Peak Blood Alcohol Concentration Research Articles

Effect of repeated alcohol exposure during the third trimester-equivalent on messenger RNA levels for interleukin-1β, chemokine (C–C motif) ligand 2, and interleukin 10 in the developing rat brain after injection of lipopolysaccharide

Microglia undergo maturation during the third trimester of human development (equivalent to the first 1–2 weeks of postnatal life in rodents), during which these cells may be particularly sensitive to insult. Alcohol exposure during this period can activate the neuroimmune system, an effect that may contribute to the pathophysiology of fetal alcohol spectrum disorders. Here, we investigated whether repeated alcohol exposure during the third trimester-equivalent in rats has a priming effect on the neuroimmune response to injection of bacterial lipopolysaccharide (LPS). Pups were exposed to alcohol in vapor chambers for 4 h daily from postnatal day (PD)2 to PD16 (peak blood alcohol concentrations ∼150 mg/dL). On PD17, rats were injected with either saline or LPS (50 μg/kg) and the frontal cortex, cerebellar vermis, and dentate gyrus were collected 2 h later. Messenger RNA (mRNA) levels for the pro-inflammatory agents interleukin 1β (IL-1β) and chemokine (C–C) motif ligand 2 (CCL2), as well as levels of the anti-inflammatory cytokine interleukin 10 (IL-10), were measured using reverse transcriptase polymerase chain reaction. LPS consistently increased IL-1β and CCL2 mRNA levels in the dentate gyrus, frontal cortex, and cerebellum of both male and female rats. Furthermore, the LPS-induced increase of IL-1β mRNA levels was significantly blunted in the frontal cortex of alcohol-exposed female rats. Conversely, LPS only minimally affected IL-10 mRNA expression and there were no significant differences between air- and alcohol-exposed rats. Taken together with the literature regarding the effect of third-trimester alcohol exposure on the neuroimmune system, our findings suggest that chronic exposure to lower levels is less disruptive to the neuroimmune system than binge-like exposure to high doses of alcohol.

Effects of all three trimester moderate binge alcohol exposure on the foetal hippocampal formation and olfactory bulb

Objective: Pre-natal alcohol exposure results in injury to the hippocampus and olfactory bulb, but currently there is no consensus on the critical window of vulnerability. This study tested the hypothesis that pre-natal exposure to a moderate dose of alcohol during all three trimester-equivalents alters development of the hippocampal formation and olfactory bulb in an ovine model, where all brain development occurs pre-natally as it does in humans.Research design and methods: Pregnant sheep were divided into saline control and a binge drinking groups (alcohol dose 1.75 g kg−1; mean peak blood alcohol concentration 189 + 19 mg dl−1).Outcome and results: The density, volume and total cell number were not different between groups for the dentate gyrus, pyramidal cells in the CA1 and CA2/3 fields and mitral cells in the olfactory bulb.Conclusions: A moderate dose of alcohol administered in a binge pattern throughout gestation does not alter cell numbers in the hippocampus or olfactory bulb and exposure during the third trimester-equivalent is required for hippocampal injury, unless very high doses of alcohol are administered. This has important implications in establishing the sensitivity of imaging modalities such as MRI in which volumetric measures are being studied as biomarkers for pre-natal alcohol exposure.

Alcohol metabolism is not affected by sleeve gastrectomy.

