Acute Alcohol Research Articles

Retrospective Investigation of Alcohol Intoxications Followed in Intensive Care Unit

Aim: The majority of alcohol-related deaths are due to acute alcohol consumption. There are many factors affecting the prognosis of alcohol toxicity. It has been reported that by determining these factors, mortality rates can be reduced by early diagnosis and early initiation of treatment. In this study, we aimed to determine the prognosis by evaluating the clinical status and laboratory factors of patients followed up in intensive care unit (ICU) due to acute alcohol intoxication. Materials and Methods: The study included 21 patients with acute alcohol intoxication who were followed up in the ICU of our hospital between 2013-2021.Laboratory parameters, demographic characteristics and clinical status of the patients were recorded. Patients were divided into both exitus and survivors and according to the type of alcohol consumed (ethanol and methanol). Results: All patients were male with a mean age of 40.10 ± 15.9 years. 52.4% of the admissions were ethanol poisoning and 47.6% were methanol poisoning. Mortality rate was 33.3%. It was observed that symptoms appeared later in methanol intoxication compared to ethanol intoxication (p

Neuropathology of deaths due to acute alcohol toxicity in Australia, 2011–2022

BackgroundA major alcohol-related harm is structural pathology affecting the brain. The study aimed to: 1. Determine the frequency and nature of neuropathology amongst cases of death due to acute alcohol toxicity; 2. Compare diagnoses of brain atrophy with pathology in other organs; 3. Determine the demographic, clinical and organ pathology correlates of brain atrophy. Methods:Retrospective study of 500 cases of death attributed to acute alcohol toxicity in Australia, 2011–2022. Data on clinical characteristics, toxicology, neuropathology and other organ pathology were retrieved from police reports, autopsies, toxicology and coronial findings. ResultsMean age was 49.5 years, 69.4 % were male, with alcohol use problems documented in 70.2 %. Brain atrophy was diagnosed in 60 cases (12.0 %), most commonly in the cerebellum (32 cases, 6.4 %). Atrophy at other sites was present in 37 (7.4 %). The presence of brain atrophy was lower than other major pathologies: cardiomegaly (32.6 %, p<.001), nephro/arteriosclerosis (30.2 %, p<.001), and chronic obstructive pulmonary disease (21.8 %, p<.001) but not hepatic cirrhosis (11.9 % p=1.0). Those diagnosed with atrophy were older (53.4v 49.0 years, p<.001), more likely to have documented alcohol problems (85.0v 68.2 %, Odds ratio: OR 2.53) and seizure history (10.0v 3.0 %, OR 2.92), to have cardiomegaly (43.3v 31.0 %, OR 1.90, COPD (48.3v 18.2 %, 3.57) and nephro/arteriosclerosis (50.0 v 27.4 %, OR 2.27). Conclusions:Despite the majority of cases having a history of alcohol problems, the level of neuropathology amongst cases of death due to acute alcohol toxicity was comparatively low.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

Association between acute pre-injury alcohol use and 12-month health outcomes for survivors of major trauma: A registry-based study

IntroductionAlcohol is commonly detected in patients presenting to hospital after major trauma and is a key preventable risk factor for injury. While it has been suggested that alcohol intoxication at the time of injury results in worse acute patient outcomes, there is currently limited knowledge on the impact of alcohol on health outcomes following hospital discharge. The aim of this study was to examine the relationship between acute pre-injury alcohol exposure and the self-reported health outcomes of survivors of major trauma 12-months post-injury. MethodsData from the Victorian State Trauma Registry (January 1, 2018 to December 31, 2020) were used to identify major trauma patients who: (1) were aged ≥18 years; (2) survived to 12-months post-injury; and (3) had blood alcohol data available in the registry. Logistic regression analyses were used to examine differences in self-reported health status (EQ-5D) and return to work at 12-months post-injury by blood alcohol concentration (BAC) at the time of presentation to hospital. Analyses were adjusted for potential confounders including a range of demographic, hospital and injury characteristics. ResultsA total of 2957 patients met inclusion criteria, of which 857 (29.0 %) had a BAC >0 and 690 (23.3 %) had a BAC ≥0.05 g/100 mL. After adjusting for potential confounders, having any alcohol detected (i.e., BAC >0) was associated with lower odds of reporting problems on the EQ-5D mobility (aOR = 0.72, 95 %CI = 0.53 to 0.99) and usual activities dimensions (aOR = 0.79, 95 %CI = 0.63 to 0.99). Having a BAC ≥0.05 g/100 mL was only associated with lower adjusted odds of reporting problems on the usual activities dimension (aOR = 0.69, 95 %CI = 0.55 to 0.88) of the EQ-5D. Alcohol detection was not associated with the self-care, pain/discomfort or anxiety/depression dimensions of the EQ-5D, or with return to work in adjusted analyses. ConclusionAcute pre-injury alcohol exposure was not associated with increased reporting of problems on the EQ-5D or with return to work at 12-months post-injury. Further research is needed to understand why patients with alcohol detections were sometimes associated with paradoxically better 12-month post-injury outcomes relative to patients without alcohol detections.

Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.

Determinants of perceived pain relief from acute alcohol intake in a laboratory setting

BackgroundStudies of alcohol analgesia often assume that changes in pain sensitivity reflect the negative reinforcing effects of alcohol in pain self-management. However, factors that may influence perceived pain relief due to alcohol use remain incompletely characterized. Thus, the primary aim of this study was to identify which factors are most strongly related to self-reported pain relief in individuals with and without chronic pain after alcohol consumption. MethodsThis study combined data from two studies of alcohol analgesia in individuals who regularly consume alcohol with and without chronic pain. Alcohol analgesia expectancies were assessed during screening. In laboratory sessions, participants received an alcohol-containing (.08g/dL target BrAC) or placebo beverage and rated subjective intoxication and subjective response (positive/negative aspects of stimulation/sedation). Participants underwent quantitative sensory testing to measure pain intensity, pain threshold, and relief. Paired sample t-tests determined effects of alcohol on pain measures. Hierarchical linear models determined factors associated with pain relief ratings in the alcohol condition. ResultsPain relief and pain threshold were higher in the alcohol session relative to placebo, but pain intensity did not differ. In a 4-step hierarchical linear model, expectancy of pain relief, subjective intoxication, and high positive affect, but not pain threshold or pain intensity, were significantly and uniquely associated with perceived relief. ConclusionsTaken together, results suggest the negative-reinforcing effects of alcohol for pain-management are not completely reflected by changes in pain sensitivity in a laboratory setting. Expectancies and subjective response may be important in determining an individual’s evaluation of alcohol’s efficacy for pain self-management.

Mild Traumatic Brain Injury by the Glasgow Coma Scale Score and Early CT-Brain Findings in Acute Alcohol Intoxication Patients: A Prospective Observational Study.

Introduction Traumatic brain injuries (TBI) in recent years have proved to be a significant public health problem, with potentially life-changing consequences for the individual and their family. Alcohol consumption is a regular, well-documented problem among persons sustaining TBIdue to road traffic accidents and accidental falls. The primary objective of this study was to find out the correlation between the Glasgow Coma Scale (GCS) score and CT brain findings among mild TBI patients under acute alcohol intoxication and determine if early CT-brain is indicated in this group. Methods A prospective observational study was conducted involving 111 alcohol-intoxicated patients with mild head injuries admitted to the surgical wards of Thanjavur Medical College Hospitalover a period of three months. The Glasgow Coma Scale was used to assess the patient'sneurological status and determine the severity of the brain injury. A semi-structured CT-brain findings chart and a severity of alcohol intoxication objective-based scoring system were developed and validated by experts. Descriptive statistics tools such as frequency, percentage, and mean were used, along with inferential statistics tools like the Chi-squared test, Fisher exact test, and Pearson's correlation coefficient test. Results The study findings showed that the comparison of GCS with early CT-brain was significant at a p-value of 0.012, and a negative correlation (r=-0.253) was found between GCS and CT-brain findings. A comparison of CT-brain findings with the severity of alcohol intoxication was non-significant at a p-value of 0.433. Conclusions Early CT-brain in intoxicated mild TBI patients may have a positive impact on early diagnosis and management, even in centers with limited resources catering to low-income population groups. The results of our short-term study show that early CT-Brain picks up lesions and helps initiate early management while it is up to the attending physician to keep in mind an adverse cost-benefit ratio in overuse of hospital resources and misdiagnosis leading to undertreatment causing long-term sequelae and morbidity before prescribing early CT-brain in this cohort of patients.

