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Showing 1 - 200 of 3043 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 22, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 21, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 84, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 30, 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: 351, 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: 238, SJR: 3.683, h-index: 202)
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Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
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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  
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Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Acute Pain     Full-text available via subscription   (Followers: 13)
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: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 135, 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: 17, SJR: 0.739, h-index: 33)
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Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
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Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
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Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
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Advances in Digestive Medicine     Open Access   (Followers: 6)
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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)
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Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 41, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 50, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
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)
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Advances in Heat Transfer     Full-text available via subscription   (Followers: 22, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
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: 6)
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: 8, 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: 17)
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Advances in Psychology     Full-text available via subscription   (Followers: 61)
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: 3, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 353, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
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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: 17)
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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: 325, 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: 39, 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: 54, 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: 10, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
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)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 8, 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: 6)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 49, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 47, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 39, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 8, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 15, 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: 25, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 45, 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: 235, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 57, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 26, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 22, 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: 57, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 11)
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  
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Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 167, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
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Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 161, 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)
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Journal Cover Alcohol
  [SJR: 0.922]   [H-I: 66]   [10 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0741-8329
   Published by Elsevier Homepage  [3043 journals]
  • Acute ethanol intoxication suppresses pentraxin 3 expression in a mouse
           sepsis model involving cecal ligation and puncture
    • Authors: Shogo Kasuda; Risa Kudo; Katsuya Yuui; Yoshihiko Sakurai; Katsuhiko Hatake
      Pages: 1 - 9
      Abstract: Publication date: November 2017
      Source:Alcohol, Volume 64
      Author(s): Shogo Kasuda, Risa Kudo, Katsuya Yuui, Yoshihiko Sakurai, Katsuhiko Hatake
      Acute ethanol intoxication impairs immunological reactions and increases the risk of sepsis; however, the underlying mechanism remains unclear. Pentraxin (PTX) 3 is a humoral pattern recognition receptor whose levels rapidly increase in response to inflammation. PTX3 production is triggered by tumor necrosis factor (TNF)-α and is mediated by c-Jun N-terminal kinase (JNK). As PTX3 exerts protective effects against sepsis as well as acute lung injury, we investigated whether acute ethanol exposure exacerbates sepsis by altering PTX3 expression. Sepsis was induced in C57/BL6 mice by cecal ligation and puncture (CLP) after ethanol/saline administration. Survival rates were significantly lower in ethanol-treated than in saline-treated mice. Increased vascular permeability and attenuation of PTX3 expression were observed in the lungs of ethanol-treated mice 4 h after CLP. Concomitant with a delayed increase of plasma TNF-α in ethanol-treated mice, plasma PTX3 was also suppressed in the early phase of sepsis. Although TNF-α level in ethanol-treated mice exceeded that in saline-treated mice 16 h after CLP, PTX3 levels were still suppressed in the former group. JNK phosphorylation in lung tissue was suppressed in both groups 4 and 16 h after CLP. Furthermore, JNK phosphorylation in ethanol-treated human umbilical vein endothelial cells was suppressed even in the presence of exogenous TNF-α, resulting in inhibition of PTX3 mRNA and protein expression. Our results suggest that ethanol suppresses de novo PTX3 synthesis via two mechanisms – i.e., suppression of TNF-α production and inhibition of JNK phosphorylation. PTX3 suppression may therefore contribute to exacerbation of sepsis in acute ethanol intoxication.
