-
Methodist DeBakey Cardiovascular Journal Apr 2021Catheter-based radiofrequency (RF) ablation is an effective, well-established therapy for ventricular tachycardia (VT). However, a large number of patients still have... (Review)
Review
Catheter-based radiofrequency (RF) ablation is an effective, well-established therapy for ventricular tachycardia (VT). However, a large number of patients still have recurrences, particularly those with substrates arising from intramural locations that are inaccessible through endo- or epicardial catheter approaches. Several unconventional ablation techniques have been proposed to treat RF-refractory VT, including transarterial coronary ethanol ablation and retrograde coronary venous ethanol ablation. We review the evidence regarding the mechanisms, procedural aspects, and alcohol ablation outcomes for ventricular arrhythmias.
Topics: Ablation Techniques; Action Potentials; Ethanol; Heart Rate; Humans; Tachycardia, Ventricular; Treatment Outcome
PubMed: 34104316
DOI: 10.14797/NECT9586 -
Frontiers in Neural Circuits 2023Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs,... (Review)
Review
Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.
Topics: Humans; Alcoholism; Alcohol Drinking; Ethanol
PubMed: 37929054
DOI: 10.3389/fncir.2023.1218737 -
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 -
Alcohol Research : Current Reviews 2022A growing body of evidence has implicated the endocannabinoid (eCB) system in the acute, chronic, and withdrawal effects of alcohol/ethanol on synaptic function. These... (Review)
Review
PURPOSE
A growing body of evidence has implicated the endocannabinoid (eCB) system in the acute, chronic, and withdrawal effects of alcohol/ethanol on synaptic function. These eCB-mediated synaptic effects may contribute to the development of alcohol use disorder (AUD). Alcohol exposure causes neurobiological alterations similar to those elicited by chronic cannabinoid (CB) exposure. Like alcohol, cannabinoids alter many central processes, such as cognition, locomotion, synaptic transmission, and neurotransmitter release. There is a strong need to elucidate the effects of ethanol on the eCB system in different brain regions to understand the role of eCB signaling in AUD.
SEARCH METHODS
For the scope of this review, preclinical studies were identified through queries of the PubMed database.
SEARCH RESULTS
This search yielded 459 articles. Clinical studies and papers irrelevant to the topic of this review were excluded.
DISCUSSION AND CONCLUSIONS
The endocannabinoid system includes, but is not limited to, cannabinoid receptors 1 (CB), among the most abundantly expressed neuronal receptors in the brain; cannabinoid receptors 2 (CB); and endogenously formed CB ligands, including arachidonoylethanolamide (AEA; anandamide), and 2-arachidonoylglycerol (2-AG). The development of specific CB agonists, such as WIN 55,212-2 (WIN), and antagonists, such as SR 141716A (rimonabant), provide powerful pharmacological tools for eCB research. Alcohol exposure has brain region-specific effects on the eCB system, including altering the synthesis of endocannabinoids (e.g., AEA, 2-AG), the synthesis of their precursors, and the density and coupling efficacy of CB. These alcohol-induced alterations of the eCB system have subsequent effects on synaptic function including neuronal excitability and postsynaptic conductance. This review will provide a comprehensive evaluation of the current literature on the synaptic interactions of alcohol exposure and eCB signaling systems, with an emphasis on molecular and physiological synaptic effects of alcohol on the eCB system. A limited volume of studies has focused on the underlying interactions of alcohol and the eCB system at the synaptic level in the brain. Thus, the data on synaptic interactions are sparse, and future research addressing these interactions is much needed.
Topics: Alcoholism; Cannabinoids; Endocannabinoids; Ethanol; Humans; Receptors, Cannabinoid; Synaptic Transmission
PubMed: 35223337
DOI: 10.35946/arcr.v42.1.03 -
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 -
Revista Portuguesa de Cardiologia Jul 2019
Topics: Cardiomyopathy, Hypertrophic; Ethanol; Humans
PubMed: 31526558
DOI: 10.1016/j.repc.2019.08.005 -
International Journal of Molecular... May 2023Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy... (Review)
Review
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can modulate cerebral AD pathology include Toll-like receptors, protein kinase-B (Akt)/mammalian target of rapamycin (mTOR) pathway, cyclic adenosine monophosphate (cAMP) response element-binding protein phosphorylation pathway, glycogen synthase kinase 3-β, cyclin-dependent kinase-5, insulin-like growth factor type-1 receptor, modulation of β-amyloid (Aβ) synthesis and clearance, microglial mediated, and brain endothelial alterations. Besides these brain-centric pathways, alcohol-mediated liver injury may significantly affect brain Aβ levels through alterations in the peripheral-to-central Aβ homeostasis. This article reviews published experimental studies (cell culture and AD rodent models) to summarize the scientific evidence and probable mechanisms (both cerebral and hepatic) by which alcohol promotes or protects against AD progression.
Topics: Mice; Animals; Alzheimer Disease; Neurodegenerative Diseases; Amyloid beta-Peptides; Brain; Ethanol; Risk Factors; Disease Models, Animal; Mice, Transgenic; Mammals
PubMed: 37298443
DOI: 10.3390/ijms24119492 -
Journal of Lipid Research Aug 2023Alcoholic-related liver disease (ALD) is one of the leading causes of chronic liver disease and morbidity. Unfortunately, the pathogenesis of ALD is still incompletely...
Alcoholic-related liver disease (ALD) is one of the leading causes of chronic liver disease and morbidity. Unfortunately, the pathogenesis of ALD is still incompletely understood. StARD1 has emerged as a key player in other etiologies of chronic liver disease, and alcohol-induced liver injury exhibits zonal distribution. Here, we report that StARD1 is predominantly expressed in perivenous (PV) zone of liver sections from mice-fed chronic and acute-on-chronic ALD models compared to periportal (PP) area and is observed as early as 10 days of alcohol feeding. Ethanol and chemical hypoxia induced the expression of StARD1 in isolated primary mouse hepatocytes. The zonal-dependent expression of StARD1 resulted in the accumulation of cholesterol in mitochondria and increased lipid peroxidation in PV hepatocytes compared to PP hepatocytes, effects that were abrogated in PV hepatocytes upon hepatocyte-specific Stard1 KO mice. Transmission electron microscopy indicated differential glycogen and lipid droplets content between PP and PV areas, and alcohol feeding decreased glycogen content in both areas while increased lipid droplets content preferentially in PV zone. Moreover, transmission electron microscopy revealed that mitochondria from PV zone exhibited reduced length with respect to PP area, and alcohol feeding increased mitochondrial number, particularly, in PV zone. Extracellular flux analysis indicated lower maximal respiration and spared respiratory capacity in control PV hepatocytes that were reversed upon alcohol feeding. These findings reveal a differential morphology and functional activity of mitochondria between PP and PV hepatocytes following alcohol feeding and that StARD1 may play a key role in the zonal-dependent liver injury characteristic of ALD.
Topics: Animals; Mice; Ethanol; Hepatocytes; Liver; Mitochondria, Liver; Oxidative Stress
PubMed: 37473919
DOI: 10.1016/j.jlr.2023.100413