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Molecular Toxicology and Alcohol Dependence
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Molecular Toxicology and Alcohol Dependence

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 6338

Special Issue Editor

Dr. Guido Viel

E-Mail Website
Guest Editor
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Section of Legal Medicine and Forensic Toxicology, University of Padova, 35122 Padova, Italy
Interests: forensic toxicology; pathology; radiology; alcohol use and abuse (in particular markers of chronic excessive drinking); substance use disorders

Special Issue Information

Dear Colleagues,

As you know, alcohol dependence represents a major health burden for modern societies because of its high mortality, morbidity and associated disability. The pathway from an initial drink of ethanol to chronic excessive drinking and alcohol dependence is a long and complex one. However, in recent years there has been much progress in understanding the molecular complexity and dynamicity of the mechanisms at play.

This special issue is dedicated to both “state markers”, that is novel biological screening tools with good diagnostic sensitivity and specificity for identifying at risk alcohol behaviors (e.g., binge drinking, heavy drinking, alcohol abuse, alcohol dependence) and “trait markers”, capable of providing information on the genetically determined predisposing and protective factors in the development of alcohol dependence.

Systematic reviews and original articles are highly encouraged for this special issue.

Please note that, for IJMS’paper, theoretical studies should offer new insights into the understanding of experimental results or suggest new experimentally testable hypotheses

Dr. Guido Viel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • alcohol dependence
  • alcohol abuse
  • chronic excessive drinking
  • alcoholism
  • alcohol use disorders
  • trait markers
  • state markers
  • clinical toxicology
  • forensic toxicology
  • molecular toxicology
  • metabolomics
  • mass spectrometry

Published Papers (3 papers)

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Research

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16 pages, 4563 KiB  
Article
Ethanol Kinetics in the Human Brain Determined by Magnetic Resonance Spectroscopy
by Annette Thierauf-Emberger, Dominik Schuldis, Michael Dacko and Thomas Lange
Int. J. Mol. Sci. 2023, 24(17), 13499; https://doi.org/10.3390/ijms241713499 - 31 Aug 2023
Viewed by 1135
Abstract
In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain [...] Read more.
In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain by magnetic resonance spectroscopy (MRS). In this study, the same method is used to demonstrate the kinetics of the ethanol concentration in the human brain after oral ethanol uptake. A drinking study was performed with 10 healthy participants. After the uptake of ethanol in a calculated amount leading to a plasma ethanol concentration of 0.92 g/L (19.95 mM corresponding to a blood ethanol concentration of 0.7 g/kg), brain ethanol concentrations were continuously measured by means of MRS on a 3 Tesla human magnetic resonance imaging (MRI) system. For the data acquisition a single-voxel sLASER sequence was used, with the volume of interest located in the occipital cortex. Intermittently, blood samples were taken and plasma was analyzed for ethanol using headspace gas chromatography with flame ionization detection (HS-GC-FID). The obtained MRS brain ethanol curves showed distinct inter-individual differences; however, a good intra-individual correlation of plasma and brain ethanol concentrations was observed. The results suggest a rapid equilibration between blood and brain. The ethanol concentrations measured in the brain were substantially lower than the measured plasma ethanol results, suggesting an MRS visibility of about 63% for ethanol in brain tissue. The maximum individual ethanol concentrations in the brain (normalized to water content) ranged between 7.1 and 14.1 mM across the cohort, while the highest measured plasma concentrations were in the range between 0.35 g/L (9.41 mM) and 0.95 g/L (20.52 mM). Full article
(This article belongs to the Special Issue Molecular Toxicology and Alcohol Dependence)
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Review

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17 pages, 3411 KiB  
Review
Phosphatidylethanol (PEth) in Blood as a Marker of Unhealthy Alcohol Use: A Systematic Review with Novel Molecular Insights
by Matteo Perilli, Federico Toselli, Lisa Franceschetto, Alessandro Cinquetti, Arianna Ceretta, Giovanni Cecchetto and Guido Viel
Int. J. Mol. Sci. 2023, 24(15), 12175; https://doi.org/10.3390/ijms241512175 - 29 Jul 2023
Cited by 9 | Viewed by 2084
Abstract
The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of [...] Read more.
The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through “MeSH” and “free-text” protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58–100% and 64–100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary. Full article
(This article belongs to the Special Issue Molecular Toxicology and Alcohol Dependence)
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23 pages, 882 KiB  
Review
Molecular Toxicology and Pathophysiology of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder Associated with Traumatic Brain Injury
by Zufeng Wang, Chengliang Luo, Edward W. Zhou, Aaron F. Sandhu, Xiaojing Yuan, George E. Williams, Jialu Cheng, Bharati Sinha, Mohammed Akbar, Pallab Bhattacharya, Shuanhu Zhou, Byoung-Joon Song and Xin Wang
Int. J. Mol. Sci. 2023, 24(10), 8805; https://doi.org/10.3390/ijms24108805 - 15 May 2023
Cited by 3 | Viewed by 2500
Abstract
The increasing comorbidity of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) associated with traumatic brain injury (TBI) is a serious medical, economic, and social issue. However, the molecular toxicology and pathophysiological mechanisms of comorbid AUD and PTSD are not well understood [...] Read more.
The increasing comorbidity of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) associated with traumatic brain injury (TBI) is a serious medical, economic, and social issue. However, the molecular toxicology and pathophysiological mechanisms of comorbid AUD and PTSD are not well understood and the identification of the comorbidity state markers is significantly challenging. This review summarizes the main characteristics of comorbidity between AUD and PTSD (AUD/PTSD) and highlights the significance of a comprehensive understanding of the molecular toxicology and pathophysiological mechanisms of AUD/PTSD, particularly following TBI, with a focus on the role of metabolomics, inflammation, neuroendocrine, signal transduction pathways, and genetic regulation. Instead of a separate disease state, a comprehensive examination of comorbid AUD and PTSD is emphasized by considering additive and synergistic interactions between the two diseases. Finally, we propose several hypotheses of molecular mechanisms for AUD/PTSD and discuss potential future research directions that may provide new insights and translational application opportunities. Full article
(This article belongs to the Special Issue Molecular Toxicology and Alcohol Dependence)
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