      Graphical abstract image

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

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.05.002
      Issue No: Vol. 64 (2017)
  • 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)
  • Binge drinking and anxiety at the end of the nocturnal period in
           alcohol-preferring sP rats
    • Authors: Giancarlo Colombo; Carla Lobina; Irene Lorrai; Carla Acciaro; Paola Maccioni; Gian Luigi Gessa
      Pages: 27 - 32
      Abstract: Publication date: September 2017
      Source:Alcohol, Volume 63
      Author(s): Giancarlo Colombo, Carla Lobina, Irene Lorrai, Carla Acciaro, Paola Maccioni, Gian Luigi Gessa
      Previous studies suggested that exposure of Sardinian alcohol-preferring (sP) rats to daily drinking sessions of 1 h, during the dark phase of the light/dark cycle, with multiple alcohol concentrations, and unpredictable access to alcohol, resulted in exceptionally high intakes of alcohol when the drinking session occurred over the last hours of the dark phase. Additionally, higher levels of anxiety-related behaviors were observed at the 12th, rather than 1st, hour of the dark phase, suggesting that uncertainty of time of alcohol access and expectation of alcohol availability produced an emotional “distress”. The present study was designed to provide pharmacological support to the hypothesis that high alcohol intake under this drinking procedure is secondary to exacerbation of the anxiety-like state of sP rats. To this end, sP rats were initially exposed to daily 1-h drinking sessions during the dark phase and with multiple alcohol concentrations (0%, 10%, 20%, and 30%; v/v); time of alcohol exposure was changed each day and was unpredictable to rats. Rats were then treated acutely with non-sedative doses of diazepam (0, 1, 2, and 3 mg/kg; intraperitoneally [i.p.]) before two drinking sessions occurring at the 1st and 12th hour of the dark phase, respectively. Treatment with diazepam was ineffective at the 1st hour; conversely, it selectively reduced alcohol intake (up to 50% at the dose of 3 mg/kg) at the 12th hour. The preferential effectiveness of diazepam in reducing alcohol intake when the drinking session occurred at the 12th hour of the dark phase is consistent with the hypothesis that uncertainty of time of alcohol access and expectation of alcohol availability generated an emotional “distress” that rats counterbalanced with high alcohol drinking; the results of the present study are interpreted as the anxiolytic effects of diazepam substituting for those of alcohol, resulting in the observed reduction in alcohol intake.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.04.002
      Issue No: Vol. 63 (2017)
  • Ethanol suppresses carbamylcholine-induced intracellular calcium
           oscillation in mouse pancreatic acinar cells
    • Authors: Mi Na Yoon; Min Jae Kim; Hwa Soo Koong; Dong Kwan Kim; Se Hoon Kim; Hyung Seo Park
      Pages: 53 - 59
      Abstract: Publication date: September 2017
      Source:Alcohol, Volume 63
      Author(s): Mi Na Yoon, Min Jae Kim, Hwa Soo Koong, Dong Kwan Kim, Se Hoon Kim, Hyung Seo Park
      Oscillation of intracellular calcium levels is closely linked to initiating secretion of digestive enzymes from pancreatic acinar cells. Excessive alcohol consumption is known to relate to a variety of disorders in the digestive system, including the exocrine pancreas. In this study, we have investigated the role and mechanism of ethanol on carbamylcholine (CCh)-induced intracellular calcium oscillation in murine pancreatic acinar cells. Ethanol at concentrations of 30 and 100 mM reversibly suppressed CCh-induced Ca2+ oscillation in a dose-dependent manner. Pretreatment of ethanol has no effect on the store-operated calcium entry induced by 10 μM of CCh. Ethanol significantly reduced the initial calcium peak induced by low concentrations of CCh and therefore, the CCh-induced dose-response curve of the initial calcium peak was shifted to the right by ethanol pretreatment. Furthermore, ethanol significantly dose-dependently reduced inositol 1,4,5-trisphosphate-induced calcium release from the internal stores in permeabilized acinar cells. These results provide evidence that excessive alcohol intake could impair cytosolic calcium oscillation through inhibiting calcium release from intracellular stores in mouse pancreatic acinar cells.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.03.006
      Issue No: Vol. 63 (2017)
  • Is catalase involved in the effects of systemic and pVTA administration of
           4-methylpyrazole on ethanol self-administration'
