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Sample records for alcohol exposure including

  1. Fetal alcohol exposure: consequences, diagnosis, and treatment.

    PubMed

    Pruett, Dawn; Waterman, Emily Hubbard; Caughey, Aaron B

    2013-01-01

    Maternal alcohol use during pregnancy is prevalent, with as many as 12% of pregnant women consuming alcohol. Alcohol intake may vary from an occasional drink, to weekly binge drinking, to chronic alcohol use throughout pregnancy. Whereas there are certain known consequences from fetal alcohol exposure, such as fetal alcohol syndrome, other effects are less well defined. Craniofacial dysmorphologies, abnormalities of organ systems, behavioral and intellectual deficits, and fetal death have all been attributed to maternal alcohol consumption. This review article considers the theoretical mechanisms of how alcohol affects the fetus, including the variable susceptibility to fetal alcohol exposure and the implications of ethanol dose and timing of exposure. Criteria for diagnosis of fetal alcohol syndrome are discussed, as well as new methods for early detection of maternal alcohol use and fetal alcohol exposure, such as the use of fatty acid ethyl esters. Finally, current and novel treatment strategies, both in utero and post utero, are reviewed.

  2. Fetal Alcohol Exposure

    MedlinePlus

    ... of the National Academies (IOM) diagnostic categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder ( ... 301.443.3860 Relevant Clinical Diagnoses IOM Diagnoses Fetal Alcohol Syndrome (FAS) Fetal Alcohol Syndrome (FAS) was the first ...

  3. Psychiatric Conditions Associated with Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    O'Connor, Mary J.; Paley, Blair

    2009-01-01

    Since the identification of fetal alcohol syndrome (FAS) over 35 years ago, mounting evidence about the impact of maternal alcohol consumption during pregnancy has prompted increased attention to the link between prenatal alcohol exposure (PAE) and a constellation of developmental disabilities that are characterized by physical, cognitive, and…

  4. Prenatal Alcohol Exposure Selectively Enhances Young Adult Perceived Pleasantness of Alcohol Odors

    PubMed Central

    Hannigan, John H.; Chiodo, Lisa M.; Sokol, Robert J.; Janisse, James; Delaney-Black, Virginia

    2015-01-01

    Prenatal Alcohol Exposure (PAE) can lead to life-long neurobehavioral and social problems that can include a greater likelihood of early use and/or abuse of alcohol compared to older teens and young adults without PAE. Basic research in animals demonstrates that PAE influences later postnatal responses to chemosensory cues (i.e., odor & taste) associated with alcohol. We hypothesized that PAE would be related to poorer abilities to identify odors of alcohol-containing beverages, and would alter perceived alcohol odor intensity and pleasantness. To address this hypothesis we examined responses to alcohol and other odors in a small sample of young adults with detailed prenatal histories of exposure to alcohol and other drugs. The key finding from our controlled analyses is that higher levels of PAE were related to higher relative ratings of pleasantness for alcohol odors. As far as we are aware, this is the first published study to report the influence of PAE on responses to alcohol beverage odors in young adults. These findings are consistent with the hypothesis that positive associations (i.e., “pleasantness”) to the chemosensory properties of alcohol (i.e., odor) are acquired prenatally and are retained for many years despite myriad interceding postnatal experiences. Alternate hypotheses may also be supported by the results. There are potential implications of altered alcohol odor responses for understanding individual differences in initiation of drinking, and alcohol seeking and high-risk alcohol-related behaviors in young adults. PMID:25600468

  5. Genes and pathways co-associated with the exposure to multiple drugs of abuse, including alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine, and/or nicotine: a review of proteomics analyses.

    PubMed

    Wang, Ju; Yuan, Wenji; Li, Ming D

    2011-12-01

    Drug addiction is a chronic neuronal disease. In recent years, proteomics technology has been widely used to assess the protein expression in the brain tissues of both animals and humans exposed to addictive drugs. Through this approach, a large number of proteins potentially involved in the etiology of drug addictions have been identified, which provide a valuable resource to study protein function, biochemical pathways, and networks related to the molecular mechanisms underlying drug dependence. In this article, we summarize the recent application of proteomics to profiling protein expression patterns in animal or human brain tissues after the administration of alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine/heroin/butorphanol, or nicotine. From available reports, we compiled a list of 497 proteins associated with exposure to one or more addictive drugs, with 160 being related to exposure to at least two abused drugs. A number of biochemical pathways and biological processes appear to be enriched among these proteins, including synaptic transmission and signaling pathways related to neuronal functions. The data included in this work provide a summary and extension of the proteomics studies on drug addiction. Furthermore, the proteins and biological processes highlighted here may provide valuable insight into the cellular activities and biological processes in neurons in the development of drug addiction.

  6. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  7. [Exposure to phtalates and their presence in alcoholic beverages].

    PubMed

    Jurica, Karlo; Uršulin-Trstenjak, Natalija; Vukić Lušić, Darija; Lušić, Dražen; Smit, Zdenko

    2013-06-01

    Phthalates are phthalic acid and aliphatic alcohol esters used as additives to plastic in order to improve its softness, flexibility, and elongation. Phthalates are highly mobile and migrate easily from plastic products into the environment due to their physical and chemical properties. This study briefly describes the characteristics and distribution of phthalates in the environment, their toxic effects on human health, the legislation regarding the maximum allowed concentration of phthalates in drinking water and products intended for infants, as well as the tolerable daily intake. Special attention is given to the methods of determining phthalates and their levels in alcoholic beverages, with an overview of phthalate occurrences and concentrations in plum brandy made in Croatia. A segment on denatured alcohol and illegally marketed alcohol is also included, as well as guidelines for the effective monitoring of the routes of human exposure to phthalates.

  8. Discriminating the Effects of Prenatal Alcohol Exposure From Other Behavioral and Learning Disorders

    PubMed Central

    Coles, Claire D.

    2011-01-01

    Fetal alcohol syndrome and fetal alcohol spectrum disorders are underdiagnosed in general treatment settings. Among the factors involved in identifying the effects of prenatal alcohol exposure are (1) the evidence for prenatal alcohol exposure; (2) the effects of the postnatal, caregiving environment; (3) comorbidities; and (4) differential diagnosis, which includes identifying the neurodevelopmental effects of alcohol and discriminating these effects from those characterizing other conditions. This article reviews findings on the neurodevelopmental effects of prenatal alcohol exposure, including learning and memory, motor and sensory/motor effects, visual/spatial skills, and executive functioning and effortful control. Encouraging clinicians to discriminate the effects of prenatal alcohol exposure from other conditions may require more education and training but ultimately will improve outcomes for affected children. PMID:23580040

  9. Paternal Alcohol Exposure Reduces Alcohol Drinking and Increases Behavioral Sensitivity to Alcohol Selectively in Male Offspring

    PubMed Central

    Finegersh, Andrey; Homanics, Gregg E.

    2014-01-01

    Alcohol use disorder (AUD) is heritable, but the genetic basis for this disease remains poorly understood. Although numerous gene variants have been associated with AUD, these variants account for only a small fraction of the total risk. The idea of inheritance of acquired characteristics, i.e. “epigenetic inheritance,” is re-emerging as a proven adjunct to traditional modes of genetic inheritance. We hypothesized that alcohol drinking and neurobiological sensitivity to alcohol are influenced by ancestral alcohol exposure. To test this hypothesis, we exposed male mice to chronic vapor ethanol or control conditions, mated them to ethanol-naïve females, and tested adult offspring for ethanol drinking, ethanol-induced behaviors, gene expression, and DNA methylation. We found that ethanol-sired male offspring had reduced ethanol preference and consumption, enhanced sensitivity to the anxiolytic and motor-enhancing effects of ethanol, and increased Bdnf expression in the ventral tegmental area (VTA) compared to control-sired male offspring. There were no differences among ethanol- and control-sired female offspring on these assays. Ethanol exposure also decreased DNA methylation at the BdnfÆpromoter of sire's germ cells and hypomethylation was maintained in the VTA of both male and female ethanol-sired offspring. Our findings show that paternal alcohol exposure is a previously unrecognized regulator of alcohol drinking and behavioral sensitivity to alcohol in male, but not female, offspring. Paternal alcohol exposure also induces epigenetic alterations (DNA hypomethylation) and gene expression changes that persist in the VTA of offspring. These results provide new insight into the inheritance and development of alcohol drinking behaviors. PMID:24896617

  10. Paternal alcohol exposure reduces alcohol drinking and increases behavioral sensitivity to alcohol selectively in male offspring.

    PubMed

    Finegersh, Andrey; Homanics, Gregg E

    2014-01-01

    Alcohol use disorder (AUD) is heritable, but the genetic basis for this disease remains poorly understood. Although numerous gene variants have been associated with AUD, these variants account for only a small fraction of the total risk. The idea of inheritance of acquired characteristics, i.e. "epigenetic inheritance," is re-emerging as a proven adjunct to traditional modes of genetic inheritance. We hypothesized that alcohol drinking and neurobiological sensitivity to alcohol are influenced by ancestral alcohol exposure. To test this hypothesis, we exposed male mice to chronic vapor ethanol or control conditions, mated them to ethanol-naïve females, and tested adult offspring for ethanol drinking, ethanol-induced behaviors, gene expression, and DNA methylation. We found that ethanol-sired male offspring had reduced ethanol preference and consumption, enhanced sensitivity to the anxiolytic and motor-enhancing effects of ethanol, and increased Bdnf expression in the ventral tegmental area (VTA) compared to control-sired male offspring. There were no differences among ethanol- and control-sired female offspring on these assays. Ethanol exposure also decreased DNA methylation at the BdnfÆpromoter of sire's germ cells and hypomethylation was maintained in the VTA of both male and female ethanol-sired offspring. Our findings show that paternal alcohol exposure is a previously unrecognized regulator of alcohol drinking and behavioral sensitivity to alcohol in male, but not female, offspring. Paternal alcohol exposure also induces epigenetic alterations (DNA hypomethylation) and gene expression changes that persist in the VTA of offspring. These results provide new insight into the inheritance and development of alcohol drinking behaviors.

  11. Race, Ethnicity, and Exposure to Alcohol Outlets

    PubMed Central

    Morrison, Christopher; Gruenewald, Paul J.; Ponicki, William R.

    2016-01-01

    Objective: Prior studies suggest that Black and Hispanic minority populations are exposed to greater concentrations of alcohol outlets, potentially contributing to health disparities between these populations and the White majority. We tested the alternative hypothesis that urban economic systems cause outlets to concentrate in low-income areas and, controlling for these effects, lower demand among minority populations leads to fewer outlets. Method: Market potential for alcohol sales, a surrogate for demand, was estimated from survey and census data across census block groups for 50 California cities. Hierarchical Bayesian conditional autoregressive Poisson models then estimated relationships between observed geographic distributions of outlets and the market potential for alcohol, income, population size, and racial and ethnic composition. Results: Market potentials were significantly smaller among lower income Black, Hispanic, and Asian populations. Block groups with greater market potential and lower income had greater concentrations of outlets. When we controlled for these effects, the racial and ethnic group composition of block groups was mostly unrelated to outlet concentrations. Conclusions: Health disparities related to exposure to alcohol outlets are primarily driven by distributions of income and population density across neighborhoods. PMID:26751356

  12. Functional significance of subjective response to alcohol across levels of alcohol exposure.

    PubMed

    Bujarski, Spencer; Hutchison, Kent E; Prause, Nicole; Ray, Lara A

    2017-01-01

    Pre-clinical neurobiological models of addiction etiology including both the allostatic model and incentive sensitization theory suggest that alcohol consumption among alcohol-dependent (AD) individuals will be dissociated from hedonic reward as positive reinforcement mechanisms wane in later stage dependence. The aims of this study are to test this claim in humans by examining the relationship between dimensions of subjective responses to alcohol (SR) and alcohol craving across levels of alcohol exposure. Non-treatment-seeking drinkers (n = 205) completed an i.v. alcohol challenge (final target breath alcohol concentration = 0.06 g/dl) and reported on SR and craving. Participants were classified as light-to-moderate drinkers (LMD), heavy drinkers (HD) or AD. Analyses examined group differences in SR and craving response magnitude, as well as concurrent and predictive associations between SR domains and craving. At baseline, LMD and AD reported greater stimulation than HD, which carried over post-alcohol administration. However, stimulation was dose-dependently associated with alcohol craving in HD only. Furthermore, lagged models found that stimulation preceded craving among HD only, whereas this hypothesized pattern of results was not observed for craving preceding stimulation. Sedation was also positively associated with craving, yet no group differences were observed. In agreement with the prediction of diminished positive reinforcement in alcohol dependence, this study showed that stimulation/hedonic reward from alcohol did not precede craving in AD, whereas stimulation was dose-dependently associated with and preceded craving among non-dependent HD.

  13. Exposure to Televised Alcohol Ads and Subsequent Adolescent Alcohol Use

    ERIC Educational Resources Information Center

    Stacy, Alan W.; Zogg, Jennifer B.; Unger, Jennifer B.; Dent, Clyde W.

    2004-01-01

    Objective : To assess the impact of televised alcohol commercials on adolescents' alcohol use. Methods : Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. Results : A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated…

  14. Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn.

    PubMed

    Burd, L; Blair, J; Dropps, K

    2012-09-01

    Fetal alcohol spectrum disorders (FASDs) are a common cause of intellectual impairment and birth defects. More recently, prenatal alcohol exposure (PAE) has been found to be a risk factor for fetal mortality, stillbirth and infant and child mortality. This has led to increased concern about detection and management of PAE. One to 2 h after maternal ingestion, fetal blood alcohol concentrations (BACs) reach levels nearly equivalent to maternal levels. Ethanol elimination by the fetus is impaired because of reduced metabolic capacity. Fetal exposure time is prolonged owing to the reuptake of amniotic-fluid containing ethanol by the fetus. Alcohol elimination from the fetus relies on the mother's metabolic capacity. Metabolic capacity among pregnant women varies eightfold (from 0.0025 to 0.02 g dl(-1)  h(-1)), which may help explain how similar amounts of ethanol consumption during pregnancy results in widely varying phenotypic presentations of FASD. At birth physiological changes alter the neonate's metabolic capacity and it rapidly rises to a mean value of 83.5% of the mother's capacity. FASDs are highly recurrent and younger siblings have increased risk. Detection of prenatal alcohol use offers an important opportunity for office-based interventions to decrease exposure for the remainder of pregnancy and identification of women who need substance abuse treatment. Mothers of children with FAS have been found to drink faster, get drunk quicker and to have higher BACs. A modest increase in the prevalence of a polymorphism of alcohol dehydrogenase, which increases susceptibility to adverse outcomes from PAE has been reported. Lastly, detection of alcohol use and appropriate management would decrease risk from PAE for subsequent pregnancies.

  15. Media exposure and marijuana and alcohol use among adolescents.

    PubMed

    Primack, Brian A; Kraemer, Kevin L; Fine, Michael J; Dalton, Madeline A

    2009-01-01

    We aimed to determine which media exposures are most strongly associated with marijuana and alcohol use among adolescents. In 2004, we surveyed 1,211 students at a large high school in suburban Pittsburgh regarding substance use, exposure to entertainment media, and covariates. Of the respondents, 52% were female, 8% were non-White, 27% reported smoking marijuana, and 60% reported using alcohol. They reported average exposure to 8.6 hr of media daily. In adjusted models, exposure to music was independently associated with marijuana use, but exposure to movies was independently associated with alcohol use. Implications, limitations, and suggestions for further research are discussed.

  16. Prenatal Alcohol Exposure Damages Brain Signal Transduction System

    DTIC Science & Technology

    2004-09-01

    phosphatidylinositol-specific Materials and methods phospholipase C isozymes, phospholipase C-71, found in rodent brain. Phospholipase C isozymes catalyze...alcohol syndrome and animal models of fetal alcohol exposure (FAE). alcohol-related neurodevelopmental disorder (Streissguth Most studies on fetal alcohol...1999). In learning and memory deficits. In rodents , FAE is associated our study, the 10% ethanol mice reacted to the presenta- with impaired learning

  17. Adolescent Alcohol Exposure: Burden of Epigenetic Reprogramming, Synaptic Remodeling, and Adult Psychopathology

    PubMed Central

    Kyzar, Evan J.; Floreani, Christina; Teppen, Tara L.; Pandey, Subhash C.

    2016-01-01

    Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can disrupt these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD) and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood. PMID:27303256

  18. Factors associated with younger adolescents' exposure to online alcohol advertising.

    PubMed

    D'Amico, Elizabeth J; Martino, Steven C; Collins, Rebecca L; Shadel, William G; Tolpadi, Anagha; Kovalchik, Stephanie; Becker, Kirsten M

    2017-03-01

    Little is known about the extent and nature of youth exposure to online alcohol advertising, or factors that may be associated with exposure. The current study recruited middle school students who completed a paper survey and then logged each alcohol advertisement that they encountered over a 2-week period using cell phones as part of an ecological momentary assessment design. We examined the percentage of youth who reported exposure to online alcohol advertising in the past 2 weeks, average weekly rate of exposure, types of online alcohol advertisements youth reported seeing, and factors that increased youths' risk of exposure to online alcohol advertising. Analyses are based on 485 participants (47% female; 25% Hispanic, 25% White, 27% Black; 6% Asian, 16% other). Youth logged exposures to a total of 3,966 (16,018 weighted for underreporting) alcohol advertisements across the monitoring period; 154 (568 weighted) or 3.6% were online ads. Seventeen percent of youth reported seeing any online alcohol ad; the majority of online ads seen were video commercials (44.8%) and banner/side ads (26.6%). Factors associated with greater ad exposure were being older, rebellious, and Black race; greater parental monitoring and more hours spent on social media were associated with less exposure. Findings provide important information about adolescents' exposure to online alcohol advertising and what might contribute to a greater likelihood of exposure. Given that online ad exposure is linked to drinking behavior, prevention programming for younger adolescents should continue to address this issue to help youth make healthy choices regarding alcohol use. (PsycINFO Database Record

  19. Communication Effects of Prenatal Alcohol Exposure.

    ERIC Educational Resources Information Center

    Abkarian, G. G.

    1992-01-01

    This literature review addresses studies of speech, language, and communication skills evidenced by children diagnosed with fetal alcohol syndrome and fetal alcohol effects. Concomitant physical, behavioral, intellectual, and learning patterns are reviewed, and symptoms presented by alcohol-exposed children are compared to those seen in other…

  20. Prenatal Alcohol Exposure and the Developing Immune System.

    PubMed

    Gauthier, Theresa W

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

  1. Youth Exposure to Alcohol Use and Brand Appearances in Popular Contemporary Movies

    PubMed Central

    DAL CIN, Sonya; WORTH, Keilah A.; DALTON, Madeline A.; SARGENT, James D.

    2010-01-01

    Aims To describe alcohol use and alcohol brand appearances in popular movies and estimate adolescents’ exposure to this alcohol-related content. Design and setting Nationally representative, random-digit dialed survey in the United States and content analysis of alcohol depictions in the top 100 U.S. box office hits each year from 1998 to 2002 and 34 top movies from early 2003. Participants 6522 U.S. adolescents aged 10-14. Measurements Frequency of alcohol use and brand appearances in movies by Motion Picture Association of America (MPAA) rating. Estimated exposure to minutes of movie alcohol use and brand appearances among U.S. adolescents in this age group. Findings Most movies (83%, including 57% of G/PG-rated movies) depicted alcohol use and 52% (including 19% of G/PG movies) contained at least one alcohol brand appearance, which consisted of branded use by an actor 30% of the time. These movies exposed the average U.S. adolescent 10-14 years of age to 5.6 (95% CI 5.4,5.7) hours of movie alcohol use and 244 (95% CI 238,250) alcohol brand appearances (5 billion in total), mostly from youth-rated movies. Exposure to movie alcohol content was significantly higher among African American youth than youth of other races. Conclusions Alcohol use and brand appearances are frequently portrayed in popular U.S. movies (which are distributed worldwide). Children and adolescents in the U.S. are exposed to hours of alcohol use depictions and numerous brand appearances in movies and most of this exposure is from movies rated for this segment of the population. PMID:18705684

  2. Movie exposure to alcohol cues and adolescent alcohol problems: a longitudinal analysis in a national sample.

    PubMed

    Wills, Thomas A; Sargent, James D; Gibbons, Frederick X; Gerrard, Meg; Stoolmiller, Mike

    2009-03-01

    The authors tested a theoretical model of how exposure to alcohol cues in movies predicts level of alcohol use (ever use plus ever and recent binge drinking) and alcohol-related problems. A national sample of younger adolescents was interviewed by telephone with 4 repeated assessments spaced at 8-month intervals. A structural equation modeling analysis performed for ever-drinkers at Time 3 (N = 961) indicated that, controlling for a number of covariates, movie alcohol exposure at Time 1 was related to increases in peer alcohol use and adolescent alcohol use at Time 2. Movie exposure had indirect effects to alcohol use and problems at Times 3 and 4 through these pathways, with direct effects to problems from Time 1 rebelliousness and Time 2 movie exposure also found. Prospective risk-promoting effects were also found for alcohol expectancies, peer alcohol use, and availability of alcohol in the home; protective effects were found for mother's responsiveness and for adolescent's school performance and self-control. Theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  3. Movie Exposure to Alcohol Cues and Adolescent Alcohol Problems: A Longitudinal Analysis in a National Sample

    PubMed Central

    Wills, Thomas A.; Sargent, James D.; Gibbons, Frederick X.; Gerrard, Meg; Stoolmiller, Mike

    2009-01-01

    The authors tested a theoretical model of how exposure to alcohol cues in movies predicts level of alcohol use (ever use plus ever and recent binge drinking) and alcohol-related problems. A national sample of younger adolescents was interviewed by telephone with 4 repeated assessments spaced at 8-month intervals. A structural equation modeling analysis performed for ever-drinkers at Time 3 (N = 961) indicated that, controlling for a number of covariates, movie alcohol exposure at Time 1 was related to increases in peer alcohol use and adolescent alcohol use at Time 2. Movie exposure had indirect effects to alcohol use and problems at Times 3 and 4 through these pathways, with direct effects to problems from Time 1 rebelliousness and Time 2 movie exposure also found. Prospective risk-promoting effects were also found for alcohol expectancies, peer alcohol use, and availability of alcohol in the home; protective effects were found for mother’s responsiveness and for adolescent’s school performance and self-control. Theoretical and practical implications are discussed. PMID:19290687

  4. Fetal alcohol spectrum disorders-- implications for child neurology, part 1: prenatal exposure and dosimetry.

    PubMed

    Paintner, Ashley; Williams, Andrew D; Burd, Larry

    2012-02-01

    In the United States, approximately 80 000 women consume ethanol through all 3 trimesters of pregnancy each year. In this article, we review prevalence rates of prenatal alcohol exposure in the United States and discuss the mechanisms of prenatal alcohol exposure and placental-umbilical effects. Cigarette smoking and delayed prenatal care are often associated with prenatal alcohol exposure. In addition, increased risk for postnatal adversity is common, including maternal depression, foster care placement, and developmental delay. In part 2, we review prevalence rates and the diagnostic criteria for fetal alcohol spectrum disorder and the implications for child neurologists. We discuss management strategies and the importance of a long-term management plan and anticipatory management to prevent the development of secondary disabilities in fetal alcohol spectrum disorders. Child neurologists play a key role in diagnosis and the development of appropriate intervention programs for affected children and their families.

