Oxidative Effects in Early Stages of Embryo Development Due to Alcohol Consumption.

Alcohol, a widely consumed drug, exerts significant toxic effects on the human organism. This review focuses on its impact during fetal development, when it leads to a spectrum of disorders collectively termed Fetal Alcohol Spectrum Disorders (FASD). Children afflicted by FASD exhibit distinct clinical manifestations, including facial dysmorphism, delayed growth, and neurological and behavioral disorders. These behavioral issues encompass diminished intellectual capacity, memory impairment, and heightened impulsiveness. While the precise mechanisms underlying alcohol-induced fetal damage remain incompletely understood, research indicates a pivotal role for reactive oxygen species (ROS) that are released during alcohol metabolism, inciting inflammation at the cerebral level. Ethanol metabolism amplifies the generation of oxidant molecules, inducing through alterations in enzymatic and non-enzymatic systems responsible for cellular homeostasis. Alcohol consumption disrupts endogenous enzyme activity and fosters lipid peroxidation in consumers, potentially affecting the developing fetus. Addressing this concern, administration of metformin during the prenatal period, corresponding to the third trimester of human pregnancy, emerges as a potential therapeutic intervention for mitigating FASD. This proposed approach holds promise for ameliorating the adverse effects of alcohol exposure on fetal development and warrants further investigation.

Reduced fetal cerebral blood flow predicts perinatal mortality in a mouse model of prenatal alcohol and cannabinoid exposure.

BACKGROUND: Children exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain, and teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development. STUDY DESIGN: To determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow, we performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12-15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55,940 (750 µg/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30 min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day 16 (post-exposure). RESULTS: All drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid co-exposure reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in cannabis-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p = 0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p = 0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%). CONCLUSIONS: Fetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure.

Is There a Safe Alcohol Consumption Limit for the General Population and in Patients with Liver Disease?

Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.

An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders.

The adverse use of alcohol is a serious global public health problem. Maternal alcohol consumption during pregnancy usually causes prenatal alcohol exposure (PAE) in the developing fetus, leading to a spectrum of disorders known as fetal alcohol spectrum disorders (FASD) and even fetal alcohol syndrome (FAS) throughout the lifelong sufferers. The prevalence of FASD is approximately 7.7 per 1,000 worldwide, and is even higher in developed regions. Generally, Ethanol in alcoholic beverages can impair embryonic neurological development through multiple pathways leading to FASD. Among them, the leading mechanism of FASDs is attributed to ethanol-induced neuroinflammatory damage to the central nervous system (CNS). Although the underlying molecular mechanisms remain unclear, the remaining multiple pathological mechanisms is likely due to the neurotoxic damage of ethanol and the resultant neuronal loss. Regardless of the molecular pathway, the ultimate outcome of the developing CNS exposed to ethanol is almost always the destruction and apoptosis of neurons, which leads to the reduction of neurons and further the development of FASD. In this review, we systematically summarize the current research progress on the pathogenesis of FASD, which hopefully provides new insights into differential early diagnosis, treatment and prevention for patents with FASD.

Melosira nummuloides Ethanol Extract Ameliorates Alcohol-Induced Liver Injury by Affecting Metabolic Pathways.

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury.

Delayed pericarditis following ethanol ablation of the vein of Marshall in the treatment of atrial fibrillation: a case report.

In this case report, we will discuss a 74-year-old female who presented with a chief complaint of abdominal pain, bloating, anorexia, and nausea for four days which preceded after catheter ablation and anhydrous ethanol infusion vein of Marshall (VOM) one month prior. She was admitted and treated as a general patient in the general ward. After hospital admission, a pericardiocentesis was guided by B-scan ultrasonography, resulting in the extraction of 20ml of pericardial effusion, followed by catheterization for drainage. The key takeaway in this report is that anhydrous ethanol infusion VOM may not always be without risks. Hence, during the procedure, it is imperative to carefully administer the appropriate volume of anhydrous ethanol into the VOM to prevent vessel damage and associated complications.

MASLD is related to impaired alcohol dehydrogenase (ADH) activity and elevated blood ethanol levels: Role of TNFα and JNK.

