Quantifying the contribution of alcohol to cardiomyopathy: A systematic review
Alcohol has a direct toxic impact on the heart, and while there is an ICD code for alcoholic cardiomyopathy, the burden of alcohol-attributable cardiomyopathy is not clear. For the usual estimation of this burden via population-attributable fractions, one would need to determine the risk relationships, i.e., average risk associated with different dimensions of alcohol exposure. The most important among these risk relationships is the dose-response relationship with different levels of average alcohol consumption. (Source: Alcohol)
Source: Alcohol - April 19, 2017 Category: Addiction Authors: J ürgen Rehm, Omer Syed Muhammad Hasan, Sameer Imtiaz, Maria Neufeld Source Type: research
Effects of moderate alcohol consumption on gene expression related to colonic inflammation and antioxidant enzymes in rats
Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some studies have reported that moderate alcohol consumption may not contribute additional risk for developing colorectal cancer while others suggest that moderate alcohol consumption provides a protective effect that reduces colorectal cancer risk. The purpose of this study was to determine the effects of moderate voluntary alcohol (20% ethanol) intake on alternate days for 3 months in outbred Wistar rats on risk factors associated with colorectal cancer development. (Source: Alcohol)
Source: Alcohol - April 18, 2017 Category: Addiction Authors: DawnKylee S. Klarich, Jerrold Penprase, Patricia Cintora, Octavio Medrano, Danielle Erwin, Susan M. Brasser, Mee Young Hong Source Type: research
Emerging roles for ncRNAs in alcohol use disorders
Chronic alcohol exposure produces widespread neuroadaptations and alterations in gene expression in human alcoholics and animal models. Technological advances in the past decade have increasingly highlighted the role of non-protein-coding RNAs (ncRNAs) in the regulation of gene expression and function. These recently characterized molecules were discovered to mediate diverse processes in the central nervous system, from normal development and physiology to regulation of disease, including alcoholism and other psychiatric disorders. (Source: Alcohol)
Source: Alcohol - April 15, 2017 Category: Addiction Authors: R. Dayne Mayfield Source Type: research
Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)
Among animals at risk for excessive ethanol consumption such as the HDID selected lines, there is considerable individual variation in the amount of ethanol consumed and the associated blood ethanol concentrations (BECs). For the HDID lines, this variation occurs even though the residual genetic variation associated with the DID phenotype has been largely exhausted and thus is most likely associated with epigenetic factors. Here we focus on the question of whether the genes associated with individual variation in HDID-1 mice are different from those associated with selection (risk) (Iancu et al. (Source: Alcohol)
Source: Alcohol - April 13, 2017 Category: Addiction Authors: Robert Hitzemann, Denesa Oberbeck, Ovidiu Iancu, Priscila Darakjian, Shannon McWeeney, Stephanie Spence, Jason Schlumbohm, Pamela Metten, John Crabbe Source Type: research
The BAF (BRG1/BRM-Associated Factor) chromatin-remodeling complex exhibits ethanol sensitivity in fetal neural progenitor cells and regulates transcription at the miR-9-2 encoding gene locus
Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs) including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs. (Source: Alcohol)
Source: Alcohol - April 6, 2017 Category: Addiction Authors: Sasha G. Burrowes, Nihal A. Salem, Alexander M. Tseng, Sridevi Balaraman, Marisa R. Pinson, Cadianna Garcia, Rajesh C. Miranda Source Type: research
Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence
Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (...
Source: Alcohol - March 15, 2017 Category: Addiction Authors: Joel G. Hashimoto, David P. Gavin, Kristine M. Wiren, John C. Crabbe, Marina Guizzetti Source Type: research
Binge alcohol alters PNPLA3 levels in liver through epigenetic mechanism involving histone H3 acetylation
The human PNPLA3 (patatin-like phospholipase domain-containing 3) gene codes for a protein which is highly expressed in adipose tissue and liver, and is implicated in lipid homeostasis. While PNPLA3 protein contains regions homologous to functional lipolytic proteins, the regulation of its tissue expression is reflective of lipogenic genes. A naturally occurring genetic variant of PNPLA3 in humans has been linked to increased susceptibility to alcoholic liver disease. We have examined the modulatory effect of alcohol on PNPLA3 protein and mRNA expression as well as the association of its gene promoter with acetylated histo...