  5. Alcohol exposure during development: Impact on the epigenome.

    PubMed

    Perkins, Amy; Lehmann, Claudia; Lawrence, R Charles; Kelly, Sandra J

    2013-10-01

    Fetal alcohol spectrum disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes to some of the enzymatic regulators of the epigenome in adolescence. Combined pre- and post-natal alcohol exposureresulted in a significant increase in DNA methyltransferase activity (DNMT), without affecting histone deacetylase activity (HDAC). Developmental alcohol exposure also caused a change in gene expression of regulators of the epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2 (MeCP2). The modifications of the activity and expression of epigenetic regulators in the hippocampus of rodents perinatally exposed to alcohol suggest that alcohol's impact on the epigenome and its regulators may be one of the underlying mechanisms of alcohol teratogenesis.

  6. Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

    PubMed

    2008-01-01

    produced minimal effects. A spray formula containing 12% SD Alcohol 40-B was found to be nonirritating when evaluated for vaginal mucosal irritation in New Zealand white rabbits. Cosmetic formulations containing SD Alcohol 40-B (denatured with Denatonium Benzoate) were not sensitizers in repeated insult patch tests. A gel formula containing 29% SD Alcohol 40-B and a spray liquid containing 12% SD Alcohol 40-B did not induce photoallergy, dermal sensitization, or phototoxic response in human subjects. Although the absorption of ethanol (aka Alcohol for purposes of cosmetic ingredient labeling) occurs through skin, ethanol does not appear to affect the integrity of the skin barrier nor reach a very high systemic concentration following dermal exposure. Ethanol may be found in the bloodstream as a result of inhalation exposure and ingestion. Topically applied, ethanol can act as a penetration enhancer. Most of the systemic toxicity of ethanol appears to be associated with chronic abuse of alcohol. Although ethanol is denatured to make it unfit for consumption, there have been reports of intentional and unintentional consumption of products containing denatured alcohol. Ethanol is a reproductive and developmental toxicant. Ethanol is genotoxic in some test systems and it has been proposed that the genotoxic effects of ethanol are mediated via its metabolite, acetaldehyde. A brief summary is provided of the effects of chronic ingestion of alcohol including intoxication, liver damage, brain damage, and possible carcinogenicity. The CIR Expert Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. Because dermal application or inhalation of cosmetic products containing these ingredients will not produce significant systemic exposure to ethanol, the CIR Expert Panel concluded that safety of the ingredients should be predicated on the safety of the denaturants used. The Panel considered

  7. Children’s Exposure to Parental Conflict after Father’s Treatment for Alcoholism

    PubMed Central

    Rounsaville, Daniel; O’Farrell, Timothy J.; Andreas, Jasmina Burdzovic; Murphy, Christopher M.; Murphy, Marie M.

    2014-01-01

    Objective This study investigated children of alcoholics’ (COAs’) exposure to inter-parental conflict before and after their fathers received alcohol treatment and compared exposure levels to a community comparison sample. Method This study included 67 couples with a treatment-seeking male alcoholic partner and children aged 4–16. The alcoholic fathers and their relationship partners provided data at baseline and at six and twelve months follow-up. A community comparison sample of 78 couples with children in the target age range completed similar longitudinal assessments. It was hypothesized that treatment of paternal alcoholism would be associated with a decrease in COAs’ exposure to conflict, and that among remitted patients exposure to conflict would decrease to the level found in the community sample. Results Prior to the father’s alcohol treatment, the children of the treatment sample were exposed to significantly more conflict between their parents than in the community comparison sample. After the fathers received alcohol treatment, COAs’ exposure to conflict significantly decreased at both the six and twelve month follow-ups compared to baseline. Children of remitted alcoholics did not differ significantly in levels of exposure to conflict at six months follow-up compared with the community sample as predicted. However, at twelve months remitted alcoholics reported significantly more exposure to conflict compared to the community sample. Conclusions Decreased child exposure to parental conflict is a benefit associated with the father’s treatment for alcoholism, and it may lead to improvements in COAs’ functioning after parental treatment. PMID:24727114

  8. Adoption and Prenatal Alcohol and Drug Exposure: Research, Policy, and Practice.

    ERIC Educational Resources Information Center

    Barth, Richard P., Ed.; Freundlich, Madelyn, Ed.; Brodzinsky, David, Ed.

    As child welfare professionals have become aware of the impact of prenatal substance exposure on children in the adoption process or who are available for adoption, there is a heightened need for understanding a range of issues connected with prenatal alcohol and drug exposure. This book addresses many of these issues, including the impact of…

  9. Operant Responding for Alcohol Following Alcohol Cue Exposure in Social Drinkers

    PubMed Central

    Van Dyke, Nicholas; Fillmore, Mark T.

    2015-01-01

    Introduction Cue reactivity paradigms have found that alcohol-related cues increase alcohol consumption in heavy drinkers and alcoholics. However, evidence of this relationship among non-alcohol dependent “social” drinkers is mixed, suggesting that individual differences must be considered when examining cue-induced drinking behavior. One important individual difference factor that might contribute to cue-induced drinking in the laboratory is the amount of alcohol that participants typically drink during occasions outside the laboratory. That is, those who typically consume more alcohol per occasion could display greater cue-induced drinking than those who typically drink less. The present study examined this hypothesis in healthy, non-dependent beer drinkers. Methods The drinkers were exposed to either a series of beer images intended to prime their motivation to drink beer or to a series of non-alcoholic images of food items that served as a control condition. Following cue exposure, motivation to drink was measured by giving participants an opportunity to work for glasses of beer by performing an operant response task. Results Results indicated that drinkers exposed to alcohol cues displayed greater operant responding for alcohol and earned more drinks compared with those exposed to non-alcohol (i.e., food) cues. Moreover, individual differences in drinking habits predicted subjects’ responding for alcohol following exposure to the alcohol cues, but not following exposure to food cues. Conclusions The findings suggest that cue-induced drinking in non-dependent drinkers likely results in consumption levels commensurate with their typical consumption outside the laboratory, but not excessive consumption that is sometimes observed in alcohol-dependent samples. PMID:25841089

  10. Reducing youth exposure to alcohol ads: targeting public transit.

    PubMed

    Simon, Michele

    2008-07-01

    Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conducted a survey of alcohol ads on San Francisco bus shelters. The survey received sufficient media attention to lead the billboard company, CBS Outdoor, into taking down the ads. Marin Institute also surveyed the 25 largest transit agencies; results showed that 75 percent of responding agencies currently have policies that ban alcohol advertising. However, as the experience in San Francisco demonstrated, having a policy on paper does not necessarily mean it is being followed. Communities must be diligent in holding accountable government officials, the alcohol industry, and the media companies through which advertising occurs.

  11. The margin of exposure to formaldehyde in alcoholic beverages.

    PubMed

    Monakhova, Yulia B; Jendral, Julien A; Lachenmeier, Dirk W

    2012-06-01

    Formaldehyde has been classified as carcinogenic to humans (WHO IARC group 1). It causes leukaemia and nasopharyngeal cancer, and was described to regularly occur in alcoholic beverages. However, its risk associated with consumption of alcohol has not been systematically studied, so this study will provide the first risk assessment of formaldehyde for consumers of alcoholic beverages.Human dietary intake of formaldehyde via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data and literature on formaldehyde contents of different beverage groups (beer, wine, spirits, and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMD) for 10 % effect obtained from dose-response modelling of animal experiments.For tumours in male rats, a BMD of 30 mg kg(-1) body weight per day and a "BMD lower confidence limit" (BMDL) of 23 mg kg(-1) d(-1) were calculated from available long-term animal experiments. The average human exposure to formaldehyde from alcoholic beverages was estimated at 8·10(-5) mg kg(-1) d(-1). Comparing the human exposure with BMDL, the resulting MOE was above 200,000 for average scenarios. Even in the worst-case scenarios, the MOE was never below 10,000, which is considered to be the threshold for public health concerns.The risk assessment shows that the cancer risk from formaldehyde to the alcohol-consuming population is negligible and the priority for risk management (e.g. to reduce the contamination) is very low. The major risk in alcoholic beverages derives from ethanol and acetaldehyde.

  12. Ecological Momentary Assessment of the Association Between Exposure to Alcohol Advertising and Early Adolescents' Beliefs About Alcohol

    PubMed Central

    Martino, Steven C.; Kovalchik, Stephanie A.; Collins, Rebecca L.; Becker, Kirsten M.; Shadel, William G.; D'Amico, Elizabeth J.

    2015-01-01

    Purpose To evaluate the momentary association between exposure to alcohol advertising and middle school students' beliefs about alcohol in real-world settings and to explore racial/ethnic differences in this association. Methods Middle school students (N = 588) carried handheld data collection devices for 14 days, recording their exposures to all forms of alcohol advertising during the assessment period. Students also responded to three investigator-initiated control prompts (programmed to occur randomly) on each day of the assessment period. After each exposure to advertising and at each control prompt, students reported their beliefs about alcohol. Mixed effects regression models compared students' beliefs about alcohol between moments of exposure to alcohol advertising and control prompts. Results Students perceived the typical person their age who drinks alcohol (prototype perceptions) more favorably and perceived alcohol use as more normative at times of exposure to alcohol advertising than at times of non-exposure (i.e., at control prompts). Exposure to alcohol advertising was not associated with shifts in the perceived norms of Black and Hispanic students, however, and the association between exposure and prototype perceptions was stronger among non-Hispanic students than among Hispanic students. Conclusions Exposure to alcohol advertising is associated with acute shifts in adolescents' perceptions of the typical person that drinks alcohol and the normativeness of drinking. These associations are both statistically and substantively meaningful. PMID:26480846

  13. Exposure to alcohol commercials in movie theaters affects actual alcohol consumption in young adult high weekly drinkers: an experimental study.

    PubMed

    Koordeman, Renske; Anschutz, Doeschka J; Engels, Rutger C M E

    2011-01-01

    The present pilot study examined the effects of alcohol commercials shown in movie theaters on the alcohol consumption of young adults who see these commercials. A two (alcohol commercials vs. nonalcohol commercials) by two (high weekly alcohol consumption vs. low weekly alcohol consumption) between-participant design was used, in which 184 young adults (age: 16-28 years) were exposed to a movie that was preceded by either alcohol commercials or nonalcohol commercials. Participants' actual alcohol consumption while watching the movie ("Watchmen") was examined. An analysis of variance (ANOVA) was conducted to examine the effects of the commercial condition on alcohol consumption. An interaction effect was found between commercial condition and weekly alcohol consumption (p < .001). Alcohol consumption among high weekly alcohol drinkers was higher in the alcohol commercial condition than in the nonalcohol commercial condition, whereas no differences were found in alcohol consumption between commercial conditions among low weekly alcohol drinkers. No gender differences were found in the association between exposure to alcohol commercials, weekly drinking, and alcohol use. Thus, exposure to alcohol commercials prior to a movie in a movie theater can directly influence alcohol consumption among high weekly alcohol consumers.

  14. Health risks of including alcohol and tobacco in PICTA free trade.

    PubMed

    Hill, Linda

    2004-03-01

    In April 2005 Pacific Forum leaders will decide whether to include alcohol and tobacco in the Pacific Island Countries Trade Agreement (PICTA). This article presents arguments for keeping alcohol out of regional free trade agreements. Inclusion will allow regional rationalisation of production, increased alcohol availability, competition and marketing, and lower prices. These trade goals are inappropriate for alcohol and tobacco. Pacific public health organisations are concerned that official advice has focused on fiscal impacts, not health and social impacts. The World Health Organization has identified alcohol as the leading factor in injury and disease for low-mortality developing countries. Effective policies to reduce alcohol related harm include restrictions on availability, as well as excise taxes affecting price. Under trade agreements elsewhere, national alcohol policies have been challenged as 'non-tariff barriers to trade'. Hazardous drinking is of increasingly concern in the Pacific and decisions about alcohol should not reflect commercial interests.

  15. Effects of pre-natal alcohol exposure on hippocampal synaptic plasticity: Sex, age and methodological considerations.

    PubMed

    Fontaine, Christine J; Patten, Anna R; Sickmann, Helle M; Helfer, Jennifer L; Christie, Brian R

    2016-05-01

    The consumption of alcohol during gestation is detrimental to the developing central nervous system (CNS). The severity of structural and functional brain alterations associated with alcohol intake depends on many factors including the timing and duration of alcohol consumption. The hippocampal formation, a brain region implicated in learning and memory, is highly susceptible to the effects of developmental alcohol exposure. Some of the observed effects of alcohol on learning and memory may be due to changes at the synaptic level, as this teratogen has been repeatedly shown to interfere with hippocampal synaptic plasticity. At the molecular level alcohol interferes with receptor proteins and can disrupt hormones that are important for neuronal signaling and synaptic plasticity. In this review we examine the consequences of prenatal and early postnatal alcohol exposure on hippocampal synaptic plasticity and highlight the numerous factors that can modulate the effects of alcohol. We also discuss some potential mechanisms responsible for these changes as well as emerging therapeutic avenues that are beginning to be explored.

  16. Associations of alcohol use with mental health and alcohol exposure among school-going students in Cambodia

    PubMed Central

    Peltzer, Karl; Pengpid, Supa; Tepirou, Chher

    2016-01-01

    ABSTRACT The aim of this study was to examine the associations of alcohol use with sociodemographic factors, mental health and alcohol exposure among school-going adolescents in Cambodia. The analysis included 3,806 school children, mean age 15.7 years (SD=1.8), from Cambodia who participated in the “Global School-based Student Health Survey” (GSHS) in 2013. The results indicate that overall, 10.0% of the students reported current alcohol use, 10.8% lifetime drunkenness, and 2.8% problem drinking. In multivariate logistic regression analysis, sociodemographic factors (older age and being male), mental health and other variables (bullying victimization, OR (odds ratio) = 1.99; 95% Confidence Interval (CI) [1.50, 2.65] and OR = 2.15; 95% CI [1.58, 3.21], respectively; having attempted suicide, OR = 2.04; 95% CI [1.35, 3.08] and OR = 2.06; 95% CI [1.29, 3.28], respectively and illicit drug use, OR = 4.97; 95% CI [2.41, 10.24] OR = 5.05; 95% CI [2.14, 11.98], respectively) and alcohol exposure variables (peer influence on drinking alcohol, OR = 6.68; 95% CI [4.75, 9.39] and OR = 7.83; 95% CI [5.73, 10.66], respectively and daily or almost daily to alcohol advertising in the past 30 days OR = 1.61; 95% CI [1.03, 2.51] and OR = 2.30; 95% CI [1.40, 3.77], respectively) were significantly positively associated with current alcohol use and drunkenness. Moreover, older age, being male, bullying victimization, having close friends, suicide attempt, drug use, father or male guardian drinks alcohol and peer influence were associated with problem drinking. There is a need to implement public health interventions with a special focus on the determinants of alcohol consumption, including exposure to alcohol advertising, in this age group. PMID:28008197

  17. Ethanol exposure alters zebrafish development: a novel model of fetal alcohol syndrome.

    PubMed

    Bilotta, Joseph; Barnett, Jalynn A; Hancock, Laura; Saszik, Shannon

    2004-01-01

    Prenatal exposure to alcohol has been shown to produce the overt physical and behavioral symptoms known as fetal alcohol syndrome (FAS) in humans. Also, it is believed that low concentrations and/or short durations of alcohol exposure can produce more subtle effects. The purpose of this study was to investigate the effects of embryonic ethanol exposure on the zebrafish (Danio rerio) in order to determine whether this species is a viable animal model for studying FAS. Fertilized embryos were reared in varying concentrations of ethanol (1.5% and 2.9%) and exposure times (e.g., 0-8, 6-24, 12-24, and 48-72 h postfertilization; hpf); anatomical measures including eye diameter and heart rate were compared across groups. Results found that at the highest concentration of ethanol (2.9%), there were more abnormal physical distortions and significantly higher mortality rates than any other group. Embryos exposed to ethanol for a shorter duration period (0-8 hpf) at a concentration of 1.5% exhibited more subtle effects such as significantly smaller eye diameter and lower heart rate than controls. These results indicate that embryonic alcohol exposure affects external and internal physical development and that the severity of these effects is a function of both the amount of ethanol and the timing of ethanol exposure. Thus, the zebrafish represents a useful model for examining basic questions about the effects of embryonic exposure to ethanol on development.

  18. Prenatal alcohol exposure and long-term developmental consequences

    SciTech Connect

    Spohr, H.L.; Willms, J. . Dept. of Pediatrics); Steinhausen, H.C. . Dept. of Child and Adolescent Psychiatry)

    1993-04-10

    Fetal alcohol syndrome (FAS) is a leading cause of congenital mental retardation but little is known about the long-term development and adolescent outcome of children with FAS. In a 10-year follow-up study of 60 patients diagnosed as having FAS in infancy and childhood, the authors investigated the long-term sequelae of intrauterine alcohol exposure. The authors found that the characteristic craniofacial malformations of FAS diminish with time, but microcephaly and, to a lesser degree, short stature and underweight (in boys) persist; in female adolescents body weight normalizes. Persistent mental retardation is the major sequela of intrauterine alcohol exposure in many cases, and environmental and educational factors do not have strong compensatory effects on the intellectual development of affected children.

  19. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  20. Biomarkers for the Detection of Prenatal Alcohol Exposure: A Review.

    PubMed

    Bager, Heidi; Christensen, Lars Porskjaer; Husby, Steffen; Bjerregaard, Lene

    2017-02-01

    Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation to detection of PAE. To review each biomarker in a clinical context, we have compared the advantages and disadvantages of each biomarker, in relation to its window of detectability, ease of collection, and the ease and cost of analysis of each biomarker. The biomarkers PEth, FAEEs, and EtG were found to be applicable for detection of even low levels of alcohol exposure. Meconium is an accessible matrix for determination of FAEEs and EtG, and blood an accessible matrix for determination of PEth.

  1. Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study.

    PubMed

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Jurijević, Branka Šošić; Balind, Snežana Raus; Brajković, Gordana; Perčinić-Popovska, Florina; Milošević, Verica

    2016-05-01

    Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically. Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats. Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary.

