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1.
Alcohol and Cancer: Epidemiology and Biological Mechanisms.
Rumgay, H, Murphy, N, Ferrari, P, Soerjomataram, I
Nutrients. 2021;(9)
Abstract
Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol's metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.
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2.
Alcohol's Impact on the Fetus.
Popova, S, Dozet, D, Shield, K, Rehm, J, Burd, L
Nutrients. 2021;(10)
Abstract
BACKGROUND Alcohol is a teratogen and prenatal exposure may adversely impact the developing fetus, increasing risk for negative outcomes, including Fetal Alcohol Spectrum Disorder (FASD). Global trends of increasing alcohol use among women of childbearing age due to economic development, changing gender roles, increased availability of alcohol, peer pressure and social acceptability of women's alcohol use may put an increasing number of pregnancies at risk for prenatal alcohol exposure (PAE). This risk has been exacerbated by the ongoing COVID-19 pandemic in some countries. METHOD This literature review presents an overview on the epidemiology of alcohol use among childbearing age and pregnant women and FASD by World Health Organization regions; impact of PAE on fetal health, including FASD; associated comorbidities; and social outcomes. RESULTS/CONCLUSION The impact of alcohol on fetal health and social outcomes later in life is enormous, placing a huge economic burden on countries. Prevention of prenatal alcohol exposure and early identification of affected individuals should be a global public health priority.
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Consensus and Controversy in the Debate over the Biphasic Impact of Alcohol Consumption on the Cardiovascular System.
Stătescu, C, Clement, A, Șerban, IL, Sascău, R
Nutrients. 2021;(4)
Abstract
In the past few decades, research has focused on the importance of addressing modifiable risk factors as a means of lowering the risk of cardiovascular disease (CVD), which represents the worldwide leading cause of death. For quite a long time, it has been considered that ethanol intake has a biphasic impact on the cardiovascular system, mainly depending on the drinking pattern, amount of consumption, and type of alcoholic beverage. Multiple case-control studies and meta-analyses reported the existence of a "U-type" or "J-shaped" relationship between alcohol and CVD, as well as mortality, indicating that low to moderate alcohol consumption decreases the number of adverse cardiovascular events and deaths compared to abstinence, while excessive alcohol use has unquestionably deleterious effects on the circulatory system. However, beginning in the early 2000s, the cardioprotective effects of low doses of alcohol were abnegated by the results of large epidemiological studies. Therefore, this narrative review aims to reiterate the association of alcohol use with cardiac arrhythmias, dilated cardiomyopathy, arterial hypertension, atherosclerotic vascular disease, and type 2 diabetes mellitus, highlighting literature disagreements over the risk and benefits of low to moderate drinking on the cardiovascular system.
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Bactericidal and virucidal activity of ethanol and povidone-iodine.
Sauerbrei, A
MicrobiologyOpen. 2020;(9):e1097
Abstract
Ethanol and povidone-iodine (PVP-I) are important microbicides that inactivate bacteria and viruses. The present study provides a review of literature data on the concentration-dependent bactericidal and virucidal activity of ethanol and PVP-I in vitro. A systematic search was performed using the meta-database for biomedicine PubMed. Eventually, 74 studies with original data on the reduction of bacterial and viral infectivity using in vitro tests were analyzed. A safe bactericidal effect of ethanol can be expected at concentrations between 60% and 85%, and the exposure times vary between ≤0.5 and ≥5 min. Within an exposure of up to 5 min, 80%-90% ethanol also exerts virucidal/low-level activity, which includes its action against enveloped viruses plus adeno-, noro-, and rotaviruses. For PVP-I, the best bactericidal and virucidal/high-level effect is present at a concentration range of approx. 0.08%-0.9% depending on the free iodine concentration. The maximum exposure times are 5 min for bacteria and 60 min for viruses. The available data may help optimize the significant inactivation of bacteria and viruses in various areas. However, as the conditions in application practice can vary, concrete recommendations for the application can only be derived to a limited extent.