    • Authors: Alessandra T. Peana; Francesca A. Pintus; Federico Bennardini; Gaia Rocchitta; Gianfranco Bazzu; Pier Andrea Serra; Simona Porru; Michela Rosas; Elio Acquas
      Pages: 61 - 73
      Abstract: Publication date: September 2017
      Source:Alcohol, Volume 63
      Author(s): Alessandra T. Peana, Francesca A. Pintus, Federico Bennardini, Gaia Rocchitta, Gianfranco Bazzu, Pier Andrea Serra, Simona Porru, Michela Rosas, Elio Acquas
      The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (H2O2). In this regard, while it is well known that 4-methylpyrazole (4-MP) acts by inhibiting ADH in the liver, little attention has been placed on its ability to interfere with fatty acid oxidation-mediated generation of H2O2, a mechanism that may indirectly affect catalase whose enzymatic activity requires H2O2. The aim of our investigation was twofold: 1) to evaluate the effect of systemic (i.p. [intraperitoneal]) and local (into the posterior ventral tegmental area, pVTA) administration of 4-MP on oral ethanol self-administration, and 2) to assess ex vivo whether or not systemic 4-MP affects liver and brain H2O2 availability. The results show that systemic 4-MP reduced ethanol but not acetaldehyde or saccharin self-administration, and decreased the ethanol deprivation effect. Moreover, local intra-pVTA administration of 4-MP reduced ethanol but not saccharin self-administration. In addition, although unable to affect basal catalase activity, systemic administration of 4-MP decreased H2O2 availability both in liver and in brain. Overall, these results indicate that 4-MP interferes with ethanol self-administration and suggest that its behavioral effects could be due to a decline in catalase-H2O2 system activity as a result of a reduction of H2O2 availability, thus highlighting the role of central catalase-mediated metabolism of ethanol and further supporting the key role of acetaldehyde in the reinforcing properties of ethanol.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.04.001
      Issue No: Vol. 63 (2017)
  • Role of Corticotropin Releasing Factor Binding Protein in the stress
           system: a strange case of Dr. Jekyll and Mr. Hyde in the stress
    • Authors: Carolina L. Haass-Koffler
      Abstract: Publication date: Available online 13 October 2017
      Author(s): Carolina L. Haass-Koffler
      The corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP). Extensive literature suggests a role of CRF in alcohol use disorder (AUD). Less is known on the specific role, if any, of CRFBP in AUD. In this review, we summarize recent interdisciplinary efforts towards identifying the contribution of CRFBP in mediating CRF activation. The role of CRFBP in alcohol-related behaviors has been evaluated with the ultimate goal of designing effective novel therapeutic strategies for AUD. A series of in vitro, in vivo, ex vivo and genetic studies presented here provide initial evidence that CRFBP may possess both inhibitory and excitatory roles and support the original hypothesis that it represents a novel pharmacological target for the treatment of AUD. This report summarizes the proceedings of one of the talks at the Young Investigator Award symposium at the Alcoholism and Stress: A Framework for Future Treatment Strategies Conference, Volterra, Italy.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.06.001
  • Persistent Light to Moderate Alcohol Intake and Lung Function: A
           Longitudinal Study
    • Authors: Monica M. Vasquez; Duane L. Sherrill; Tricia D. LeVan; Wayne J. Morgan; Joseph H. Sisson; Stefano Guerra
      Abstract: Publication date: Available online 1 September 2017
      Author(s): Monica M. Vasquez, Duane L. Sherrill, Tricia D. LeVan, Wayne J. Morgan, Joseph H. Sisson, Stefano Guerra
      Alcohol intake has been associated with lung function levels inconsistently in cross-sectional studies. The goal of our study was to determine whether longitudinally-assessed light-to-moderate alcohol intake is associated with levels and decline of lung function. We examined data from 1,333 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease. Alcohol intake was assessed at four surveys between 1972 and 1992. Subjects who completed at least two surveys were classified into longitudinal drinking categories (“never”, “inconsistent”, or “persistent drinker”). Spirometric lung function was measured in up to 11 surveys between 1972 and 1992. Random coefficient models were used to test for differences in lung function by drinking categories. After adjustment for sex, age, height, education, BMI categories, smoking status, and pack-years, as compared to never drinkers, persistent drinkers had higher FVC (coefficient: 157 ml, p<0.001), but lower FEV1/FVC ratio (-2.3%, p<0.001). Differences were due to a slower decline of FVC among persistent than never drinkers (p=0.003) and these trends were present independent of smoking status. Inconsistent drinking showed similar, but weaker associations. After adjustment for potential confounders, light-to-moderate alcohol consumption was associated with a significantly decreased rate of FVC decline over adult life.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.08.013
