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American Journal of Preventive Medicine Sep 2021More comprehensive state-level alcohol policy environments are associated with lower alcohol-attributable homicide rates in the U.S., but few studies have explored this...
INTRODUCTION
More comprehensive state-level alcohol policy environments are associated with lower alcohol-attributable homicide rates in the U.S., but few studies have explored this internationally. This study tests whether 3 national-level alcohol policy scores are associated with alcohol-attributable homicide rates.
METHODS
Data were from the 2016 WHO Global Survey on Alcohol and Health and the 2017 Global Burden of Disease Study (N=150 countries). In 2020, the authors calculated domain-specific alcohol policy scores for physical availability, marketing, and pricing policies. Higher scores represented more comprehensive/restrictive alcohol policy environments. Negative binomial regressions with Benjamini-Simes-Hochberg multiple testing correction measured the associations between policies and alcohol-attributable homicide rates. Authors stratified countries by World Bank income group to determine whether the associations differed among low- and middle-income countries.
RESULTS
A 10% increase in the alcohol policy score for pricing was associated with an 18% lower alcohol-attributable homicide rate among all the countries (incidence rate ratio=0.82, adjusted p-value or q<0.001) and with a 14% (incidence rate ratio=0.86, q=0.01) decrease among 107 low- and middle-income countries. More controls on days and times of retail sales (incidence rate ratio=0.96, q=0.01) and affordability of alcohol (incidence rate ratio=0.95, q=0.04) as well as adjusting excise taxes for inflation (incidence rate ratio=0.96, q<0.01) were associated with a 4%-5% lower alcohol-attributable homicide rate in the full sample.
CONCLUSIONS
Countries with policies that reduce alcohol's affordability or days/hours of sales tend to have fewer alcohol-attributable homicides, regardless of their income level. Alcohol-attributable homicide rates are highest in low- and middle-income countries; policies that raise alcohol-relative prices may hold promise for curbing these harms.
Topics: Alcohol Drinking; Commerce; Ethanol; Homicide; Humans; Public Policy; Taxes
PubMed: 34229927
DOI: 10.1016/j.amepre.2021.03.020 -
Alcoholism, Clinical and Experimental... Oct 2021Alcohol-associated liver disease (AALD) encompasses a spectrum of liver diseases that includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis. The adverse... (Review)
Review
Alcohol-associated liver disease (AALD) encompasses a spectrum of liver diseases that includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis. The adverse effects of alcohol in liver and the mechanisms by which ethanol (EtOH) promotes liver injury are well studied. Although liver is known to be the primary organ affected by EtOH exposure, alcohol's effects on other organs are also known to contribute significantly to the development of liver injury. It is becoming increasingly evident that adipose tissue (AT) is an important site of EtOH action. Both AT storage and secretory functions are altered by EtOH. For example, AT lipolysis, stimulated by EtOH, contributes to chronic alcohol-induced hepatic steatosis. Adipocytes secrete a wide variety of biologically active molecules known as adipokines. EtOH alters the secretion of these adipokines from AT, which include cytokines and chemokines that exert paracrine effects in liver. In addition, the level of EtOH-metabolizing enzymes, in particular, CYP2E1, rises in the AT of EtOH-fed mice, which promotes oxidative stress and/or inflammation in AT. Thus, AT dysfunction characterized by increased AT lipolysis and free fatty acid mobilization and altered secretion of adipokines can contribute to the severity of AALD. Of note, moderate EtOH exposure results in AT browning and activation of brown adipose tissue which, in turn, can promote thermogenesis. In this review article, we discuss the direct effects of EtOH consumption in AT and the mechanisms by which EtOH impacts the functions of AT, which, in turn, increases the severity of AALD in animal models and humans.
Topics: Adipocytes; Adipose Tissue; Animals; Central Nervous System Depressants; Ethanol; Humans; Liver Diseases, Alcoholic; Oxidative Stress; Thermogenesis
PubMed: 34558087
DOI: 10.1111/acer.14698 -
Microbial Cell Factories Jun 2017The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the... (Review)
Review
The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the generation of reducing equivalents, as well as the (reduction)-oxidation metabolic cycle and the thiol redox homeostasis system. As a main oxidation pathway of reducing equivalents, the biosynthesis of most alcohols includes redox reactions, which are dependent on cofactors such as NADH or NADPH. Thus, when engineering alcohol-producing strains, the availability of cofactors and redox homeostasis must be considered. In this review, recent advances on the engineering of cellular redox homeostasis systems to accelerate alcohol biosynthesis are summarized. Recent approaches include improving cofactor availability, manipulating the affinity of redox enzymes to specific cofactors, as well as globally controlling redox reactions, indicating the power of these approaches, and opening a path towards improving the production of a number of different industrially-relevant alcohols in the near future.