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To Infuse or Ingest in Human Laboratory Alcohol Research.
Cyders, MA, Plawecki, MH, Corbin, W, King, A, McCarthy, DM, Ramchandani, VA, Weafer, J, O'Connor, SJ
Alcoholism, clinical and experimental research. 2020;(4):764-776
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Abstract
Human alcohol laboratory studies use two routes of alcohol administration: ingestion and infusion. The goal of this paper was to compare and contrast these alcohol administration methods. The work summarized in this report was the basis of a 2019 Research Society on Alcoholism Roundtable, "To Ingest or Infuse: A Comparison of Oral and Intravenous Alcohol Administration Methods for Human Alcohol Laboratory Designs." We review the methodological approaches of each and highlight strengths and weaknesses pertaining to different research questions. We summarize methodological considerations to aid researchers in choosing the most appropriate method for their inquiry, considering exposure variability, alcohol expectancy effects, safety, bandwidth, technical skills, documentation of alcohol exposure, experimental variety, ecological validity, and cost. Ingestion of alcohol remains a common and often a preferable, methodological practice in alcohol research. Nonetheless, the main problem with ingestion is that even the most careful calculation of dose and control of dosing procedures yields substantial and uncontrollable variability in the participants' brain exposures to alcohol. Infusion methodologies provide precise exposure control but are technically complex and may be limited in ecological validity. We suggest that alcohol ingestion research may not be the same thing as alcohol exposure research; investigators should be aware of the advantages and disadvantages that the choice between ingestion and infusion of alcohol invokes.
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Microbial metabolites in non-alcoholic fatty liver disease.
Zhou, D, Fan, JG
World journal of gastroenterology. 2019;(17):2019-2028
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising exponentially worldwide. The spectrum of NAFLD includes non-alcoholic fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and even hepatocellular carcinoma. Evidence shows that microbial metabolites play pivotal roles in the onset and progression of NAFLD. In this review, we discuss how microbe-derived metabolites, such as short-chain fatty acids, endogenous ethanol, bile acids and so forth, contribute to the pathogenesis of NAFLD.
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Therapeutic Applications of Ethanol: A Review.
Le Daré, B, Gicquel, T
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 2019;(1):525-535
Abstract
PURPOSE To review knowledge on therapeutic uses of ethanol and the latter's effectiveness and safety profiles in a range of indications. METHODS MEDLINE and PubMed databases were searched for relevant peer-reviewed papers published in English between 1888 and 2018 using the following search terms: ethanol, therapeutic, alcohol withdrawal syndrome, antiseptic, antidote, methanol, ethylene glycol, neurolysis, embolization, cyst, sclerosing agent, sclerotherapy, arteriovenous malformations, ablating agent. Studies providing information about association between alcohol and therapeutic indications, or mechanic explanation for the association were included for review. RESULTS According to the World Health Organization, approximately three millions deaths worldwide are attributable to alcohol consumption each year. However, the low-to-moderate consumption of ethanol has a number of beneficial effects (mainly on cardiovascular mortality and diabetes). Hence, ethanol has an unusual spectrum of effects that seems interesting for therapeutic purposes. Ethanol's risk-benefit ratio appears to be positive in some therapeutic indications such as antidote to methanol or ethylene glycol poisoning, neurolysis, alcohol withdrawal syndrome, or antiseptic. CONCLUSION With the development of interventional radio technologies, and thus extremely precise access to anatomical structures, alcohol has been given new indications - particularly as an embolization, sclerosing or ablation agent. Moreover, constant progress in our knowledge of ethanol's pharmacodynamics might highlight other therapeutic indications for this compound in the future. Ethanol's low cost and wide availability make it a valuable therapeutic agent, compared with other reference treatments. Furthermore, ethanol has a long track record of safety and effectiveness in the indications mentioned above.