It has been published that patients who underwent gastric bypass surgery have impaired alcohol metabolism, predisposing them to higher rates of intoxication and DUI arrests. Yet the impact of laparoscopic sleeve gastrectomy (LSG) on alcohol metabolism and in particular the long-term effects are still unclear. We hypothesized that LSG does not alter alcohol metabolism. A prospective cohort study of patients undergoing LSG was evaluated. Blood alcohol concentration (BAC) was extrapolated using a Breathalyzer(®). Alcohol metabolism was evaluated by determining BAC every 5 min after a single dose of alcohol (5 oz. glass of 14% v/v Malbec wine), until BAC was equal to zero. Subjects were queried about alcohol intoxication symptoms. All parameters were obtained and analyzed preoperatively and at 3 and 12 months postoperatively. Our study consisted of 10 patients (9 female) with a mean age of 46.6 ± 2.2 years and BMI of 43.5 ± 2.2 kg/m(2). The mean percentage excess weight loss was 39.5 ± 3.3 at 3 months and 55.6 ± 4.4 at 12 months. Peak BAC at 20 min was not different at 3 months (0.068 ± 0.007, p = 0.77) or at 12 months (0.047 ± 0.008, p = 0.19) when compared to the preoperative assessment (0.059 ± 0.014). In addition, the time to BAC equal to zero was not significantly different between baseline and the follow-up values (preoperative: 70 ± 9 min, 3 months: 95 ± 18 min, and 12 months: 57 ± 8 min, (p > 0.05). Symptoms of intoxication were not significantly different in patients before and after surgery. Our study suggests that LSG does not alter alcohol metabolism. Patients who undergo LSG do not have higher levels of intoxication following alcohol consumption and are therefore not prone to higher rates of DUI charges than the general public, in contrast to that previously reported following in patients who undergo gastric bypass surgery.

Effects of alcohol and energy drink on mood and subjective intoxication: a double-blind, placebo-controlled, crossover study.

There is concern that combining energy drinks with alcohol may 'mask' subjective intoxication leading to greater alcohol consumption. This study examines the effects of alcohol alone and combined with energy drink on objective and subjective intoxication and mood over the course of 3 h. Using a double-blind, placebo-controlled, balanced, crossover design, 24 participants (mean age 22.23 years) were administered with double placebo, 0.6 g/kg alcohol (mean peak blood alcohol content of 0.051%), 250 ml energy drink and alcohol/energy drink, according to a Latin square design, with a washout of >48 h. On each visit, they were breathalysed and rated themselves on a comprehensive battery of mood items at baseline and then at 45, 90 and 180 min post-drink. Blood alcohol and subjective intoxication were significantly increased following both alcohol alone and alcohol/energy drink. Both measures were statistically indistinguishable between alcohol conditions. In keeping with its (80 mg) caffeine content, the energy drink alone significantly increased self-rated 'alertness' and reduced 'depression-dejection' scores compared with the combined alcohol/energy drink. The alcohol/energy drink increased 'vigor' and 'contentment' at 45 min and decreased 'contentment' at 180 min. The co-ingestion of an energy drink with alcohol does not differently influence blood alcohol content recordings or subjective intoxication compared with alcohol alone, although some mood items are differentially affected.

Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.

Alcohol exposure during pregnancy results in an array of structural and functional abnormalities called fetal alcohol spectrum disorders (FASD). Alcohol dysregulates the exquisite coordination and regulation of gestational adaptations at the level of the uterine vasculature. We herein hypothesized that chronic binge-like alcohol results in uterine vascular dysfunction and impairs maternal uterine artery reactivity to vasoconstrictors and dilators. We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day 7 to 17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction. Alcohol did not produce altered uterine vascular reactivity to α1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired acetylcholine (ACh)-mediated uterine artery vasodilation but exogenous endothelium-independent vasodilators like sodium nitroprusside exhibited no alcohol effect; ACh significantly decreased vessel relaxation (p = 0.003; ↓pD2 [negative log molar ACh concentration producing the half maximum response], -7.004 ± 0.215 vs. -6.310 ± 0.208; EMax [maximal ACh response], 92% vs. 75%). We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs agonist-induced uterine artery vasodilation. In summary, the maternal uterine compartment may play a significant role in the pathogenesis of FASD. Thus, the mechanistic targets of alcohol at the level of both the mother and the fetus need to be considered in order to develop effective therapeutic treatment strategies for FASD.

Drinking reductions following alcohol-related sanctions are associated with social norms among college students.

