Single Dose Of Alcohol Research Articles

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.

Physical and geographical correlates of deviant behavior

AIM: To study the potential role of physical environmental factors in the development of deviant behavior in population groups residing in different territories.&#x0D; MATERIAL AND METHODS: At the initial phase of the study, we identified the key physical and geographical factors of the environment and assessed the indicators of social and criminal tension in 14 regions of Russia. In total, 1815 male and female students, aged 18–28 years, who were native residents of the selected regions, participated in the field research. During the field stage, the psychological state of the participants was assessed using the Freiburg multifactorial personality questionnaire. This assessment included evaluating character accentuations, suggestibility, frustration, irritability, adventurousness, as well as social activity and destructiveness. Additionally, the participants’ «prosociality-asociality» and type of behavioral activity (A–B) were examined. The subjects’ experience with psychoactive substances was self-reported. Associations between the variables were studied by correlation analysis.&#x0D; RESULTS: The average annual temperature was inversely associated with crime rates (p=0.012), number of abortions (p=0.0001), degree of alcoholization (p=0.004), and the proportion of smokers (p=0.011) in the population. Positive correlations were observed between annual temperature, and the level of narcotic substances consumption (p=0.05 and p=0.23 for men and women, respectively), spontaneous aggressiveness (p=0.63 and p=0.024), frustration (p=0.63 and p=0.024), irritability (p=0.068 and p=0.004), asociality (p=0.004 and p=0.247). Lower temperatures were associated with, greater single dose of alcohol (p=0.086 and p=0.033 in men and women, respectively), suggestibility (p=0.189 and p=0.049), emotivity (p=0.21 and p=0.05). The comfort of the environment was inversely associated with suicide rates (p=0.039). In men, comfort was positively associated with consumption of narcotic substances (p=0.05), reactive aggressiveness (p=0.024), irritability (p=0.041), asociality (p=0.011), adventurism (p=0.001), and severity of cardiotype A (p=0.018) while political activity correlated inversely with comfort (p=0.035).&#x0D; CONCLUSION: Our findings suggest that physical and geographical factors correlate with social, psychological and behavioral deviations among Russian students.

ВЛИЯНИЕ ПОТРЕБЛЕНИЯ АЛКОГОЛЯ НА УРОВНИ БЕЛКОВ СУРФАКТАНТА SP-A И SP-D КРОВИ У МУЖЧИН И ЖЕНЩИН Г. НОВОСИБИРСКА

Introduction. Currently, there are a few experimental data on the effect of alcohol consumption on the surfactant proteins SP-A and SP-D, while these aspects remain unexplored in humans. In view of the high social significance of the problem of alcohol abuse, and also due to the fact that the lungs are one of the "target organs" in excessive alcohol consumption, the study of the effect of alcohol consumption on the levels of surfactant proteins SP-A and SP-D in men and women is undoubtedly topical direction of modern medical science. The aim of the work is to determine the effect of alcohol consumption on the levels of surfactant proteins SP-A and SP-D in men and women in Novosibirsk. Materials and methods. On the basis of the NIITPM-branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, in 2022, 174 people (87 men and 87 women), aged 45 to 69 years, randomly selected from the residents of Novosibirsk, were examined. Alcohol consumption was assessed using the AUDIT questionnaire. The content of surfactant proteins SP-A and SP-D in blood serum was determined by enzyme immunoassay using standard ELISA kits. Statistical analysis used parametric and non-parametric methods of descriptive statistics, correlation analysis was carried out using the Spearman test, and multivariate analysis using binary logistic regression. ROC-analysis was used to assess the diagnostic significance of variables with the determination of sensitivity and specificity. In all procedures of statistical analysis, the critical significance level of the null statistical hypothesis (p) was taken equal to 0.05. Results. In the general sample of men and women aged 45-69 years, it was determined that the usual single dose of alcohol consumed equal to 7-9 alcohol units is inversely associated with SP-A (r=-0.154, p=0.043). Using ROC analysis, it was found that SP-A is a marker (the area under the ROC curve is 71.2%) of alcohol intake in a typical single dose of alcohol consumed equal to 7-9 alcohol units. With an SP-A level of no more than 921 pg / ml, its sensitivity in relation to the determination of alcohol consumption in a typical single dose of 7-9 alcohol units is 68.7%, and the specificity is 87.5%. Using regression analysis, it was determined that the variable "usual single dose of alcohol consumed equal to 7-9 alcohol units" directly affects the presence of SP-A no more than 921 pg / ml (Exp (B) = 13.0; 95% CI = 1, 5; 111.0, p=0.019) regardless of age and male sex. Conclusion. Thus, it has been established that in men and women of Novosibirsk aged 45-69 years, a high single dose of alcohol consumed equal to 7-9 alcohol units is an independent factor that directly affects the presence of SP-A levels in the blood that do not exceed 921 pg/ml .