  • Evaluation of a novel method for the analysis of alcohol biomarkers: ethyl
           glucuronide, ethyl sulfate and phosphatidylethanol
    • Authors: Van Long Nguyen; Phillip Paull; Paul S. Haber; Kate Chitty; Devanshi Seth
      Abstract: Publication date: Available online 31 August 2017
      Author(s): Van Long Nguyen, Phillip Paull, Paul S. Haber, Kate Chitty, Devanshi Seth
      Currently available markers and methods to evaluate alcohol consumption are indirect and sub-optimal, or rely on self-report which have inherent problems. Direct metabolites of alcohol, phosphatidylethanol (PEth), ethyl sulfate (EtS) and ethyl glucuronide (EtG), are known to improve diagnostic accuracy. In this study methods were established for the identification of PEth in erythrocytes and EtG and EtS in serum using ultra-high performance liquid chromatography-tandem-mass spectrometry (UHPLC-MS/MS). The three biomarkers were tested and validated in volunteer teetotallers (n=4) and drinkers (n=10), and applied in patients (n=8) hospitalised with alcohol-related problems. Linearity of each assay was demonstrated from 22.5 to 900 nM for EtG, 40 to 3175 nM for EtS and 21 to 750 nM for PEth. The methods were highly selective, precise (<5% coefficient of variation) and had optimal accuracy (within 10% of the nominal value) for all three analytes. Recovery for all three compounds exceeded 90%. A preliminary investigation into the window of detection of these biomarkers after a single occasion of moderate alcohol consumption revealed that EtG and EtS could be detected and quantitated over the short term (days) and PEth over the long term (weeks). All three biomarkers showed high sensitivity and specificity in distinguishing between abstinence and any alcohol use at the cut-off values of 22.5 nM for EtG, 40 nM for EtS and 21 nM for PEth. We have established simultaneous assays for EtG, EtS and PEth for routine clinical use in confirming abstinence and exposure, and detecting underreporting of alcohol use, relevant in clinical and non-clinical settings.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.08.009
  • Maternal hair testing to disclose self-misreporting in drinking and
           smoking behaviour during pregnancy
    • Authors: Maria Dolores Gomez-Roig; Emilia Marchei; Sally Sabra; Francesco Paolo Busardò; Luisa Mastrobattista; Simona Pichini; Eduard Gratacós; Oscar Garcia-Algar
      Abstract: Publication date: Available online 31 August 2017
      Author(s): Maria Dolores Gomez-Roig, Emilia Marchei, Sally Sabra, Francesco Paolo Busardò, Luisa Mastrobattista, Simona Pichini, Eduard Gratacós, Oscar Garcia-Algar
      This study aimed to objectively verify smoking and drinking behaviour during pregnancy and to disclose self-misreporting through maternal hair analysis. A total of 153 women attending a university hospital in Barcelona (Spain) were selected and interviewed after delivery, on their smoking and drinking habits during pregnancy. A 9 cm hair strand was collected and analyzed by liquid chromatography tandem mass spectrometry for the presence of nicotine (NIC) and ethyl-glucuronide (EtG) as biomarkers of tobacco and alcohol consumption. Concentrations of EtG < 7 pg/mg hair and ≥30 pg/mg hair in the 0–3 cm hair segment have been used to assess respectively total abstinence and chronic excessive consumption in the previous three months, with repetitive moderate drinking lying in the interval 7–30 pg EtG per mg hair. Hair NIC less than 1 ng/mg hair indicates non exposure to tobacco smoke while hair NIC indicates daily active smoking. In the interview, 28.1% women declared to have smoked occasionally during gestation, while only 2.6% stated to have consumed alcohol in more than one occasion during pregnancy. Hair testing of smoking biomarkers disclosed that 7.2% women remained active smokers during the whole pregnancy (hair NIC: 3.21-56.98 ng/mg hair), 16.3% were passive non-smokers or occasional smokers(hair NIC: 1.04-2.99 ng/mg hair), while 76.5 % were not exposed to any cigarette smoke (hair NIC <limit of quantification- 