Elevated fasting ethanol levels in peripheral blood frequently found in metabolic dysfunction-associated steatohepatitis (MASLD) patients even in the absence of alcohol consumption are discussed to contribute to disease development. To test the hypothesis that besides an enhanced gastrointestinal synthesis a diminished alcohol elimination through alcohol dehydrogenase (ADH) may also be critical herein, we determined fasting ethanol levels and ADH activity in livers and blood of MASLD patients and in wild-type ± anti-TNFα antibody (infliximab) treated and TNFα-/- mice fed a MASLD-inducing diet. Blood ethanol levels were significantly higher in patients and wild-type mice with MASLD while relative ADH activity in blood and liver tissue was significantly lower compared to controls. Both alterations were significantly attenuated in MASLD diet-fed TNFα-/- mice and wild-type mice treated with infliximab. Moreover, alcohol elimination was significantly impaired in mice with MASLD. In in vitro models, TNFα but not IL-1ß or IL-6 significantly decreased ADH activity. Our data suggest that elevated ethanol levels in MASLD patients are related to TNFα-dependent impairments of ADH activity.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

The effectiveness of regulations preventing alcohol-related road traffic crashes and fatalities in the European Union countries.

INTRODUCTION: This article addresses the impact of policy measures on the number of alcohol-related crashes and fatalities in European Union countries. In particular, it assesses (1) whether mild or severe penalty measures should be used to reduce the number of crashes and fatalities caused by alcohol; and (2) whether alcoholic beverages should be treated differently or proportionally to their alcohol content. METHODS: This study analyzed the number of alcohol-related crashes and fatalities in 24 European Union countries between 2002 and 2014. The methodology involved fixed-effects panel models, models with instrumental variables, the Hausman-Taylor model, and seemingly unrelated regressions (SUR). SUR improve the results of coefficient estimates when the data are not complete. RESULTS: The results of the SUR indicated that vehicle impoundment, community service, and alcolocks correlate with lower crashes, while detention correlates with lower fatalities. Furthermore, a higher alcohol content in beverages is positively associated with fatalities and negatively associated with the number of crashes. CONCLUSIONS: Mild and harsh measures for preventing alcohol-related crashes and fatalities differ in effectiveness; therefore, they should be used simultaneously. Blood alcohol concentration limits were found to be an ineffective tool for preventing crashes and fatalities under the influence of alcohol. PRACTICAL IMPLICATIONS: The regulatory restrictions on different types of alcohol should be stricter for hard alcohol (especially spirits) and lower for low-alcohol beverages, such as beer, if fewer fatalities are preferred to fewer crashes.

Ginseng-derived nanoparticles alleviate alcohol-induced liver injury by activating the Nrf2/HO-1 signalling pathway and inhibiting the NF-κB signalling pathway in vitro and in vivo.