Topics: Alcohols; Bacteria; Biosynthetic Pathways; Coenzymes; Escherichia coli; Ethanol; Fungi; Glucose; Homeostasis; Industrial Microbiology; Metabolic Engineering; NAD; NADP; Oxidation-Reduction; Saccharomyces cerevisiae
PubMed: 28646866
DOI: 10.1186/s12934-017-0728-3 -
Nutrients Apr 2021Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances... (Review)
Review
Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing T cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol's negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate's effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.
Topics: Acetaldehyde; Acetates; Alcohol Drinking; Arthritis, Rheumatoid; Ethanol; Humans; Immune System; Protective Agents
PubMed: 33923766
DOI: 10.3390/nu13041324 -
Biomolecules Jun 2016Chronic alcohol consumption induces multi-organ damage, including alcoholic liver disease (ALD), pancreatitis and hypertension. Ethanol and ethanol metabolic products... (Review)
Review
Chronic alcohol consumption induces multi-organ damage, including alcoholic liver disease (ALD), pancreatitis and hypertension. Ethanol and ethanol metabolic products play a significant role in the manifestation of its toxicity. Ethanol metabolizes to acetaldehyde and produces reduced nicotinamide adenine dinucleotide (NADH) by cytosolic alcohol dehydrogenase. Ethanol metabolism mediated by cytochrome-P450 2E1 causes oxidative stress due to increased production of reactive oxygen species (ROS). Acetaldehyde, increased redox cellular state and ROS activate transcription factors, which in turn activate genes for lipid biosynthesis and offer protection of hepatocytes from alcohol toxicity. Sterol regulatory element binding proteins (SREBPs) and peroxisome proliferator activated-receptors (PPARs) are two key lipogenic transcription factors implicated in the development of fatty liver in alcoholic and non-alcoholic steatohepatitis. SREBP-1 is activated in the livers of chronic ethanol abusers. An increase in ROS activates nuclear factor erythroid-2-related factor-2 (Nrf2) and hypoxia inducible factor (HIF) to provide protection to hepatocytes from ethanol toxicity. Under ethanol exposure, due to increased gut permeability, there is release of gram-negative bacteria-derived lipopolysaccharide (LPS) from intestine causing activation of immune response. In addition, the metabolic product, acetaldehyde, modifies the proteins in hepatocyte, which become antigens inviting auto-immune response. LPS activates macrophages, especially the liver resident macrophages, Kupffer cells. These Kupffer cells and circulating macrophages secrete various cytokines. The level of tumor necrosis factor-α (TNFα), interleukin-1beta (IL-1β), IL-6, IL-8 and IL-12 have been found elevated among chronic alcoholics. In addition to elevation of these cytokines, the peripheral iron (Fe(2+)) is also mobilized. An increased level of hepatic iron has been observed among alcoholics. Increased ROS, IL-1β, acetaldehyde, and increased hepatic iron, all activate nuclear factor-kappa B (NF-κB) transcription factor. Resolution of increased reactive oxygen species requires increased expression of genes responsible for dismutation of increased ROS which is partially achieved by IL-6 mediated activation of signal transducers and activators of transcription 3 (STAT3). In addition to these transcription factors, activator protein-1 may also be activated in hepatocytes due to its association with resolution of increased ROS. These transcription factors are central to alcohol-mediated hepatotoxicity.
Topics: Alcohol Drinking; Animals; Ethanol; Fatty Liver; Humans; Hypertension; Oxidative Stress; Transcription Factors
PubMed: 27348013
DOI: 10.3390/biom6030029 -
Cellular and Molecular Gastroenterology... 2023
Topics: Humans; Fatty Acids; Ethanol; Ethyl Ethers; Chemical and Drug Induced Liver Injury
PubMed: 36435276
DOI: 10.1016/j.jcmgh.2022.11.002 -
International Journal of Molecular... Sep 2021Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic... (Review)
Review
Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.
Topics: Acetaldehyde; Alcohol Dehydrogenase; Alcohol Drinking; Alcohol-Related Disorders; Ethanol; Gene Expression Regulation, Enzymologic; Humans; Metabolic Networks and Pathways; Organ Specificity; Oxidative Stress
PubMed: 34575850
DOI: 10.3390/ijms22189686 -
Food Research International (Ottawa,... Aug 2023The use of non-conventional brewing yeasts as alternative starters is a very promising approach which received increasing attention from worldwide scientists and...