0.91 ng/mg hair). Conversely, alcohol hair biomarkers showed that only 35.3% women were totally abstinent during gestation (hair EtG: 3.89-6.73 pg/mg hair), while 62.7% drunk a non-negligible amount of alcohol during pregnancy (hair EtG: 7.06-26.57 pg/mg hair) and 2% were chronic excessive drinkers (hair EtG: 35.33- 47.52 pg/mg hair). Maternal hair analysis has shown to be significantly more sensitive than the interviews in revealing an alarming misreported prevalence of alcohol use during pregnancy. These findings stress the need to use objective measures to assess alcohol exposure and to consider the inclusion of targeted actions to reduce alcohol consumption in maternal-child health policies.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.08.010
  • Alcohol Affects the P3 Component of an Adaptive Stop Signal Task ERP
    • Authors: Martin H. Plawecki; Kyle A. Windisch; Leah Wetherill; Ann E.K. Kosobud; Mario Dzemidzic; David A. Kareken; Sean J. O’Connor
      Abstract: Publication date: Available online 31 August 2017
      Author(s): Martin H. Plawecki, Kyle A. Windisch, Leah Wetherill, Ann E.K. Kosobud, Mario Dzemidzic, David A. Kareken, Sean J. O’Connor
      BACKGROUND The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduces P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). METHODS One hundred and forty eight nondependent moderate to heavy social drinkers, age 21 to 27, participated in 2 single-blind, alcohol or placebo, counterbalanced sessions approximately one week apart. During each session, subjects performed an adaptive stop signal task (aSST) at (1) baseline, (2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and (3) approximately 135 minutes later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial based on the subject’s performance. RESULTS The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring “going” over “stopping,” and SLOW SSD favoring “stopping” over “going”. Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to SLOW SSD group. CONCLUSIONS The aSST is a robust and sensitive task for detecting alcohol induced changes in inhibition behavior as measured by the P3 component in a within subject design. Alcohol was associated with P3 component changes which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response related AUD risk.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.08.012
  • Broad-spectrum protein kinase inhibition by the staurosporine analog
           KT-5720 reverses ethanol withdrawal-associated loss of NeuN/Fox-3
    • Authors: Anna R. Reynolds; Meredith A. Saunders; Jennifer N. Berry; Lynda J. Sharrett-Field; Sydney Winchester; Mark A. Prendergast
      Abstract: Publication date: Available online 30 August 2017
      Author(s): Anna R. Reynolds, Meredith A. Saunders, Jennifer N. Berry, Lynda J. Sharrett-Field, Sydney Winchester, Mark A. Prendergast
      Chronic, intermittent ethanol (CIE) exposure is known to produce neuroadaptive alterations in excitatory neurotransmission that contribute to the development of dependence. Although activation of protein kinases (e.g., cyclic AMP [cAMP]-dependent protein kinase) is implicated in the synaptic trafficking of these receptors following CIE exposure, the functional consequences of these effects are yet to be fully understood. The present study sought to delineate the influence of protein kinase in regulating cytotoxicity following CIE exposure, as well as to examine the relative roles of ethanol exposure and ethanol withdrawal (EWD) in promoting these effects. Rat hippocampal explants were exposed to a developmental model of CIE with or without co-application of broad-spectrum protein kinase inhibitor KT-5720 (1 μM) either during ethanol exposure or EWD. Hippocampal cytotoxicity was assessed via immunofluorescence (IF) of neuron-specific nuclear protein (NeuN) with thionine staining of Nissl bodies to confirm IF findings. Concomitant application of ethanol and KT-5720 restored the loss of NeuN/Fox-3 IF in pyramidal CA1 and granule DG cell layers produced by CIE, but there was no restoration in CA3. Application of KT-5720 during EWD failed to significantly alter levels of NeuN IF, implying that ethanol exposure activates protein kinases that, in part, mediate the effects of EWD. KT-5720 application during EWD also restored thionine staining in CA1, suggesting kinase regulation of both neurons and non-neuronal cells. These data demonstrate that CIE exposure alters protein kinase activity to promote ethanol withdrawal-associated loss of NeuN/Fox-3 and highlight the influence of kinase signaling on distinct cell types in the developing hippocampus.