Students mandated for intervention following an alcohol-related sanction event often reduce their drinking prior to intervention. Knowing the determinants of self-initiated change may help identify intervention targets for individuals who do not reduce their drinking. Guided by self-regulation theory, we tested whether fewer past alcohol consequences and higher descriptive and injunctive norms would be associated with higher levels of postsanction drinking. College students referred for a campus alcohol violation (N = 658, 64% male) reported on their drinking during the month before and after their sanction event. Results show that postsanction drinking was significantly lower than presanction drinking across 4 outcomes: (a) drinks per drinking day, (b) drinks per week, (c) peak drinks, and (d) peak blood alcohol concentration. Hypothesized social influence variables (i.e., descriptive and injunctive norms) were consistently associated with all 4 drinking outcomes; that is, students who perceived that their friends drank more and held more accepting views of drinking were less reactive to alcohol-related sanctions. Past consequences of drinking did not consistently predict subsequent drinking. Therefore, we conclude that alcohol interventions for mandated students should target both descriptive and injunctive norms to optimize their efficacy.

Take One for the Team? Influence of Team and Individual Sport Participation on High School Athlete Substance Use Patterns

The current Web-based survey investigated the association between team or individual sport participation (or both) and self-reported alcohol and tobacco use among high school athletes (N = 1,275) transitioning to college. Peak blood alcohol concentration, weekly drinking, and alcohol-related problems were significantly lower among athletes in individual sports compared to other groups. Athletes competing in both team and individual sports reported greater lifetime tobacco use and combined alcohol/tobacco use compared to individual or team sports alone. Preventive strategies targeting high school athletes in general and those participating in team sports in particular may be useful in minimizing future alcohol use and related problems.

Effects of acute alcohol tolerance on perceptions of danger and willingness to drive after drinking.

Drinking and driving is associated with elevated rates of motor vehicle accidents and fatalities. Previous research suggests that alcohol impairs judgments about the dangers of risky behaviors; however, how alcohol affects driving-related judgments is less clear. Impairments have also been shown to differ across limbs of the blood alcohol concentration (BAC) curve, which is known as acute tolerance. The objectives of this study were to examine whether perceptions about the dangerousness of driving after drinking and willingness to drive differed across the ascending and descending limbs of the BAC curve and to test whether reductions in perceived danger were associated with willingness to drive on the descending limb. Fifty-six participants were randomly assigned to receive either a moderate dose of alcohol (peak BAC = 0.10g%) or placebo. We assessed perceived dangerousness and willingness to drive at matched BACs (~0.067-0.068g%) on the ascending and descending limbs. Both perceived danger and willingness to drive showed acute tolerance in the alcohol group. Participants judged driving to be significantly less dangerous and were more willing to drive on the descending limb compared to the ascending limb. The magnitude of change in perceived danger significantly predicted willingness to drive on the descending limb. Decreased impairment associated with acute tolerance may lead individuals to underestimate the dangerousness of driving after drinking and in turn make poor decisions regarding driving. This study further emphasizes the descending limb as a period of increased risk and offers support for enhancing prevention efforts by targeting drivers at declining BAC levels.

Web-based alcohol screening and brief intervention for university students: a randomized trial.

Unhealthy alcohol use is a leading contributor to the global burden of disease, particularly among young people. Systematic reviews suggest efficacy of web-based alcohol screening and brief intervention and call for effectiveness trials in settings where it could be sustainably delivered. To evaluate a national web-based alcohol screening and brief intervention program. A multisite, double-blind, parallel-group, individually randomized trial was conducted at 7 New Zealand universities. In April and May of 2010, invitations containing hyperlinks to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening test were e-mailed to 14,991 students aged 17 to 24 years. Participants who screened positive (AUDIT-C score ≥4) were randomized to undergo screening alone or to 10 minutes of assessment and feedback (including comparisons with medical guidelines and peer norms) on alcohol expenditure, peak blood alcohol concentration, alcohol dependence, and access to help and information. A fully automated 5-month follow-up assessment was conducted that measured 6 primary outcomes: consumption per typical occasion, drinking frequency, volume of alcohol consumed, an academic problems score, and whether participants exceeded medical guidelines for acute harm (binge drinking) and chronic harm (heavy drinking). A Bonferroni-corrected significance threshold of .0083 was used to account for the 6 comparisons and a sensitivity analysis was used to assess possible attrition bias. Of 5135 students screened, 3422 scored 4 or greater and were randomized, and 83% were followed up. There was a significant effect on 1 of the 6 prespecified outcomes. Relative to control participants, those who received intervention consumed less alcohol per typical drinking occasion (median 4 drinks [interquartile range {IQR}, 2-8] vs 5 drinks [IQR 2-8]; rate ratio [RR], 0.93 [99.17% CI, 0.86-1.00]; P = .005) but not less often (RR, 0.95 [99.17% CI, 0.88-1.03]; P = .08) or less overall (RR, 0.95 [99.17% CI, 0.81-1.10]; P = .33). Academic problem scores were not lower (RR, 0.91 [99.17% CI, 0.76-1.08]; P = .14) and effects on the risks of binge drinking (odds ratio [OR], 0.84 [99.17% CI, 0.67-1.05]; P = .04) and heavy drinking (OR, 0.77 [99.17% CI, 0.56-1.05]; P = .03) were not significantly significant. In a sensitivity analysis accounting for attrition, the effect on alcohol per typical drinking occasion was no longer statistically significant. A national web-based alcohol screening and brief intervention program produced no significant reductions in the frequency or overall volume of drinking or academic problems. There remains a possibility of a small reduction in the amount of alcohol consumed per typical drinking occasion. anzctr.org.au Identifier: ACTRN12610000279022.