  2. Reducing Youth Exposure to Alcohol Ads: Targeting Public Transit

    PubMed Central

    2008-01-01

    Underage drinking is a major public health problem. Youth drink more heavily than adults and are more vulnerable to the adverse effects of alcohol. Previous research has demonstrated the connection between alcohol advertising and underage drinking. Restricting outdoor advertising in general and transit ads in particular, represents an important opportunity to reduce youth exposure. To address this problem, the Marin Institute, an alcohol industry watchdog group in Northern California, conducted a survey of alcohol ads on San Francisco bus shelters. The survey received sufficient media attention to lead the billboard company, CBS Outdoor, into taking down the ads. Marin Institute also surveyed the 25 largest transit agencies; results showed that 75 percent of responding agencies currently have policies that ban alcohol advertising. However, as the experience in San Francisco demonstrated, having a policy on paper does not necessarily mean it is being followed. Communities must be diligent in holding accountable government officials, the alcohol industry, and the media companies through which advertising occurs. PMID:18389374

  3. Youth exposure to alcohol advertising in magazines--United States, 2001-2005.

    PubMed

    2007-08-03

    Alcohol consumption among persons aged 12-20 years contributes to the three leading causes of death (unintentional injury, homicide, and suicide) in this age group in the United States and is associated with other health-risk behaviors, including high-risk sexual activity, smoking, and physical fighting. Recent studies have documented the contribution of alcohol marketing to underage drinking. In 2000, the trade association for the wine industry changed its voluntary marketing code to stop advertising in magazines in which youths aged 12-20 years were >30% of the audience. In 2003, this threshold was adopted by the trade associations for beer and liquor producers. To determine the proportion of alcohol advertisements placed in magazines with disproportionately large youth readerships (i.e., >15% of readers aged 12-20 years) and to assess the proportion of youths exposed to these advertisements, the Center on Alcohol Marketing and Youth (Health Policy Institute, Georgetown University, District of Columbia) evaluated the placement of alcohol advertisements in 143 national magazines for which readership composition data were available for 2001-2005; these 143 publications accounted for approximately 90% of expenditures for all alcohol advertising in national print magazines. This report summarizes the results of that study, which indicated that alcohol advertising remained common in magazines with >15% youth readership but decreased substantially in magazines with >30% youth readership. These results suggest that although voluntary industry standards have reduced youth exposure to alcohol advertising in magazines, strengthening these standards by establishing a >15% youth readership threshold would further reduce exposure. In addition, independent monitoring of youth exposure to alcohol advertising should continue, as recommended by the U.S. Congress and Surgeon General.

  4. Alcohol exposure in utero is associated with decreased gray matter volume in neonates.

    PubMed

    Donald, Kirsten A; Fouche, J P; Roos, Annerine; Koen, Nastassja; Howells, Fleur M; Riley, Edward P; Woods, Roger P; Zar, Heather J; Narr, Katherine L; Stein, Dan J

    2016-02-01

    Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions. However, the temporal specificity of such changes and their behavioral consequences are less known. Here we explore the brain structure of infants with in utero exposure to alcohol shortly after birth. T2 structural MRI images were acquired from 28 alcohol-exposed infants and 45 demographically matched healthy controls at 2-4 weeks of age on a 3T Siemens Allegra system as part of large birth cohort study, the Drakenstein Child Health Study (DCHS). Neonatal neurobehavior was assessed at this visit; early developmental outcome assessed on the Bayley Scales of Infant Development III at 6 months of age. Volumes of gray matter regions were estimated based on the segmentations of the University of North Carolina neonatal atlas. Significantly decreased total gray matter volume was demonstrated for the alcohol-exposed cohort compared to healthy control infants (p < 0.001). Subcortical gray matter regions that were significantly different between groups after correcting for overall gray matter volume included left hippocampus, bilateral amygdala and left thalamus (p < 0.01). These findings persisted even when correcting for infant age, gender, ethnicity and maternal smoking status. Both early neurobehavioral and developmental adverse outcomes at 6 months across multiple domains were significantly associated with regional volumes primarily in the temporal and frontal lobes in infants with prenatal alcohol exposure. Alcohol exposure during the prenatal period has potentially enduring neurobiological consequences for exposed children. These findings suggest the effects of prenatal alcohol exposure on brain growth is present very early in the first year of life, a period during which the most rapid growth and maturation occurs.

  5. Prologue: Understanding Children Who Have Been Affected by Maltreatment and Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    Hyter, Yvette D.

    2007-01-01

    This prologue introduces an important topic for multiple disciplines involved with children and their families. This introduction includes a review of some of the current literature on the effects of maltreatment and prenatal alcohol exposure on child development, an explanation of why this topic is essential learning for communication…

  6. Alcohol Environment, Perceived Safety, and Exposure to Alcohol, Tobacco, and Other Drugs in Early Adolescence

    PubMed Central

    Milam, AJ; Furr-Holden, CDM; Bradshaw, CP; Webster, DW; Cooley-Strickland, MC; Leaf, PJ

    2013-01-01

    This study examined the association between the count of alcohol outlets around children's homes and opportunities to use alcohol, tobacco, and other drugs (ATOD) during pre-adolescence. Data were collected in 2007 from 394 Baltimore City children aged 8-13 (86% African American). Participants' residential address and alcohol outlet data were geocoded with quarter mile (i.e., walking distance) buffers placed around each participant's home to determine the number of outlets within walking distance. The unadjusted logistic regression models revealed that each unit increase in the number of alcohol outlets was associated with a 14% increase in the likelihood of children seeing people selling drugs (OR=1.14, p=.04) and a 15% increase in the likelihood of seeing people smoking marijuana (OR=1.15, p<.01). After adjusting for neighborhood physical disorder, the relationship between alcohol outlets and seeing people selling drugs and seeing people smoking marijuana was fully attenuated. These results suggest that alcohol outlets are one aspect of the larger environmental context that is related to ATOD exposure in children. Future studies should examine the complex relationship between neighborhood physical disorder and the presence of alcohol outlets. PMID:25125766

  7. Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats.

    PubMed

    Thomas, Jennifer D; Abou, Elizabeth J; Dominguez, Hector D

    2009-01-01

    Prenatal alcohol exposure can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Variability in outcome observed among children with FASD is likely related to various pre- and postnatal factors, including nutritional variables. Choline is an essential nutrient that influences brain and behavioral development. Recent animal research indicates that prenatal choline supplementation leads to long-lasting cognitive enhancement, as well as changes in brain morphology, electrophysiology and neurochemistry. The present study examined whether choline supplementation during ethanol exposure effectively reduces fetal alcohol effects. Pregnant dams were exposed to 6.0g/kg/day ethanol via intubation from gestational days (GD) 5-20; pair-fed and lab chow controls were included. During treatment, subjects from each group received choline chloride (250mg/kg/day) or vehicle. Physical development and behavioral development (righting reflex, geotactic reflex, cliff avoidance, reflex suspension and hindlimb coordination) were examined. Subjects prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol's effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Importantly, choline supplementation did not influence peak blood alcohol level or metabolism, indicating that choline's effects were not due to differential alcohol exposure. These data indicate early dietary supplements may reduce the severity of some fetal alcohol effects, findings with important implications for children of women who drink alcohol during pregnancy.

  8. Exposure to alcohol use in motion pictures and teen drinking in Latin America

    PubMed Central

    Mejia, Raul; Pérez, Adriana; Abad-Vivero, Erika N.; Kollath-Cattano, Christy; Gutierrez, Inti Barrientos; Thrasher, James F.; Sargent, James D.

    2015-01-01

    Objectives To assess whether exposure to alcohol use in films (AUF) is associated with alcohol use susceptibility, current alcohol use, and binge drinking in adolescents from two Latin American countries. Methods Cross-sectional study with 13,295 middle school students from public and private schools in Mexico and Argentina. Exposure to alcohol use in over 400 contemporary top box office films in each country was estimated using previously validated methods. Outcome measures included current drinking (i.e., any drink in the last 30 days), ever binge-drinking (i.e., more than 4 or 5 drinks in a row for females and males, respectively) and, among never drinkers, alcohol susceptibility (i.e., might drink in the next year or accept a drink from a friend). Multivariate models were adjusted for age, sex, parental education, peer drinking, sensation seeking, parenting style and media access. Results Mean age was 12.5 years (SD = 0.7) and the prevalence of alcohol consumption and binge drinking was 19.8% and 10.9% respectively. Mean exposure to alcohol from the film sample was about 7 hours in both countries. Adjusted models indicated independent dose-response associations between higher levels of exposure to AUF and all outcomes; the adjusted odds ratios (OR) comparing quartiles 4 and 1 1.99 (95% CI 1.73 - 2.30) for current drinking, 1.68 (1.39 - 2.02) for binge drinking, and 1.80 (1.52 - 2.12) for alcohol susceptibility. Compared to Mexican adolescents, Argentine adolescents were significantly more likely to have engaged in binge drinking (OR 1.40, 95% CI 1.12 - 1.76.) and, among never drinkers, were more susceptible to trying drinking (OR 1.40, 95% CI 1.20 - 1.64). Conclusions Higher levels of exposure to alcohol use in films was associated with higher likelihood of alcohol use, binge drinking, and alcohol susceptibility in Latin American adolescents. PMID:26857804

  9. Prenatal alcohol exposure alters the patterns of facial asymmetry.

    PubMed

    Klingenberg, C P; Wetherill, L; Rogers, J; Moore, E; Ward, R; Autti-Rämö, I; Fagerlund, A; Jacobson, S W; Robinson, L K; Hoyme, H E; Mattson, S N; Li, T K; Riley, E P; Foroud, T

    2010-01-01

    Directional asymmetry, the systematic differences between the left and right body sides, is widespread in human populations. Changes in directional asymmetry are associated with various disorders that affect craniofacial development. Because facial dysmorphology is a key criterion for diagnosing fetal alcohol syndrome (FAS), the question arises whether in utero alcohol exposure alters directional asymmetry in the face. Data on the relative position of 17 morphologic landmarks were obtained from facial scans of children who were classified as either FAS or control. Shape data obtained from the landmarks were analyzed with the methods of geometric morphometrics. Our analyses showed significant directional asymmetry of facial shape, consisting primarily of a shift of midline landmarks to the right and a displacement of the landmarks around the eyes to the left. The asymmetry of FAS and control groups differed significantly and average directional asymmetry was increased in those individuals exposed to alcohol in utero. These results suggest that the developmental consequences of fetal alcohol exposure affect a wide range of craniofacial features in addition to those generally recognized and used for diagnosis of FAS.

  10. Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

    PubMed

    Spear, Linda Patia

    2015-09-01

    There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing

  11. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-12-14

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

  12. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

    PubMed Central

    Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  13. Prenatal alcohol exposure and miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome.

    PubMed

    Bailey, Beth A; Sokol, Robert J

    2011-01-01

    In addition to fetal alcohol syndrome and fetal alcohol spectrum disorders, prenatal alcohol exposure is associated with many other adverse pregnancy and birth outcomes. Research suggests that alcohol use during pregnancy may increase the risk of miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome. This research has some inherent difficulties, such as the collection of accurate information about alcohol consumption during pregnancy and controlling for comorbid exposures and conditions. Consequently, attributing poor birth outcomes to prenatal alcohol exposure is a complicated and ongoing task, requiring continued attention to validated methodology and to identifying specific biological mechanisms.

  14. Assessing teratogenic changes in a zebrafish model of fetal alcohol exposure.

    PubMed

    Loucks, Evyn; Ahlgren, Sara

    2012-03-20

    Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States. With 50% of child-bearing age women reporting consumption of alcohol, and half of all pregnancies being unplanned, unintentional exposure is a continuing issue. In order to best understand the damage produced by ethanol, plus produce a model with which to test potential interventions, we developed a model of developmental ethanol exposure using the zebrafish embryo. Zebrafish are ideal for this kind of teratogen study. Each pair lays hundreds of eggs, which can then be collected without harming the adult fish. The zebrafish embryo is transparent and can be readily imaged with any number of stains. Analysis of these embryos after exposure to ethanol at different doses and times of duration and application shows that the gross developmental defects produced by ethanol are consistent with the human birth defect. Described here are the basic techniques used to study and manipulate the zebrafish FAS model.

  15. Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor-based brain morphometry and discriminant analysis.

    PubMed

    Sowell, Elizabeth R; Leow, Alex D; Bookheimer, Susan Y; Smith, Lynne M; O'Connor, Mary J; Kan, Eric; Rosso, Carly; Houston, Suzanne; Dinov, Ivo D; Thompson, Paul M

    2010-03-17

    Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5-15 years), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally and in right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and, within the MAA group, a negative correlation between full-scale intelligence quotient (FSIQ) scores and caudate volume was observed. Limbic structures, including the anterior and posterior cingulate, the inferior frontal gyrus (IFG), and ventral and lateral temporal lobes bilaterally, were increased in volume in both exposure groups. Furthermore, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure and that more severe striatal damage is associated with more severe cognitive deficit.

  16. Prologue: understanding children who have been affected by maltreatment and prenatal alcohol exposure.

    PubMed

    Hyter, Yvette D

    2007-04-01

    This prologue introduces an important topic for multiple disciplines involved with children and their families. This introduction includes a review of some of the current literature on the effects of maltreatment and prenatal alcohol exposure on child development, an explanation of why this topic is essential learning for communication professionals, prevalence figures for the occurrence of these effects, and a summarization of the articles that have been contributed by a cross section of researchers from various disciplines.

  17. Chronic alcohol exposure alters transcription broadly in a key integrative brain nucleus for homeostasis: the nucleus tractus solitarius.

    PubMed

    Covarrubias, Maria Yolanda; Khan, Rishi L; Vadigepalli, Rajanikanth; Hoek, Jan B; Schwaber, James S

    2005-12-14

    Chronic exposure to alcohol modifies physiological processes in the brain, and the severe symptoms resulting from sudden removal of alcohol from the diet indicate that these modifications are functionally important. We investigated the gene expression patterns in response to chronic alcohol exposure (21-28 wk) in the rat nucleus tractus solitarius (NTS), a brain nucleus with a key integrative role in homeostasis and cardiorespiratory function. Using methods and an experimental design optimized for detecting transcriptional changes less than twofold, we found 575 differentially expressed genes. We tested these genes for significant associations with physiological functions and signaling pathways using Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, respectively. Chronic alcohol exposure resulted in significant NTS gene regulation related to the general processes of synaptic transmission, intracellular signaling, and cation transport as well as specific neuronal functions including plasticity and seizure behavior that could be related to alcohol withdrawal symptoms. The differentially expressed genes were also significantly enriched for enzymes of lipid metabolism, glucose metabolism, oxidative phosphorylation, MAP kinase signaling, and calcium signaling pathways from KEGG. Intriguingly, many of the genes we found to be differentially expressed in the NTS are known to be involved in alcohol-induced oxidative stress and/or cell death. The study provides evidence of very extensive alterations of physiological gene expression in the NTS in the adapted state to chronic alcohol exposure.

  18. 99HRT Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

    DTIC Science & Technology

    2003-09-01

    NEUROTRANSMITTERS, * ELECTROPHYSIOLOGY , *DRUG ABUSE, *ETHANOLS, VAPORS, SENSITIVITY, LONG RANGE(TIME), EXPOSURE(PHYSIOLOGY), CENTRAL NERVOUS SYSTEM, RECEPTOR SITES(PHYSIOLOGY), ALCOHOLS, HIPPOCAMPUS, CEREBELLUM.

  19. The clinical utility and specificity of parent report of executive function among children with prenatal alcohol exposure.

    PubMed

    Nguyen, Tanya T; Glass, Leila; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth L; Riley, Edward P; Mattson, Sarah N

    2014-08-01

    Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8-16 years): alcohol-exposed with ADHD (AE+, n=80), alcohol-exposed without ADHD (AE-, n=36), non-exposed with ADHD (ADHD, n=93), and controls (CON, n=167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure.

  20. Prenatal Exposure to Drugs/Alcohol: Characteristics and Educational Implications of Fetal Alcohol Syndrome and Cocaine/Polydrug Effects.

    ERIC Educational Resources Information Center

    Soby, Jeanette M.

    This book presents the characteristics of children affected by prenatal drug exposure, fetal alcohol syndrome, fetal alcohol effects, and fetal cocaine/polydrug effects. It outlines incidence, service needs, prevention, and identification. The medical literature on the physical, cognitive, and behavioral characteristics of this population is…

  1. Are You Insulting Me? Exposure to Alcohol Primes Increases Aggression Following Ambiguous Provocation

    PubMed Central

    Pedersen, William C.; Vasquez, Eduardo A.; Bartholow, Bruce D.; Grosvenor, Marianne; Truong, Ana

    2014-01-01

    Considerable research has shown that alcohol consumption can increase aggression and produce extremes in other social behaviors. Although most theories posit that such effects are caused by pharmacological impairment of cognitive processes, recent research indicates that exposure to alcohol-related constructs, in the absence of consumption, can produce similar effects. Here we tested the hypothesis that alcohol priming is most likely to affect aggression in the context of ambiguous provocation. Experiment 1 showed that exposure to alcohol primes increased aggressive retaliation but only when an initial provocation was ambiguous; unambiguous provocation elicited highly aggressive responses regardless of prime exposure. Experiment 2 showed that alcohol prime exposure effects are relatively short-lived and that perceptions of the provocateur's hostility mediated effects of prime exposure on aggression. These findings suggest modification and extension of existing models of alcohol-induced aggression. PMID:24854477

  2. Alarming prevalence of fetal alcohol exposure in a Mediterranean city.

    PubMed

    Garcia-Algar, Oscar; Kulaga, Vivan; Gareri, Joey; Koren, Gideon; Vall, Oriol; Zuccaro, Piergiorgio; Pacifici, Roberta; Pichini, Simona

    2008-04-01

    The prevalence of gestational ethanol exposure and subsequent fetal exposure has been assessed in a cohort of mother-infant dyads in a Mediterranean city (Barcelona, Spain) by meconium analysis of fatty acid ethyl esters (FAEEs) after showing in this population a high prevalence of meconium opiates (8.7%), cocaine (4.4%), and cannabis (5.3%). Of the 353 meconium samples analyzed for FAEEs, 159 (45%) contained a total amount of seven FAEEs equal or above 2 nmol/g meconium, the cutoff internationally accepted to differentiate heavy maternal alcohol consumption during pregnancy from occasional use or no use at all. No parental sociodemographic differences or maternal features differentiated exposed from unexposed newborns. The prevalence of gestational consumption of ethanol was similar between women using and not using drugs of abuse during pregnancy (45.7% and 44.7% of samples with total FAEEs equal or higher than 2 nmol/g meconium, respectively). Meconium samples from newborns exposed in utero to ethanol, and positive for at least one illicit drug (cocaine, opiates, or cannabis), had total FAEEs and five of nine individual FAEEs statistically higher than the meconium samples that were negative for the most frequently used illicit drugs of abuse. Among the most prevalent FAEEs, oleic acid ethyl ester showed the best correlation to total FAEE concentration followed by palmitoleic acid ethyl ester . This study, which highlights a 45% ethanol consumption during pregnancy in a low socioeconomic status cohort, may serve as an eye opener for Europeans that gestational alcohol exposure is not endemic only in areas outside of Europe.

  3. Ocular deficits associated with alcohol exposure during zebrafish development.

    PubMed

    Dlugos, Cynthia A; Rabin, Richard A

    2007-06-01

    Approximately 90% of fetal alcohol syndrome cases are accompanied by ocular abnormalities. The zebrafish (Danio rerio) is a well-known developmental model that provides an opportunity for better understanding the histological and cytological effects of developmental exposure to ethanol on the vertebrate eye. The purpose of the present study was to determine the gross, microscopic, and ultrastructual effects of developmental exposure to ethanol in the zebrafish model. Eggs were obtained from WT outbred zebrafish and exposed to 0%, 0.1%, 0.2%, 0.4%, 0.5%, or 1.0% (v/v) ethanol to assess viability and the effect of dose and duration of exposure on eye size. Light and electron microscopy were performed on ethanol-treated and control larvae. Results showed that ethanol treatment decreased viability by about 20% at concentrations of 0.1-0.5% ethanol and by 50% at 1.0% ethanol. Ethanol-related decreases in eye size were recorded at 6 days postfertilization (dpf) and were dose dependent. There were significant decreases in the volumes of the photoreceptor, inner nuclear, and ganglionic layers and in the lens of 9 dpf ethanol-exposed compared with control larvae. Ultrastructural examination showed signs of developmental lags in the ethanol-treated fish as well as abnormal retinal apoptosis in the 6 dpf ethanol-treated larvae compared with their controls. These results demonstrate that the developing zebrafish eye is sensitive to perturbation with ethanol and displays some of the eye deficits present in fetal alcohol syndrome.

  4. Reversible loss of reproductive fitness in zebrafish on chronic alcohol exposure.

    PubMed

    Dewari, Pooran Singh; Ajani, Funmilola; Kushawah, Gopal; Kumar, Damera Santhosh; Mishra, Rakesh K

    2016-02-01

    Alcoholism is one of the most prevalent diseases in society and causes significant health and social problems. Alcohol consumption by pregnant women is reported to cause adverse effects on the physical and psychological growth of the fetus. However, the direct effect of chronic alcohol consumption on reproductive fitness has not been tested. In recent years, the zebrafish (Danio rerio) has emerged as a versatile model system to study the effects of alcohol on behavior and embryonic development. We utilized the zebrafish model system to address the effect of chronic alcohol exposure (0.5% alcohol in the holding tank for 9 weeks) on reproductive capacity. We found a dramatic decrease in fecundity, measured by counting the number of eggs laid, when at least one of the parents is subject to chronic alcohol exposure. Interestingly, a 9-week alcohol withdrawal program completely restored the reproductive capacity of the treated subjects. In agreement with observations on fecundity, the chronic alcohol exposure leads to increased anxiety, as measured by the novel-tank diving assay. Conversely, the withdrawal program diminished heightened anxiety in alcohol-exposed subjects. Our results highlight the adverse effects of chronic alcohol exposure on the reproductive capacity of both males and females, and underscore the utility of the zebrafish model system to understand the biology of chronic alcoholism.

  5. Neuropsychological comparison of children with heavy prenatal alcohol exposure and an IQ-matched comparison group.

    PubMed

    Vaurio, Linnea; Riley, Edward P; Mattson, Sarah N

    2011-05-01

    An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual-motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. Group differences were marginally significant (measures within the broad neuropsychological comparison) or not significant (visual attention, retention of verbal material) on the remaining comparisons. Therefore, some deficits (e.g., verbal learning and behavior problems) in children with heavy prenatal alcohol exposure cannot be explained by the lower FSIQ observed in the population. These areas of relative weakness could be useful in distinguishing children with FASD from other children with lowered IQ.

