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Alcohol Research : Current Reviews 2017Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse... (Review)
Review
Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.
Topics: Alcoholism; Animals; Endocrine System; Ethanol; Humans; Hypothalamo-Hypophyseal System; Immune System; Pituitary-Adrenal System
PubMed: 28988577
DOI: No ID Found -
Cells Nov 2021Diabetes mellitus (DM), one of the metabolic diseases which is characterized by sustained hyperglycemia, is a life-threatening disease. The global prevalence of DM is on... (Review)
Review
Diabetes mellitus (DM), one of the metabolic diseases which is characterized by sustained hyperglycemia, is a life-threatening disease. The global prevalence of DM is on the rise, mainly in low- and middle-income countries. Diabetes is a major cause of blindness, heart attacks, kidney failure, stroke, and lower limb amputation. Type 2 diabetes mellitus (T2DM) is a form of diabetes that is characterized by high blood sugar and insulin resistance. T2DM can be prevented or delayed by a healthy diet, regular physical activity, maintaining normal body weight, and avoiding alcohol and tobacco use. Ethanol and its metabolites can cause differentiation defects in stem cells and promote inflammatory injury and carcinogenesis in several tissues. Recent studies have suggested that diabetes can be treated, and its consequences can be avoided or delayed with proper management. DM has a greater risk for several cancers, such as breast, colorectal, endometrial, pancreatic, gallbladder, renal, and liver cancer. The incidence of cancer is significantly higher in patients with DM than in those without DM. In addition to DM, alcohol abuse is also a risk factor for many cancers. We present a review of the recent studies investigating the association of both DM and alcohol abuse with cancer incidence.
Topics: Alcoholism; Diabetes Mellitus, Type 2; Ethanol; Humans; Models, Biological; Neoplasms; Risk Factors
PubMed: 34831299
DOI: 10.3390/cells10113077 -
Progress in Molecular Biology and... 2016Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The... (Review)
Review
Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic-cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions.
Topics: Alcoholism; Animals; Animals, Genetically Modified; Humans; Nicotine; Receptors, Nicotinic; Signal Transduction
PubMed: 26810002
DOI: 10.1016/bs.pmbts.2015.10.004 -
American Journal of Physiology.... Sep 2016This review summarizes the American Physiological Society (APS) Presidential Symposium 1 entitled "Physiological Processes Underlying Organ Injury in Alcohol Abuse" at... (Review)
Review
This review summarizes the American Physiological Society (APS) Presidential Symposium 1 entitled "Physiological Processes Underlying Organ Injury in Alcohol Abuse" at the 2016 Experimental Biology meeting. The symposium was organized by Dr. Patricia Molina, past president of the APS, was held on April 3 at the Convention Center in San Diego, CA, and was funded by the National Institute on Alcohol Abuse and Alcoholism. The "Physiological Processes Underlying Organ Injury in Alcohol Abuse Symposium" assembled experts and leaders in the field and served as a platform to discuss and share knowledge on the latest developments and scientific advances on the mechanisms underlying organ injury in alcohol abuse. This symposium provided unique, interdisciplinary alcohol research, including several organs, liver, muscle, adipose, and brain, affected by excessive alcohol use.
Topics: Adipose Tissue; Alcoholism; Animals; Brain; Endocannabinoids; Humans; Liver; Muscular Atrophy
PubMed: 27436613
DOI: 10.1152/ajpendo.00270.2016 -
Alcohol Research : Current Reviews 2018
Topics: Alcoholism; Comorbidity; Humans; Stress Disorders, Post-Traumatic
PubMed: 31198650
DOI: No ID Found -
Neuropharmacology Aug 2017Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of... (Review)
Review
Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50-60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled "Alcoholism".