Absorption and Peak Blood Alcohol Concentration After Drinking Beer, Wine, or Spirits

Both the amount and the rate of absorption of ethanol (EtOH) from alcoholic beverages are key determinants of the peak blood alcohol concentration (BAC) and exposure of organs other than gut and liver. Previous studies suggest EtOH is absorbed more rapidly in the fasting than in the postprandial state. The concentration of EtOH and the type of beverage may determine gastric emptying/absorption of EtOH. The pharmacokinetics of EtOH were measured in 15 healthy men after consumption of 0.5 g of EtOH/kg body weight. During this 3-session crossover study, subjects consumed in separate sessions, beer (5.1% v/v), white wine (12.5% v/v), or vodka/tonic (20% v/v) over 20 minutes following an overnight fast. BAC was measured by gas chromatography at multiple points after consumption. Peak BAC (Cmax ) was significantly higher (p < 0.001) after vodka/tonic (77.4 ± 17.0 mg/dl) than after wine (61.7 ± 10.8 mg/dl) or beer (50.3 ± 9.8 mg/dl) and was significantly higher (p < 0.001) after wine than beer. The time to Cmax occurred significantly earlier (p < 0.01) after vodka/tonic (36 ± 10 minutes) compared to wine (54 ± 14 minutes) or beer (62 ± 23 minutes). Six subjects exceeded a Cmax of 80 mg/dl after vodka/tonic, but none exceeded this limit after beer or wine. The area under the concentration-time curve (AUC) was significantly greater after drinking vodka/tonic (p < 0.001) than after wine or beer. Comparison of AUCs indicated the relative bioavailability of EtOH was lower after drinking beer. Findings indicate that BAC is higher after drinking vodka/tonic than beer or wine after fasting. A binge pattern is significantly more likely to result in BAC above 80 mg/dl after drinking vodka/tonic than beer or wine. Men drinking on an empty stomach should know BAC will vary depending on beverage type and the rate and amount of EtOH.

Maternal and Neonatal Plasma MicroRNA Biomarkers for Fetal Alcohol Exposure in an Ovine Model

Plasma or circulating miRNAs (cir miRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol (EtOH) altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate. Pregnant sheep were exposed to a binge model of EtOH consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a third-trimester-equivalent period from gestational day 4 (GD4) to GD132. MiRNA profiles were assessed by quantitative PCR analysis in plasma, erythrocyte, and leukocytes obtained from nonpregnant ewes, and plasma from pregnant ewes 24 hours following the last binge EtOH episode, and from newborn lambs, at birth on ~GD147. Pregnant ewe and newborn lamb cir miRNA profiles were similar to each other and different from nonpregnant female plasma, erythrocyte, or leukocyte miRNAs. Significant changes in cir miRNA profiles were observed in the EtOH-exposed ewe and, at birth, in the in utero, EtOH-exposed lamb. Cir miRNAs including miR-9, -15b, -19b, and -20a were sensitive and specific measures of EtOH exposure in both pregnant ewe and newborn lamb. Additionally, EtOH exposure altered guide-to-passenger strand cir miRNA ratios in the pregnant ewe, but not in the lamb. Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. Cir miRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and neonate, and may constitute an important shared endocrine biomarker that is vulnerable to the maternal environment.