The use of non-conventional brewing yeasts as alternative starters is a very promising approach which received increasing attention from worldwide scientists and brewers. Despite the feasible application of non-conventional yeasts in brewing processes, their regulations and safety assessment by the European Food Safety Authority still represent a bottlenecked hampering their commercial release, at least into EU market. Thus, research on yeast physiology, accurate taxonomic species identification and safety concerns associated with the use of non-conventional yeasts in food chains is needed to develop novel healthier and safer beers. Currently, most of the documented brewing applications catalysed by non-conventional yeasts are associated to ascomycetous yeasts, while little is known about analogous uses of basidiomycetous taxa. Therefore, in order to extend the phenotypic diversity of basidiomycetous brewing yeasts the aim of this investigation is to check the fermentation aptitudes of thirteen Mrakia species in relation to their taxonomic position within the genus Mrakia. The volatile profile, ethanol content and sugar consumption were compared with that produced by a commercial starter for low alcohol beers, namely Saccharomycodes ludwigii WSL 17. The phylogeny of Mrakia genus showed three clusters that clearly exhibited different fermentation aptitudes. Members of M. gelida cluster showed a superior aptitude to produce ethanol, higher alcohols, esters and sugars conversion compared to the members of M. cryoconiti and M. aquatica clusters. Among M. gelida cluster, the strain M. blollopis DBVPG 4974 exhibited a medium flocculation profile, a high tolerance to ethanol and to iso-α-acids, and a considerable production of lactic and acetic acids, and glycerol. In addition, an inverse relationship between fermentative performances and incubation temperature is also displayed by this strain. Possible speculations on the association between the cold adaptation exhibited by M. blollopis DBVPG 4974 and the release of ethanol in the intracellular matrix and in the bordering environment are presented.
Topics: Aptitude; Fermentation; Temperature; Basidiomycota; Ethanol
PubMed: 37316073
DOI: 10.1016/j.foodres.2023.113004 -
The Journal of General Physiology Feb 2023Normal alcohols (n-alcohols) can induce anesthetic effects by acting on neuronal ion channels. Recent studies have revealed the effects of n-alcohols on various ion...
Normal alcohols (n-alcohols) can induce anesthetic effects by acting on neuronal ion channels. Recent studies have revealed the effects of n-alcohols on various ion channels; however, the underlying molecular mechanisms remain unclear. Here, we provide evidence that long-chain n-alcohols have dual effects on Kv7.2/7.3 channels, resulting in channel activation as the net effect. Using heterologous expression systems, we found that n-alcohols could differentially regulate the Kv7.2/7.3 channel depending on their chain length. Treatment with short-chain ethanol and propanol diminished Kv7.2/7.3 currents, whereas treatment with long-chain hexanol and octanol enhanced the currents. However, the long-chain alcohols failed to potentiate Kv7.2 currents pre-activated by retigabine. Instead, they inhibited the currents, similar to short-chain ethanol. The stimulatory effect of the long-chain n-alcohols was also converted into an inhibitory one in the mutant Kv7.2(W236L) channels, while the inhibitory effect of ethanol did not differ between wild-type Kv7.2 and mutant Kv7.2(W236L). The inhibition of currents by n-alcohols was also seen in Kv7.1 channel which does not have the tryptophan (W) residue in S5. These findings suggest that long-chain n-alcohols exhibit dual effects through independent working sites on the Kv7.2 channel. Finally, we confirmed that the hydroxyl group with a negative electrostatic potential surface is essential for the dual actions of n-alcohol. Together, our data suggest that long-chain n-alcohols regulate Kv7.2/7.3 channels by interacting with both stimulatory and inhibitory sites and that their stimulatory action depends on the conserved tryptophan 236 residue in S5 and could be important for triggering their anesthetic effects.
Topics: Tryptophan; Ethanol; Octanols
PubMed: 36534082
DOI: 10.1085/jgp.202213191 -
Analytical Biochemistry Feb 2023We described a mass spectrometry-based assay to rapidly quantify the production of primary alcohols directly from cell cultures. This novel assay used the combination of...
We described a mass spectrometry-based assay to rapidly quantify the production of primary alcohols directly from cell cultures. This novel assay used the combination of TEMPO-based oxidation chemistry and oxime ligation, followed by product analysis based on Nanostructure-Initiator Mass Spectrometry. This assay enables quantitative monitor both C5 to C18 alcohols as well as glucose and gluconate in the growth medium to support strain characterization and optimization. We find that this assay yields similar results to gas chromatography for isoprenol production but required much less acquisition time per sample. We applied this assay to gain new insights into P. Putida's utilization of alcohols and find that this strain largely could not grow on heptanol and octanol.
Topics: Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Nanostructures; Glucose; Ethanol
PubMed: 36435200
DOI: 10.1016/j.ab.2022.114997