Topics: Alcoholism; Behavior, Addictive; Gene-Environment Interaction; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide
PubMed: 28118990
DOI: 10.1016/j.neuropharm.2017.01.017 -
Cellular and Molecular Life Sciences :... Aug 2017The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours.... (Review)
Review
The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing social models that reflect the addictive behaviour in a free-living social environment. Furthermore, this review also reports on the advancement of interventions for drug addiction and takes into account the emerging roles of histone deacetylase (HDAC) inhibitors in the etiology of drug addiction and that HDAC may be a potential therapeutic target at nucleosomal level to improve treatment outcomes.
Topics: Alcoholism; Animals; Chromatin Assembly and Disassembly; DNA Methylation; Disease Models, Animal; Drug Discovery; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Humans; Social Environment; Stress, Psychological; Substance-Related Disorders
PubMed: 28255755
DOI: 10.1007/s00018-017-2493-1 -
Expert Opinion on Drug Discovery Nov 2014Globally, alcohol abuse and dependence are significant contributors to chronic disease and injury and are responsible for nearly 4% of all deaths annually. Acamprosate... (Review)
Review
INTRODUCTION
Globally, alcohol abuse and dependence are significant contributors to chronic disease and injury and are responsible for nearly 4% of all deaths annually. Acamprosate (Campral), one of only three pharmacological treatments approved for the treatment of alcohol dependence, has shown mixed efficacy in clinical trials in maintaining abstinence of detoxified alcoholics since studies began in the 1980s. Yielding inconsistent results, these studies have prompted skepticism.
AREAS COVERED
Herein, the authors review the preclinical studies which have assessed the efficacy of acamprosate in various animal models of alcohol dependence and discuss the disparate findings from the major clinical trials. Moreover, the authors discuss the major limitations of these preclinical and clinical studies and offer explanations for the often-contradictory findings. The article also looks at the importance of the calcium moiety that accompanies the salt form of acamprosate and its relevance to its activity.
EXPERT OPINION
The recent discovery that large doses of calcium largely duplicate the effects of acamprosate in animal models has introduced a serious challenge to the widely held functional association between this drug and the glutamate neurotransmission system. Future research on acamprosate or newer pharmacotherapeutics should consider assessing plasma and/or brain levels of calcium as a correlate or mediating factor in anti-relapse efficacy. Further, preclinical research on acamprosate has thus far lacked animal models of chemical dependence on alcohol, and the testing of rodents with histories of alcohol intoxication and withdrawal is suggested.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Animals; Humans; Recurrence; Taurine
PubMed: 25258174
DOI: 10.1517/17460441.2014.960840 -
Australian Family Physician Dec 2016
Topics: Adolescent; Adult; Age Factors; Aged; Alcoholism; Australia; Binge Drinking; Female; Guideline Adherence; Humans; Male; Middle Aged; Prevalence; Sex Factors; Young Adult
PubMed: 27903033
DOI: No ID Found -
Pharmacogenomics Dec 2016Transcriptome profiling enables discovery of gene networks that are altered in alcoholic brains. This technique has revealed involvement of the brain's neuroimmune... (Review)
Review
Transcriptome profiling enables discovery of gene networks that are altered in alcoholic brains. This technique has revealed involvement of the brain's neuroimmune system in regulating alcohol abuse and dependence, and has provided potential therapeutic targets. In this review, we discuss Toll-like-receptor pathways, hypothesized to be key players in many stages of the alcohol addiction cycle. The growing appreciation of the neuroimmune system's involvement in alcoholism has also led to consideration of crucial roles for glial cells, including astrocytes and microglia, in the brain's response to alcohol abuse. We discuss current knowledge and hypotheses on the roles that specific neuroimmune cell types may play in addiction. Current strategies for repurposing US FDA-approved drugs for the treatment of alcohol use disorders are also discussed.
Topics: Alcoholism; Animals; Astrocytes; Calcium Signaling; Humans; Microglia; Neuroimmunomodulation; Toll-Like Receptors; Transcriptome
PubMed: 27918243
DOI: 10.2217/pgs-2016-0062