Differential trajectories of alcohol-related behaviors across the first year of college by parenting profiles.

This study examined the extent to which profiles of perceived parenting are associated with trajectories of alcohol-related behaviors across the first year of college. Participants were surveyed five times from the summer before college to the fall of the second year. A total 285 college students were enrolled from the incoming classes of consecutive cohorts of students at a large, public university in the Northeastern United States. At baseline, participants provided information on their parents' alcohol-related behaviors (e.g., parental modeling of use; perceived approval of underage use) and parenting characteristics (e.g., parental monitoring; parent-child relationship quality). Students also reported on their personal alcohol-related behaviors at each time point. Latent profile analysis was used to identify four subgroups based on the set of parenting characteristics: High Quality (14%) - highest parent-teen relationship quality; High Monitoring (31%) - highest parental monitoring and knowledge; Low Involvement (30%) - poor relationship quality, little monitoring and communication; and Pro-Alcohol (21%) - highest parental modeling and approval. Students were then assigned to profiles, and their alcohol-related behaviors were examined longitudinally using latent growth curve modeling. In general, students in the Pro-Alcohol profile displayed the highest baseline levels of typical weekend drinking, heavy episodic drinking, and peak blood alcohol content, in addition to showing steeper increases in typical weekend drinking across the first year of college. Results support the notion that parental behaviors remain relevant across the first year of college. Differential alcohol-related behaviors across parenting profiles highlight the potential for tailored college intervention.

Effects of one- and three-day binge alcohol exposure in neonatal C57BL/6 mice on spatial learning and memory in adolescence and adulthood

Binge-like alcohol exposure during the early postnatal period in rats and mice causes deficits in spatial learning and memory that persist into adulthood. Wozniak et al. (2004) reported that heavy binge alcohol exposure on postnatal day 7 (PD 7) in C57BL/6 (B6) mice produced profound spatial learning deficits in the Morris water maze when tested in adolescence (P30–39); when tested in adulthood, however, the deficits were greatly attenuated. Using a similar PD 7 binge alcohol exposure paradigm in B6 mice, we tested whether a single-day (PD 7 only) alcohol treatment produced place learning deficits in both adolescence and in adulthood, and further tested whether a more extended (3-day, PD 7–9) alcohol exposure would induce more severe and enduring deficits. B6 mice were given either 2 subcutaneous injections of alcohol (2.5 g/kg each) 2 h apart on PD 7 or on PD 7–9, and compared with controls that received saline vehicle injections and controls that received no injections. The alcohol injections on PD 7 produced average peak blood alcohol concentrations of 472 mg/dL and evoked typical patterns of activated caspase-3-positive neurons in the cortex, hippocampal formation, and striatum 6 h after the last injection. Mice were given standard place training or random location training in the Morris water maze either as adolescents (PD 30–39) or adults (PD 70–79). The adolescents acquired the place learning more slowly than adults, and the alcohol treatments produced only modest place acquisition deficits. In contrast, both the PD7 and the PD 7–9 alcohol treatments resulted in large and significant spatial learning impairments in adults. In contrast to the previous findings of Wozniak et al. (2004), these results indicate that binge alcohol exposure in the 3rd trimester equivalent produces significant and enduring deficits in spatial learning in B6 mice.

Risk behaviors and drug use: A latent class analysis of heavy episodic drinking in first-year college students.