BACKGROUND: Previous studies have confirmed the antioxidant and anti-inflammatory effects of active ginseng components that protect against liver injury. However, ginseng-derived nanoparticles (GDNPs), low-immunogenicity nanovesicles derived from ginseng, have not been reported to be hepatoprotective. PURPOSE: In this study, we investigated whether GDNPs could attenuate alcohol-induced liver injury in LO2 cells and mice by modulating oxidative stress and inflammatory pathways, thereby advancing the theoretical basis for the development of novel pharmacological treatments. STUDY DESIGN: Alcohol was used to construct in vitro and in vivo models of alcoholic liver injury. To explore the mechanisms by which GDNPs exert their protective effects against alcoholic liver injury, we examined the expression of oxidative stress-related genes and analysed inflammatory responses in vitro and in vivo. The experimental findings were verified using network pharmacology. METHODS: The composition of the GDNPs was analysed using liquid chromatography-mass spectrometry. GDNPs were extracted and purified using differential ultracentrifugation and sucrose density gradient centrifugation. In vitro models of alcoholic liver injury were established using LO2 cells, whereas C57BL/6 J mice were used as in vivo models. Oxidative stress, inflammation, and liver injury indicators were measured using appropriate kits. Levels of proteins associated with oxidative stress and inflammation were measured via western blot, while nuclear factor erythroid2-related factor 2 (Nrf2) and NF-κB protein expression was tested using immunofluorescence, immunohistochemistry, and flow cytometry. The levels of relevant transcription factors were determined using qPCR. Experimental haematoxylin and eosin staining was used to characterise the liver histological appearance and damage in mice. Network pharmacological analysis of GDNP mRNA sequencing of GDNPs was used to predict drug targets and disease associations using TCMSP. RESULTS: GDNPs primarily included 77 compounds, including organic acids and their derivatives, amino acids and their derivatives, sugars, terpenoids, and flavonoids. GDNPs have features that allow them to be taken up by LO2 cells and promote their proliferation. In vitro data indicated that GDNPs reduced the levels of alcohol-induced reactive oxygen species by activating the Nrf2/HO-1 signalling pathway, whilst inhibiting the NF-κB pathway and thereby reducing NO, tumour necrosis factor-α, and interleukin-1ß levels to alleviate inflammation. An in vivo model showed that GDNPs improved the liver parameters and pathology in mice with alcoholic liver injury. GDNPs activate the Nrf2/HO-1/Keap1 signalling pathway in a p62-dependent manner to exert antioxidant effects. Furthermore, the TLR4/NF-κB signalling pathway was involved in the in vivo anti-inflammatory effect. Network pharmacology also confirmed that the effects of GDNPs on liver disease were associated with oxidative stress and inflammation-related targets and pathways. CONCLUSION: This study showed for the first time that GDNPs can alleviate alcohol-induced liver damage by activating the Nrf2/HO1 signalling pathway and blocking the NF-κB signalling pathway, thus lowering oxidative stress and inflammatory responses. Hereby, we present the Nrf2/HO1 and NF-κB signalling pathways as potential targets and GDNPs as a novel therapeutic approach for the management of alcohol-induced liver damage.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

No Association of Blood Alcohol Concentration on Burn Patient Outcomes.

INTRODUCTION: Alcohol abuse is common among burn patients. Burn patients under the influence of alcohol are at risk for developing organ failure, prolonged hospital duration, and increased intensive care unit (ICU) resources. Our study aims to analyze the association between presenting alcohol levels and the outcomes of burn patients. METHODS: A retrospective analysis of admitted burn patients was performed from 2016 to 2021. Patients were divided into two groups based on blood alcohol content (BAC), low (<80), and high (≥80) mg/dL. Data included demographics, comorbidities, and outcomes. Univariate analyses were performed, and a P value <0.05 was significant. RESULTS: A total of 197 patients were included (32.5% females, mean age 47.2 ± 15.2, 26.9% smokers, 28.4% illegal drug abuse, and 56.3% no comorbidities). Mortality was 7.6%, morbidity 20.8%, 39.1% required burn ICU admission, and 25.9% were intubated. When comparing BAC groups, we found no differences in demographics, comorbidities, inhalational injury incidence, carbon monoxide level, intubation, or burn ICU admission rates. The high-BAC group had longer ventilator days (high BAC 16.7 ± 19.3 versus low BAC 7.5 ± 9.1, P = 0.026) and longer stays in the ICU (18.6 ± 21.8 versus 10.7 ± 15.4, P = 0.075). The low-BAC group had more 3rd-degree burn percentage (5.0 ± 15.3 versus 15.4 ± 27.5, P = 0.024). Both morbidity and in-house mortality rates were similar for both groups (23.8% versus 16.0%, P = 0.192, and 6.6% versus 9.3%, P = 0.476, respectively). CONCLUSIONS: Burn patients with higher BAC had significantly longer mechanical ventilator days. However, higher alcohol concentrations had no association with regard to mortality, overall length of stay, or complication rates.

Ethanol endometrioma sclerotherapy: safety through 8 years of experience.