Behavioral changes and dendritic remodeling of hippocampal neurons in adolescent alcohol-treated rats.

Objective: Earlier, we and others have reported that alcohol exposure in adolescent rat impaired performance of a spatial memory task in the Morris water maze. The goal of the present study was to investigate the effects of acute adolescent alcohol treatment on the hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear) memories. The study also looked at the structural changes in anterior CA1 hippocampal neurons in adolescent alcohol-treated rats. Methods: Adolescent female rats were administered with a single dose of alcohol (1.0, 1.5, or 2.0g/kg) or vehicle either before training (pre-training) or after training (pre-testing). Experimental and control rats were trained in the fear conditioning paradigm, and 24h later tested for both contextual fear conditioning as well as cued fear memory. Separate groups of rats were treated with either alcohol (2g/kg) or vehicle and sacrificed 24h later. Their brains were harvested and processed for rapid Golgi staining. Randomly selected CA1 pyramidal neurons were analyzed for dendritic branching and dendritic spine density. Results: Pre-training alcohol dose-dependently attenuated acquisition of hippocampus-dependent contextual fear conditioning but had no effect on the acquisition of amygdala-associated cued fear. When administered following training (pre-testing), alcohol did not alter either contextual conditioning or cued fear memory. Golgi stained CA1 pyramidal neurons in alcohol treated female rats had reduced basilar tree branching and less complex dendritic arborization. Conclusion: Alcohol specifically impaired hippocampal learning in adolescent rats but not amygdala-associated cued fear memory. Compared to vehicle-treated rats, CA1 hippocampal pyramidal neurons in alcohol-treated rats had less complex dendritic morphology. Together, these data suggest that adolescent alcohol exposure produces changes in the neuronal organization of the hippocampus, and these changes may be related to impairments in hippocampus-dependent memory formation.

Maternal binge alcohol consumption leads to distinctive acute perturbations in embryonic cardiac gene expression profiles.

Excessive alcohol consumption during pregnancy is associated with high risk of congenital heart defects, but it is unclear how alcohol specifically affects heart development during the acute aftermath of a maternal binge drinking episode. We hypothesize that administration of a single maternal binge dose of alcohol to pregnant mice at embryonic day 9.5 (E9.5) causes perturbations in the expression patterns of specific genes in the developing heart in the acute period (1-3 days) following the binge episode. To test this hypothesis and identify strong candidate ethanol-sensitive target genes of interest, we adapted a mouse binge alcohol model that is associated with a high incidence of congenital heart defects as described below. Pregnant mice were administered a single dose of alcohol (2.5g/kg in saline) or control (saline alone) via oral gavage. To evaluate the impact of maternal binge alcohol on cardiac gene expression profiles, we isolated embryonic hearts from both groups (n=5/group) at 24, 48, and 72 h post-gavage for transcriptomic analyses. RNA was extracted and evaluated using quantitative RNA-sequencing (RNA-Seq) methods. To identify a cohort of binge-altered cardiac genes, we set the threshold for change at >2.0-fold difference with adjusted p < 0.05 versus control. RNA-Seq analysis of cardiac gene expression revealed that of the 17 genes that were altered within the first 48 h post-binge, with the largest category consisting of transcription factors (Alx1, Alx4, HoxB7, HoxD8, and Runx2), followed by signaling molecules (Adamts18, Dkk2, Rtl1, and Wnt7a). Furthermore, multiple comparative and pathway analyses suggested that several of the candidate genes identified through differential RNA-Seq analysis may interact through certain common pathways. To investigate this further, we performed gene-specific qPCR analyses for three representative candidate targets: Runx2, Wnt7a, and Mlxipl. Notably, only Wnt7a showed significantly (p < 0.05) decreased expression in response to maternal binge alcohol in the qPCR assays. These findings identify Wnt7a and a short list of potential other candidate genes and pathways for further study, which could provide mechanistic insights into how maternal binge alcohol consumption produces congenital cardiac malformations.