Examining individual characteristics may not yield an understanding of the complex array of factors that affect college student alcohol use. Utilizing a latent class analysis, the present study investigated an alcohol and drug use database of first-year college students at 89 U.S. colleges and universities (N = 21,945). These data were collected between December, 2010 and September, 2011. This study identified: (1) classes based on alcohol consumption, alcohol-related behaviors, and past-year use of illegal drugs and nonmedical use of prescriptions medications (NMUPM); (2) demographic covariates of these classes; and (3) differential social norms awareness, perceived harmfulness of illegal drugs and NMUPM, and protective strategies. Four classes were identified: (1) Low Risk Drinking/Low Prevalence Drug Use (Class 1); (2) Lower Intake Drinking/Moderate Prevalence Drug Use (Class 2); (3) Moderate Risk Drinking/Moderate Prevalence Drug Use (Class 3); and (4) High Risk Drinking/High Prevalence Drug Use (Class 4). Classes differed in self-reported typical week drinking, estimated peak blood alcohol content over the past 2 weeks, high-risk alcohol use, negative alcohol-related consequences, driving under the influence or riding with drinking drivers, alcohol-related protective behaviors, and past-year substance use. Of particular interest was the identification of a latent class (Class 2) composed primarily of females with a relatively low alcohol intake, but with a high probability of past-year other substance use. This group reported negative alcohol-related consequences despite their relatively low intake. To our knowledge, this is the first latent class analysis of college student alcohol use that includes a drug use indicator and compares social norms awareness, harmfulness perceptions, and alcohol-related protective behaviors between classes.

Protective effects of the alcohol dehydrogenase-ADH1B*3 allele on attention and behavior problems in adolescents exposed to alcohol during pregnancy

Alcohol dehydrogenase is a critical enzyme in the metabolism of alcohol. Expression of three alleles at the ADH1B locus results in enzymes that differ in turnover rate and affinity for alcohol. The ADH1B*3 allele, which appears to be unique to individuals of African descent, is associated with more rapid alcohol metabolism than the more prevalent ADH1B*1 allele. It has been previously demonstrated that the presence of at least one maternal ADH1B*3 allele confers a protective effect against alcohol teratogenicity in infants and children. This study was conducted to determine whether the presence of the ADH1B*3 allele in the mother or child continues to be protective in alcohol-exposed individuals during adolescence. 186 adolescents and 167 mothers participating in a 14-year follow-up of the Detroit Longitudinal Cohort were genotyped for ADH1B alleles. Behavioral reports were obtained from classroom teachers. Frequencies of the ADH1B*3 allele were 17.6% in the mothers and 21.0% in the adolescents, which are consistent with the 15–20% expected for African Americans. Prenatal alcohol exposure was associated with increased attention problems and externalizing behaviors in adolescents born to mothers with two ADH1B*1 alleles but not in those whose mothers had at least one ADH1B*3 allele. A similar pattern was seen in relation to the presence or absence of an ADH1B*3 allele in the adolescent, which may have reflected the presence/absence of the maternal variant. This study is the first to demonstrate that the protective effects of the maternal ADH1B*3 allele continue to be evident during adolescence. These persistent individual differences in vulnerability of offspring to the behavioral effects of fetal alcohol exposure are likely attributable to more rapid metabolism of alcohol that the ADH1B*3 variant confers on the mother, leading to a reduction of the peak blood alcohol concentration to which the fetus is exposed during each drinking episode.

Urinary biomarkers and cytokine response in recent drinkers compared to non-recent drinkers after binge ethanol dosing and phytohemagglutinin-M (PHA) stimulation