STUDY QUESTION: What are the complications of transvaginal ethanol sclerotherapy for the treatment of endometriomas? SUMMARY ANSWER: Sclerotherapy is a reliable, minimally invasive method applicable in outpatient procedures but with specific and potential life-threatening complications that need to be identified and prevented. WHAT IS KNOWN ALREADY: There are currently few data on the use of transvaginal ethanol sclerotherapy, and we mainly note septic complications. STUDY DESIGN, SIZE, DURATION: A retrospective observational cohort study was carried out. The study was conducted at an academic hospital and included 126 women aged 31.9 ± 5.5 years (mean ± SD), between November 2013 and June 2021. We analyzed a total of 157 ethanol sclerotherapy treatment (EST), treated by 131 EST procedures, in 126 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with an indication for transvaginal ethanol sclerotherapy. Indications were women with at least one endometrioma over 10 mm, isolated or associated with other endometriosis locations, requiring treatment for pain or infertility before assisted reproductive treatment. We followed a standardized transvaginal ethanol sclerotherapy procedure consisting of an ultrasound-guided transvaginal puncture of one or more endometriomas under general anesthesia. The cyst content was completely removed and flushed with saline solution. Ethanol (96%) was injected at 60% of the initial volume of the endometrioma, remained in the cyst for 10 min and was then completely removed. Ethanol loss was defined as a loss of 5 ml or more than 10% of the initial volume of the injected ethanol. Failure was defined by the contraindication of endometrioma puncture because of interposition of the digestive tract, ethanol loss in the previous endometrioma treated (in case of multiple ESTs), failure to aspirate the endometriotic fluid, contraindication to start ethanol injection owing to saline solution leakage, or contraindication to continue ethanol injection owing to suspicions of ethanol leakage at sonography. Intraoperative complications were defined by ethanol loss, positive blood alcohol level, and ethanol intoxication. Postoperative complications were defined by fever, biological inflammatory syndrome, and ovarian abscess. Complications were classified according to the Clavien and Dindo surgical classification, which is a system for classifying postoperative complications in five grades of increasing severity. MAIN RESULTS AND THE ROLE OF CHANCE: We reported a total of 17/157 (10.8%) transvaginal ethanol sclerotherapy failures during 14/131 (10.7%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. In the same sets of data, complication was reported for 15/157 (9.5%) transvaginal ethanol sclerotherapy in 13/131 (9.9%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. Nine of 126 women (7.1%) had a grade I complication, one (0.8%) had a grade II complication (medical treatment for suspicion of pelvic infection), two (1.6%) had a grade III complication (ovarian abscess) and one (0.8%) had a grade IV complication (ethanol intoxication). We did not observe any grade V complications. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study and pain assessment not considered. The benefit-risk balance of endometrioma transvaginal ethanol sclerotherapy was not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: Our study is the first to evaluate the complications of transvaginal ethanol sclerotherapy with such a large cohort of women in a standardized protocol. Transvaginal ethanol sclerotherapy seems to be an effective alternative to laparoscopic surgery in the management of endometriomas and limits the alteration of ovarian reserve. Transvaginal ethanol sclerotherapy is a reliable, minimally invasive method applicable on an outpatient basis. The majority of complications are Clavien-Dindo ≤IV, for which preventative measures, or at least early diagnosis and treatment, can be easily performed. The risk of ethanol intoxication is rare, but it is a life-threatening risk that must be avoided by appropriate implementation and promotion of the sclerotherapy procedures. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Aix Marseille University's ethics committee registration number 2021-06-03-01.

Alcohol-induced gut microbiome dysbiosis enhances the colonization of Klebsiella pneumoniae on the mouse intestinal tract.