  6. Social Information Processing Skills in Children with Histories of Heavy Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    McGee, Christie L.; Bjorkquist, Olivia A.; Price, Joseph M.; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge's reformulated…

  7. Neurobiology and Neurodevelopmental Impact of Childhood Traumatic Stress and Prenatal Alcohol Exposure

    ERIC Educational Resources Information Center

    Henry, Jim; Sloane, Mark; Black-Pond, Connie

    2007-01-01

    Purpose: Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic…

  8. Benzyl alcohol as a marker of occupational exposure to toluene.

    PubMed

    Kawai, Toshio; Yamauchi, Tsuneyuki; Miyama, Yuriko; Sakurai, Haruhiko; Ukai, Hirohiko; Takada, Shiro; Ohashi, Fumiko; Ikeda, Masayuki

    2007-01-01

    Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p<0.01), where X was toluene in air (in ppm as 8-h TWA) and Y was BeOH in urine (in microg/l of end-of-shift urine). The levels of BeOH in the urine of the non-exposed was about 50 microg/l, and ingestion of benzoate as a preservative in soft drinks did not affect the BeOH level in urine. The findings as a whole suggest that BeOH is a promising candidate for biological monitoring of occupational exposure to toluene.

  9. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    PubMed

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  10. Effects of periadolescent ethanol exposure on alcohol preference in two BALB substrains.

    PubMed

    Blizard, David A; Vandenbergh, David J; Jefferson, Akilah L; Chatlos, Cynthia D; Vogler, George P; McClearn, Gerald E

    2004-01-01

    Ethanol exposure during adolescence is a rite of passage in many societies, but only a subset of individuals exposed to ethanol becomes dependent on alcohol. To explore individual differences in response to ethanol exposure, we compared the effects of periadolescent ethanol exposure on alcohol drinking in an animal model. Male and female mice of two BALB substrains were exposed to ethanol in one of three forms--choice [water vs. 10% (volume/volume) ethanol], forced (10% ethanol in a single bottle), or gradual (single bottle exposure, starting with 0.5% ethanol and increasing at 2-day intervals to 10% ethanol)--from the 6th through the 12th week of age and administered two-bottle alcohol preference tests (10% ethanol vs. water) for 15 days immediately thereafter. All three forms of ethanol exposure increased alcohol preference in male and female BALB/cByJ mice, relative to findings for ethanol-naive control animals. Only gradual ethanol exposure produced an increase in alcohol preference in BALB/cJ mice. During extended alcohol preference testing (for a total of 39 days) of mice in the gradual ethanol exposure group, the higher alcohol preference of the gradual ethanol-exposed BALB/cByJ male mice persisted, but alcohol preference of control group female mice in this strain--formerly ethanol naive, but at this point having received 10% ethanol in the two-bottle paradigm for 15 days--rose to the level of alcohol preference of female mice in the gradual ethanol exposure group. This finding demonstrated that both adolescent and adult ethanol exposure stimulated alcohol preference in female mice of this strain. Across days of testing in adulthood, alcohol preference of the gradual ethanol-exposed BALB/cJ mice decreased, resulting in a lack of effect of gradual exposure to ethanol on alcohol preference in both male and female mice of this strain during the period of extended testing. These strain differences support a genetic basis for the effects of ethanol exposure on

  11. Effects of prenatal alcohol exposure on social behavior in humans and other species.

    PubMed

    Kelly, S J; Day, N; Streissguth, A P

    2000-01-01

    Alcohol exposure during development causes central nervous system alterations in both humans and animals. Although the most common behavioral manifestation of these alterations is a reduction in cognitive abilities, it is becoming increasingly apparent that deficits in social behavior may be very prevalent sequelae of developmental alcohol exposure. In infancy and early childhood, deficits in attachment behavior and state regulation are seen in both alcohol-exposed people and animals, suggesting that these changes are largely the result of the alcohol exposure rather than maternal behavior. In the periadolescent period, people exposed to alcohol during development show a variety of difficulties in the social domain as measured by checklists filled out by either a parent or teacher. Rats exposed to alcohol during development show changes in play and parenting behaviors. In adulthood, prenatal alcohol exposure is related to high rates of trouble with the law, inappropriate sexual behavior, depression, suicide, and failure to care for children. These high rates all suggest that there may be fundamental problems in the social domain. In other animals, perinatal alcohol exposure alters aggression, active social interactions, social communication and recognition, maternal behavior, and sexual behavior in adults. In conclusion, research suggests that people exposed to alcohol during development may exhibit striking changes in social behavior; the animal research suggests that these changes may be largely the result of the alcohol insult and not the environment.

  12. Exposure to alcohol among adolescent students and associated factors

    PubMed Central

    Malta, Deborah Carvalho; Mascarenhas, Márcio Dênis Medeiros; Porto, Denise Lopes; Barreto, Sandhi Maria; de Morais, Otaliba Libânio

    2014-01-01

    OBJECTIVE To describe the prevalence of alcohol consumption among adolescent school students and identify its individual and contextual associated factors. METHODS The present research used data from the 2009 National School Health Survey (PeNSE), which included a sample of 59,699 9th grade students in Brazilian capitals and the Federal District. The association between regular alcohol consumption and independent explanatory variables was measured by means of the Pearson’s Chi-square test, with a 0.05 significance level. The explanatory variables were divided into four groups based on affinity (sociodemographic; school and family context; risk factors; and protection factors). A multivariate analysis was carried out for each group, always adjusting for age and sex. Variables with p < 0.10 were used in the final multivariate analysis model. RESULTS The highest alcohol consumption in the preceding 30 days was independently associated with pupils aged 15 years (OR = 1.46) and over, female (OR = 1.72), white, children of mothers with higher education, studying in private school, students who had tried smoking (OR = 1.72) and drug use (OR = 1.81), with regular tobacco consumption (OR = 2.16) and those who have had sexual intercourse (OR = 2.37). The factors related to family were skipping school without parental knowledge (OR = 1.49), parents not knowing what children do in their free time (OR = 1.34), having fewer meals with their parents (OR = 1.22), reporting that parents do not care (OR = 3.05), or care little (OR = 3.39) if they go home drunk, and having suffered domestic violence (OR = 1.36). CONCLUSIONS The results reinforce the importance of viewing alcohol consumption among adolescents as a complex, multifactorial and socially determined phenomenon. PMID:24789637

  13. Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

    PubMed

    Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

    2017-04-14

    The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p<0.05) and beta (p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), and Coprococcus (p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress.

  14. Brief and extended alcohol-cue-exposure effects on craving and attentional bias.

    PubMed

    Ramirez, Jason J; Monti, Peter M; Colwill, Ruth M

    2015-06-01

    Past research has shown that underage college-student drinkers (UCSDs) report increased subjective craving and exhibit stronger attentional biases to alcohol following alcohol-cue exposure. To date, less research has examined whether momentary decreases in alcohol craving are associated with reductions in attentional bias. One experimental manipulation that has been used to produce within-session decreases in alcohol craving is to extend the duration of laboratory-based alcohol-cue exposure protocols. The aim of this study was to examine the effects of both brief and extended alcohol-cue exposure on subjective craving and attentional bias among UCSDs. Eighty participants were randomized either to a group that received a short, in vivo, alcohol-cue-exposure period (short-exposure group [SE], 2 3-min blocks) or to a group that received a long-exposure period (long-exposure group [LE], 6 3-min blocks). Both groups completed a visual probe task before and after cue exposure to assess changes in attentional bias. Analyses revealed no group differences in mean craving or mean attentional bias before or after cue exposure. Further, exploratory analyses revealed no sex differences in our measures of craving or attentional bias. For Group LE, but not Group SE, within-session changes in craving positively predicted within-session changes in attentional bias. However, further analyses revealed that this relationship was significant only for women in the LE group. Implications for treatments that aim to reduce craving and/or attentional bias are discussed.

  15. Alcohol-cue exposure effects on craving and attentional bias in underage college-student drinkers.

    PubMed

    Ramirez, Jason J; Monti, Peter M; Colwill, Ruth M

    2015-06-01

    The effect of alcohol-cue exposure on eliciting craving has been well documented, and numerous theoretical models assert that craving is a clinically significant construct central to the motivation and maintenance of alcohol-seeking behavior. Furthermore, some theories propose a relationship between craving and attention, such that cue-induced increases in craving bias attention toward alcohol cues, which, in turn, perpetuates craving. This study examined the extent to which alcohol cues induce craving and bias attention toward alcohol cues among underage college-student drinkers. We designed within-subject cue-reactivity and visual-probe tasks to assess in vivo alcohol-cue exposure effects on craving and attentional bias on 39 undergraduate college drinkers (ages 18-20). Participants expressed greater subjective craving to drink alcohol following in vivo cue exposure to a commonly consumed beer compared with water exposure. Furthermore, following alcohol-cue exposure, participants exhibited greater attentional biases toward alcohol cues as measured by a visual-probe task. In addition to the cue-exposure effects on craving and attentional bias, within-subject differences in craving across sessions marginally predicted within-subject differences in attentional bias. Implications for both theory and practice are discussed. (PsycINFO Database Record

  16. What Research Is Being Done on Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorders in the Russian Research Community?

    PubMed Central

    Popova, Svetlana; Yaltonskaya, Aleksandra; Yaltonsky, Vladimir; Kolpakov, Yaroslav; Abrosimov, Ilya; Pervakov, Kristina; Tanner, Valeria; Rehm, Jürgen

    2014-01-01

    Aims: Although Russia has one of the highest rates of alcohol consumption and alcohol-attributable burden of disease, little is known about the existing research on prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders (FASDs) in this country. The objective of this study was to locate and review published and unpublished studies related to any aspect of PAE and FASD conducted in or using study populations from Russia. Methods: A systematic literature search was conducted in multiple English and Russian electronic bibliographic databases. In addition, a manual search was conducted in several major libraries in Moscow. Results: The search revealed a small pool of existing research studies related to PAE and/or FASD in Russia (126: 22 in English and 104 in Russian). Existing epidemiological data indicate a high prevalence of PAE and FASD, which underlines the strong negative impact that alcohol has on mortality, morbidity and disability in Russia. High levels of alcohol consumption by women of childbearing age, low levels of contraception use, and low levels of knowledge by health and other professionals regarding the harmful effects of PAE put this country at great risk of further alcohol-affected pregnancies. Conclusions: Alcohol preventive measures in Russia warrant immediate attention. More research focused on alcohol prevention and policy is needed in order to reduce alcohol-related harm, especially in the field of FASD. PMID:24158024

  17. Impairment of social behaviour persists two years after embryonic alcohol exposure in zebrafish: A model of fetal alcohol spectrum disorders.

    PubMed

    Fernandes, Yohaan; Rampersad, Mindy; Gerlai, Robert

    2015-10-01

    Zebrafish naturally form social groups called shoals. Previously, we have shown that submerging zebrafish eggs into low concentrations of alcohol (0.00, 0.25, 0.50, 0.75 and 1.00 vol/vol% external bath concentration) during development (24h post-fertilization) for two hours resulted in impaired shoaling response in seven month old young adult zebrafish. Here we investigate whether this embryonic alcohol exposure induced behavioural deficit persists to older age. Zebrafish embryos were exposed either to fresh system water (control) or to 1% alcohol for two hours, 24h after fertilization, and were raised in a high-density tank system. Social behaviour was tested by presenting the experimental fish with a computer animated group of zebrafish images, while automated tracking software measured their behaviour. Control fish were found to respond strongly to animated conspecific images by reducing their distanceand remaining close to the images during image presentation, embryonic alcohol treated fish did not. Our results suggest that the impaired shoaling response of the alcohol exposed fish was not due to altered motor function or visual perception, but likely to a central nervous system alteration affecting social behaviour itself. We found the effects of embryonic alcohol exposure on social behaviour not to diminish with age, a result that demonstrates the deleterious and potentially life-long consequences of exposure to even small amount of alcohol during embryonic development in vertebrates.

  18. The relationship between exposure to alcohol-related content on Facebook and predictors of alcohol consumption among female emerging adults.

    PubMed

    Miller, Joseph; Prichard, Ivanka; Hutchinson, Amanda; Wilson, Carlene

    2014-12-01

    Consuming an unhealthy level of alcohol is a significant problem for some young women. Potential determinants of excess consumption include perceptions of usual consumption among peers-perceptions of what is "normal." The present study examined whether perceptions of social normative endorsement of drinking, operationalized by measures of perceived alcohol consumption of close friends (proximal norms), the consumption of the "average student" (distal norms), and the extent of alcohol-related content posted by peers on Facebook were related to alcohol-related attitudes and self-reported consumption. Female university students (n=129; Mage=21.48 years, SD=3.00) completed an online questionnaire assessing Facebook use, perceived alcohol-related norms, and self-reported alcohol attitudes and consumption. Perceptions of the consumption of the average female student were a negative predictor of attitudes. Positive alcohol attitudes, extent of own alcohol-related photographic posts on Facebook, average female student alcohol consumption, and report of male close friend consumption predicted self-report of own alcohol consumption. Interestingly, female close friend norms failed to predict consumption, whereas male close friend norms predicted consumption but not attitudes, suggesting the possibility of separate cognitive pathways for alcohol-related attitudes and behavior. This study builds on existing research by casting new light on predictors of alcohol-related attitudes, as well as describing the potential role of social networking sites such as Facebook in the formation of social norms and the modulation of drinking behavior.

  19. Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

    PubMed

    Chauhan, Ved; Chauhan, Abha

    2016-06-01

    Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders.

  20. Influence of the degree of exposure to lead on relations between alcohol consumption and the biological indices of lead exposure: epidemiological study in a lead acid battery factory.

    PubMed Central

    Cezard, C; Demarquilly, C; Boniface, M; Haguenoer, J M

    1992-01-01

    Alcohol has been shown to interact with lead to influence haem biosynthesis. The aim of this study was to define the dependence of this interaction on the degree of exposure to lead. Exposure to alcohol was estimated by measurement of alcohol concentrations in a sample of urine collected during the morning (AlcUM) (0.82 (SD 4.36) mmol/l) and in a sample collected during the afternoon (AlcUA) (1.15 (SD 3.49) mmol/l). The biological monitoring of exposure to lead included measurements of blood lead (Pb-B) (1.82 (SD 0.72) mumol/l), urinary delta-aminolaevulinic acid (ALAU) (35.33 (SD 28.00) mumol/l; d = 1.015), and erythrocyte zinc-protoporphyrin (ZPP) (112.90 (SD 83.71) nmol/mmol Hb) concentrations. The study of the influence of the degree of occupational exposure to lead on relations between alcohol consumption and effects of the exposure to lead led to the consideration of two different groups--namely, mildly and strongly exposed subjects. In the first group, individual biological susceptibility seemed to play a preponderant part. In the second, the pool of lead present in the body seemed to be sufficiently important to mask the effects of individual susceptibility. PMID:1390270

  1. Adolescents’ exposure to tobacco and alcohol content in YouTube music videos

    PubMed Central

    Murray, Rachael; Lewis, Sarah; Leonardi‐Bee, Jo; Dockrell, Martin; Britton, John

    2015-01-01

    Abstract Aims To quantify tobacco and alcohol content, including branding, in popular contemporary YouTube music videos; and measure adolescent exposure to such content. Design Ten‐second interval content analysis of alcohol, tobacco or electronic cigarette imagery in all UK Top 40 YouTube music videos during a 12‐week period in 2013/14; on‐line national survey of adolescent viewing of the 32 most popular high‐content videos. Setting Great Britain. Participants A total of 2068 adolescents aged 11–18 years who completed an on‐line survey. Measurements Occurrence of alcohol, tobacco and electronic cigarette use, implied use, paraphernalia or branding in music videos and proportions and estimated numbers of adolescents who had watched sampled videos. Findings Alcohol imagery appeared in 45% [95% confidence interval (CI) = 33–51%] of all videos, tobacco in 22% (95% CI = 13–27%) and electronic cigarettes in 2% (95% CI = 0–4%). Alcohol branding appeared in 7% (95% CI = 2–11%) of videos, tobacco branding in 4% (95% CI = 0–7%) and electronic cigarettes in 1% (95% CI = 0–3%). The most frequently observed alcohol, tobacco and electronic cigarette brands were, respectively, Absolut Tune, Marlboro and E‐Lites. At least one of the 32 most popular music videos containing alcohol or tobacco content had been seen by 81% (95% CI = 79%, 83%) of adolescents surveyed, and of these 87% (95% CI = 85%, 89%) had re‐watched at least one video. The average number of videos seen was 7.1 (95% CI = 6.8, 7.4). Girls were more likely to watch and also re‐watch the videos than boys, P < 0.001. Conclusions Popular YouTube music videos watched by a large number of British adolescents, particularly girls, include significant tobacco and alcohol content, including branding. PMID:25516167

  2. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    PubMed Central

    Peñasco, Sara; Mela, Virginia; López-Moreno, Jose Antonio; Viveros, María-Paz; Marco, Eva M.

    2015-01-01

    In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9), on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v) was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake. PMID:25821601

  3. Evaluation of furfuryl alcohol sensitization potential following dermal and pulmonary exposure: enhancement of airway responsiveness.

    PubMed

    Franko, Jennifer; Jackson, Laurel G; Hubbs, Ann; Kashon, Michael; Meade, B J; Anderson, Stacey E

    2012-01-01

    Furfuryl alcohol is considered by the U.S. Environmental Protection Agency to be a high volume production chemical, with over 1 million pounds produced annually. Due to its high production volume and its numerous industrial and consumer uses, there is considerable potential for work-related exposure, as well as exposure to the general population, through pulmonary, oral, and dermal routes of exposure. Human exposure data report a high incidence of asthma in foundry mold workers exposed to furan resins, suggesting potential immunologic effects. Although furfuryl alcohol was nominated and evaluated for its carcinogenic potential by the National Toxicology Program, studies evaluating its immunotoxicity are lacking. The studies presented here evaluated the immunotoxic potential of furfuryl alcohol following exposure by the dermal and pulmonary routes using a murine model. When tested in a combined irritancy local lymph node assay, furfuryl alcohol was identified to be an irritant and mild sensitizer (EC3 = 25.6%). Pulmonary exposure to 2% furfuryl alcohol resulted in enhanced airway hyperreactivity, eosinophilic infiltration into the lungs, and enhanced cytokine production (IL-4, IL-5, and interferon-γ) by ex vivo stimulated lung-associated draining lymphoid cells. Airway hyperreactivity and eosinophilic lung infiltration were augmented by prior dermal exposure to furfuryl alcohol. These results suggest that furfuryl alcohol may play a role in the development of allergic airway disease and encourage the need for additional investigation.

  4. Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood.

    PubMed

    Pandey, Subhash C; Sakharkar, Amul J; Tang, Lei; Zhang, Huaibo

    2015-10-01

    Binge drinking is common during adolescence and can lead to the development of psychiatric disorders, including alcoholism in adulthood. Here, the role and persistent effects of histone modifications during adolescent intermittent ethanol (AIE) exposure in the development of anxiety and alcoholism in adulthood were investigated. Rats received intermittent ethanol exposure during post-natal days 28-41, and anxiety-like behaviors were measured after 1 and 24 h of the last AIE. The effects of AIE on anxiety-like and alcohol-drinking behaviors in adulthood were measured with or without treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). Amygdaloid brain regions were collected to measure HDAC activity, global and gene-specific histone H3 acetylation, expression of brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated (Arc) protein and dendritic spine density (DSD). Adolescent rats displayed anxiety-like behaviors after 24 h, but not 1 h, of last AIE with a concomitant increase in nuclear and cytosolic amygdaloid HDAC activity and HDAC2 and HDAC4 levels leading to deficits in histone (H3-K9) acetylation in the central (CeA) and medial (MeA), but not in basolateral nucleus of amygdala (BLA). Interestingly, some of AIE-induced epigenetic changes such as, increased nuclear HDAC activity, HDAC2 expression, and decreased global histone acetylation persisted in adulthood. In addition, AIE decreased BDNF exons I and IV and Arc promoter specific histone H3 acetylation that was associated with decreased BDNF, Arc expression and DSD in the CeA and MeA during adulthood. AIE also induced anxiety-like behaviors and enhanced ethanol intake in adulthood, which was attenuated by TSA treatment via normalization of deficits in histone H3 acetylation of BDNF and Arc genes. These novel results indicate that AIE induces long-lasting effects on histone modifications and deficits in synaptic events in the amygdala, which are

  5. Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.

    PubMed

    McClain, Justin A; Hayes, Dayna M; Morris, Stephanie A; Nixon, Kimberly

    2011-09-01

    Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromodeoxyuridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration. Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle. Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. These studies suggest the mechanism of alcohol inhibition of neurogenesis and also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure.

  6. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    PubMed

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

  7. Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury.

    PubMed

    Lim, Yi Wei; Meyer, Nathan P; Shah, Alok S; Budde, Matthew D; Stemper, Brian D; Olsen, Christopher M

    2015-01-01

    Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC) and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions) and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure.