s / Alcohol 47 (2013) 567–576 568 1. Urinary biomarkers and cytokine response in recent drinkers compared to non-recent drinkers after binge ethanol dosing and phytohemagglutinin-M (PHA) stimulation M. Afshar, J. Hasday, G. Netzer, G.S. Smith, Pulmonary and Critical Care Medicine, Shock Trauma and Anesthesiology Research (STAR) – Organized Research Center, University of Maryland Medical Center, Baltimore, MD, USA Ethanol intoxication is present in up to 50% of trauma patients. Severe injury may activate the systemic inflammatory response syndrome (SIRS). How binge ethanol affects patients with SIRS is unclear. We performed a pilot study evaluating binge ethanol consumption prior to ex-vivo endotoxin challenge and its effects on immune responsiveness. Urinary EtG (Ethyl Glucuronide) and EtS (Ethyl Sulfate) were used to compare subjects consuming ethanol 24–48 h prior to ethanol dosing (recent drinkers) to those who did not (non-recent drinkers). Ten healthy human volunteers characterized as low to moderate drinkers provided urine samples prior to and 24 h after ethanol dosing (vodka drink over 20 min: males 0.89 g/kg, females 0.81 g/kg). Blood alcohol content (BAC) and heparinized blood was collected prior to dosing, 20 min, 2 h, and 5 h after dosing. Aliquots of blood were diluted 1:1 RPMI 1640 medium and incubated for 24 h with 0.6–6% PHA. Culture supernatants were collected by centrifugation and cytokine levels were measured by ELISA. Four subjects were recent drinkers and had elevated pre-dosing EtG and EtS levels (23,921 35,178 ng/ml and 4418 6262 ng/ml), and the 6 non-recent drinkers had no measurable levels. The mean peak BAC was 142 36 mg/ dl. No difference in BAC between recent and non-recent drinkers was found at the three sampling points. No differences in cytokine expressions by drinking type were found in PHA-stimulated blood prior to binge ethanol dosing. Similar elevations of PHA-stimulated IFN-g, and IL-8 levels occurred after binge ethanol dosing. IL-2 expression was greater in recent drinkers after binge (p 1⁄4 0.03) compared to non-recent drinkers. This suggests that recent drinkers of ethanol may have a modulated immune response after binging compared to non-recent drinkers. EtG and EtS are useful to identify recent drinkers who have no detectable BAC. Studies investigating the immunomodulatory effects of ethanol exposure after injury or SIRS should further delineate exposure to include recent drinkers utilizing EtG and EtS. 2. Role of microRNA-155 in alcoholic liver disease S. Bala, T. Csak, J. Zatsiorsky, D. Catalano, K. Kodys, G. Szabo, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA MicroRNAs (miRNAs) are small non-coding RNAs that emerged as new crucial regulatory players of all cellular processes. miRNA-155 is a multifunctional miRNA that regulates various immune and non-immune biological processes. Previously, we showed the induction of miR-155 in alcoholic liver disease (ALD) where it contributes to inflammation via regulating TNF alpha. To further elucidate its biological role in ALD, we employed miR-155 deficient (KO) mice. Female wild type (C57/BL6J) or miR-155 KO or TLR4 KO mice (n 1⁄4 8–10) were fed the Lieber-DeCarli diet containing either ethanol or control diet for 5 weeks. Our results indicate that miR-155 KO mice are protective from alcohol-induced liver inflammation and gut permeability. A significant attenuation in liver TNF alpha, IL-1beta and MCP1 (mRNA and protein) was found in alcohol-fed miR-155 KO mice compared to wild type mice treated with or without LPS (0.5 mg/ kg for 3 h prior to conclusion of the experiment). Surprisingly, there was no increase in plasma endotoxin levels in miR-155 deficient mice after chronic alcohol feeding, indicative of intact gut epithelium. Further, a partial, but significant decrease in fat accumulation was observed in alcohol-fed miR-155 KO mice compared to wild type mice. Alcohol feeding resulted in a significant induction of oxidative stress (measured by TBAR assay) in wild type mice and this increase was prevented in miR-155 KO mice. Interestingly, alcohol-induced decrease in hepatic miR-122 levels observed in wild type mice was prevented in miR-155 KO mice, suggesting miR-155 plays a causal role in alcoholic liver injury. Our results also indicate that alcohol induces miR-155 via TLR4 pathway as TLR4 KO mice in contrast to wild type mice showed no increase in miR-155 after alcohol feeding. In summary, our results suggest that miR-155 plays an essential role in the pathogenesis of ALD and therapeutic inhibition of this miRNA might be an attractive strategy to ameliorate ALD (Supported by NIH AA020744 [GS]). 3. Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury: A critical role for E-selectin A. Bertola, O. Park, B. Gao, Laboratory of Liver Diseases, NIAAA, NIH,

Do drinking games matter? An examination by game type and gender in a mandated student sample