A Computation Model to Estimate Interaction Intensity through Non-Verbal Behavioral Cues: A Case Study of Intimate Couples under the Impact of Acute Alcohol Consumption

This work introduced a novel analysis method to estimate interaction intensity, i.e., the level of positivity/negativity of interaction, for intimate couples (married and heterosexual) under the impact of alcohol, which has great influences on behavioral health. Non-verbal behaviors are critical in interpersonal interactions. However, whether computer vision-detected non-verbal behaviors can effectively estimate the interaction intensity of intimate couples is still unexplored. In this work, we proposed novel measurements and investigated their feasibility to estimate interaction intensities through machine learning regression models. Analyses were conducted based on a conflict-resolution conversation video dataset of intimate couples before and after acute alcohol consumption. Results showed the estimation error was at the lowest in the no-alcohol state but significantly increased if the model trained using no-alcohol data was applied to after-alcohol data, indicating that alcohol altered the interaction data in the feature space. While training a model using rich after-alcohol data is ideal to address the performance decrease, data collection in such a risky state is challenging in real life. Thus, we proposed a new State-Induced Domain Adaptation (SIDA) framework, which allows for improving estimation performance using only a small after-alcohol training dataset, pointing to a future direction of addressing data scarcity issues.

Vitreoretinal surgical performance after acute alcohol consumption and hangover

AimRoutine alcohol testing of practicing physicians remains controversial since there are no uniform guidelines or legal regulations in the medical field. Our aim was to quantitatively study the acute and...

Low-dose alcohol exacerbates hyperdynamic circulation and shunting in non-alcoholic cirrhotic rats.

Portal hypertension affects hepatic, splanchnic and portosystemic collateral systems. Although alcohol is a well-known risk factor for liver cirrhosis, it also affects vascular contractility. However, the relevant effects on portal hypertension have not been evaluated in non-alcoholic cirrhosis. The present study aimed to investigate the impacts of low-dose alcohol on portal hypertension-related derangements in non-alcoholic cirrhotic rats. Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The chronic or acute effects of low-dose alcohol (2.4 g/kg/day, oral gavage, approximately 1.3 drinks/day in humans) were evaluated. The chronic administration of low-dose alcohol did not precipitate liver fibrosis in the sham or cirrhotic rats; however, it significantly increased splanchnic blood inflow (P=0.034) and portosystemic collaterals (P=0.001). Mesenteric angiogenesis and pro-angiogenic proteins were up-regulated in the alcohol-treated cirrhotic rats, and poorer collateral vasoresponsiveness to vasoconstrictors (P<0.001) was noted. Consistently, acute alcohol administration reduced splenorenal shunt resistance. Collateral vasoresponsiveness to vasoconstrictors also significantly decreased (P=0.003). In non-alcoholic cirrhosis rats, a single dose of alcohol adversely affected portosystemic collateral vessels due to vasodilatation. Long-term alcohol use precipitated splanchnic hyperdynamic circulation, in which mesenteric angiogenesis played a role. Further studies are warranted to evaluate the benefits of avoiding low-dose alcohol consumption in patients with non-alcoholic cirrhosis.

The Effects of Acute and Chronic Alcohol Administration and Withdrawal on Bone Microstructure, Mechanical Strength, and Remodeling Protein Expression and Their Relation to an Antioxidant and FGF23 In Vivo.

Alcohol's detrimental effects on bone health are well established, yet some literature suggests moderate consumption may offer benefits. With alcohol use on the rise, we investigate the impact of acute and chronic alcohol administration, along with withdrawal, on male Wistar rat femurs. We observed a transient cortical thickness increase with acute alcohol (AA) compared to chronic exposure (CA) but no significant changes in trabecular parameters or mechanical properties. High osteocalcin and osteopontin expression levels were noted in AA, alongside elevated RANKL expression. Conversely, CA showed low TRAP levels. FGF23 expression significantly increased during alcohol withdrawal (AW), while GPX decreased after chronic exposure but rose during withdrawal. Although mechanical strength changes were insignificant, biochemical shifts suggest alcohol exposure promotes bone resorption, reduces antioxidant protection, and potentially hampers active vitamin D and phosphate reabsorption via FGF23 upregulation.

Effect of N-acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial.

Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options. This preliminary study examined the effect of N-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6-19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of N-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after N-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving. In the full sample (n = 31), there was no effect of N-acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; s = 0.00-0.07) or self-reported acute alcohol craving (p = 0.18, = 0.06). However, N-acetylcysteine did reduce self-reported generalized alcohol craving (p = 0.03, = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (n = 19), results remained unchanged. N-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.

