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Nature Medicine Aug 2023Alcohol use disorder (AUD) exacts enormous personal, social and economic costs globally. Return to alcohol use in treatment-seeking patients with AUD is common,...
Alcohol use disorder (AUD) exacts enormous personal, social and economic costs globally. Return to alcohol use in treatment-seeking patients with AUD is common, engendered by a cycle of repeated abstinence-relapse episodes even with use of currently available pharmacotherapies. Repeated ethanol use induces dopaminergic signaling neuroadaptations in ventral tegmental area (VTA) neurons of the mesolimbic reward pathway, and sustained dysfunction of reward circuitry is associated with return to drinking behavior. We tested this hypothesis by infusing adeno-associated virus serotype 2 vector encoding human glial-derived neurotrophic factor (AAV2-hGDNF), a growth factor that enhances dopaminergic neuron function, into the VTA of four male rhesus monkeys, with another four receiving vehicle, following induction of chronic alcohol drinking. GDNF expression ablated the return to alcohol drinking behavior over a 12-month period of repeated abstinence-alcohol reintroduction challenges. This behavioral change was accompanied by neurophysiological modulations to dopamine signaling in the nucleus accumbens that countered the hypodopaminergic signaling state associated with chronic alcohol use, indicative of a therapeutic modulation of limbic circuits countering the effects of alcohol. These preclinical findings suggest gene therapy targeting relapse prevention may be a potential therapeutic strategy for AUD.
Topics: Animals; Male; Alcohol Drinking; Alcoholism; Dopamine; Dopaminergic Neurons; Ethanol; Genetic Therapy; Glial Cell Line-Derived Neurotrophic Factor; Nucleus Accumbens; Primates; Ventral Tegmental Area
PubMed: 37580533
DOI: 10.1038/s41591-023-02463-9 -
Molecules (Basel, Switzerland) Dec 2022Chromeno[2,3-]pyridines are substances demanded in medicinal and material chemistry. (pot, atom, and step economy) and in particular approaches are key green chemistry...
Chromeno[2,3-]pyridines are substances demanded in medicinal and material chemistry. (pot, atom, and step economy) and in particular approaches are key green chemistry techniques that are applied for the synthesis of heterocyclic compounds. In this case, the approach was extended with 'component economy', as solvent was used also as reactant (solvent-involved reaction). This approach was adopted for the synthesis of previously unknown -substituted 5-alkoxy-5-chromeno[2,3-]pyridines via transformation, namely the reaction of salicylaldehydes and malononitrile dimer, with the subsequent addition of alcohol. The mechanistic studies revealed the possibility of concurrent reaction. The studies aided in optimizing the reaction conditions for the best yields (77-93%). Thus, the reaction proceeds efficient and quickly, and the work-up procedure (only simple filtering) is very convenient. The structure of synthesized chromeno[2,3-]pyridines was confirmed by 2D NMR spectroscopy.
Topics: Pyridines; Solvents; Ethanol; Heterocyclic Compounds
PubMed: 36615259
DOI: 10.3390/molecules28010064 -
Journal of Medical Internet Research Apr 2022There are a range of wearable transdermal alcohol sensors that are available and are being developed. These devices have the potential to monitor alcohol consumption... (Review)
Review
BACKGROUND
There are a range of wearable transdermal alcohol sensors that are available and are being developed. These devices have the potential to monitor alcohol consumption continuously over extended periods in an objective manner, overcoming some of the limitations of other alcohol measurement methods (blood, breath, and urine).
OBJECTIVE
The objective of our systematic review was to assess wearable transdermal alcohol sensor accuracy.
METHODS
A systematic search of the CINAHL, Embase, Google Scholar, MEDLINE, PsycINFO, PubMed, and Scopus bibliographic databases was conducted in February 2021. In total, 2 team members (EB and SH) independently screened studies for inclusion, extracted data, and assessed the risk of bias. The methodological quality of each study was appraised using the Mixed Methods Appraisal Tool. The primary outcome was transdermal alcohol sensor accuracy. The data were presented as a narrative synthesis.