Background: College students who violate alcohol policies engage in riskier alcohol use and demonstrate more problems related to their use than non-violating peers. Drinking games (DG) have been linked to increased alcohol use and negative consequences. Objectives: The present study sought to assess potential differences in DG participation among mandated males and females by examining rates of endorsement, types of DG played, and how types of games are related to alcohol use and related consequences. Methods: Participant data were obtained from 154 undergraduate students mandated to receive an alcohol intervention, Results: DG players were found to have higher typical and peak blood alcohol concentrations, consume more drinks per week on average, consume more standard drinks per highest drinking occasion, and to experience a considerably greater number of alcohol-related consequences than non-players. Males endorsed greater participation in DG and cited “team” and “motor” games more often than females. “Gambling” games were endorsed equally by both sexes, but resulted in increased consequences for females only. Conclusion: Engaging in DG results in higher levels of alcohol consumption. The likelihood of consequences experienced may vary by type of DG in which individuals choose to participate, as well as by gender. Results from this study provide information that can be utilized in targeted alcohol programming efforts, not only for a high-risk population such as mandated students, but tailored to the specific needs of males and females.

Case Management Reduces Drinking During Pregnancy among High Risk Women.

Estimate the efficacy of Case Management (CM) for women at high risk for bearing a child with Fetal Alcohol Spectrum Disorders (FASD). Women were recruited from antenatal clinics and engaged in 18 months of CM. A South African community with a subculture of heavy, regular, weekend, recreational drinking and high documented rates of FASD. Forty-one women who were high risk for bearing a child with FASD. Statistical analysis of trends in drinking and other risk factors. At intake 87.8% were pregnant, most had previous alcohol-exposed pregnancies, most/all of their friends drink alcohol (67.5%), and 50.0% had stressful lives. CM was particularly valuable for pregnant women, as statistically significant reductions in alcohol risk were obtained for them in multiple variables: total drinks on weekends after six months of CM (p = .026) and estimated peak blood alcohol concentration (BAC) at six (p < .001) and 18 months (p < .001). For participants completing 18 months of CM, AUDIT scores improved significantly by 6-month follow-up (from 19.8 to 9.7, p = .000), and even though rising at 12 and 18 months, AUDIT scores indicate that problematic drinking remained statistically significantly lower than baseline throughout CM. Happiness scale scores correlated significantly with reduced drinking in most time periods. An enduring change in drinking behavior is difficult in this social setting. Yet, CM provided by skilled and empathic case managers reduced maternal drinking at critical times, and therefore, alcohol exposure levels to the fetus.

Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma

Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21-30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model.

Evaluation of Timing and Dosage of a Parent-Based Intervention to Minimize College Students’ Alcohol Consumption

The study evaluated the timing and dosage of a parent-based intervention to minimize alcohol consumption for students with varying drinking histories. First-year students (N = 1,900) completed Web assessments during the summer before college (baseline) and two follow-ups (fall of first and second years). Students were randomized to one of four conditions (pre-college matriculation [PCM], pre-college matriculation plus boosters [PCM+B], after college matriculation [ACM], and control conditions). Seven indicators of drinking (drink in past month, been drunk in past month, weekday [Sunday to Wednesday] drinking, Thursday drinking, weekend [Friday, Saturday] drinking, heavy episodic drinking in past 2 weeks, and peak blood alcohol concentration <.08) were used in a latent transition analysis (LTA) to examine a stage-sequential model of drinking. LTA models with dummy-coded intervention variables were used to examine the effects of the intervention conditions on changes in drinking patterns. Results indicated that four patterns of drinking were present at all waves: (a) nondrinkers, (b) weekend light drinkers, (c) weekend heavy episodic drinkers, and (d) heavy drinkers. Results indicated that the PCM condition was most effective at influencing baseline heavy drinkers' transition out of this pattern to lower risk patterns at first follow-up, whereas the ACM condition was not effective at preventing drinking escalation for baseline nondrinkers at first follow-up. No decay of effects was observed at long-term follow-up for the PCM condition. Finally, the results also indicated that increased dosage of the parental intervention was not significantly associated with either reduction or escalation of use. The results underscore the value of pre-college parental interventions and targeted efforts to reduce high-risk drinking among college students.