Diagnostic Usefulness of Disialotransferrin as an Indicator of Binge Drinking in Children and Adolescents.

Background/Objective: The aim of the study was to evaluate the diagnostic usefulness of changes in transferrin isoforms, especially disialo-Tf, in identifying binge drinking children and adolescents admitted to hospital emergency. Methods: The study group consisted of 122 ambulatory children and adolescents below 18 years of age and 30 healthy subjects. From the group of drinkers, those with acute alcohol intoxication (AAI) were identified (ICD-11, code F10.0). The isoforms of transferrin were separated by capillary electrophoresis into five major fractions: asialo-Tf, disialo-Tf, trisialo-Tf, tetrasialo-Tf, and pentasialo-Tf. The differences between binge drinking youth and nondrinking subjects were evaluated by Mann-Whitney U-test. Results: In the total study group and in both genders, the concentration of disialo-Tf was significantly higher in the binge drinkers compared to the nondrinking youth (p = 0.006). With respect to the gender, the level of disialo-Tf was significantly higher in binge drinking than nondrinking girls (p = 0.028) and the value of trisialo-Tf was lower in binge drinking than nondrinking boys (p = 0.011). In the AAI subgroup, the concentrations of disialo-Tf and tetrasialo-Tf were significantly higher in comparison to nondrinking subjects (p = 0.002, p = 0.039, respectively). There were no significant correlations between the BAC and the transferrin isoforms in the total group and the AAI subgroup. The disialo-Tf reached the highest diagnostic power (AUC = 0.718) in identifying binge drinkers at diagnostic specificity and sensitivity of 86.7% and 51.6%, respectively (at cut-off 0.70), in the total group and it was growing up to AUC = 0.761 with the diagnostic sensitivity of 60% in the AAI subgroup. Conclusions: The disialo-Tf might be a useful biomarker to identify binge drinking children and adolescents.

Dysregulation of neurotrophin expression in prefrontal cortex and nucleus basalis magnocellularis during and after adolescent intermittent ethanol exposure

A preclinical model of human adolescent binge drinking, adolescent intermittent ethanol exposure (AIE) recreates the heavy binge withdrawal consummatory patterns of adolescents and has identified the loss of basal forebrain cholinergic neurons as a pathological hallmark of this model. Cholinergic neurons of the nucleus basalis magnocellularis (NbM) that innervate the prefrontal cortex (PFC) are particularly vulnerable to alcohol related neurodegeneration. Target derived neurotrophins (nerve growth factor [NGF] and brain-derived neurotrophic factor [BDNF]) regulate cholinergic phenotype expression and survival. Evidence from other disease models implicates the role of immature neurotrophin, or proneurotrophins, activity at neurotrophic receptors in promoting cholinergic degeneration; however, it has yet to be explored in adolescent binge drinking. We sought to characterize the pro- and mature neurotrophin expression, alongside their cognate receptors and cholinergic markers in an AIE model. Male and female Sprague Dawley rats underwent 5 g/kg 20% EtOH or water gavage on two-day-on, two-day-off cycles from post-natal day 25–57. Rats were sacrificed 2 h, 24 h, or 3 weeks following the last gavage, and tissue were collected for protein measurement. Western blot analyses revealed that ethanol intoxication reduced the expression of BDNF and vesicular acetylcholine transporter (vAChT) in the PFC, while NGF was lower in the NbM of AIE treated animals. During acute alcohol withdrawal, proNGF in the PFC was increased while proBDNF decreased, and in the NbM proBDNF increased while NGF decreased. During AIE abstinence, the expression of neurotrophins, their receptors, and vAChT did not differ from controls in the PFC. In contrast, in the NbM the expression of both NGF and choline acetyltransferase (ChAT) were reduced long-term following AIE. Taken together these findings suggest that AIE alters the expression of proneurotrophins and neurotrophins during intoxication and withdrawal that favor prodegenerative mechanisms by increasing the expression of proNGF and proBDNF, while also reducing NGF and BDNF.

Estrogen and alcohol use in women: a targeted literature review.