Energy and Personality: A Bridge between Physics and Psychology

The objective of this paper is to present a mathematical formalism that states a bridge between physics and psychology, concretely between analytical dynamics and personality theory, in order to open new insights in this theory. In this formalism, energy plays a central role. First, the short-term personality dynamics can be measured by the General Factor of Personality (GFP) response to an arbitrary stimulus. This GFP dynamical response is modeled by a stimulus–response model: an integro-differential equation. The bridge between physics and psychology appears when the stimulus–response model can be formulated as a linear second order differential equation and, subsequently, reformulated as a Newtonian equation. This bridge is strengthened when the Newtonian equation is derived from a minimum action principle, obtaining the current Lagrangian and Hamiltonian functions. However, the Hamiltonian function is non-conserved energy. Then, some changes lead to a conserved Hamiltonian function: Ermakov–Lewis energy. This energy is presented, as well as the GFP dynamical response that can be derived from it. An application case is also presented: an experimental design in which 28 individuals consumed 26.51 g of alcohol. This experiment provides an ordinal scale for the Ermakov–Lewis energy that predicts the effect of a single dose of alcohol.

Acute tolerance to alcohol-induced impairment in cognitive performance.

Acute tolerance is a rapid decrease in the effect of alcohol relative to the blood alcohol concentration (BAC) occurring within the duration of a single dose of alcohol. It remains uncertain which cognitive domains are susceptible to acute tolerance, because findings vary between tasks used to measure the effect of alcohol. This study examined acute tolerance in subjective intoxication and in 2 cognitive domains: information processing, measured using the Inspection Time Task (ITT), and response inhibition, measured with the Sustained Attention to Response Task (SART). Forty participants were allocated to either an alcohol or placebo group. After baseline measures, the alcohol group were given an active dose to produce a peak BAC of 0.07%, whereas the placebo group received a placebo beverage. ITT and SART performance were measured at a BAC of 0.05% twice during the course of the dose, once when BAC was ascending and again when descending. The placebo group was tested at equivalent times. When BAC was ascending, the alcohol group showed increased ratings of subjective intoxication and impaired performance on the ITT. Consistent with an acute tolerance effect, ratings of subjective intoxication and impairment on the ITT in the alcohol group were lower when BAC was descending. Performance on the SART was not found to be affected by alcohol. The findings suggest information processing is a domain of behavior that shows acute tolerance to alcohol and that the subjective intoxication felt at a BAC of 0.05% can decrease substantially within the duration of a single dose. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Changes in the brain directly following alcohol consumption-a study of healthy male individuals, with the use of proton magnetic resonance spectroscopy (1HMRS) and diffusion (DWI).

To use proton magnetic resonance spectroscopy (1HMRS) and diffusion weighted imaging (DWI) to identify ethanol in the brain directly after consumption, and examine changes in brain metabolite levels and brain microstructure relative to the duration of time following exposure to alcohol. The study involved 44 male volunteers (18-55years). All brain changes were assessed in the frontal lobes, occipital lobes, basal ganglia and cerebellum, however the detailed analyses focused on the frontal lobes. All participants were examined four times, i.e. before and 0.5-hour, 1hour and 2hours after consumption of 150mL pure vodka (60g of ethanol). The highest ethanol levels were identified between 0.5 and 1hour following alcohol intake. There were significant increases in the concentrations of lipids and lactates approximately one hour after alcohol consumption, and the concentration levels were found to normalise during the following two hours. Some statistically insignificant trends of changes were found for tCr, tCho, mI, GABA, Glc, Glx and tNAA. For the DWI and ADC (Apparent Diffusion Coefficient of water) values, the findings showed statistically insignificant decrease and increase, followed by a tendency towards normalisation. Similar associations in changes of metabolite concentrations and DWI and ADC values were found in the other locations investigated in the study. A single dose of alcohol as used in this experiment produces increases in lipids and lactates in brain tissues that appear reversible.

Effect of alcohol on blood pressure.