Source: Alcohol - March 11, 2017 Category: Addiction Authors: Ricardo J. Restrepo, Robert W. Lim, Ronald J. Korthuis, Shivendra D. Shukla Source Type: research
Mechanistic insights into epigenetic modulation of ethanol consumption
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking. (Source: Alcohol)
Source: Alcohol - March 11, 2017 Category: Addiction Authors: Igor Ponomarev, Claire E. Stelly, Hitoshi Morikawa, Yuri A. Blednov, R. Dayne Mayfield, R. Adron Harris Source Type: research
Epigenetic mediators and consequences of excessive alcohol consumption
Alcohol has pleiotropic effects across multiple organ systems, including brain, cardio-vascular, endocrine, immune, musculoskeletal, and gastrointestinal systems. Moreover, some effects, such as intoxication, can be brief, but others, such as the development of Alcohol Use Disorders (AUDs), cardiovascular disease, and liver damage, can persist for a lifetime. Effects resulting in encoding of endocrine and other dysfunctions can also persist across generations. This complexity creates a barrier to the creation of therapeutics and discovery of biomarkers. (Source: Alcohol)
Source: Alcohol - March 9, 2017 Category: Addiction Authors: Amanda H. Mahnke, Rajesh C. Miranda, Gregg E. Homanics Source Type: research
Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology
Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. (Source: Alcohol)
Source: Alcohol - March 6, 2017 Category: Addiction Authors: Lucy G. Chastain, Dipak K. Sarkar Source Type: research
Epigenetic mechanisms of alcoholism and stress-related disorders
Stress-related disorders, such as anxiety, early life stress, and posttraumatic stress disorder appear to be important factors in promoting alcoholism, as alcohol consumption can temporarily attenuate the negative affective symptoms of these disorders. Several molecules involved in signaling pathways may contribute to the neuroadaptation induced during alcohol dependence and stress disorders, and among these, brain-derived neurotrophic factor (BDNF), corticotropin releasing factor (CRF), neuropeptide Y (NPY) and opioid peptides (i.e., nociceptin and dynorphin) are involved in the interaction of stress and alcohol. (Source: Alcohol)
Source: Alcohol - March 2, 2017 Category: Addiction Authors: Martina Palmisano, Subhash C. Pandey Source Type: research
Phosphatidylethanol as a biomarker to identify patients with alcohol misuse
Severe alcohol misuse is associated with organ dysfunction and an increased risk for death in critically-ill patients. Self-report methods like the Alcohol Use Disorder Identification Test (AUDIT) and indirect biomarkers in this population cannot be routinely collected or are confounded by acute illness. Phosphatidylethanol (PEth) is a direct alcohol biomarker with a longer half-life than blood alcohol concentration and is not altered with organ dysfunction. PEth has been validated in outpatient settings to identify recent and moderate alcohol use but no test characteristics are available on its performance to identify alc...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: M. Afshar, E.L. Burnham, E.J. Kovacs, R.S. Cooper, M. Yong, J. Gaydos, B.J. Clark, E.M. Lowery Source Type: research
Alcohol induces epigenetic immunomodulation of human monocyte-derived dendritic cells
Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. Our group is interested in studying the epigenetic mechanisms involved in the modulation of alcohol-induced oxidative stress and inflammation in human primary monocyte-derived dendritic cells (MDDCs). Therefore, in the current study, the role of histone deacetylases (class I HDACs) and histones (H3 and H4) in peripheral inflammation and the epigenetic mechanisms of alcohol-induced oxidative stress were analyzed ex vivo and in vitro. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: M. Agudelo Source Type: research
Chronic ethanol consumption disrupts intestinal microbiota and mucosal gene expression
The intestines primarily function in digesting food, absorbing nutrients, and providing a defense barrier. Intestinal epithelial cells, gut-resident immune cells, as well as the microbiome regulate gut homeostasis. Alcohol use disorder (AUD) disrupts the mucosal barrier, resulting in increased intestinal permeability, nutrient malabsorption, and increased risk of colorectal cancer. Our understanding of the mechanisms underlying these changes remains limited because most of the studies to date have relied on short-term heavy/binge drinking rodent models and specimens collected from AUD subjects with advanced liver disease. (Source: Alcohol)
Source: Alcohol - March 1, 2017 Category: Addiction Authors: T. Barr, S. Sureshchandra, P. Ruegger, J. Borneman, K. Grant, I. Messaoudi Source Type: research
The effects of alcohol and cannabis abuse on TLR expression in airway epithelium
Introduction: Harmful alcohol use and cigarette smoking have been shown to alter pulmonary airway epithelial cell innate immunity. Increasingly, due to recent legislative changes, cannabis is being used in conjunction with alcohol. How cannabis affects pulmonary innate immunity alone and in conjunction with alcohol has not been fully described. Airway epithelial toll-like receptor (TLR) signaling plays a central role in coordinating the inflammatory response to inhaled pathogens. We have previously shown that those with alcohol use disorders (AUD ’s) have an upregulation in TLR2 in the airway epithelium that correlates w...
Source: Alcohol - March 1, 2017 Category: Addiction Authors: K. Bailey, D. Katafiasz, E.L. Burnham Source Type: research
