawa; Yuri A. Blednov; R. Dayne Mayfield; R. Adron Harris
      Abstract: Publication date: Available online 12 March 2017
      Author(s): Igor Ponomarev, Claire E. Stelly, Hitoshi Morikawa, Yuri A. Blednov, R. Dayne Mayfield, R. Adron Harris
      There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking. Decitabine but not SAHA reduced ethanol consumption in both tests. We further investigated decitabine's effects on the brain's reward pathway by gene expression profiling in the ventral tegmental area (VTA), using RNA sequencing and electrophysiological recordings from VTA dopaminergic neurons. Decitabine-induced decreases in EOD drinking were associated with global changes in gene expression, implicating regulation of cerebral blood flow, extracellular matrix organization, and neuroimmune functions in decitabine actions. In addition, an in vivo administration of decitabine shortened ethanol-induced excitation of VTA dopaminergic neurons in vitro, suggesting that decitabine reduces ethanol drinking via changes in the reward pathway. Taken together, our data suggest a contribution of both neuronal and non-neuronal mechanisms in the VTA in the regulation of ethanol consumption. Decitabine and other epigenetic compounds have been approved for cancer treatment, and understanding their mechanisms of actions in the brain may assist in repurposing these drugs and developing novel therapies for central disorders, including drug addiction.

      PubDate: 2017-03-12T22:40:46Z
      DOI: 10.1016/j.alcohol.2017.01.016
  • Epigenetic mediators and consequences of excessive alcohol consumption
    • Authors: Amanda H. Mahnke; Rajesh C. Miranda; Gregg E. Homanics
      Abstract: Publication date: Available online 11 March 2017
      Author(s): Amanda H. Mahnke, Rajesh C. Miranda, Gregg E. Homanics

      PubDate: 2017-03-12T22:40:46Z
      DOI: 10.1016/j.alcohol.2017.02.357
  • Alcohol effects on the epigenome in the germline: Role in the inheritance
           of alcohol-related pathology
    • Authors: Lucy G. Chastain; Dipak K. Sarkar
      Abstract: Publication date: Available online 6 March 2017
      Author(s): Lucy G. Chastain, Dipak K. Sarkar
      Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions.

      PubDate: 2017-03-10T22:27:30Z
      DOI: 10.1016/j.alcohol.2016.12.007
  • Epigenetic mechanisms of alcoholism and stress-related disorders
    • Authors: Martina Palmisano; Subhash C. Pandey
      Abstract: Publication date: Available online 3 March 2017
      Author(s): Martina Palmisano, Subhash C. Pandey
      Stress-related disorders, such as anxiety, early life stress, and posttraumatic stress disorder appear to be important factors in promoting alcoholism, as alcohol consumption can temporarily attenuate the negative affective symptoms of these disorders. Several molecules involved in signaling pathways may contribute to the neuroadaptation induced during alcohol dependence and stress disorders, and among these, brain-derived neurotrophic factor (BDNF), corticotropin releasing factor (CRF), neuropeptide Y (NPY) and opioid peptides (i.e., nociceptin and dynorphin) are involved in the interaction of stress and alcohol. In fact, alterations in the expression and function of these molecules have been associated with the pathophysiology of stress-related disorders and alcoholism. In recent years, various studies have focused on the epigenetic mechanisms that regulate chromatin architecture, thereby modifying gene expression. Interestingly, epigenetic modifications in specific brain regions have been shown to be associated with the neurobiology of psychiatric disorders, including alcoholism and stress. In particular, the enzymes responsible for chromatin remodeling (i.e., histone deacetylases and methyltransferases, DNA methyltransferases) have been identified as common molecular mechanisms for the interaction of stress and alcohol and have become promising therapeutic targets to treat or prevent alcoholism and associated emotional disorders.

      PubDate: 2017-03-04T21:46:37Z
      DOI: 10.1016/j.alcohol.2017.01.001
  • DNA Methylation program in normal and alcohol-induced thinning cortex
    • Authors: Nail Can Öztürk; Marisol Resendiz; Hakan Öztürk; Feng C. Zhou
      Abstract: Publication date: Available online 20 February 2017
      Author(s): Nail Can Öztürk, Marisol Resendiz, Hakan Öztürk, Feng C. Zhou
      While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6J mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7–16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic markers of methylation were assessed using immunohistochemistry, Western blot, and methyl-DNA assays. We report that cortical thickness, neuroepithelial proliferation, and neuronal migration and maturity were found to be deterred by alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5 mC) and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program guiding normal embryonic cortical development, was severely affected by in utero alcohol exposure. The intricate relationship between cortical thinning and this DNA methylation program disruption is detailed and illustrated. DNA methylation, dynamic across the multiple cortical layers during the late embryonic stage, is highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with characteristic developmental abnormalities, ranging from structural to molecular. Finally, our findings point to a significant question for future exploration: whether epigenetics guides neurodevelopment or whether developmental conditions dictate epigenetic dynamics in the context of alcohol-induced cortical teratogenesis.

      PubDate: 2017-02-26T06:10:22Z
      DOI: 10.1016/j.alcohol.2017.01.006
  • Changes to histone modifications following prenatal alcohol exposure: An
           emerging picture
    • Authors: Eric J. Chater-Diehl; Benjamin I. Laufer; Shiva M. Singh
      Abstract: Publication date: Available online 4 February 2017
      Author(s): Eric J. Chater-Diehl, Benjamin I. Laufer, Shiva M. Singh
      Epigenetic mechanisms are important for facilitating gene-environment interactions in many disease etiologies, including Fetal Alcohol Spectrum Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs in animal models has illuminated the complex role of these mechanisms in FASD. In contrast, histone modifications have not been as well researched, due in part to being less stable than DNA methylation and less well-characterized in disease. It is now apparent that even changes in transient marks can have profound effects if they alter developmental trajectories. In addition, many histone methylations are now known to be relatively stable and can propagate themselves. As technologies and knowledge have advanced, a small group has investigated the role of histone modifications in FASD. Here, we synthesize the data on the effects of prenatal alcohol exposure (PAE) on histone modifications. Several key points are evident. AS with most alcohol-induced outcomes, timing and dosage differences yield variable effects. Nevertheless, these studies consistently find enrichment of H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone acetyltransferases and methyltransferases. The consistency of these alterations may implicate them as key mechanisms underlying FASD. Histone modification changes do not often correlate with gene expression changes, though some important examples exist. Encouragingly, attempts to reproduce specific histone modification changes are very often successful. We comment on possible directions for future studies, focusing on further exploration of current trends, expansion of time-point and dosage regimes, and evaluation of biomarker potential.

      PubDate: 2017-02-05T23:29:51Z
      DOI: 10.1016/j.alcohol.2017.01.005
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