Alcohol is consumed by over 2 billion people worldwide. It is a common substance of abuse and its use can lead to more than 200 disorders including hypertension. Alcohol has both acute and chronic effects on blood pressure. This review aimedto quantify the acute effects of different doses of alcohol over time on blood pressure and heart rate in an adult population. Primary objective To determine short-term dose-related effects of alcohol versus placebo on systolic blood pressure and diastolic blood pressure in healthy and hypertensive adults over 18 years of age. Secondary objective To determine short-term dose-related effects of alcohol versus placebo on heart rate in healthy and hypertensive adults over 18 years of age. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2019: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), in the Cochrane Library; MEDLINE (from 1946); Embase (from 1974); the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant articlesregarding further published and unpublished work. These searches had no language restrictions. Randomised controlled trials (RCTs) comparing effects of a single dose of alcohol versus placebo on blood pressure (BP) or heart rate (HR) in adults(≥ 18 years of age). Two review authors (ST and CT) independentlyextracted data and assessed the quality of included studies. We also contacted trial authors for missing or unclear information. Mean difference (MD) from placebo with 95% confidence interval (CI) was the outcome measure, and a fixed-effect model was used to combine effect sizes across studies. MAIN RESULTS: We included 32RCTs involving 767 participants.Most of the study participants were male (N = 642) and were healthy. The mean age of participants was 33 years, and mean body weight was 78 kilograms. Low-dose alcohol (< 14 g) within six hours (2 RCTs, N = 28) did not affect BP but did increase HR by 5.1 bpm (95% CI 1.9 to 8.2) (moderate-certainty evidence). Medium-dose alcohol (14 to 28 g) within six hours (10 RCTs, N = 149) decreasedsystolic blood pressure (SBP) by 5.6 mmHg (95% CI -8.3 to -3.0) anddiastolic blood pressure (DBP) by 4.0 mmHg (95% CI -6.0 to -2.0)and increased HR by 4.6 bpm (95% CI 3.1 to 6.1) (moderate-certainty evidence for all). Medium-dose alcohol within 7 to 12 hours (4 RCTs, N = 54) did not affect BP or HR. Medium-dose alcohol > 13 hours after consumption (4 RCTs, N = 66) did not affect BP or HR. High-dose alcohol (> 30 g) within six hours (16 RCTs, N = 418) decreased SBP by 3.5 mmHg (95% CI -6.0 to -1.0),decreased DBP by 1.9 mmHg (95% CI-3.9 to 0.04), and increased HR by 5.8 bpm (95% CI 4.0 to 7.5).The certainty of evidence was moderate for SBP and HR, and was low for DBP. High-dose alcohol within 7 to 12hours of consumption (3 RCTs, N = 54) decreased SBP by 3.7 mmHg (95% CI -7.0 to -0.5)and DBP by 1.7 mmHg (95% CI -4.6 to 1.8) and increased HR by6.2 bpm (95% CI 3.0 to 9.3). The certainty of evidence was moderate for SBP and HR, and low for DBP. High-dose alcohol ≥ 13hours after consumption (4 RCTs, N = 154) increased SBP by 3.7 mmHg (95% CI 2.3 to 5.1),DBP by 2.4 mmHg (95% CI 0.2 to 4.5), and HR by 2.7 bpm (95% CI 0.8 to 4.6) (moderate-certainty evidence for all). AUTHORS' CONCLUSIONS: High-dose alcohol has a biphasic effect on BP; it decreases BP up to 12 hours after consumption and increases BP > 13 hours after consumption. High-dose alcohol increases HR at all times up to 24 hours. Findingsof this review are relevant mainly to healthy males, as only small numbers of womenwere included in the included trials.

Dosage scaling of alcohol in binge exposure models in mice: An empirical assessment of the relationship between dose, alcohol exposure, and peak blood concentrations in humans and mice.

Binge drinking is a remarkably prevalent behavior. In 2015, 27% of U.S. residents 18 years old or older reported at least one episode of binge drinking in the previous month. Rodent models for binge drinking are widely used to study the mechanisms by which alcohol causes a variety of adverse health effects in humans. Concerns have been raised that many binge-drinking studies in rodents involve alcohol doses that would be unrealistically high in humans. Allometric dosage scaling can be used to estimate the dose of a drug or chemical in mice that would be necessary to achieve similar biological effects at a realistic dose in humans. However, it has become apparent that no single allometric conversion factor is applicable for all drugs and chemicals, so it is necessary to evaluate each compound empirically. In the present study, we compared the area under the blood alcohol concentration vs. time curve (AUC) and the peak blood alcohol concentration following oral alcohol administration at various doses in mice and humans, using data from previously published studies. The results demonstrated that the oral dose of alcohol must be larger in mice (on a g of alcohol to kg of body weight basis) than in humans to achieve similar alcohol AUC values or to achieve similar peak concentrations in the blood. The dose required in mice was about 2-fold greater than the dose required in humans to achieve similar alcohol AUC and peak concentrations. The results shown here were substantially different from the average 5-12-fold difference between mice and humans calculated in previous studies using agents other than alcohol. Results shown here demonstrate that an empirical approach using data from several independent experiments provides information needed to determine the alcohol dose in mice that produces a similar level of exposure (AUC and peak concentration) as in humans. The results indicate that a single alcohol dose in the range of 5-6g/kg, a range often used in mouse models for binge drinking, is not excessive when modeling human binge drinking. Results presented here illustrate that in mice both alcohol AUC and peak alcohol concentration correlate well with an important biological effect - activation of the hypothalamic-pituitary-adrenal axis - as indicated by increased corticosterone AUC values.