Chronic alcohol consumption, an important risk factor for diseases and deaths, can cause intestinal microbiota dysbiosis and increase the infection of some opportunistic pathogens. However, the current studies on the effects of alcohol-induced intestinal microbiota dysbiosis on gut colonization of Klebsiella pneumoniae are still scarce. In the present study, we established a binge-on-chronic alcohol model in mice to identify the characteristics of alcohol-induced intestinal microbiome and metabolite dysbiosis using multi-omics and explored the effects and potential mechanisms of these dysbioses on the intestinal colonization of K. pneumoniae. The results show that chronic alcohol consumption alters the diversity and composition of gut microbiota (including bacteria and fungi), decreases the complexity of the interaction between intestinal bacteria and fungi, disturbs the gut metabolites, and promotes the colonization of K. pneumoniae on the gut of mice. The relevance analyses find that alcohol-induced gut microbiome dysbiosis has a strong correlation with the alteration of secondary bile acids. In vitro results suggest that the high concentration of lithocholic acid, a secondary bile acid, could significantly inhibit the proliferation of K. pneumoniae, and the adhesion of K. pneumoniae to Caco-2 cells. Our results indicate that alcohol-induced microbiome dysbiosis contributes to decreased levels of secondary bile acids, which was one of the main reasons affecting the colonization of K. pneumoniae in mice's intestines. Some secondary bile acids (e.g., lithocholic acid) might be a potential drug to prevent the colonization and spread of K. pneumoniae.IMPORTANCEAlcohol is one of the most commonly misused substances in our lives. However, long-term heavy drinking will increase the colonization of some opportunistic pathogens (e.g., Klebsiella pneumoniae) in the body. Here, we revealed that binge-on-chronic alcohol consumption disrupted the balance between gut bacteria and fungi, induced the gut microbiome and metabolites dysbiosis, and promoted the colonization of K. pneumoniae in the intestine of mice. In particular, alcohol-taking disrupted intestinal bile acid metabolism and reduced the lithocholic acid concentration. However, a high concentration of lithocholic acid can protect against intestinal colonization of K. pneumoniae by inhabiting the bacterial growth and adhesion to the host cell. Hence, regulating the balance of gut microbiota and intestinal bile acid metabolism may be a potential strategy for reducing the risk of K. pneumoniae infection and spread.

Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development.

Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.

Modeling Fetal Alcohol Spectrum Disorders in Zebrafish to Characterize the Impact of an Adverse Embryonic Environment on Adult Social Behavior.

Fetal alcohol spectrum disorders (FASD) describe all alcohol-induced birth defects. Birth defects such as growth deficiencies, craniofacial, behavioral, and cognitive abnormalities are associated with FASD. Social difficulties are common behavioral abnormalities associated with FASD and often result in serious health issues. Animal models are critical to understanding the mechanisms responsible for ethanol-induced social defects. Zebrafish are social vertebrates that produce externally fertilized transparent eggs; these characteristics provide researchers with a precise yet simple procedure for creating the FASD phenotype and an innate behavior that can be leveraged to model the social deficits associated with FASD. Thus, zebrafish are ideal for characterizing the social deficits of FASD. The goal of the current protocol is to provide the user with a simple behavioral assay that can be used to characterize the consequences of a negative environment early during development and the effects it can have on social behavior in adulthood. The protocol can be used to characterize the effect mutations or teratogens have on adult social behavior. The protocol outlined here demonstrates how to characterize the social behavior of individual fish during a 20-min social assay. Furthermore, the data obtained using the current protocol provides evidence that the protocol can be used to characterize the effects of embryonic ethanol-induced social defects in adult zebrafish.

COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023?

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.

Altered sleep architecture following consecutive nights of presleep alcohol.

STUDY OBJECTIVES: Alcohol consumption before sleep decreases sleep latency, explaining the common use of alcohol as a sleep aid. The full impact of alcohol on sleep architecture is not well understood, particularly the potential cumulative effects of presleep alcohol consumption across consecutive nights. Here, we describe the effects of presleep alcohol on sleep architecture across three consecutive nights. METHODS: Thirty adult participants took part in a crossover, within-participants study consisting of two sets of three consecutive nights of in-lab polysomnography. For each series of nights, participants drank one of the two beverages: a mixer only or a mixer plus alcohol (targeting a BrAC of 0.08 mg/L), ending 1 hour before lights out. Polysomnography (PSG) was used to stage sleep, and standard sleep variables were extracted. Linear mixed-effect analysis and generalized additive modeling were used to examine the effect of alcohol on sleep architecture. RESULTS: Alcohol before sleep increased the rate of slow wave sleep (SWS) accumulation across all three nights and decreased the rate of rapid eye movement (REM) sleep accumulation at the start of each night. Alcohol also decreased the total amount of REM sleep but did not affect the total amount of SWS each night. CONCLUSIONS: These data indicate that drinking alcohol before sleep substantially affects sleep architecture, including changes to the rate of accumulation of SWS and REM sleep. We show that alcohol disrupts normal sleep architecture, leading to a significant decrease in REM sleep; thus, the use of alcohol as a sleep aid remains a public health concern.

Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: a systematic review and network meta-analysis.

This study was to compare multiple classes of medications and medication combinations to find alternatives or additives for patients not applicable to benzodiazepines (BZDs). We performed a network meta-analysis to assess the comparative effect of 11 pharmacologic treatments in patients with alcohol withdrawal syndrome. Forty-one studies were included, comprising a total sample size of 4187 participants. The pooled results from the randomized controlled trials showed that there was no significant difference in the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) reduction with other medications or medication combinations compared to BZDs. Compared to BZDs, the mean difference in ICU length of stay of anticonvulsants + BZDs was -1.71 days (95% CI = -2.82, -0.59). Efficacy rankings from cohort studies showed that anticonvulsant + BZDs were superior to other treatments in reducing CIWA-Ar scores and reducing the length of stay in the ICU. Synthesis results from randomized controlled trials indicate that there are currently no data suggesting that other medications or medication combinations can fully replace BZDs. However, synthetic results from observational studies have shown that BZDs are effective in the context of adjuvant anticonvulsant therapy, particularly with early use of gabapentin in combination with BZDs in the treatment of alcohol withdrawal syndrome, which represents a promising treatment option.

Tamoxifen Alleviates Endometrial Fibrosis Induced by Anhydrous Ethanol in Rats.

BACKGROUND: As an estrogen receptor modulator, tamoxifen has been utilized in the treatment of fibrotic diseases. However, there is a limited body of research focusing on its potential application in addressing endometrial fibrosis conditions. Our research aims to investigate the effects of tamoxifen at different dosage levels in alleviating endometrial fibrosis and to elucidate its mechanisms of action during the initial stages of endometrial damage. METHODS: A total of thirty sexually mature, unmated female Sprague-Dawley (SD) rats were divided into six distinct groups. To establish the rat uterine adhesion model, the uterine cavity was subjected to perfusion with anhydrous ethanol. The control group received a saline solution, while the treatment group was administered oral estrogen in combination with tamoxifen at doses of 4 mg/kg/d, 20 mg/kg/d, and 40 mg/kg/d. Various techniques, including Hematoxylin and Eosin (HE) staining, Masson's Trichrome staining, Western Blotting analysis, and immunohistochemistry, were employed to assess changes in endometrial thickness, fibrosis, as well as alterations in indicators related to epithelial-mesenchymal transition (EMT), fibrosis, estrogen receptors within the endometrium, and vascular endothelial growth factor (VEGF). RESULTS: In the model group, the levels of endometrial thickness, E-cadherin, Vimentin, estrogen receptor α (ERα), G protein-coupled receptor 30 (GPR30), and VEGF proteins were significantly lower compared to the control group. Conversely, the levels of collagen accumulation, Smooth Muscle Actin (SMA), Transforming Growth Factor ß1 (TGFß1), Drosophila mothers against decapentaplegic protein 2 (Smad2) , and Smad3 were markedly higher than those observed in the control group (p < 0.05, p < 0.01, p < 0.001, p < 0.0001). In contrast, the low-dose tamoxifen group demonstrated significant increases in endometrial thickness, E-cadherin, Vimentin, ERα, GPR30, and VEGF when compared to the model group (p < 0.05, p < 0.01, p < 0.001, p < 0.0001). Moreover, the levels of collagen accumulation, TGFß1, SMA, Smad2, and Smad3, which are indicative of fibrosis and the TGFß1/Drosophila mothers against decapentaplegic (smad) pathway, were notably reduced compared to the model group (p < 0.05, p < 0.0001). CONCLUSIONS: The results of this study suggest that the administration of a low dose (4 mg/kg/d) of tamoxifen in the early stages of endometrial injury may mitigate epithelial-mesenchymal transition (EMT) indicators and reduce fibrosis within the endometrium induced by anhydrous ethanol.