      PubDate: 2017-09-05T23:12:51Z
      DOI: 10.1016/j.alcohol.2017.05.006
  • Instructions to Authors
    • Abstract: Publication date: September 2017
      Source:Alcohol, Volume 63

      PubDate: 2017-08-27T23:05:21Z
  • The new kisspeptin derivative – kissorphin (KSO) – attenuates acute
    • Authors: Ewa Gibula-Bruzda; Marta Marszalek-Grabska; Kinga Gawel; Roza Trzcinska; Jerzy Silberring; Jolanta H. Kotlinska
      Abstract: Publication date: Available online 24 August 2017
      Author(s): Ewa Gibula-Bruzda, Marta Marszalek-Grabska, Kinga Gawel, Roza Trzcinska, Jerzy Silberring, Jolanta H. Kotlinska
      Kissorphin (KSO) is a new peptide derived from kisspeptin-10. This peptide possesses neuropeptide FF (NPFF)-like biological activity in vitro; NPFF, in many cases, inhibits opioid and ethanol effects in rodents. Therefore, the current study explored the influence of KSO on acute ethanol- and morphine-induced hyperactivity, and on the development and expression of locomotor sensitization induced by these drugs. In the present study, sensitization to locomotor effects was induced by repeated exposure to ethanol (2.4 g/kg, intraperitoneally [i.p.], 1 × 4 days) or morphine (10 mg/kg, subcutaneously [s.c.], 1 × 7 days). We found that KSO (1–10 nmol/300 μL, intravenously [i.v.]) did not have an impact on locomotor activity of naïve mice. However, it reduced both acute ethanol- (10 nmol/300 μL) and morphine-induced hyperactivity (3 and 10 nmol/300 μL). Pretreatment of animals with KSO (10 nmol/300 μL), before every ethanol or morphine injection during development of sensitization or before the ethanol or morphine challenge, attenuated the development, as well as the expression of locomotor sensitization to both substances. Moreover, prior administration of the NPFF receptor antagonist RF9 (10 nmol/300 μL, i.v.) inhibited the ability of KSO (10 nmol/300 μL) to reduce the expression of ethanol and morphine sensitization. KSO given alone, at all used doses, did not influence the motor coordination measured via the rotarod test. The results from this study show that KSO effectively attenuated acute and repeated effects of ethanol and morphine. Thus, KSO possesses NPFF-like anti-opioid activity in these behavioral studies.