Drinking ‘Off’ the Clock: Effects of Binge Alcohol on the Skeletal Muscle Core Clock

IntroductionCircadian rhythms are ~24‐hour oscillations generated by a transcription‐translation feedback loop known as the core molecular clock. The core clock is comprised of a positive arm, which includes the genes circadian locomotor output cycles kaput (Clock) and brain and muscle arnt‐like (Bmal1), and a negative arm, which includes period (Per)1/2/3 and cryptochrome (Cry)1/2. Several physiological processes are ‘Clock’ controlled, and disruptions to these rhythms is linked to many chronic diseases, such as cardiovascular disease, diabetes, depression, and cancer. Previous studies have shown that alcohol (EtOH) intoxication disrupts circadian rhythms within liver, brain and intestines, but the effects of alcohol intoxication on skeletal muscle circadian rhythms has not been assessed. Our objective is to assess the effects of EtOH on regulation of components of the core molecular clock in skeletal muscle.MethodsFemale C57BL6 mice (n=39) were randomized into one of three groups: Baseline (n=3), Control (Saline; n=18), or Alcohol (EtOH; n=18). Mice in Control and EtOH received an IP injection of either saline, or EtOH (5g/kg BW) at the start of the dark cycle (Zeitgeber time (ZT12)), with ab libitum food and water. Baseline mice were euthanized at ZT12, while 3 saline and 3 EtOH mice were euthanized every 4h thereafter. The gastrocnemius was used for RNA isolation, and RT‐PCR was performed to measure circadian gene expression. Data were analyzed by two‐way ANOVA (Time, EtOH) with Fisher’s LSD Post hoc testing (p&lt;0.05).ResultsExpression of the core clock components Bmal1, Cry1/2, and Per1/2/3 was disrupted by EtOH when compared to saline. EtOH increased expression of Per1 and eliminated the normal circadian oscillation for 20 hr post injection. Per2 expression was also increased by alcohol for the first 8h post injection, ZT12–ZT24. EtOH increased Per3 expression at the end of the dark cycle (ZT24), before decreasing it at ZT8 in the light cycle. Alcohol prevented the normal increase in Cry1 throughout the dark phase and the usual suppression during the light cycle (ZT8 and ZT12), while Cry2 expression was increased (&gt;2 fold) over both the dark and light cycles in EtOH when compared to control. In the positive arm of the core clock, EtOH did not significantly disrupt the normal circadian expression of Clock but did cause a rightward shift of the normal oscillation of Bmal1. EtOH also significantly altered gene expression of several downstream targets of the core clock, including D‐box binding protein (DBP), retinoid‐related orphan receptor‐α (ROR‐α), and myogenic differentiation (MyoD), suggesting functional implications of core clock disruption by alcohol. Finally, circadian expression of Redd1 (i.e. regulated in development and DNA damage response‐1), a metabolic regulator, was disrupted by EtOH, as a ~35‐fold induction occurred during the dark cycle compared with controls.ConclusionA single dose of alcohol significantly disrupted several components of the core molecular clock, as well as downstream targets within skeletal muscle. Therefore, dysregulation of the skeletal muscle core clock may contribute to alcoholic myopathy and other co‐morbidities associated with high levels of alcohol consumption.

The association between alcohol metabolism and genetic variants of ADH1A, SRPRB, and PGM1 in Korea.

Excessive alcohol consumption is a major public health problem in East Asian countries. Alcohol use leads to a cascade of problems including increased chances of risky behavior and a wide range of negative health consequences, from alcoholic liver disease to upper gastric and liver cancer. These alcohol effects are known to be influenced by ethnic variability and genetics. In this study, subjects were administered a single dose of alcohol (0.6g/kg for men or 0.4g/kg for women), and blood alcohol and acetaldehyde concentrations were measured eight times over 5 hours. To investigate genetically susceptible factors to alcohol metabolism, we selected single-nucleotide polymorphisms (SNP) of genes identified by prior genetic association studies for alcohol metabolism, alcohol consumption, alcohol dependence, and related traits, and performed genotyping on all subjects (n=104). We identified variations in the ADH1A, SRPRB, and PGM1 genes, which are directly associated with blood alcohol or acetaldehyde concentrations. Namely, the T allele of SRPRB rs17376019 and the C allele of PGM1 rs4643 were associated with lower blood alcohol levels, while the ADH1 rs1229976C allele group exhibited markedly higher blood acetaldehyde levels than those of the ADH1 rs1229976T allele group. This study demonstrates that genetic variations in ADH1A, SRPRB, and PGM1 are associated with variations in blood alcohol and acetaldehyde concentration after alcohol intake.