  8. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism

  9. In Utero Exposure to Low-Dose Alcohol Induces Reprogramming of Mammary Development and Tumor Risk in MMTV-erbB-2 Transgenic Mice

    PubMed Central

    Ma, Zhikun; Blackwelder, Amanda J.; Lee, Harry; Zhao, Ming; Yang, Xiaohe

    2015-01-01

    There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation. PMID:25853264

  10. Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

    PubMed Central

    Tyler, Christina R.; Allan, Andrea M.

    2014-01-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15–17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics

  11. Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model.

    PubMed

    Tyler, Christina R; Allan, Andrea M

    2014-08-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15-17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics analysis

  12. 76 FR 2617 - Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ...' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors AGENCY: Mine Safety and... rule addressing Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal..., Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors....

  13. Youth exposure to alcohol advertising on radio--United States, June-August 2004.

    PubMed

    2006-09-01

    In the United States, more underage youth drink alcohol than smoke tobacco or use illicit drugs. Excessive alcohol consumption leads to many adverse health and social consequences and results in approximately 4,500 deaths among underage youth each year. Recent studies have emphasized the contribution of alcohol marketing to underage drinking and have demonstrated that a substantial proportion of alcohol advertising appears in media for which the audience composition is youth-oriented (i.e., composed disproportionately of persons aged 12-20 years). To determine the proportion of radio advertisements that occurred on radio programs with audiences composed disproportionately of underage youth and the proportion of total youth exposure to alcohol advertising that occurs as a result of such advertising, researchers at the Center on Alcohol Marketing and Youth (Health Policy Institute, Georgetown University, District of Columbia) evaluated the placement of individual radio advertisements for the most advertised U.S. alcohol brands and the composition of audiences in the largest 104 markets in the United States. This report summarizes the results of that study, which indicate that alcohol advertising is common on radio programs which have disproportionately large youth audiences and that this advertising accounts for a substantial proportion of all alcohol radio advertising heard by underage youth. These results further indicate that 1) the current voluntary standards limiting alcohol marketing to youth should be enforced and ultimately strengthened, and 2) ongoing monitoring of youth exposure to alcohol advertising should continue.

  14. Measuring youth exposure to alcohol marketing on social networking sites: challenges and prospects.

    PubMed

    Jernigan, David H; Rushman, Anne E

    2014-02-01

    Youth exposure to alcohol marketing has been linked to increased alcohol consumption and problems. On relatively new and highly interactive social networking sites (SNS) that are popular with youth, tools for measuring youth exposure to alcohol marketing in traditional media are inadequate. We critically review the existing policies of Facebook, Twitter, and YouTube designed to keep branded alcohol content away from underage youth. Looking at brand and user activity on Facebook for the 15 alcohol brands most popular among US youth, we found activity has grown dramatically in the past 3 years, and underage users may be accounting for some of this activity. Surveys of youth and adult participation in alcohol marketing on SNS will be needed to inform debate over these marketing practices.

  15. Association among work exposure, alcohol intake, smoking and Dupuytren's disease in a large cohort study (GAZEL)

    PubMed Central

    Descatha, Alexis; Carton, Matthieu; Mediouni, Zakia; Dumontier, Christian; Roquelaure, Yves; Goldberg, Marcel; Zins, Marie; Leclerc, Annette

    2014-01-01

    Objectives In view of the debate of factors in Dupuytren’s disease, we aimed to describe its relationship with certain occupational factors, alcohol intake and smoking. Setting The French GAZEL cohort (employees of Electricité de France and Gaz de France). Participants Participants of the cohort who answered a questionnaire in 2012, that is, 13 587 participants (73.7% of the questionnaire sent). In 2007, self-assessed lifetime occupational biomechanical exposure was recorded (carrying loads, manipulating a vibrating tool and climbing stairs), as well as alcohol intake, smoking and diabetes mellitus. Analyses were performed on high alcohol intake, smoking and duration of relevant work exposure, stratified by gender. Primary and secondary outcome measures From a specific question on Dupuytren’s disease assessed in 2012, the outcome measures were self-reported Dupuytren’s disease (yes/no) and disabling Dupuytren’s disease (including surgery). Results A total of 10 017 men and 3570 women, aged 64–73 years, were included; the mean age for men was 68 years and for women was 65 years. Among men, the following were significantly associated with Dupuytren’s disease: age (OR 1.03 (1.00; 1.06)), diabetes (OR 1.31 (1.07; 1.60)), heavy drinking (OR 1.36 (1.10; 1.69)) and over 15 years of manipulating a vibrating tool at work (OR 1.52 (1.15; 2.02)); except for diabetes, the association with these factors was stronger for disabling Dupuytren’s disease (or surgery), with OR 1.07 (1.03; 1.11), 1.71 (1.25; 2.33) and 1.98(1.34; 2.91), respectively, for age, heavy drinking and over 15 years of manipulating a vibrating tool at work. Among the 3570 women included, 160 reported Dupuytren’s disease (4.5%). The number of cases in the group of women was too low to reach conclusions, although the findings seemed similar for age, diabetes and vibration exposure. Conclusions In this large French cohort study, Dupuytren’s disease in men was associated with high

  16. Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

    PubMed Central

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2014-01-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

  17. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation.

    PubMed

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2015-03-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.

  18. An examination of sex differences in the effects of early-life opiate and alcohol exposure.

    PubMed

    Terasaki, Laurne S; Gomez, Julie; Schwarz, Jaclyn M

    2016-02-19

    Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure.

  19. An examination of sex differences in the effects of early-life opiate and alcohol exposure

    PubMed Central

    Terasaki, Laurne S.; Gomez, Julie; Schwarz, Jaclyn M.

    2016-01-01

    Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure. PMID:26833841

  20. Epilogue: Understanding Children Who Have Been Affected by Maltreatment and Prenatal Alcohol Exposure--Future Directions

    ERIC Educational Resources Information Center

    Hyter, Yvette D.; Way, Ineke

    2007-01-01

    This epilogue summarizes the six articles presented in the clinical forum focused on understanding children who have been affected by maltreatment and prenatal alcohol exposure. It presents common themes that emerged among the articles and future research directions.

  1. Media Exposure and Tobacco, Illicit Drugs, and Alcohol Use among Children and Adolescents: A Systematic Review

    ERIC Educational Resources Information Center

    Nunez-Smith, Marcella; Wolf, Elizabeth; Huang, Helen Mikiko; Chen, Peggy G.; Lee, Lana; Emanuel, Ezekiel J.; Gross, Cary P.

    2010-01-01

    The authors systematically reviewed 42 quantitative studies on the relationship between media exposure and tobacco, illicit drug, and alcohol use among children and adolescents. Overall, 83% of studies reported that media was associated with increased risk of smoking initiation, use of illicit drugs, and alcohol consumption. Of 30 studies…

  2. Prenatal Alcohol and Cocaine Exposure: Influences on Cognition, Speech, Language, and Hearing

    ERIC Educational Resources Information Center

    Cone-Wesson, B.

    2005-01-01

    This paper reviews research on the consequences of prenatal exposure to alcohol and cocaine on children's speech, language, hearing, and cognitive development. The review shows that cognitive impairment, learning disabilities, and behavioral disorders are the central nervous system manifestations of fetal alcohol syndrome (FAS), and cranio-facial…

  3. Fetal Alcohol Spectrum Disorders: Understanding the Effects of Prenatal Alcohol Exposure and Supporting Students

    ERIC Educational Resources Information Center

    Green, Jennifer H.

    2007-01-01

    Background: Fetal Alcohol Spectrum Disorders (FASD) affect a significant number of children in this country. This article addresses diagnostic issues related to fetal alcohol syndrome (FAS) and other alcohol-related disabilities, discusses associated features and behaviors of FASD, and introduces interventions to support children with FASD in…

  4. The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.

    PubMed

    Perkins, Amy E; Fadel, Jim R; Kelly, Sandra J

    2015-05-01

    Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability

  5. 76 FR 25277 - Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ...' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors AGENCY: Mine Safety and... period on the proposed rule addressing Lowering Miners' Exposure to Respirable Coal Mine Dust, Including... FR 64412), MSHA published a proposed rule, Lowering Miners' Exposure to Respirable Coal Mine...

  6. The incidence of prenatal alcohol exposure in Montevideo Uruguay as determined by meconium analysis.

    PubMed

    Hutson, Janine R; Magri, Raquel; Gareri, Joey N; Koren, Gideon

    2010-06-01

    Prenatal alcohol exposure can lead to a wide range of deficits known as fetal alcohol spectrum disorder. Epidemiologic studies regarding alcohol consumption in pregnancy have concentrated on North America, but recent reports have suggested that consumption is significant in many parts of the world. In Uruguay, alcohol consumption has changed into more risky and dangerous patterns and thus has a theoretical risk of having a high rate of prenatal alcohol exposure. This study characterizes the incidence of prenatal alcohol exposure in Montevideo, Uruguay, using a novel biomarker, fatty acid ethyl esters, in meconium as well as a survey to mothers. Nine hundred five meconium samples were collected from Hospital Pereira Rossell and Hospital de Clínicas in Montevideo, Uruguay. A maternal questionnaire was also completed. Meconium was analyzed for fatty acid ethyl esters using liquid-liquid and solid phase extraction with gas chromatography-flame ionization detection. Meconium was also analyzed for other drugs of abuse using enzyme-linked immunosorbent assay. Forty-four percent of meconium samples were above the positive cutoff for fatty acid ethyl esters and represent those newborns with risky prenatal exposure during the final two trimesters of pregnancy. Infants with prenatal alcohol exposure were more likely to have prenatal exposure to tobacco (odds ratio, 1.56; 95% confidence interval, 1.11-2.20) or any illicit drug (odds ratio, 2.29; 95% confidence interval, 0.98-5.31). Ethyl linoleate was a significant predictor of infant birth weight along with prenatal tobacco exposure, maternal body mass index, and infant sex. This study highlights a 44% incidence of prenatal alcohol exposure.

  7. Exposure of African-American Youth to Alcohol Advertising.

    ERIC Educational Resources Information Center

    2003

    The marketing of alcohol products in African-American communities has, on occasion, stirred national controversy and met with fierce resistance from African Americans and others. Despite occasional media and community spotlights on the marketing of alcohol products in the African-American community, there has been no systematic review of the…

  8. Exposure of piglet coronary arterial muscle cells to low alcohol results in elevation of intracellular free Ca2+: relevance to fetal alcohol syndrome.

    PubMed

    Altura, M B; Zhang, A; Cheng, T P; Altura, B T

    1996-10-31

    Chronic exposure of cultured piglet neonatal coronary arterial smooth muscle cells to low concentrations of ethanol (46-115 mg/dl) for 7 days resulted in concentration-dependent elevation in intracellular free Ca2+ ions ([Ca2+i); these rises (22-56%) in [Ca2+]i were not reversible upon short-term exposure to normal, Ca2(+)-containing physiological salt solution. These findings help to provide a rational basis for why ethanol can result in the well-known fetal alcohol syndrome, including cardiac defects and in-utero death.

  9. Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study

    PubMed Central

    Sanders, James L.; Breen, Rebecca E. Hudson; Netelenbos, Nicole

    2017-01-01

    Background: Diagnostic criteria have recently been introduced in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). The purpose of this study is to assess the classification of this condition using the Canadian fetal alcohol spectrum disorder (FASD) multidisciplinary diagnostic guidelines as the standard of comparison. First, classification of ND-PAE was compared with Canadian FASD diagnoses of fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorder. Second, classification of ND-PAE was compared with FAS and pFAS only, a criterion for which includes facial features highly predictive of prenatal alcohol exposure and effects. Methods: Eighty-two patients underwent multidisciplinary clinical evaluations using the Canadian FASD diagnostic guidelines between 2011 and 2015. Two clinicians independently reviewed patient files for evidence of diagnostic criteria for ND-PAE when applying an impairment cut-off level of 2 or more standard deviations below the mean, or clinically significant impairment in the absence of standardized norm-referenced measures. Results: Good interrater reliability was established between clinicians (κ = 0.79). Classifications of ND-PAE and Canadian FASD diagnoses, including alcohol-related neurodevelopmental disorder, were moderately correlated (Cramer V [82] = 0.44, p < 0.01). However, ND-PAE possessed low sensitivity in FASD identification. Further, there was no correlation between ND-PAE and FAS/pFAS classifications (Cramer V [82] = 0.05, p > 0.05). Interpretation: Although there is considerable overlap between both sets of criteria, ND-PAE was less likely to identify patients with FASD. Although the neurobehavioral domains assessed by ND-PAE are supported in research, its diagnostic structure restricts the identification of FASD at the impairment threshold of 2 or more standard deviations. A

  10. Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

    PubMed Central

    Treit, Sarah; Zhou, Dongming; Chudley, Albert E.; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M.; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

    2016-01-01

    Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol

  11. Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

    PubMed

    Treit, Sarah; Zhou, Dongming; Chudley, Albert E; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

    2016-01-01

    Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol

  12. Vasopressin Regulation and Renal Fluid and Electrolyte Handling in Rat Models of Acute and Chronic alcohol Exposure

    DTIC Science & Technology

    2004-10-01

    evaluating fluid and electrolyte regulating ability in models of acute and chronic alcohol exposure and alcohol withdrawal, and 2) uncovering mechanisms ...be used to define mechanisms behind alcohol effects better than study of humans because conditions of alcohol dosing, hydration status, and fluid...vasopressin receptor regulation, and have determined that altered renal responsiveness to vasopressin is the main mechanism behind fluid balance perturbations

  13. Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats.

    PubMed

    Jaramillo, Anel A; Randall, Patrick A; Frisbee, Suzanne; Fisher, Kristen R; Besheer, Joyce

    2015-09-01

    Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long-Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3-3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 μg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0-3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3-1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions.

  14. Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

    PubMed Central

    Jaramillo, Anel A.; Randall, Patrick A.; Frisbee, Suzanne; Fisher, Kristen R.; Besheer, Joyce

    2015-01-01

    Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long-Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3–3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 μg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0–3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3–1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in Water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions. PMID:26142564

  15. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure.

    PubMed

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R; Palmour, Roberta M

    2015-05-01

    Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65-70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume.

  16. Impaired odor identification in children with histories of heavy prenatal alcohol exposure.

    PubMed

    Bower, Emily; Szajer, Jacquelyn; Mattson, Sarah N; Riley, Edward P; Murphy, Claire

    2013-06-01

    Prenatal alcohol exposure can lead to behavioral and cognitive impairments across multiple domains. Many of the brain regions impacted by prenatal alcohol exposure are also linked with olfactory processing, and odor identification deficits have been documented in certain neurological disorders associated with these brain regions. As odor identification following prenatal alcohol exposure is not well studied, we compared odor identification in children with prenatal exposure to alcohol (AE) to typically developing controls (CON) (N = 16/group). It was hypothesized that children in the AE group would perform more poorly than children in the CON group on the San Diego Odor Identification Test, an identification test of 8 common household odorants. Children exposed to alcohol during prenatal development were significantly impaired in olfactory identification (M = 5.95, SE = 0.37) compared to typically developing controls (M = 7.24, SE = 0.37). These findings confirmed the hypothesis that prenatal exposure to alcohol is associated with odor identification deficits, and suggest that further research is warranted to identify the mechanisms underlying these deficits, the integrity of brain areas that are involved, and to determine whether olfactory performance might contribute to better identification of children at risk for behavioral and cognitive deficits.

  17. Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher; Quandt, Lorna C; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Sowell, Elizabeth R

    2011-02-14

    Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.

  18. Prenatal Alcohol Exposure Is Associated with Conduct Disorder in Adolescence: Findings from a Birth Cohort

    ERIC Educational Resources Information Center

    Larkby, Cynthia A.; Goldschmidt, Lidush; Hanusa, Barbara H.; Day, Nancy L.

    2011-01-01

    Objective: To evaluate the association between prenatal alcohol exposure and the rate of conduct disorder in exposed compared with unexposed adolescents. Method: Data for these analyses are from a longitudinal study of prenatal substance exposures. Women were interviewed at their fourth and seventh prenatal months, and with their children, at…

  19. Behavioral Outcomes of Young Children with Prenatal Exposure to Alcohol: Review and Analysis of Experimental Literature.

    ERIC Educational Resources Information Center

    Williams, Rosanne C.; Carta, Judith J.

    1996-01-01

    Analysis of 51 studies of developmental effects of prenatal exposure to alcohol in children from birth to 72 months found that, although adverse outcomes were found within each domain, age grouping, and exposure category, they comprised fewer than 50% of all outcomes measured. Most adverse outcomes were found in the neurobehavioral domain with…

  20. Exposure to the Lebanon War of 2006 and effects on alcohol use disorders: The moderating role of childhood maltreatment☆

    PubMed Central

    Keyes, Katherine M.; Shmulewitz, Dvora; Greenstein, Eliana; McLaughlin, Kate; Wall, Melanie; Aharonovich, Efrat; Weizman, Abraham; Frisch, Amos; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah

    2013-01-01

    Background Civilian populations now comprise the majority of casualties in modern warfare, but effects of war exposure on alcohol disorders in the general population are largely unexplored. Accumulating literature indicates that adverse experiences early in life sensitize individuals to increased alcohol problems after adult stressful experiences. However, child and adult stressful experiences can be correlated, limiting interpretation. We examine risk for alcohol disorders among Israelis after the 2006 Lebanon War, a fateful event outside the control of civilian individuals and uncorrelated with childhood experiences. Further, we test whether those with a history of maltreatment are at greater risk for an alcohol use disorder after war exposure compared to those without such a history. Methods Adult household residents selected from the Israeli population register were assessed with a psychiatric structured interview; the analyzed sample included 1306 respondents. War measures included self-reported days in an exposed region. Results Among those with a history of maltreatment, those in a war-exposed region for 30+ days had 5.3 times the odds of subsequent alcohol disorders compared to those exposed 0 days (95%C.I. 1.01–27.76), controlled for relevant confounders; the odds ratio for those without this history was 0.5 (95%C.I. 0.25–1.01); test for interaction: X2 = 5.28, df = 1, P = 0.02. Conclusions Experiencing a fateful stressor outside the control of study participants, civilian exposure to the 2006 Lebanon War, is associated with a heightened the risk of alcohol disorders among those with early adverse childhood experiences. Results suggest that early life experiences may sensitize individuals to adverse health responses later in life. PMID:24262650

  1. Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

    PubMed

    Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

    2015-05-01

    The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner.

  2. Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice

    PubMed Central

    Wieczorek, Lindsay; Fish, Eric W.; O’Leary-Moore, Shonagh K.; Parnell, Scott E.; Sulik, Kathleen K.

    2015-01-01

    The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. PMID:25709101

  3. Alcohol Use and Trauma Exposure among Male and Female Veterans Before, During, and After Military Service

    PubMed Central

    Kelley, Michelle L.; Runnals, Jennifer; Pearson, Matthew R.; Miller, Marinell; Fairbank, John A.; Brancu, Mira

    2017-01-01

    The present study examined lifespan and combat-related trauma exposure as predictors of alcohol use among male and female veterans. Posttraumatic stress and depressive symptoms were examined as mediators of the effects of trauma exposure on alcohol use. Data were examined from 1825 (1450 male, 375 female) veterans and active duty service members who took part in a multi-site research study conducted through the Department of Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Centers (VISN 6 MIRECC). For both men and women, depressive symptoms significantly mediated the effects of non-combat trauma exposure experienced before, during and after the military, as well as combat- exposure, on alcohol use. With posttraumatic stress symptoms, the models for men and women differed. For men, the effects of non-combat trauma exposure during and after military service, and combat exposure, on alcohol use were mediated by PTSD symptoms; however, for women, PTSD symptoms did not mediate these relationships. Findings are discussed in the context of potential gender differences in response to trauma such as use of alcohol to cope with traumatic events. PMID:24054989

  4. Prenatal marijuana and alcohol exposure and academic achievement at age 10.

    PubMed

    Goldschmidt, Lidush; Richardson, Gale A; Cornelius, Marie D; Day, Nancy L

    2004-01-01

    The effects of prenatal marijuana and alcohol exposure on school achievement at 10 years of age were examined. Women were interviewed about their substance use at the end of each trimester of pregnancy, at 8 and 18 months, and at 3, 6, 10, 14, and 16 years. The women were of lower socioeconomic status, high-school-educated, and light-to-moderate users of marijuana and alcohol. The sample was equally divided between Caucasian and African-American women. At the 10-year follow-up, the effects of prenatal exposure to marijuana or alcohol on the academic performance of 606 children were assessed. Exposure to one or more marijuana joints per day during the first trimester predicted deficits in Wide Range Achievement Test-Revised (WRAT-R) reading and spelling scores and a lower rating on the teachers' evaluations of the children's performance. This relation was mediated by the effects of first-trimester marijuana exposure on the children's depression and anxiety symptoms. Second-trimester marijuana use was significantly associated with reading comprehension and underachievement. Exposure to alcohol during the first and second trimesters of pregnancy predicted poorer teachers' ratings of overall school performance. Second-trimester binge drinking predicted lower reading scores. There was no interaction between prenatal marijuana and alcohol exposure. Each was an independent predictor of academic performance.

  5. Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

    PubMed Central

    Vetreno, Ryan P.; Broadwater, Margaret A.; Robinson, Donita L.

    2016-01-01

    Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity

  6. Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior.