RESULTS
We identified and analyzed 32 studies. Study designs included laboratory, ambulatory, and mixed designs, as well as randomized controlled trials; the length of time for which the device was worn ranged from days to weeks; and the analyzed sample sizes ranged from 1 to 250. The results for transdermal alcohol concentration data from various transdermal alcohol sensors were generally found to positively correlate with breath alcohol concentration, blood alcohol concentration, and self-report (moderate to large correlations). However, there were some discrepancies between study reports; for example, WrisTAS sensitivity ranged from 24% to 85.6%, and specificity ranged from 67.5% to 92.94%. Higher malfunctions were reported with the BACtrack prototype (16%-38%) and WrisTAS (8%) than with SCRAM (2%); however, the former devices also reported a reduced time lag for peak transdermal alcohol concentration values when compared with SCRAM. It was also found that many companies were developing new models of wearable transdermal alcohol sensors.
CONCLUSIONS
As shown, there is a lack of consistency in the studies on wearable transdermal alcohol sensor accuracy regarding study procedures and analyses of findings, thus making it difficult to draw direct comparisons between them. This needs to be considered in future research, and there needs to be an increase in studies directly comparing different transdermal alcohol sensors. There is also a lack of research investigating the accuracy of transdermal alcohol sensors as a tool for monitoring alcohol consumption in clinical populations and use over extended periods. Although there is some preliminary evidence suggesting the accuracy of these devices, this needs to be further investigated in clinical populations.
TRIAL REGISTRATION
PROSPERO CRD42021231027; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=231027.
Topics: Alcohol Drinking; Blood Alcohol Content; Ethanol; Humans; Monitoring, Physiologic; Wearable Electronic Devices
PubMed: 35436239
DOI: 10.2196/35178 -
World Journal of Microbiology &... Oct 2018Microbes are capable of producing alcohols, making them an important source of alternative energy that can replace fossil fuels. However, these alcohols can be toxic to... (Review)
Review
Microbes are capable of producing alcohols, making them an important source of alternative energy that can replace fossil fuels. However, these alcohols can be toxic to the microbes themselves, retaring or inhibiting cell growth and decreasing the production yield. One solution is improving the alcohol tolerance of such alcohol-producing organisms. Advances in omics technologies, including transcriptomic, proteomic, metabolomic, and genomic technologies, have helped us understand the complex mechanisms underlying alcohol toxicity, and such advances could assist in devising strategies for engineering alcohol-tolerant strains. This review highlights these advances and discusses strategies for improving alcohol tolerance using omics analyses.
Topics: Adaptation, Biological; Alcohols; Bacteria; Bacterial Physiological Phenomena; Drug Tolerance; Ethanol; Genomics; Metabolic Engineering; Metabolomics; Proteomics
PubMed: 30341456
DOI: 10.1007/s11274-018-2542-4 -
Neuropharmacology Aug 2017Alcohol has many effects on brain function and hence on human behavior, ranging from anxiolytic and mild disinhibitory effects, sedation and motor incoordination,... (Review)
Review
Alcohol has many effects on brain function and hence on human behavior, ranging from anxiolytic and mild disinhibitory effects, sedation and motor incoordination, amnesia, emesis, hypnosis and eventually unconsciousness. In recent years a variety of studies have shown that acute and chronic exposure to alcohol can modulate ion channels that regulate excitability. Modulation of intrinsic excitability provides another way in which alcohol can influence neuronal network activity, in addition to its actions on synaptic inputs. In this review, we review "low dose" effects [between 2 and 20 mM EtOH], and "medium dose"; effects [between 20 and 50 mM], by considering in turn each of the many networks and brain regions affected by alcohol, and thereby attempt to integrate in vitro physiological studies in specific brain regions (e.g. amygdala, ventral tegmental area, prefrontal cortex, thalamus, cerebellum etc.) within the context of alcohol's behavioral actions in vivo (e.g. anxiolysis, euphoria, sedation, motor incoordination). This article is part of the Special Issue entitled "Alcoholism".