Unique Skeletal Muscle Gene Expression Signature Induced by Acute Alcohol Intoxication in mice

High levels of alcohol intake lead to skeletal muscle myopathy and subsequent dysfunction both acutely and chronically. Our previous work has shown that a single dose of alcohol, as well as chronic intake, decreases rates of protein synthesis concurrent with suppression of the mTOR signaling pathway. Although evidence exists for the contribution of other anabolic and catabolic factors (myostatin, inflammation, insulin like growth factor, etc.), to the induction of alcoholic myopathy, no definitive mechanism(s) or pathway(s) has been identified. Therefore, the objective of this work was to identify novel pathways for future therapeutic targeting in the treatment of alcoholic myopathy via an unbiased screen of skeletal muscle specific genes differentially regulated by acute alcohol intoxication. Male, 12 week old, C57BL/6 mice were fasted overnight prior to receiving an intraperitoneal injection of 3g/kg BW alcohol or saline (Control group). The gastrocnemius/plantaris muscle complex was excised 1 hour post alcohol intoxication for isolation of RNA and preparation of cDNA prior to RNA deep sequencing. The data were mapped to the mouse genome (mm10, GRCm38) using TopHat 2 software. Using DESeq2 software, differentially expressed genes were determined based on an FDR‐adjusted p‐value of &lt;0.05. Under these parameters, 48 transcripts were identified in response to acute alcohol intoxication. Using the DAVID Bioinformatics Resource, 8 functional groups were recognized including Collagen, Extracellular matrix, Secreted, Hydroxylation, Cell Adhesion, Cytoplasm, Signal and Glycoprotein. Of the 48 genes, 15 were suppressed by alcohol intoxication including Regulator of Cell Cycle (Rgcc), previously shown to be upregulated in models of skeletal muscle hypertrophy and regrowth; Leiomodin2 (Lmod2) which is important in actin polymerization; and xin actin‐binding repeat containing 1 (Xirp1) which protects actin filaments from depolymerization and may be a marker of muscle damage. The remaining 32 genes were increased by acute alcohol intoxication including EMILIN1 which relies on the inhibition of TGF‐β; Aquaporin7 which is implicated in lipolysis and glycerol efflux via regulation of mTOR‐mediated leptin expression; and MAP3K14, also known as NF‐κB inducible kinase, indicating potential modulation of the NF‐κB pathway by acute alcohol. Of the differentially expressed gene transcripts, several do not appear to have a known functional role in skeletal muscle and will therefore provide novel targets for the further characterization of the effects of alcohol on skeletal muscle.Support or Funding InformationFunds provided by Florida State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Soy Isoflavone Extract Does Not Increase the Intoxicating Effects of Acute Alcohol Ingestion in Human Volunteers.

Soy beans contain isoflavones, including daidzein and genistein, with biological activities related to therapeutic effects in reducing osteoporosis, decreasing adverse menopausal manifestations, providing protection from cardiovascular diseases, and reducing hormone-dependent cancers and age-related cognitive-decline. Daidzein has been described as inhibiting the aldehyde-dehydrogenase-2 enzyme (ALDH2), and reducing alcohol use in clinical pilot studies. Our aim was to evaluate the possible interactions between a soy extract product and alcohol in a crossover, single blind, randomized study. Ten healthy male volunteers participated in two experimental sessions: one with a single dose of alcohol (0.5 g/kg, Vodka Absolut, Sweden), and the other with four capsules of a soy extract product (Super-Absorbable Soy Isoflavones, Life-Extension, United States) and, 2 h later, the same dose of alcohol. Results showed no differences in vital signs except a slightly higher significative reduction in diastolic blood pressure at 2, 3, 4, and 8 h after administration with alcohol alone in comparison with soy extract+alcohol. Ethanol-induced subjective and adverse effects were similar for both conditions with the exception of headache (higher at 8 h after alcohol alone). Our results demonstrate that a single dose of a soy isoflavone extract did not influence alcohol pharmacokinetics and pharmacological effects and did not induce any disulfiram-reaction symptoms. Soy extract and alcohol did not interact and can be administered safely.