    PubMed

    Crews, Fulton T; Vetreno, Ryan P; Broadwater, Margaret A; Robinson, Donita L

    2016-10-01

    Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative-motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to

  7. Variations on the "Whoosh" Bottle Alcohol Explosion Demonstration Including Safety Notes.

    ERIC Educational Resources Information Center

    Fortman, John J.; Rush, Andrea C.; Stamper, Jennifer E.

    1999-01-01

    Presents several variations on a demonstration in which alcohol vapors are combusted in large small-necked bottles, causing a blue flame to shoot from the bottle's mouth. Describes variations with different pure alcohols, temperature, alcohol/water solution concentration, oxygen concentration, type of container, and the addition of salt for color.…

  8. The Margin of Exposure of 5-Hydroxymethylfurfural (HMF) in Alcoholic Beverages

    PubMed Central

    Monakhova, Yulia B

    2012-01-01

    Objectives 5-Hydroxymethylfurfural (HMF) regularly occurs in foods and in alcoholic beverages. However, the risk of HMF associated with alcohol consumption has not been systematically studied, so that this study will provide the first quantitative risk assessment of HMF for consumers of alcoholic beverages. Methods Human dietary intake of HMF via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data combined with our own survey data (n=944) and literature data (n=147) about the HMF contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach. Results For olfactory epithelium metaplasia in female mice, a benchmark dose (BMD) of 127 mg/kg bodyweight (bw)/d and a BMD lower confidence limit (BMDL) of 79 mg/kg bw/d were calculated from National Toxicology Program oral long-term animal experiments. The average human exposure to HMF from alcoholic beverages was estimated at 6.0E-3 mg/kg bw/d, which is approximately 8.5% of the total dietary exposure. In comparison of the human exposure with BMDL, the MOE was 13,167 for average alcohol consumption scenarios, which is a value that would be generally assumed as safe for threshold based compounds. Conclusions The results show that the risk from HMF to the alcohol-consuming population is rather low and the priority for risk management (e.g. to reduce the contamination) is also low. Further toxicological research about HMF is required to further elucidate its mechanism. PMID:23106038

  9. Youth exposure to alcohol advertising on television--25 markets, United States, 2010.

    PubMed

    2013-11-08

    Excessive alcohol consumption accounted for an estimated 4,700 deaths and 280,000 years of potential life lost among youths aged <21 years each year during 2001-2005. Exposure to alcohol marketing increases the likelihood to varying degrees that youths will initiate drinking and drink at higher levels. By 2003, the alcohol industry voluntarily agreed not to advertise on television programs where >30% of the audience is reasonably expected to be aged <21 years. However, the National Research Council/Institute of Medicine (NRC/IOM) proposed in 2003 that "the industry standard should move toward a 15% threshold for television advertising". Because local media markets might have different age distributions, the Center on Alcohol Marketing and Youth, Johns Hopkins Bloomberg School of Public Health, evaluated the proportion of advertisements that appeared on television programs in 25 local television markets* and resulting youth exposure that exceeded the industry standard (i.e., >30% aged 2-20 years) or the proposed NRC/IOM standard (i.e., >15% aged 12-20 years). Among national television programs with alcohol advertising, placements were assessed for the 10 programs with the largest number of youth viewers within each of four program categories: network sports, network nonsports, cable sports, and cable nonsports (40 total). Of the 196,494 alcohol advertisements that aired on television programs with the largest number of youth viewers in these local markets, placement of 23.7% exceeded the industry threshold and 35.4% exceeded the NRC/IOM threshold. These results indicate that the alcohol industry's self-regulation of its advertising could be improved, and youth exposure to alcohol advertising could be further reduced by adopting and complying with the NRC/IOM standard. In addition, continued public health surveillance would allow for sustained assessment of youth exposure to alcohol advertising and inform future interventions.

  10. Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Rudie, Jeffrey D; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Narr, Katherine L; Sowell, Elizabeth R

    2012-01-01

    Various abnormalities in frontal and striatal regions have been reported in children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI study, we observed a correlation between accuracy on a working-memory task and functional activation in the putamen in children with prenatal methamphetamine and polydrug exposure. Because the putamen is part of the corticostriatal motor loop whereas the caudate is involved in the executive loop, we hypothesized that a loss of segregation between distinct corticostriatal networks may occur in these participants. The current study was designed to test this hypothesis using functional connectivity MRI. We examined 50 children ranging in age from 7 to 15, including 19 with prenatal methamphetamine exposure (15 of whom had concomitant prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not methamphetamine, and 18 unexposed controls. We measured the coupling between blood oxygenation level dependent (BOLD) fluctuations during a working-memory task in four striatal seed regions and those in the rest of the brain. We found that the putamen seeds showed increased connectivity with frontal brain regions involved in executive functions while the caudate seeds showed decreased connectivity with some of these regions in both groups of exposed subjects compared to controls. These findings suggest that localized brain abnormalities resulting from prenatal exposure to alcohol and/or methamphetamine lead to a partial rewiring of corticostriatal networks. These results represent important progress in the field, and could have substantial clinical significance in helping devise more targeted treatments and remediation strategies designed to better serve the needs of this population.

  11. Enriched environment attenuates changes in water-maze performance and BDNF level caused by prenatal alcohol exposure

    PubMed Central

    Tipyasang, Rungpiyada; Kunwittaya, Sarun; Mukda, Sujira; Kotchabhakdi, Nittaya J.; Kotchabhakdi, Naiphinich

    2014-01-01

    Prenatal exposure to alcohol can result in fetal alcohol syndrome (FAS), characterized by significant changes in the physiology, structural plasticity of hippocampal function, including long-term deficits in learning and memory. Environmental enrichment has long been known to improve motor and cognitive function levels, causes several neurochemical and morphological alterations in the brain. Therefore, the effects of environmental enrichment on the neurobehavioral and neurotrophic changes in mice exposed prenatally to alcohol were investigated in this study. The pregnant dams were given 25 % ethanol (w/v) or isocaloric sucrose by liquid diet from gestation day 7 to 20. After weaning on postnatal day 28, offspring were exposed to standard cage (CC, CFAS) or enriched living conditions (CE, EFAS) for 8 weeks. Neurobehavioral studies both on hippocampus-dependent spatial learning and place and cue learning strategy, a striatum-dependent test, were measured by the Morris water maze task. Moreover, the reverse-transcriptase polymerase chain reaction (RT-PCR) technique was also used in order to study the expression of brain-derived neurotrophic factor (BDNF) level in both the hippocampus and striatum of mice. Neurobehavioral studies show that animals exposed prenatally to alcohol were impaired as shown in both hippocampal-dependent spatial/place and striatal-dependent response/cue learning tests. Moreover, the levels of BDNF expression both in the hippocampus and striatum of mice were also decreased. Interestingly, environmental enrichment can ameliorate the effects of prenatal alcohol exposure both on the neurobehavioral and neurotrophic levels. These observations indicated that enriched environment attenuated memory impairment of prenatal alcohol exposure both in hippocampal and striatal circuitry. PMID:26417281

  12. RE-AIM evaluation of the Alcohol and Pregnancy Project: educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder.

    PubMed

    Payne, Janet M; France, Kathryn E; Henley, Nadine; D'Antoine, Heather A; Bartu, Anne E; O'Leary, Colleen M; Elliott, Elizabeth J; Bower, Carol; Geelhoed, Elizabeth

    2011-03-01

    The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http://www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

  13. Alcohols toxicology

    SciTech Connect

    Wimer, W.W.; Russell, J.A.; Kaplan, H.L.

    1984-01-01

    A comprehensive reference volume which summarizes literature reports of the known consequences of human and animal contact with alcohols and alcohol-derived substances is presented. Following a discussion of alcohol nomenclature and a brief history of alcohols, the authors have provided detailed chapters on the toxicology of methanol, ethanol, normal and isopropanol, and the butanols. Properties of these alcohols are compared; industrial hygiene and exposure limits are discussed. Additional sections are included covering processing and production technology and exhaust emissions studies. Of particular interest are the section containing abstracts and synopses of principal works and the extensive bibliography of studies dating from the 1800s. 331 references, 26 figures, 56 tables

  14. Effect of alcohol exposure on fetal brain development

    NASA Astrophysics Data System (ADS)

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    Alcohol consumption during pregnancy can be severely damage to the brain development in fetuses. This study investigates the effects of maternal ethanol consumption on brain development in mice embryos. Pregnant mice at gestational day 12.5 were intragastrically gavaged with ethanol (3g/Kg bwt) twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde and imaged using a swept-source optical coherence tomography (SSOCT) system. 3D images of the mice embryo brain were obtained and the volumes of the left and right ventricles of the brain were measured. The average volumes of the left and the right volumes of 5 embryos each alcohol-exposed and control embryos were measured to be 0.35 and 0.15 mm3, respectively. The results suggest that the left and right ventricle volumes of brain are much larger in the alcohol-exposed embryos as compared to control embryos indicating alcohol-induced developmental delay.

  15. Tobacco and alcohol use during pregnancy and risk of oral clefts. Occupational Exposure and Congenital Malformation Working Group.

    PubMed Central

    Lorente, C; Cordier, S; Goujard, J; Aymé, S; Bianchi, F; Calzolari, E; De Walle, H E; Knill-Jones, R

    2000-01-01

    OBJECTIVES: This study examined the relationship between maternal tobacco and alcohol consumption during the first trimester of pregnancy and oral clefts. METHODS: Data were derived from a European multicenter case-control study including 161 infants with oral clefts and 1134 control infants. RESULTS: Multivariate analyses showed an increased risk of cleft lip with or without cleft palate associated with smoking (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.07, 3.04) and an increased risk of cleft palate associated with alcohol consumption (OR = 2.28, 95% CI = 1.02, 5.09). The former risk increased with the number of cigarettes smoked. CONCLUSIONS: This study provides further evidence of the possible role of prevalent environmental exposures such as tobacco and alcohol in the etiology of oral clefts. PMID:10705862

  16. Central and Peripheral Timing Variability in Children with Heavy Prenatal Alcohol Exposure

    PubMed Central

    Simmons, Roger W.; Levy, Susan S.; Riley, Edward P.; Madra, Naju M.; Mattson, Sarah N.

    2008-01-01

    Background The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system (PNS). Methods Eighteen children with histories of prenatal alcohol exposure and 22 control children were assigned to young (7–11 years) or older (12–17 years) groups. Children tapped a single response key with the index finger in synchrony with a series of externally generated tones (the paced phase). At the conclusion of these tones, children continued tapping (the continuation phase) while attempting to maintain the same rate of tapping imposed by the paced phase. Two blocks of tapping were completed with inter-tone-intervals set at either 400 or 900 ms. Inter-response interval, central clock variability, and motor delay variability produced during the continuation phase were the dependent variables. Results Mean inter-response interval for the four groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 ms interval and all other groups for the 900 ms interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced. Conclusions Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central

  17. In vivo genotoxicity of alcohol consumption and lead exposure in printing press workers.

    PubMed

    Rajah, T T; Ahuja, Y R

    1996-01-01

    The objective of the present study was to evaluate the genotoxicity of a double exposure to alcohol and lead in subjects from the printing industry, and the possible interaction between the two agents. Individuals were classified into four different groups: controls, lead-exposed individuals, alcohol consumers, and lead-exposed alcohol consumers. Chromosomal analysis was carried out according to conventional methods and data on chromosome aberrations and sister chromatid exchanges (SCEs) were obtained for each individual. Alcohol consumers had a significant increase in the frequency of SCEs compared to the controls. Though there was an increase in the frequency of chromosome aberrations and SCEs in individuals exposed to lead, it was not significant. Statistical analysis did not reveal an interaction between alcohol and lead in either assay.

  18. Co-regulation of movement speed and accuracy by children with heavy prenatal alcohol exposure.

    PubMed

    Simmons, Roger W; Madra, Naju J; Levy, Susan S; Riley, Edward P; Mattson, Sarah N

    2011-02-01

    The study investigated how children with heavy prenatal alcohol exposure regulate movement speed and accuracy during goal-directed movements. 16 children ages 7 to 17 years with confirmed histories of heavy in utero alcohol exposure, and 21 nonalcohol-exposed control children completed a series of reciprocal tapping movements between two spatial targets. 5 different targets sets were presented, representing a range of task difficulty between 2 and 6 bits of information. Estimates of percent error rate, movement time, slope, and linear fit of the resulting curve confirmed that for goal-directed, reciprocal tapping responses, performance of the group with prenatal alcohol exposure was described by a linear function, as predicted by Fitts' law, by sacrificing movement accuracy. The index of performance was the same for the two groups: it initially increased, then leveled off for more difficult movements.

  19. Alcohol-induced brain growth restrictions (microencephaly) were not affected by concurrent exposure to cocaine during the brain growth spurt.

    PubMed

    Chen, W J; Andersen, K H; West, J R

    1994-09-01

    The prevalence of concomitant use of alcohol and cocaine among drug abusers has raised concern about the possible increased risk of fetal damage. The aim of this study was to assess the interactive effects of alcohol and cocaine on lethality, somatic growth, and brain growth using an animal model system. Sprague-Dawley rat pups were used as subjects. They were randomly assigned to 1 of the 9 artificially reared groups which varied with respect to the combination treatments of cocaine (0, 40, or 60 mg/kg) and alcohol (0, 3.3, or 4.5 g/kg). All artificially reared pups were given daily cocaine and alcohol treatments during a major part of the brain growth spurt period (postnatal days 4-9). An additional group of suckled control animals raised by their natural dams was included to control for artificial rearing. The results are summarized as follows: 1) Drug-induced lethality was higher in cocaine-treated groups when compared with non-cocaine-treated groups, and the concurrent administration of high doses of alcohol and cocaine significantly increased the mortality rate. 2) Somatic growth, in terms of body weight, was not affected by alcohol, cocaine, or the combination of both drugs using the artificial rearing technique. 3) Alcohol exposure during this brain growth spurt period significantly reduced whole brain weight, as well as forebrain, cerebellum, and brain stem weights. 4) In contrast to alcohol, cocaine failed to exert a detrimental effect on brain weight measures during this early postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Acute alcohol exposure markedly influences male fertility and fetal outcome in the male rat.

    PubMed

    Cicero, T J; Nock, B; O'Connor, L; Adams, M L; Sewing, B N; Meyer, E R

    1994-01-01

    Although it is recognized that drugs ingested by pregnant females produce marked cognitive and physiological deficits in their offspring, the possibility that paternal exposure to drugs prior to mating may have adverse effects on fertility and fetal outcome has not received much attention. The purpose of the present studies was to examine whether a single, acute exposure to alcohol influences the subsequent ability of adult male rats to mate and produce healthy and viable litters. Our results showed that a relatively large dose of alcohol 24 hours prior to breeding had little effect on the mating behavior of male rats, but there were markedly fewer pregnancies in females mated with alcohol-exposed male rats than in controls. Of equal importance, we found that, even when conception occurred and live births were produced, there were striking differences in fetal outcome. Alcohol-treated males sired many fewer pups than control males and there was a markedly enhanced mortality rate in their offspring. Collectively, these data suggest that acute paternal alcohol administration 24 hours prior to breeding does not affect mating behavior, but results in a greatly diminished fertility rate and fewer and less viable offspring. These studies suggest that paternal alcohol use may be as important as maternal alcohol abuse as a negative variable in pregnancy and fetal outcome.

  1. Perinatal aromatase activity in male and female rats: effect of prenatal alcohol exposure.

    PubMed

    McGivern, R F; Roselli, C E; Handa, R J

    1988-12-01

    Fetal alcohol exposure has been shown to produce long-term feminizing and demasculinizing effects on male rat behaviors which are organizationally dependent upon perinatal androgen levels. Such exposure has previously been shown to suppress the normal surge of testosterone during the critical prenatal period. Since defeminization of male rat behavior is dependent upon estrogen derived from the aromatization of testosterone in brain, brain aromatase activity was measured during the perinatal period in males and females exposed to alcohol beginning on Day 14 of gestation. Aromatase activity was measured in whole hypothalamus of fetuses from Day 16 through 20 of gestation and in the hypothalamic preoptic area and amygdala of animals 6-12 hr postparturition. Hypothalamic aromatase activity was elevated in fetal alcohol exposed males compared to controls on Days 18 and 19 of gestation and on postnatal Day 1. No effect of prenatal alcohol exposure was found in females. A sex effect in aromatase activity in the amygdala was evident on Day 1 when activity was found to be greater in males than females. Overall, these findings indicate that fetal alcohol exposure will elevate regional brain aromatase activity in males, but not females during the perinatal period of neurobehavioral sexual differentiation.

  2. Association of arsenic exposure with smoking, alcohol, and caffeine consumption: data from NHANES 2005-2010.

    PubMed

    Jain, Ram B

    2015-03-01

    Association of arsenic exposure with smoking, alcohol, and caffeine consumption was investigated. Data from National Health and Nutrition Examination Survey for the years 2005-2010 were used for this investigation. Urinary levels of total arsenic (UAS) and dimethylarsonic acid (UDMA) were evaluated for children aged 6-12 years and adolescents and adults aged ≥ 12 years. Urinary levels of arsenobetaine (UAB) were evaluated for adolescents and adults only. Regression models were fitted for log transformed values of UAB, UAS, and UDMA. For the models for children, however, gender, race/ethnicity, SES, and fish/shell fish consumption during the last 30 days were the only independent variables that were included in the models. Nonsmokers were found to have higher levels of UAS and UDMA than smokers. Elevated levels of UAB, UAS, and UDMA were associated with higher amounts of daily alcohol consumption. The associations were in the opposite direction for daily caffeine consumption. Females were found to have statistically significantly lower adjusted levels of UDMA than males for those aged ≥ 12 years. Irrespective of age, those with unclassified race/ethnicity had the highest levels of UAB, UAS, and UDMA and non-Hispanic whites had the lowest levels. Adolescents had the higher levels of UAB, UAS, and UDMA than adults. Higher SES was associated with higher levels of UAB, UAS, and UDMA among adolescents and adults. Irrespective of age, fish consumption was associated with higher levels of UAB, UAS, and UDMA.

  3. Effects of postnatal alcohol exposure on hippocampal gene expression and learning in adult mice.

    PubMed

    Lee, Dong Hoon; Moon, Jihye; Ryu, Jinhyun; Jeong, Joo Yeon; Roh, Gu Seob; Kim, Hyun Joon; Cho, Gyeong Jae; Choi, Wan Sung; Kang, Sang Soo

    2016-04-28

    Fetal alcohol syndrome (FAS) is a condition resulting from excessive drinking by pregnant women. Symptoms of FAS include abnormal facial features, stunted growth, intellectual deficits and attentional dysfunction. Many studies have investigated FAS, but its underlying mechanisms remain unknown. This study evaluated the relationship between alcohol exposure during the synaptogenesis period in postnatal mice and subsequent cognitive function in adult mice. We delivered two injections, separated by 2 h, of ethanol (3 g/kg, ethanol/saline, 20% v/v) to ICR mice on postnatal day 7. After 10 weeks, we conducted a behavioral test, sacrificed the animals, harvested brain tissue and analyzed hippocampal gene expression using a microarray. In ethanol-treated mice, there was a reduction in brain size and decreased neuronal cell number in the cortex, and also cognitive impairment. cDNA microarray results indicated that 1,548 genes showed a > 2-fold decrease in expression relative to control, whereas 974 genes showed a > 2-fold increase in expression relative to control. Many of these genes were related to signal transduction, synaptogenesis and cell membrane formation, which are highlighted in our findings.

  4. 75 FR 69617 - Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... 30 CFR Parts 70, 71, 72, 75, and 90 RIN 1219-AB64 Lowering Miners' Exposure to Respirable Coal Mine... Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors. The proposed rule was published on... rule. The proposed rule would lower miners' exposure to respirable coal mine dust by revising...

  5. Energy integrated farm, including a solar methane digestor and alcohol plant. Final progress report

    SciTech Connect

    Meier, O.

    1982-01-01

    This final progress report summarizes the authors success in running an alcohol still. The still was to produce over 20,000 gallons of alcohol per year, the waste hot water would be used to heat a methane digestion system and for domestic space and water heating. Many problems were encountered and solutions were noted.

  6. A Smarter Pathway for Delivering Cue Exposure Therapy? The Design and Development of a Smartphone App Targeting Alcohol Use Disorder

    PubMed Central

    Stenager, Elsebeth; Nielsen, Bent; Nielsen, Anette Søgaard; Yu, Fei

    2017-01-01

    Background Although the number of alcohol-related treatments in app stores is proliferating, none of them are based on a psychological framework and supported by empirical evidence. Cue exposure treatment (CET) with urge-specific coping skills (USCS) is often used in Danish treatment settings. It is an evidence-based psychological approach that focuses on promoting “confrontation with alcohol cues” as a means of reducing urges and the likelihood of relapse. Objective The objective of this study was to describe the design and development of a CET-based smartphone app; an innovative delivery pathway for treating alcohol use disorder (AUD). Methods The treatment is based on Monty and coworkers’ manual for CET with USCS (2002). It was created by a multidisciplinary team of psychiatrists, psychologists, programmers, and graphic designers as well as patients with AUD. A database was developed for the purpose of registering and monitoring training activities. A final version of the CET app and database was developed after several user tests. Results The final version of the CET app includes an introduction, 4 sessions featuring USCS, 8 alcohol exposure videos promoting the use of one of the USCS, and a results component providing an overview of training activities and potential progress. Real-time urges are measured before, during, and after exposure to alcohol cues and are registered in the app together with other training activity variables. Data packages are continuously sent in encrypted form to an external database and will be merged with other data (in an internal database) in the future. Conclusions The CET smartphone app is currently being tested at a large-scale, randomized controlled trial with the aim of clarifying whether it can be classified as an evidence-based treatment solution. The app has the potential to augment the reach of psychological treatment for AUD. PMID:28137701

  7. Impulsive Choice, Alcohol Consumption, and Pre-Exposure to Delayed Rewards: II. Potential Mechanisms

    PubMed Central

    Stein, Jeffrey S.; Renda, C. Renee; Hinnenkamp, Jay E.; Madden, Gregory J.