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

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.05.005
  • Challenges of Diagnosing Fetal Alcohol Spectrum Disorders in Foster and
           Adopted Children
    • Authors: Ludmila N. Bakhireva; Laura Garrison; Shikhar Shrestha; Janet Sharkis; Rajesh Miranda; Karen Rogers
      Abstract: Publication date: Available online 24 August 2017
      Author(s): Ludmila N. Bakhireva, Laura Garrison, Shikhar Shrestha, Janet Sharkis, Rajesh Miranda, Karen Rogers
      Fetal Alcohol Spectrum Disorders (FASD) might be 10–15 times more prevalent among foster/adopted children compared to the general population; however, many of these children remain undiagnosed or misdiagnosed. The lack of confirmed prenatal alcohol exposure (PAE) may be a key barrier to diagnosis. Our sample included 681 patients evaluated for FASD, according to the University of Washington 4-Digit Diagnostic Code, at a pediatric specialty clinic. Guardianship status and other patient characteristics were evaluated by multinomial logistic regression as potential predictors of being classified into one of the following FASD groups: 1) full or partial Fetal Alcohol Syndrome (FAS/pFAS; n = 97); 2) Static Encephalopathy/Alcohol-Exposed (SE/AE) or Neurobehavioral Disorder/Alcohol-Exposed (ND/AE) (n = 135); and 3) some features of FASD (equivalent to pFAS, SE/AE or ND/AE phenotypes) but unknown PAE (n = 449). Median age at assessment was 7.0 years, non-Hispanic White constituted the predominant racial/ethnic group (49.5%), and the majority (81.8%) lacked involvement from a biological parent/relative. Many patients (66.0%) had some features of FASD but lacked reliable PAE information. Children classified into the ‘some features/unknown PAE’ group had higher median age of assessment (8 years) compared to other groups (6 years; p < 0.001). No association was observed between race/ethnicity or child’s sex and FASD outcomes (p > 0.05). Adopted/foster children were 2.8 times as likely (95% CI: 1.6; 4.8) to be classified into the ‘some features/unknown PAE’ group compared to children living with a parent/relative after adjusting for covariates. This study’s findings indicate that adopted/foster children are more likely to have unknown PAE and not receive a FASD diagnosis, potentially denying them access to specialized services, treatment, and rehabilitation.

      PubDate: 2017-08-27T23:05:21Z
      DOI: 10.1016/j.alcohol.2017.05.004
  • Effects of Binge Alcohol Exposure on Burkholderia thailandensis-Alveolar
           Macrophage Interaction
    • Authors: Victor Jimenez; Ryan Moreno; Emily Kaufman; Heidie Hornstra; Erik Settles; Bart J. Currie; Paul Keim; Fernando P. Monroy
      Abstract: Publication date: Available online 19 August 2017
      Author(s): Victor Jimenez, Ryan Moreno, Emily Kaufman, Heidie Hornstra, Erik Settles, Bart J. Currie, Paul Keim, Fernando P. Monroy
      Alcohol consumption has diverse and well-documented effects on the human immune system and its ability to defend against infective agents. One example is melioidosis, a disease caused by infection with Burkholderia pseudomallei, which is of public health importance in Southeast Asia and Northern Australia, with an expanding global distribution. While B. pseudomallei infections can occur in healthy humans, binge alcohol use is progressively being recognized as a major risk factor. Although binge alcohol consumption has been considered as a risk factor for the development of melioidosis, no experimental studies have investigated the outcomes of alcohol exposure on Burkholderia spp. infection. Therefore, we proposed the use of non-pathogenic B. thailandensis E264 as a useful BSL-1 model system to study the effects of binge alcohol exposure on bacteria and alveolar macrophage interactions. The MH-S alveolar macrophage (AMs) cell line was used to characterize innate immune responses to infection in vitro. Our results showed that alcohol exposure significantly suppressed the uptake and killing of B. thailandensis by AMs. Alveolar macrophages incubated in alcohol (0.08%) for 3 h prior to infection showed significantly lower bacterial uptake at 2 and 8 h post infection. Activated AMs with IFN-γ and pre and post-incubation in alcohol when exposed to B. thailandensis released lower nitric oxide (NO) concentrations, compared to activated AMs with IFN-γ from non-alcoholic controls. As a result, B. thailandensis survival and replication increased ∼2.5-fold compared to controls. The presence of alcohol (1%) also increased bacterial survival within AMs. Alcohol significantly decreased bacterial motility compared to non-alcoholic controls. Increased biofilm formation was observed at 3 and 6 h when bacteria were pre-incubated in (0.08%) alcohol. These results provide insights into binge alcohol consumption, a culturally prevalent risk factor, as a predisposing factor for melioidosis.

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

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