Topics: Animals; Brain; Ethanol; Humans; Neurons
PubMed: 28479395
DOI: 10.1016/j.neuropharm.2017.04.007 -
Frontiers in Immunology 2022Drinking alcohol, even in moderation, can affect the immune system. Studies have shown disproportionate effects of alcohol on circulating and tissue-resident myeloid... (Review)
Review
Drinking alcohol, even in moderation, can affect the immune system. Studies have shown disproportionate effects of alcohol on circulating and tissue-resident myeloid cells (granulocytes, monocytes, macrophages, dendritic cells). These cells orchestrate the body's first line of defense against microbial challenges as well as maintain tissue homeostasis and repair. Alcohol's effects on these cells are dependent on exposure pattern, with acute drinking dampening but chronic drinking enhancing production of inflammatory mediators. Although chronic drinking is associated with heightened systemic inflammation, studies on tissue resident macrophage populations in several organs including the spleen, liver, brain, and lung have also shown compromised functional and metabolic capacities of these cells. Many of these effects are thought to be mediated by oxidative stress caused by alcohol and its metabolites which can directly impact the cellular epigenetic landscapes. In addition, since myeloid cells are relatively short-lived in circulation and are under constant repopulation from the bone marrow compartment, alcohol's effects on bone marrow progenitors and hematopoiesis are important for understanding the impact of alcohol systemically on these myeloid populations. Alcohol-induced disruption of progenitor, circulating, and tissue resident myeloid populations contribute to the increased susceptibility of patients with alcohol use disorders to viral and bacterial infections. In this review, we provide an overview of the impact of chronic alcohol consumption on the function of monocytes and macrophages in host defense, tissue repair and inflammation. We then summarize our current understanding of the mechanisms underlying alcohol-induced disruption and examine changes in transcriptome and epigenome of monocytes and mcrophages. Overall, chronic alcohol consumption leads to hyper-inflammation concomitant with decreased microbial and wound healing responses by monocytes/macrophages due to a rewiring of the epigentic and transcriptional landscape. However, in advanced alcoholic liver disease, myeloid cells become immunosuppressed as a response to the surrounding hyper-inflammatory milieu. Therefore, the effect of chronic alcohol on the inflammatory response depends on disease state and the immune cell population.
Topics: Alcohol Drinking; Alcoholism; Epigenesis, Genetic; Ethanol; Graft vs Host Disease; Humans; Inflammation; Macrophages; Monocytes
PubMed: 35844518
DOI: 10.3389/fimmu.2022.911951 -
Physiology & Behavior Sep 2015Alcohol possesses complex sensory attributes that are first detected by the body via sensory receptors and afferent fibers that promptly transmit signals to brain areas... (Review)
Review
Alcohol possesses complex sensory attributes that are first detected by the body via sensory receptors and afferent fibers that promptly transmit signals to brain areas involved in mediating ingestive motivation, reinforcement, and addictive behavior. Given that the chemosensory cues accompanying alcohol consumption are among the most intimate, consistent, and immediate predictors of alcohol's postabsorptive effects, with experience these stimuli also gain powerful associative incentive value to elicit craving and related physiologic changes, maintenance of ongoing alcohol use, and reinstatement of drug seeking after periods of abstinence. Despite the above, preclinical research has traditionally dichotomized alcohol's taste and postingestive influences as independent regulators of motivation to drink. The present review summarizes current evidence regarding alcohol's ability to directly activate peripheral and central oral chemosensory circuits, relevance for intake of the drug, and provides a framework for moving beyond a dissociation between the sensory and postabsorptive effects of alcohol to understand their neurobiological integration and significance for alcohol addiction.
Topics: Alcohol Drinking; Animals; Ethanol; Humans; Limbic System; Motivation; Sensation
PubMed: 25304192
DOI: 10.1016/j.physbeh.2014.09.004 -
Neuroscience and Biobehavioral Reviews Jan 2022Understanding factors that contribute to the escalation of alcohol consumption is key to understanding how an individual transitions from non/social drinking to AUD and... (Review)
Review
Understanding factors that contribute to the escalation of alcohol consumption is key to understanding how an individual transitions from non/social drinking to AUD and to providing better treatment. In this review, we discuss how the way ethanol is consumed as well as individual and environmental factors contribute to the escalation of ethanol consumption from intermittent low levels to consistently high levels. Moreover, we discuss how these factors are modelled in animals. It is clear a vast array of complex, interacting factors influence changes in alcohol consumption. Some of these factors act early in the acquisition of ethanol consumption and initial escalation, while others contribute to escalation of ethanol consumption at a later stage and are involved in the development of alcohol dependence. There is considerable need for more studies examining escalation associated with the formation of dependence and other hallmark features of AUD, especially studies examining mechanisms, as it is of considerable relevance to understanding and treating AUD.