    2014-01-01

    In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In post-tests, delay-exposed rats made significantly fewer impulsive choices at both 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3–12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol’s pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. PMID:25418607

  8. Association between residential exposure to outdoor alcohol advertising and problem drinking among African American women in New York City.

    PubMed

    Kwate, Naa Oyo A; Meyer, Ilan H

    2009-02-01

    We evaluated the association between residential exposure to outdoor alcohol advertising and current problem drinking among 139 African American women aged 21 to 49 years in Central Harlem, New York City. We found that exposure to advertisements was positively related to problem drinking (13% greater odds), even after we controlled for a family history of alcohol problems and socioeconomic status. The results suggest that the density of alcohol advertisements in predominantly African American neighborhoods may add to problem drinking behavior of their residents.

  9. Young Adults’ Exposure to Alcohol- and Marijuana-Related Content on Twitter

    PubMed Central

    Cabrera-Nguyen, E. Peter; Cavazos-Rehg, Patricia; Krauss, Melissa; Bierut, Laura J.; Moreno, Megan A.

    2016-01-01

    Objective: Twitter is among the most popular social media platforms used by young adults, yet it has been underutilized in substance use research compared with older platforms (e.g., MySpace and Facebook). We took a first step toward studying the associations between exposure to pro–alcohol- and marijuana-related content among young adults via Twitter and current heavy episodic drinking and current marijuana use, respectively. Method: We conducted an online survey of 587 (254 men, 333 women) Twitter users between ages 18 and 25 years in February 2014 using an online survey system that has been previously used in research on health behaviors and attitudes. Results: Current heavy episodic drinking was significantly associated with higher levels of exposure to pro-alcohol content. Similarly, current marijuana use was significantly associated with higher levels of exposure to pro-marijuana content. Conclusions: Our findings suggest that in-depth research regarding young adults’ exposure to pro–alcohol- and marijuana-related content via Twitter may provide a foundation for developing effective prevention messages on this social media platform to counter the pro–alcohol and marijuana messages. PMID:26997194

  10. Violence Exposure and Early Adolescent Alcohol Use: An Exploratory Study of Family Risk and Protective Factors

    ERIC Educational Resources Information Center

    Taylor, Kelli W.; Kliewer, Wendy

    2006-01-01

    In this short-term longitudinal exploratory interview study, the relations between exposure to community violence and subsequent alcohol use were examined, with a focus on caregiver and family variables as moderators. Maternal caregivers and their children (N = 101 families; 98% African American; M child age = 11.2 yrs) were interviewed separately…

  11. Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

    DTIC Science & Technology

    2002-09-01

    interneuronal KA-Rs. Moreover, a preliminary experiment with hippocampal slices from rats withdrawn from a 6-day inhalational exposure paradigm suggests...that the function of these receptors is upregulated. During the last year of support, we will concentrate on characterizing the function of KA-Rs in the CAl and CA3 regions in alcohol withdrawn rats.

  12. Children with heavy prenatal alcohol exposure have different frequency domain signal characteristics when producing isometric force.

    PubMed

    Nguyen, Tanya T; Ashrafi, Ashkan; Thomas, Jennifer D; Riley, Edward P; Simmons, Roger W

    2013-01-01

    To extend our current understanding of the teratogenic effects of prenatal alcohol exposure on the control of isometric force, the present study investigated the signal characteristics of power spectral density functions resulting from sustained control of isometric force by children with and without heavy prenatal exposure to alcohol. It was predicted that the functions associated with the force signals would be fundamentally different for the two groups. Twenty-five children aged between 7 and 17 years with heavy prenatal alcohol exposure and 21 non-alcohol exposed control children attempted to duplicate a visually represented target force by pressing on a load cell. The level of target force (5 and 20% of maximum voluntary force) and the time interval between visual feedback (20 ms, 320 ms and 740 ms) were manipulated. A multivariate spectral estimation method with sinusoidal windows was applied to individual isometric force-time signals. Analysis of the resulting power spectral density functions revealed that the alcohol-exposed children had a lower mean frequency, less spectral variability, greater peak power and a lower frequency at which peak power occurred. Furthermore, mean frequency and spectral variability produced by the alcohol-exposed group remained constant across target load and visual feedback interval, suggesting that these children were limited to making long-time scale corrections to the force signal. In contrast, the control group produced decreased mean frequency and spectral variability as target force and the interval between visual feedback increased, indicating that when feedback was frequently presented these children used the information to make short-time scale adjustments to the ongoing force signal. Knowledge of these differences could facilitate the design of motor rehabilitation exercises that specifically target isometric force control deficits in alcohol-exposed children.

  13. The CRHR1 gene, trauma exposure, and alcoholism risk: a test of G × E effects.

    PubMed

    Ray, L A; Sehl, M; Bujarski, S; Hutchison, K; Blaine, S; Enoch, M-A

    2013-06-01

    The corticotropin-releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. On the basis of the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and single-nucleotide polymorphisms (SNPs) in predicting the risk for alcoholism. Phenotypic data on 2533 non-related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment genome-wide association study. Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes/SNPs and adulthood traumatic stress exposure in predicting alcoholism risk. Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (P = 0.029) and two haplotypes in the distal block 2 (P = 0.026, 0.042) that showed nominally significant (corrected P < 0.025) genotype × traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (P = 0.019) and rs242924 (P = 0.019). In block 2, rs17689966 (P = 0.018) showed significant and rs173365 (P = 0.026) showed nominally significant, gene × environment (G × E) effects on alcoholism status. This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci.

  14. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    PubMed

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  15. Regulation of Milk Intake After Exposure to Alcohol in Mothers’ Milk

    PubMed Central

    Mennella, Julie A.

    2009-01-01

    Objective Contrary to the folklore which claims that drinking alcohol during lactation benefits both mother and infant, previous research in our laboratory revealed that breastfed infants consumed significantly less milk during the immediate hours after their mothers’ consumption of an alcoholic beverage. Because breastfed infants are clearly capable of regulating milk intake, the present study tested the hypothesis that infants would compensate for the diminished milk intake if their mothers then refrained from drinking alcohol. Methods A within-subjects design that controlled for time of day was implemented because of the great individual and daily variation in both milk composition and intake. To this end, 12 exclusively breastfed infants and their mothers were tested on 2 days separated by 1 week. Each woman drank a 0.3 g/kg dose of alcohol in orange juice on one testing day and orange juice alone on the other; the order was counterbalanced. The infants’ behaviors were monitored for the next 16 hr, the first 4 hr of monitoring on each test day occurred at the Monell Center. The infants fed on demand and immediately before and after each feeding, infants were weighed without a change in clothing. Results Consistent with previous findings, infants consumed significantly less milk during the 4 hr immediately after exposure to alcohol in mothers’ milk compared with the control condition. Compensatory increases in intake were then observed during the 8 to 16 hr after exposure when mothers refrained from drinking alcohol. Conclusions These findings demonstrate that short-term exposure to small amounts of alcohol in mothers’ milk produces distinctive changes in the infants’ patterns of feeding. PMID:11329500

  16. Alcohol Advertising at Boston Subway Stations: An Assessment of Exposure by Race and Socioeconomic Status

    PubMed Central

    Poirier, Katie; Wilkinson, Tiana; Nhean, Siphannay; Nyborn, Justin; Siegel, Michael

    2011-01-01

    Objectives. We investigated the frequency of alcohol ads at all 113 subway and streetcar stations in Boston and the patterns of community exposure stratified by race, socioeconomic status, and age. Methods. We assessed the extent of alcohol advertising at each station in May 2009. We measured gross impressions and gross rating points (GRPs) for the entire Greater Boston population and for Boston public school student commuters. We compared the frequency of alcohol advertising between neighborhoods with differing demographics. Results. For the Greater Boston population, alcohol advertising at subway stations generated 109 GRPs on a typical day. For Boston public school students in grades 5 to 12, alcohol advertising at stations generated 134 GRPs. Advertising at stations in low-poverty neighborhoods generated 14.1 GRPs and at stations in high-poverty areas, 63.6 GRPs. Conclusions. Alcohol ads reach the equivalent of every adult in the Greater Boston region and the equivalent of every 5th- to 12th-grade public school student each day. More alcohol ads were displayed in stations in neighborhoods with high poverty rates than in stations in neighborhoods with low poverty rates. PMID:21852632

  17. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)

    PubMed Central

    Takaki, Akinobu; Kawai, Daisuke; Yamamoto, Kazuhide

    2013-01-01

    Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. PMID:24132155

  18. Assessment of Exposure to Alcohol Vapor from Alcohol-Based Hand Rubs

    PubMed Central

    Bessonneau, Vincent; Thomas, Olivier

    2012-01-01

    This study assessed the inhaled dose of alcohol during hand disinfection. Experiments were conducted with two types of hand rub using two hand disinfection procedures. Air samples were collected every 10 s from the breathing zone, by bubbling through a mixture of K2Cr2O7 and H2SO4. The reduction of dichromate ions in the presence of alcohols was followed by UV-vis spectrophotometry. The difference in intensity of the dichromate absorption peak was used to quantify the alcohol concentration expressed in ethanol equivalent. During hygienic hand disinfection, the mean ethanol equivalent concentrations peaked at around 20–30 s for both hand rubs (14.3 ± 1.4 mg/L for hand rub 1 and 13.2 ± 0.7 mg/L for hand rub 2). During surgical hand disinfection, two peaks were found at the same time (40 and 80 s) for both hand rubs. The highest mean concentrations were 20.2 ± 0.9 mg/L for hand rub 1 and 18.1 ± 0.9 mg/L for hand rub 2. For hand rub 1, the total absorbed doses, calculated from ethanol with an inhalation flow of 24 L/min and an absorption rate of 62%, were 46.5 mg after one hygienic hand disinfection and 203.9 mg after one surgical hand disinfection. Although the use of ABHRs leads to the absorption of very low doses, sudden, repeated inhalation of high alcohol concentrations raises the question of possible adverse health effects. PMID:22690169

  19. Assessment of exposure to alcohol vapor from alcohol-based hand rubs.

    PubMed

    Bessonneau, Vincent; Thomas, Olivier

    2012-03-01

    This study assessed the inhaled dose of alcohol during hand disinfection. Experiments were conducted with two types of hand rub using two hand disinfection procedures. Air samples were collected every 10 s from the breathing zone, by bubbling through a mixture of K(2)Cr(2)O(7) and H(2)SO(4). The reduction of dichromate ions in the presence of alcohols was followed by UV-vis spectrophotometry. The difference in intensity of the dichromate absorption peak was used to quantify the alcohol concentration expressed in ethanol equivalent. During hygienic hand disinfection, the mean ethanol equivalent concentrations peaked at around 20-30 s for both hand rubs (14.3 ± 1.4 mg/L for hand rub 1 and 13.2 ± 0.7 mg/L for hand rub 2). During surgical hand disinfection, two peaks were found at the same time (40 and 80 s) for both hand rubs. The highest mean concentrations were 20.2 ± 0.9 mg/L for hand rub 1 and 18.1 ± 0.9 mg/L for hand rub 2. For hand rub 1, the total absorbed doses, calculated from ethanol with an inhalation flow of 24 L/min and an absorption rate of 62%, were 46.5 mg after one hygienic hand disinfection and 203.9 mg after one surgical hand disinfection. Although the use of ABHRs leads to the absorption of very low doses, sudden, repeated inhalation of high alcohol concentrations raises the question of possible adverse health effects.

  20. Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9

    PubMed Central

    Simino, Jeannette; Sung, Yun Ju; Kume, Rezart; Schwander, Karen; Rao, D. C.

    2013-01-01

    Alcohol consumption is a known risk factor for hypertension, with recent candidate studies implicating gene-alcohol interactions in blood pressure (BP) regulation. We used 6882 (predominantly) Caucasian participants aged 20–80 years from the Framingham SNP Health Association Resource (SHARe) to perform a genome-wide analysis of SNP-alcohol interactions on BP traits. We used a two-step approach in the ABEL suite to examine genetic interactions with three alcohol measures (ounces of alcohol consumed per week, drinks consumed per week, and the number of days drinking alcohol per week) on four BP traits [systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure]. In the first step, we fit a linear mixed model of each BP trait onto age, sex, BMI, and antihypertensive medication while accounting for the phenotypic correlation among relatives. In the second step, we conducted 1 degree-of-freedom (df) score tests of the SNP main effect, alcohol main effect, and SNP-alcohol interaction using the maximum likelihood estimates (MLE) of the parameters from the first step. We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL. The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively). Each copy of the G-allele decreased SBP by 3.79 mmHg in those consuming 14 drinks per week vs. a 0.461 mmHg decrease in non-drinkers. Index SNPs in 20 other loci exhibited suggestive (p-value ≤ 1E-06) associations with BP traits by the 1 df interaction test or joint 2 df test, including 3 rare variants, one low-frequency variant, and SNPs near/in genes ESRRG, FAM179A, CRIPT-SOCS5, KAT2B, ADCY2, GLI3, ZNF716, SLIT1, PDE3A, KERA-LUM, RNF219-AS1, CLEC3A, FBXO15, and IGSF5. SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be

  1. In utero exposure to alcohol and puberty in boys: a pregnancy cohort study

    PubMed Central

    Håkonsen, Linn Berger; Brath-Lund, Mette Louise; Hounsgaard, Marie Louise; Olsen, Jørn; Ernst, Andreas; Thulstrup, Ane Marie; Bech, Bodil Hammer; Ramlau-Hansen, Cecilia Høst

    2014-01-01

    Objectives Epidemiological studies have raised concerns about the reproductive consequences of in utero exposure to alcohol. Maternal lifestyle factors have been associated with altered pubertal development, but the impact of prenatal alcohol exposure on male puberty is unknown. Thus, the objective was to explore whether prenatal alcohol exposure alters pubertal development in boys. Setting Follow-up of a Danish pregnancy cohort. Participants Sons (N=2522) of women who were enrolled in a Danish pregnancy cohort between 1984 and 1987. Primary and secondary outcome measures Indicators of pubertal development, assessed by age at first nocturnal emission, voice break, acne and regular shaving. Results We found a tendency towards a later age at first nocturnal emission and voice break following in utero exposure to binge drinking. Boys exposed to ≥5 binge drinking episodes during pregnancy experienced their first nocturnal emission 7.3 months (95% CI −2.8 to 17.4) later and voice break 4.9 months (95% CI −0.6 to 10.4) later than the unexposed boys. Results for average weekly alcohol consumption were in the same direction, but differences were smaller and not statistically significant. Conclusions We found no strong support for the hypothesis that in utero exposure to weekly alcohol consumption is a risk factor for altered pubertal development, but a tendency towards delayed pubertal development among boys exposed to binge drinking during fetal life was observed. Longitudinal studies, with data collected as children go through puberty, are needed to explore this further. PMID:24916086

  2. Effects of intermittent binge alcohol exposure on long-term motor function in young rats.

    PubMed

    Forbes, Ashley; Cooze, Jared; Malone, Craig; French, Vanessa; Weber, John T

    2013-03-01

    Ethanol has well described acute effects on motor function, and chronic alcoholism can damage the cerebellum, which is associated with motor coordination, as well as motor learning. Binge drinking is common among preadolescents and adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we analyzed the effects of periadolsecent/adolescent ethanol exposure on motor function in both male and female Sprague-Dawley rats. To simulate binge drinking, animals received an intraperitoneal injection of 25% (v/v) ethanol (3 g/kg) on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37 and 38. On PND 42 and PND 61 animals were tested on their ability to traverse both square and round beams. There were no significant differences in the time to traverse the beams, or the amount of foot slips, between treated and untreated animals. On PND 48 and PND 62, animals were tested using a horizontal ladder walking apparatus. On PND 48 there were no differences in the ability of treated and untreated animals to traverse the ladder. On PND 62, there were no differences in the time to traverse the ladder, but ethanol treated animals had more foot slips than controls. On PND 43, we conducted footprint analysis of control and treated animals, which included measurements of stride length, paw overlap, and angle of foot placement. There was a significant difference in the angle of foot placement between treated and control animals, and this finding was significant for both male and female animals. There was also a significant overall difference in paw overlap between treatment groups. Although this effect was manifested in male animals there was no significant difference in females. These findings suggest that adolescent ethanol exposure can produce long-lasting effects on motor coordination, and that overall, effects are similar in males and females. In a second set of experiments, male rats received i.p. ethanol (3 g/kg) for 7 days (P31

  3. Is It Important to Prevent Early Exposure to Drugs and Alcohol Among Adolescents?

    PubMed Central

    Odgers, Candice L.; Caspi, Avshalom; Nagin, Daniel S.; Piquero, Alex R.; Slutske, Wendy S.; Milne, Barry J.; Dickson, Nigel; Poulton, Richie; Moffitt, Terrie E.

    2013-01-01

    Exposure to alcohol and illicit drugs during early adolescence has been associated with poor outcomes in adulthood. However, many adolescents with exposure to these substances also have a history of conduct problems, which raises the question of whether early exposure to alcohol and drugs leads to poor outcomes only for those adolescents who are already at risk. In a 30-year prospective study, we tested whether there was evidence that early substance exposure can be a causal factor for adolescents’ future lives. After propensity-score matching, early-exposed adolescents remained at an increased risk for a number of poor outcomes. Approximately 50% of adolescents exposed to alcohol and illicit drugs prior to age 15 had no conduct-problem history, yet were still at an increased risk for adult substance dependence, herpes infection, early pregnancy, and crime. Efforts to reduce or delay early substance exposure may prevent a wide range of adult health problems and should not be restricted to adolescents who are already at risk. PMID:19000215

  4. Hippocampal Neuron Populations Are Reduced in Vervet Monkeys With Fetal Alcohol Exposure

    PubMed Central

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R; Palmour, Roberta M

    2015-01-01

    Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65–70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume. © 2015 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc. Dev Psychobiol 57:470–485, 2015. PMID:25913787

  5. Moderate Level Prenatal Alcohol Exposure Induces Sex Differences in Dopamine D1 Receptor Binding in Adult Rhesus Monkeys

    PubMed Central

    Converse, Alexander K.; Moore, Colleen F.; Holden, James E.; Ahlers, Elizabeth O.; Moirano, Jeffrey M.; Larson, Julie A.; Resch, Leslie M.; DeJesus, Onofre T.; Barnhart, Todd E.; Nickles, Robert J.; Murali, Dhanabalan; Christian, Bradley T.; Schneider, Mary L.

    2014-01-01

    Background We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on D1 receptor binding in a nonhuman primate model. The dopamine D1 receptor is involved in executive function, and it may play a role in cognitive behavioral deficits associated with prenatal alcohol and/or stress exposure. Little is known, however, about the effects of prenatal alcohol and/or stress exposure on the D1 receptor. We expected that prenatal insults would lead to alterations in D1 receptor binding in prefrontal cortex and striatum in adulthood. Methods Rhesus macaque females were randomly assigned to moderate alcohol exposure and/or mild prenatal stress as well as a control condition during pregnancy. Thirty eight offspring were raised identically and studied as adults by non-invasive in vivo neuroimaging using positron emission tomography (PET) with the D1 antagonist radiotracer [11C]SCH 23390. Radiotracer binding in prefrontal cortex and striatum was evaluated by 2 (alcohol) × 2 (stress) × 2 (sex) analysis of variance. Results In prefrontal cortex, a significant alcohol × sex interaction was observed with prenatal alcohol exposure leading to increased [11C]SCH 23390 binding in male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was observed. Conclusions These results suggest that prenatal alcohol exposure results in long-term increases in prefrontal dopamine D1 receptor binding in males. This may help explain gender differences in the prevalence of neurodevelopmental disorders consequent to prenatal alcohol exposure. PMID:25581649

  6. Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

    PubMed

    Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

    2016-01-01

    Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

  7. Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

    PubMed

    Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

    2014-08-01

    Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment.

  8. Development of brain vessels in human embryos and fetuses in conditions of prenatal exposure to alcohol.

    PubMed

    Solonskii, A V; Logvinov, S V; Kutepova, N A

    2008-05-01

    Light and electron microscopy were used to study the characteristics of the formation of brain vascular structures at the early stages of development in conditions of maternal alcoholization during pregnancy. Computer morphometric methods using the Scion Image system for image analysis showed that fetuses at 11-12 weeks of development in conditions of prenatal alcohol exposure showed a decrease in the mean absolute cross-sectional area of vessels in the intermediate layer of the brain, with an increase in their relative area and an increase per unit area of sections, as compared with the control group. Vessels started to differentiate into arteries and veins from 10 weeks of development.