1213. Evaluation of an Alcohol-Based Antiseptic for Nasal Decolonization of Methicillin-Resistant Staphylococcus aureus (MRSA)

BackgroundDue to concerns for emergence of mupirocin resistance, there is an interest in use of topical antiseptics for nasal decolonization of Staphylococcus aureus. Alcohol-based nasal antiseptics have recently been developed as an alternative to mupirocin, but there is limited data on efficacy, particularly among patients where the burden of carriage is often high.MethodsWe evaluated the effectiveness of a one-time application of a commercial alcohol-based nasal sanitizer for reduction in nasal methicillin-resistant Staphylococcus aureus (MRSA) in MRSA-colonized patients. Patients received either a single dose or triple dose over 3 minutes; the triple dose is recommended for preoperative dosing. Swabs were used for quantitative culture of MRSA from the anterior nares and vestibule prior to and 10 minutes, 2 hours, and 6 hours after application. For a subset of patients, cultures for MRSA were collected from hands, clothing, groin, and chest/axilla.ResultsOf 34 MRSA carriers enrolled, 27 (79%) had MRSA detected in nares, 32 (94%) were male, and the mean age was 65. Of the 27 carriers positive for nasal MRSA, 15 (56%) received a single alcohol dose and 12 (44%) received a triple dose over 3 minutes. As shown in the figure, the single and triple dose applications significantly reduced MRSA concentrations at 2 hours post-treatment when the initial burden was low (i.e., <2 log10colonies per swab), but there was no significant reduction at 6 hours; there was no significant reduction with either dose when the initial burden was high (≥2 log10colonies per swab).ConclusionA single application of an alcohol nasal sanitizer significantly reduced nasal MRSA at 2 hours post-application when the initial burden of colonization was low, but not when a high burden of carriage was present. Additional studies are needed to determine whether higher alcohol doses or repeated applications might result in improved efficacy. Figure. Efficacy of one-time application of a single- or triple-dose of alcohol-based nasal sanitizer on the burden of nasal MRSA.Disclosures All authors: No reported disclosures.

Effect of Lycosome-Formulated Phosphatidylcholine on Parameters of Biological Oxidation after Single Intake of Moderate Amount of Alcohol.

Ingestion of a single dose of alcohol, ranging from the intake of a moderate amount alcohol to binge drinking, is the most frequent form of alcohol consumption with poorly understood medical consequences and obscure prophylactics. The study was aimed to determine whether lycosome formulated phosphatidylcholine (PC-Lyc) containing two highly bioavailable antioxidants (PC and lycopene) ingested shortly before the alcohol-containing beverage may alleviate the biochemical markers of liver damage and parameters of biological oxidation associated with the intake of a moderate amount of alcohol. Healthy middle-aged volunteers were requested to consume a moderate amount of alcohol – 0.5 ml/kg or 1.0 ml/kg shortly after ingestion of a capsule containing 450 mg of regular phosphatidylcholine (PC, n=10), PC-Lyc (n=10), or placebo pill (PP, n=10). Serum levels of ethanol (EtOH), acetaldehyde (AA), liver-specific enzymes, total antioxidant capacity of serum (TAC), oxidized LDL (LDL-Px), and malonic dialdehyde (MDA) were measured at 1, 2.5, and 5 hours after dosing with alcohol. Ingestion of PC regardless of the formulation used had no effect on serum EtOH concentration dynamics. However, volunteers supplemented with PC-Lyc showed a better clearance of AA in serum as compared to other groups. There was a reduction in serum TAC values by 18.5% and 16.1% in both placebo groups ingesting 0.5 and 1.0 ml/kg of alcohol, respectively, at the end of observational period. This decline was preventable by supplementation of volunteers with PC and especially with PC-Lyc. Moreover, PC-Lyc promoted a reduction of serum MDA and reversed an increase in serum LDL-Px. In addition, ingestion of alcohol at 1.0 ml/kg dose caused a transient increase in serum alanine-aminotransferase activity which was abolished by both formulations of PC. Therefore, combinatory lycosomal formulation of PC and lycopene may prevent some metabolic abnormalities associated with single intake of moderate amount of alcohol. This trial is registered with ACTRN12617001335381.