Alcohol is posited to affect sex steroid hormone concentrations, and a growing body of research has demonstrated menstrual cycle effects on women's use of alcohol. The present targeted review synthesizes the literature examining the relationship between alcohol use and estradiol in women and suggests directions for future research. Articles were identified using the PubMed database using the following criteria: published in English, presented original findings for women, were peerreviewed, and included measures of estradiol levels in the analyses. Twenty-nine articles were identified for inclusion. Results from this review indicate acute alcohol use temporarily increases estradiol levels in women, and this may be strongest when gonadotropins are high. Regular alcohol use (≥1 drink per day) increases estradiol levels, but estradiol appears to be suppressed in women with alcohol use disorders and physiologic dependence. Alcohol use tends to be highest in women during ovulation, when estradiol is high, and progesterone is low. Alcohol use increases estradiol levels in women, particularly in the presence of gonadotropins. More research is needed to assess the effect of estradiol on alcohol use in women. Research on the relationship of estrogen and alcohol use in women is needed to elucidate health outcomes through the lifespan.

MLKL deficiency alleviates acute alcoholic liver injury via inhibition of NLRP3 inflammasome

Mixed lineage kinase domain-like protein (MLKL) is identified as the terminal executor of necroptosis. However, its role in acute alcoholic liver injury remains unclear. This study elucidates that MLKL can contribute to acute alcoholic liver injury independently of necroptosis. Although the expression of MLKL was upregulated, no significant increase in its phosphorylation or membrane translocation was observed in the liver tissues of mice treated with ethanol. This finding confirms that alcohol intake does not induce necroptosis in mouse liver tissue. Additionally, the deletion of Mlkl resulted in the downregulation of NLRP3 expression, which subsequently inhibited the activation of the NLRP3 inflammasome and the ensuing inflammatory response, thereby effectively mitigating liver injury induced by acute alcohol consumption. The knockout of Nlrp3 did not affect the expression of MLKL, further confirming that MLKL acts upstream of NLRP3. Mechanistically, inhibiting the nuclear translocation of MLKL reduced the nuclear entry of p65, the principal transcriptional regulator of NLRP3, thereby limiting the transcription of Nlrp3 mRNA and subsequent NLRP3 expression. Overall, this study unveils a novel mechanism of MLKL regulates the activation of NLRP3 inflammasomes in a necroptosis independent way in acute alcoholic liver injury

Polysaccharides from Eucommia ulmoides Oliv. leaves alleviates alcohol-induced mouse brain injury and BV-2 microglial dysfunction

Acute alcohol intoxication is a harmful clinical condition characterized by behavioral and neurological symptoms, for which few effective therapies are available at present. Dysfunction of microglial BV-2 cells has been reported to be associated with acute alcohol-induced brain injuries. In the present study, the protective effects of Eucommia ulmoides Oliv. leaves polysaccharides (EULP) on acute alcoholic brain injury and microglial dysfunction were investigated. 14-day pretreatment of EULP significantly attenuated neurobehavioral deficit and neurotransmitter damage in the brain tissue of mice caused by acute alcohol exposure. Additionally, EULP regulated the metabolic disorder of brain tissue. Consistently, it was shown that EULP pretreatment significantly improved alcohol-induced phagocytosis decrease, oxidative stress and inflammation in BV-2 cells. Therefore, EULP may be proposed and employed as a potential therapeutic agent for alcohol-induced brain damage.

Combined Insults of a MASH Diet and Alcohol Binges Activate Intercellular Communication and Neutrophil Recruitment via the NLRP3-IL-1β Axis in the Liver.

Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment.

Clinical Effect Analysis of Metadoxine in the Treatment of Acute Severe Alcoholism

Clinical Effect Analysis of Metadoxine in the Treatment of Acute Severe Alcoholism

Reduced Pharmacological Intervention of Prehospital Services for Acute Alcohol Intoxication during the COVID-19 Pandemic in A Large District of Southern Italy.

Background Stress during a pandemic increases the risk of alcohol consumption, which may require pharmacological management. Methods An observational single-center retrospective study was conducted from 1 January 2018 to 31 December 2021, and divided into 2-year periods (2018-2019 and 2020-2021). This study focused on calls to one of the emergency departments (EDs) of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ESs) who were either admitted or not admitted, due to their refusal. Results A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, an inverse association was found between pharmacological treatment and number of calls coded green (non-critical) and yellow (fairly critical) in patients admitted to EDs. An inverse association was also found for calls coded green in patients not admitted to EDs and pharmacological treatment. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. Conclusions ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.