Topics: Alcohol Drinking; Alcoholism; Animals; Ethanol
PubMed: 34839930
DOI: 10.1016/j.neubiorev.2021.11.017 -
Nutrients Jun 2023According to data from the World Health Organization, there were about 3 million deaths caused by alcohol consumption worldwide in 2016, of which about 50% were related... (Review)
Review
According to data from the World Health Organization, there were about 3 million deaths caused by alcohol consumption worldwide in 2016, of which about 50% were related to liver disease. Alcohol consumption interfering with the normal function of adipocytes has an important impact on the pathogenesis of alcoholic liver disease. There has been increasing recognition of the crucial role of adipose tissue in regulating systemic metabolism, far beyond that of an inert energy storage organ in recent years. The endocrine function of adipose tissue is widely recognized, and the significance of the proteins it produces and releases is still being investigated. Alcohol consumption may affect white adipose tissue (WAT) and brown adipose tissue (BAT), which interact with surrounding tissues such as the liver and intestines. This review briefly introduces the basic concept and classification of adipose tissue and summarizes the mechanism of alcohol affecting lipolysis and lipogenesis in WAT and BAT. The adipose tissue-liver axis is crucial in maintaining lipid homeostasis within the body. Therefore, this review also demonstrates the effects of alcohol consumption on the adipose tissue-liver axis to explore the role of alcohol consumption in the crosstalk between adipose tissue and the liver.
Topics: Humans; Lipolysis; Lipogenesis; Adipose Tissue, White; Adipose Tissue; Obesity; Adipose Tissue, Brown; Ethanol
PubMed: 37447280
DOI: 10.3390/nu15132953 -
Sensors (Basel, Switzerland) Sep 2022The field of alcohol intoxication sensing is over 100 years old, spanning the fields of medicine, chemistry, and computer science, aiming to produce the most effective... (Review)
Review
The field of alcohol intoxication sensing is over 100 years old, spanning the fields of medicine, chemistry, and computer science, aiming to produce the most effective and accurate methods of quantifying intoxication levels. This review presents the development and the current state of alcohol intoxication quantifying devices and techniques, separated into six major categories: estimates, breath alcohol devices, bodily fluid testing, transdermal sensors, mathematical algorithms, and optical techniques. Each of these categories was researched by analyzing their respective performances and drawbacks. We found that the major developments in monitoring ethanol intoxication levels aim at noninvasive transdermal/optical methods for personal monitoring. Many of the "categories" of ethanol intoxication systems overlap with each other with to a varying extent, hence the division of categories is based only on the principal operation of the techniques described in this review. In summary, the gold-standard method for measuring blood ethanol levels is through gas chromatography. Early estimation methods based on mathematical equations are largely popular in forensic fields. Breath alcohol devices are the most common type of alcohol sensors on the market and are generally implemented in law enforcement. Transdermal sensors vary largely in their sensing methodologies, but they mostly follow the principle of electrical sensing or enzymatic reaction rate. Optical devices and methodologies perform well, with some cases outperforming breath alcohol devices in terms of the precision of measurement. Other estimation algorithms consider multimodal approaches and should not be considered alcohol sensing devices, but rather as prospective measurement of the intoxication influence. This review found 38 unique technologies and techniques for measuring alcohol intoxication, which is testament to the acute interest in the innovation of noninvasive technologies for assessing intoxication.
Topics: Aged, 80 and over; Alcoholic Intoxication; Breath Tests; Ethanol; Forensic Medicine; Humans; Prospective Studies
PubMed: 36146167
DOI: 10.3390/s22186819