The Analysis of DNA Damage and Cell Loss due to Alcohol and Opiate Drug Exposure on Undifferentiated Stem Cells.

In Fetal Alcohol Spectrum Disorders (FASD), alcohol promotes mental and physical alterations accredited to vicissitudes in the proliferation, differentiation, migration, and cell death in cells within the developing neural crest. Studies show that oxidative stress and changes in cellular proliferation (S-Phase) in these cells plays a role in single and double stranded DNA breaks, leading to a heightened amount of apoptosis in exposed stem cell populations. Opiate drug abuse is common across the world, but the cellular impact is poorly understood. The way that opiate drugs affect the neural crest cells may relate to the alcohol induced apoptotic pathway. It is thought that dose may play a role in the magnitude of the cell loss from alcohol, opiate drugs may also follow this standard. Our hypothesis is that alcohol and opiate drug induced DNA damage is similar and causes an overall increased amount of apoptosis among cell populations. We used a comet assay to analyze the type and extent of DNA damage, caused by single doses of alcohol, methamphetamine, and DAMGO (opioid agonist). We show increased cell losses and heightened amounts of single and double stranded DNA breaks. Research sponsored by WV-INBRE grant P20GM103434.

Embryonic Neuronal Stemm Cell Differentiation is Drastically Effected by Single Doses of Alcohol and Methamphetamine

The objective of this study is to examine population size and differentiation of embryonic neuronal stem cells prior to and after exposure to addictive drugs and alcohol. Prior to differentiation, E14 mouse neuronal stem cells were exposed to methamphetamine, one dose of alcohol (400ug/dL), or two doses of alcohol. The cells were then allowed to differentiate for 4 days, then examined using DAPI (nuclear), anti- oligodendrocyte marker 04, mouse anti-beta 3 tubulin 9 (Neurons), and anti- GFAP antigen (astrocytes). The cells were counted to determine the total number of cells and those with marker expression for each cell type compared to controls. Exposure to both alcohol and methamphetamine caused a large decrease in both stem cell populations and differentiation of neurons. Glial cell populations remained unaffected. Methamphetamine exposure resulted in a drastic increase of un-differentiated stem cells. The results support that consumption of alcohol and methamphetamine does affect population size and differentiation of neuronal stem cells.

Analysis of the effects of drugs and alcohol on neuronal stem cell differentiation.

Drug and alcohol abuse lead to neuronal cell loss and altered CNS plasticity that effects one’s ability to understand and learn new information, as well as restructure pathways important in abstinence based recovery processes. Plasticity relies, in part, on stem cells in several regions of the adult brain that expand, migrate, differentiate and establish new neurons and supportive glial cells. Previous studies suggest that drugs of abuse, including alcohol, methamphetamine and opioids reduce the number of stem cells and affect migration and differentiation processes. Our study examined differentiation of E14 rat neuronal stem cell differentiation after drug insult. In this study, differentiated neuronal stem cells were exposed to single doses of alcohol, methamphetamine, and DAMGO (opioid agonist) to recreate the effects of adult substance abuse. We examined cells, after 5 days, to determine differentiation processes and cell numbers. Synaptogyrin-1 antibody was used to determine neuronal connectivity, and Glutamine Receptor Type 1 antibody was used to determine glutamate neurotransmission. Cells were also stained for synaptic vesicle expression. We show substantial cell loss with alterations in vesicle packaging and synaptic cleft formation. Research sponsored by WV-INBRE grant P20GM103434.

Considering the context: social factors in responses to drugs in humans

Drugs are typically used in social settings. Here, we consider two factors that may contribute to this observation: (i) the presence of other people may enhance the positive mood effects of a drug, and conversely, (ii) drugs may enhance the value of social stimuli. We review evidence from controlled laboratory studies with human volunteers, which investigated either of these interactions between social factors and responses to drugs. We examine the bidirectional effects of social stimuli and single doses of alcohol, stimulants, opioids, and cannabis. All four classes of drugs interact with social contexts, but the nature of these interactions varies across drugs, and depends on whether the context is positive or negative. Alcohol and stimulant drugs enhance the attractiveness of social stimuli and the desire to socialize, and social contexts, in turn, enhance these drugs' effects. In contrast, opioids and cannabis have subtler effects on social interactions and their effects are less influenced by the presence of others. Overall, there is stronger evidence that drugs enhance positive social contexts than that they dampen the negativity of unpleasant social settings. Controlled research is needed to understand the interactions between drugs of abuse and social contexts, to model and understand the determinants of drug use outside the laboratory.