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Glutathione and Transsulfuration in Alcohol-Associated Tissue Injury and Carcinogenesis.
Chen, Y, Han, M, Matsumoto, A, Wang, Y, Thompson, DC, Vasiliou, V
Advances in experimental medicine and biology. 2018;:37-53
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Abstract
Glutathione (GSH) is the most abundant non-protein thiol, attaining cellular concentrations in the millimolar range. GSH functions to protect cells against endogenous and exogenous electrophiles. In addition, GSH serves as a cofactor for the GSH peroxidase family of enzymes which metabolize H2O2 as well as lipid peroxides. Through the action of glutathione S-transferase family of enzymes, GSH is conjugated to a variety of electrophilic endogenous compounds and exogenous chemicals, and thereby facilitates their efficient and safe elimination. Through the transsulfuration pathway, GSH biosynthesis is metabolically linked with cellular methylation, which is pivotal for epigenetic gene regulation. Accumulating evidence suggests that the underlying mechanisms of alcohol-associated tissue injury and carcinogenesis involve: (i) generation of the electrophilic metabolite acetaldehyde, (ii) induction of CYP2E1 leading to the formation of reactive oxygen species and pro-carcinogen activation, and (iii) nutritional deficiencies, such as methyl groups, resulting in enhanced susceptibility to cancer development. In this context, clinical and experimental investigations suggest an intimate involvement of GSH and related enzymes in the development of alcohol-induced pathological conditions. The aim of this review is to provide an overview of the GSH biosynthesis, cellular transsulfuration/transmethylation pathways, and their implications in the pathogenesis and treatment of alcohol-related disease and cancer.
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Ethanol stress in Oenococcus oeni: transcriptional response and complex physiological mechanisms.
Bonomo, MG, Di Tomaso, K, Calabrone, L, Salzano, G
Journal of applied microbiology. 2018;(1):2-15
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Oenococcus oeni is the dominant species able to cope with a hostile environment of wines, comprising cumulative effects of low pH, high ethanol and SO2 content, nonoptimal growth temperatures and growth inhibitory compounds. Ethanol tolerance is a crucial feature for the activity of O. oeni cells in wine because ethanol acts as a disordering agent of its cell membrane and negatively affects metabolic activity; it damages the membrane integrity, decreases cell viability and, as other stress conditions, delays the start of malolactic fermentation with a consequent alteration of wine quality. The cell wall, cytoplasmic membrane and metabolic pathways are the main sites involved in physiological changes aimed to ensure an adequate adaptive response to ethanol stress and to face the oxidative damage caused by increasing production of reactive oxygen species. Improving our understanding of the cellular impact of ethanol toxicity and how the cell responds to ethanol stress can facilitate the development of strategies to enhance microbial ethanol tolerance; this allows to perform a multidisciplinary endeavour requiring not only an ecological study of the spontaneous process but also the characterization of useful technological and physiological features of the predominant strains in order to select those with the highest potential for industrial applications.
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Circadian Mechanisms in Alcohol Use Disorder and Tissue Injury.
Davis, BT, Voigt, RM, Shaikh, M, Forsyth, CB, Keshavarzian, A
Alcoholism, clinical and experimental research. 2018;(4):668-677
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Heavy use of alcohol can lead to addictive behaviors and to eventual alcohol-related tissue damage. While increased consumption of alcohol has been attributed to various factors including level of alcohol exposure and environmental factors such as stress, data from behavioral scientists and physiological researchers are revealing roles for the circadian rhythm in mediating the development of behaviors associated with alcohol use disorder as well as the tissue damage that drives physiological disease. In this work, we compile recent work on the complex mutually influential relationship that exists between the core circadian rhythm and the pharmacodynamics of alcohol. As we do so, we highlight implications of the relationship between alcohol and common circadian mechanisms of effected organs on alcohol consumption, metabolism, toxicity, and pathology.