  9. Prenatal exposure to alcohol affects the ability to maintain postural balance.

    PubMed

    Roebuck, T M; Simmons, R W; Mattson, S N; Riley, E P

    1998-02-01

    Prenatal exposure to alcohol is known to affect gross motor functioning. Animal studies have shown that balance is particularly affected, and there is some evidence that similar deficits exist in alcohol-exposed children. In the current study, postural balance, or the ability to maintain equilibrium, was assessed in a group of alcohol-exposed children (ALC group; n = 11) and controls (NC group; n = 11) individually matched for age and sex. Balance was measured across six conditions designed to systematically manipulate or eliminate visual or somatosensory information. Equilibrium and strategy scores for each condition and a derived composite balance score were analyzed. Although the ALC group had a lower mean composite balance score, their performance was similar to that of the NC group on all conditions where somatosensory input was reliable. However, when somatosensory input was manipulated, and when both somatosensory and visual input were inaccurate, the ALC group performed more poorly than controls. Interestingly, there were no differences between the ALC group and NC group in the type of control strategy used to maintain balance. These results suggest that alcohol-exposed children are overly reliant on somatosensory input. When this input is atypical, alcohol-exposed children display significantly greater anterior-posterior body sway and are unable to compensate using available visual or vestibular information. These deficits may be related to cerebellar anomalies previously reported in fetal alcohol syndrome children.

  10. Alcohol

    MedlinePlus

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  11. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  12. Betaine supplementation reduces congenital defects after prenatal alcohol exposure (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Sheehan, Megan M.; Ma, Pei; Peterson, Lindsy M.; Linask, Kersti K.; Jenkins, Michael W.; Rollins, Andrew M.; Watanabe, Michiko

    2016-03-01

    Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. As high as 20-50% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life-threatening. Previously we established a model of PAE (modeling a single binge drinking episode) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early-stage cardiac function/structure and late-stage cardiac defects. At early stages, alcohol/ethanol-exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and also exhibited smaller or abnormal atrio-ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other animal models, the methyl donor betaine (found naturally in many foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In our model of PAE, betaine supplementation led to a reduction in gross structural defects and appeared to protect against certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. These findings highlight the importance of betaine and potentially methylation levels in the prevention of PAE-related birth defects which could have significant implications for public health.

  13. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain.

    PubMed

    Ngai, Ying Fai; Sulistyoningrum, Dian C; O'Neill, Ryan; Innis, Sheila M; Weinberg, Joanne; Devlin, Angela M

    2015-09-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.

  14. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    PubMed Central

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  15. Effects of low-dose alcohol exposure on simulated merchant ship piloting by maritime cadets.

    PubMed

    Howland, J; Rohsenow, D J; Cote, J; Gomez, B; Mangione, T W; Laramie, A K

    2001-03-01

    The US Department of Transportation (DOT) regulates on-the-job alcohol use by operators of certain categories of commercial transport. For aircraft, trains, and commercial vessels, operators are subject to sanctions for having > or = 0.04 g% blood alcohol concentration (BAC). This study examines the effects of alcohol (between 0.04 and 0.05 g% BAC) on simulated merchant ship handling. A two-group randomized factorial design was used to compare beverage alcohol to placebo while controlling for baseline performance on a previous day. The study was conducted in the Maritime Simulation Center at Maine Maritime Academy, Castine, ME. Participants were 38 volunteer deck officer cadets in their junior or senior year, at least 21 years of age, with previous experience on a bridge simulator. Following a baseline trial on Day 1, on Day 2 participants were randomized to receive alcohol (0.6 g/kg for males and 0.5 g/kg for females) or placebo. After allowing time for absorption, participants completed a bridge simulator task. For baseline and performance trials, participants were randomized to one of four bridge simulator scenarios, each representing passage of a fully loaded container vessel through a channel with commercial traffic. The aggregate scenario score given by blinded maritime educators measured performance. A main effect for alcohol was found indicating that performance was significantly impaired by this low dose of alcohol relative to performance in the placebo condition. These findings are consistent with current federal regulations that limit low-dose alcohol exposure for the operators of commercial transport vehicles. Further research is required to determine effects at lower BACs.

  16. Variations on the "Whoosh" Bottle Alcohol Explosion Demonstration Including Safety Notes

    NASA Astrophysics Data System (ADS)

    Fortman, John J.; Rush, Andrea C.; Stamper, Jennifer E.

    1999-08-01

    The explosion or burning of methanol, ethanol, n-propanol, and isopropanol in large small-necked bottles when ignited with a match has been studied with respect to the nature of the alcohol, temperature, concentration dilutions with water, oxygen concentration, plastic versus glass bottles, and salts added for color. The various effects are explained in terms of vapor pressures. Safety guidelines are emphasized.

  17. Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review

    PubMed Central

    Spear, Linda Patia; Swartzwelder, H. Scott

    2014-01-01

    Alcohol use is typically initiated during adolescence, which, along with young adulthood, is a vulnerable period for the onset of high-risk drinking and alcohol abuse. Given across-species commonalities in certain fundamental neurobehavioral characteristics of adolescence, studies in laboratory animals such as the rat have proved useful to assess persisting consequences of repeated alcohol exposure. Despite limited research to date, reports of long-lasting effects of adolescent ethanol exposure are emerging, along with certain common themes. One repeated finding is that adolescent exposure to ethanol sometimes results in the persistence of adolescent-typical phenotypes into adulthood. Instances of adolescent -like persistence have been seen in terms of baseline behavioral, cognitive, electrophysiological and neuroanatomical characteristics, along with the retention of adolescent-typical sensitivities to acute ethanol challenge. These effects are generally not observed after comparable ethanol exposure in adulthood. Persistence of adolescent-typical phenotypes is not always evident, and may be related to regionally-specific ethanol influences on the interplay between CNS excitation and inhibition critical for the timing of neuroplasticity. PMID:24813805

  18. Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review.

    PubMed

    Spear, Linda Patia; Swartzwelder, H Scott

    2014-09-01

    Alcohol use is typically initiated during adolescence, which, along with young adulthood, is a vulnerable period for the onset of high-risk drinking and alcohol abuse. Given across-species commonalities in certain fundamental neurobehavioral characteristics of adolescence, studies in laboratory animals such as the rat have proved useful to assess persisting consequences of repeated alcohol exposure. Despite limited research to date, reports of long-lasting effects of adolescent ethanol exposure are emerging, along with certain common themes. One repeated finding is that adolescent exposure to ethanol sometimes results in the persistence of adolescent-typical phenotypes into adulthood. Instances of adolescent-like persistence have been seen in terms of baseline behavioral, cognitive, electrophysiological and neuroanatomical characteristics, along with the retention of adolescent-typical sensitivities to acute ethanol challenge. These effects are generally not observed after comparable ethanol exposure in adulthood. Persistence of adolescent-typical phenotypes is not always evident, and may be related to regionally specific ethanol influences on the interplay between CNS excitation and inhibition critical for the timing of neuroplasticity.

  19. Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Review of Evidence and Guidelines for Assessment

    PubMed Central

    Doyle, Lauren R.; Mattson, Sarah N.

    2015-01-01

    The effects of prenatal alcohol use have been well documented. In this review, we discuss the inclusion of Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) as a condition for further study in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5). We present a review of the evidence for impairment in three domains highlighted in ND-PAE: neurocognitive functioning, self2 regulation, and adaptive functioning. In addition, we provide guidelines for clinical assessment of each domain. When considering ND-PAE, it is essential to obtain as comprehensive an assessment as possible, including multidisciplinary/multimethod assessment of the individual by a qualified team. It is our aim to provide clinicians with a useful reference for assessing ND-PAE and highlight important guidelines to be followed when conducting neuropsychological assessment. PMID:26509108

  20. Alcohol vapor exposure differentially impacts mesocorticolimbic cytokine expression in a sex-, region-, and duration-specific manner.

    PubMed

    Baxter-Potter, Lydia N; Henricks, Angela M; Berger, Anthony L; Bieniasz, Kennedy V; Lugo, Janelle M; McLaughlin, Ryan J

    2017-03-27

    Alcohol exposure elicits the production of cytokines that regulate the host response to infection, immunity, inflammation, and trauma. Although increased production of pro-inflammatory cytokines has been linked to symptoms of alcoholism, few studies have evaluated whether cytokine expression changes across the development of alcohol dependence, or whether these changes are region and/or sex specific. In the present study, we subjected adult male and female rats to different regimens of alcohol vapor exposure (acute, subchronic, or chronic) and measured relative mRNA expression for tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) in reward-related brain regions. Results indicated that acute alcohol exposure increased TNFα mRNA expression in the basolateral amygdala (BLA), nucleus accumbens (NAc), and ventral tegmental area (VTA), whereas IL-6 expression was increased in the VTA, NAc, and ventromedial prefrontal cortex (vmPFC) only in males. After subchronic exposure (1week daily intermittent exposure, 14h on:10h off), TNFα expression remained elevated in the BLA, NAc, and VTA, while IL-6 expression was reduced in the male vmPFC. Chronic alcohol exposure (6week daily intermittent exposure, 14 h on: 10 h off) increased TNFα mRNA expression in the NAc and increased IL-6 mRNA in the vmPFC and NAc. Interestingly, chronic alcohol exposure also robustly increased CCL2 mRNA expression in the BLA and VTA in males but not females. Thus, alcohol vapor exposure elicits sex-, region-, and duration-specific cytokine alterations that may contribute to differences in the manifestation and progression of symptoms of alcohol dependence in male and female populations.

  1. Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: a model for fetal alcohol spectrum disorders

    PubMed Central

    Kleiber, Morgan L.; Diehl, Eric J.; Laufer, Benjamin I.; Mantha, Katarzyna; Chokroborty-Hoque, Aniruddho; Alberry, Bonnie; Singh, Shiva M.

    2014-01-01

    There is abundant evidence that prenatal alcohol exposure leads to a range of behavioral and cognitive impairments, categorized under the term fetal alcohol spectrum disorders (FASDs). These disorders are pervasive in Western cultures and represent the most common preventable source of neurodevelopmental disabilities. The genetic and epigenetic etiology of these phenotypes, including those factors that may maintain these phenotypes throughout the lifetime of an affected individual, has become a recent topic of investigation. This review integrates recent data that has progressed our understanding FASD as a continuum of molecular events, beginning with cellular stress response and ending with a long-term “footprint” of epigenetic dysregulation across the genome. It reports on data from multiple ethanol-treatment paradigms in mouse models that identify changes in gene expression that occur with respect to neurodevelopmental timing of exposure and ethanol dose. These studies have identified patterns of genomic alteration that are dependent on the biological processes occurring at the time of ethanol exposure. This review also adds to evidence that epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA regulation may underlie long-term changes to gene expression patterns. These may be initiated by ethanol-induced alterations to DNA and histone methylation, particularly in imprinted regions of the genome, affecting transcription which is further fine-tuned by altered microRNA expression. These processes are likely complex, genome-wide, and interrelated. The proposed model suggests a potential for intervention, given that epigenetic changes are malleable and may be altered by postnatal environment. This review accentuates the value of mouse models in deciphering the molecular etiology of FASD, including those processes that may provide a target for the ammelioration of this common yet entirely preventable disorder. PMID:24917881

  2. Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach.

    PubMed

    Lachenmeier, Dirk W; Przybylski, Maria C; Rehm, Jürgen

    2012-09-15

    Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4-methylimidazole, N-nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost-effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk.

  3. Alcohol

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Alcohol KidsHealth > For Kids > Alcohol Print A A A What's in this article? ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  4. Developmental alcohol exposure leads to a persistent change on astrocyte secretome.

    PubMed

    Trindade, Pablo; Hampton, Brian; Manhães, Alex C; Medina, Alexandre E

    2016-06-01

    Fetal alcohol spectrum disorder is the most common cause of mental disabilities in the western world. It has been quite established that acute alcohol exposure can dramatically affect astrocyte function. Because the effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to persistent changes in astrocyte secretome in vitro. Animals were treated with ethanol (3.5 g/kg) or saline between postnatal day (P)10-30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids. Twenty-four hour conditioned media of cells obtained from ethanol- or saline-treated animals (ET-CM or SAL-CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here, we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET-CM to SAL-CM. Among the 59 proteins that were found to be reduced in ET-CM we observed components of the extracellular matrix such as laminin subunits α2, α4, β1, β2, and γ1 and the proteoglycans biglycan, heparan sulfate proteoglycan 2, and lumican. Proteins with trophic function such as insulin-like growth factor binding protein 4, pigment epithelium-derived factor, and clusterin as well as proteins involved on modulation of proteolysis such as metalloproteinase inhibitor 1 and plasminogen activator inhibitor-1 were also reduced. In contrast, pro-synaptogeneic proteins like thrombospondin-1, hevin as well as the modulator of extracelular matrix expression, angiotensinogen, were found increased in ET-CM. The analysis of interactome maps through ingenuity pathway analysis demonstrated that the amyloid beta A4 protein precursor, which was found reduced in ET-CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET-CM. Taken together our results

  5. Prenatal Triclosan Exposure and Anthropometric Measures Including Anogenital Distance in Danish Infants

    PubMed Central

    Lassen, Tina Harmer; Frederiksen, Hanne; Kyhl, Henriette Boye; Swan, Shanna H.; Main, Katharina M.; Andersson, Anna-Maria; Lind, Dorte Vesterholm; Husby, Steffen; Wohlfahrt-Veje, Christine; Skakkebæk, Niels E.; Jensen, Tina Kold

    2016-01-01

    compatible with an anti-androgenic effect of prenatal TCS exposure on fetal growth in boys. Citation: Lassen TH, Frederiksen H, Kyhl HB, Swan SH, Main KM, Andersson AM, Lind DV, Husby S, Wohlfahrt-Veje C, Skakkebæk NE, Jensen TK. 2016. Prenatal triclosan exposure and anthropometric measures including anogenital distance in Danish infants. Environ Health Perspect 124:1261–1268; http://dx.doi.org/10.1289/ehp.1409637 PMID:26908126

  6. Risk for Exposure to Alcohol, Tobacco, and Other Drugs on the Route to and from School: The Role of Alcohol Outlets

    PubMed Central

    Milam, AJ; Furr-Holden, CDM; Cooley-Strickland, MC; Bradshaw, CP; Leaf, PJ

    2013-01-01

    Despite the national push encouraging children to walk to school, little work has been done to examine what hazards children encounter on the route to school. This study examined the association between the presence of alcohol outlets on children’s route to school and perceived safety on the route to school as well as exposure to alcohol, tobacco, and other drugs (ATOD). Data come from a community-based epidemiological study of 394 urban elementary school students. Participants’ residential address, school location, and alcohol outlet data were geocoded and the route to school was mapped. The route to school layer and the geocoded alcohol outlet data were joined to determine the number of alcohol outlets children pass on the route to school. Logistic regression models estimated the association between the presence of alcohol outlets on the route to school, alcohol and drug exposure, and self-reported safety. Children with an alcohol outlet on the route to school were more likely to be offered ATOD (OR= 2.20, p=.02) as well as be exposed to drug selling (OR=1.72, p=.02) and seeing people using drugs (OR=1.93, p=.02). After adjusting for individual-level variables the relationship between presence of alcohol outlets and being offered ATOD and seeing people using drugs remained significant. However, after adjusting for individual-level control variables and a proxy for the larger neighborhood context, the association between the presence of alcohol outlets and exposure to ATOD was no longer significant. As national campaigns are encouraging children to walk to school it is essential to consider what children are exposed to on the route to school. PMID:23408286

  7. Youth Alcohol Brand Consumption and Exposure to Brand Advertising in Magazines

    PubMed Central

    Ross, Craig S; Ostroff, Joshua; Siegel, Michael B; DeJong, William; Naimi, Timothy S; Jernigan, David H

    2014-01-01

    Objective: Recently published research has identified the alcohol brands most frequently consumed by underage youth. The present study examines alcohol magazine advertising in 2011 to report age- and sex-specific exposure to advertisements for these brands in contrast with other magazine advertising brands less popular with youth. Method: We licensed magazine advertising occurrence data from Nielsen and magazine audience data from the research company GfK MRI (Growth from Knowledge, Mediamark Research & Intelligence) for national full-run editions for 2011. We contrasted per capita advertising exposure, considering different age- and sex-specific groups, for popular youth brands versus all other magazine brands. For each brand, we reported the age group receiving the highest level of per capita advertising exposure, as well as other age groups within 10% of that peak level. Results: Underage males ages 18–20 were the most heavily exposed age group for 11 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 6 brands. Underage females ages 18–20 were most heavily exposed for 16 of the top 25 brands they consumed and were within 10% of the most heavily exposed group for another 2 brands. In contrast, those ages 18–20 were the most heavily exposed group for fewer than 10% of the remaining 308 magazine advertising brands for either sex. Conclusions: These findings suggest a relationship between advertising exposure and youth alcohol brand consumption. Current alcohol industry self-regulatory codes may not be sufficiently protective of youth. PMID:24988260

  8. Chronic exposure to alcohol alters network activity and morphology of cultured hippocampal neurons.

    PubMed

    Korkotian, Eduard; Botalova, Alena; Odegova, Tatiana; Segal, Menahem

    2015-03-01

    The effects of chronic exposure to moderate concentrations of ethanol were studied in cultured hippocampal neurons. Network activity, assessed by imaging of [Ca(2+)]i variations, was markedly suppressed following 5 days of exposure to 0.25-1% ethanol. The reduced activity was sustained following extensive washout of ethanol, but the activity recovered by blockade of inhibition with bicuculline. This reduction of network activity was associated with a reduction in rates of mEPSCs, but not in a change in inhibitory synaptic activity. Chronic exposure to ethanol caused a significant reduction in the density of mature dendritic spines, without an effect on dendritic length or arborization. These results indicate that chronic exposure to ethanol causes a reduction in excitatory network drive in hippocampal neurons adding another dimension to the chronic effects of alcohol abuse.

  9. Estimates of Ethanol Exposure in Children from Food not Labeled as Alcohol-Containing.

    PubMed

    Gorgus, Eva; Hittinger, Maike; Schrenk, Dieter

    2016-09-01

    Ethanol is widely used in herbal medicines, e.g., for children. Furthermore, alcohol is a constituent of fermented food such as bread or yogurt and "non-fermented" food such as fruit juices. At the same time, exposure to very low levels of ethanol in children is discussed as possibly having adverse effects on psychomotoric functions. Here, we have analyzed alcohol levels in different food products from the German market. It was found that orange, apple and grape juice contain substantial amounts of ethanol (up to 0.77 g/L). Furthermore, certain packed bakery products such as burger rolls or sweet milk rolls contained more than 1.2 g ethanol/100 g. We designed a scenario for average ethanol exposure by a 6-year-old child. Consumption data for the "categories" bananas, bread and bakery products and apple juice were derived from US and German surveys. An average daily exposure of 10.3 mg ethanol/kg body weight (b.w.) was estimated. If a high (acute) consumption level was assumed for one of the "categories," exposure rose to 12.5-23.3 mg/kg b.w. This amount is almost 2-fold (average) or up to 4-fold (high) higher than the lowest exposure from herbal medicines (6 mg/kg b.w.) suggested to require warning hints for the use in children.

  10. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

    PubMed

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

    2009-10-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

  11. Salivary cortisol levels are elevated in the afternoon and at bedtime in children with prenatal alcohol exposure.

    PubMed

    Keiver, Kathy; Bertram, Chris P; Orr, Alison Pritchard; Clarren, Sterling

    2015-02-01

    Prenatal alcohol exposure can cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which may underlie some of the behavioral and adaptive problems seen in individuals with Fetal Alcohol Spectrum Disorders (FASD). Infants prenatally exposed to alcohol show altered basal and post-stress cortisol levels, but it is unknown if this persists beyond 2 years of age. It is also unknown if cortisol levels can be normalized through intervention programs. In this study, we investigated the effects of a physical activity program for children with FASD to determine: 1) if HPA dysregulation persists in school-age children with FASD, and 2) the effect of our program on cortisol levels. Twenty six children (ages 6-14 years) with FASD participated in an 8 week motor skill development program. Salivary cortisol levels were measured in 24 children and compared at 4 time points: before, immediately after, 3 months, and 1 year after program completion. Cortisol levels were also compared to 32 control children to evaluate the long-term effects of prenatal alcohol exposure on HPA regulation. For each time point, saliva was collected on each of 2 days at 3 times in the diurnal cycle: awakening, after school, and just before bedtime. Cortisol levels were significantly higher in the afternoon and at bedtime in children with FASD with confirmed prenatal exposure to high levels of alcohol (alcohol exposure rank 4), compared with Control children or children with FASD with exposure to low or unknown levels of alcohol (alcohol exposure rank 3). The program did not significantly affect cortisol levels in children with FASD as a group. These results provide support for long-term effects of prenatal alcohol exposure on the HPA system in humans, which could increase vulnerability to mental health issues and diseases later in life.

  12. Cross-Lagged Associations Between Substance Use-Related Media Exposure and Alcohol Use During Middle School

    PubMed Central

    Tucker, Joan S.; Miles, Jeremy N. V.; D’Amico, Elizabeth J.

    2013-01-01

    Purpose This study examines the reciprocal longitudinal associations between alcohol or other drug (AOD)-related media exposure and alcohol use among middle school students, and explores whether these associations differ by ethnicity or gender. Methods The analytic sample is 7th grade students who were recruited from 16 California middle schools and surveyed in the spring semester of two academic years. Students reported on their background characteristics, exposure to seven types of AOD-related media content (internet videos, social networking sites, movies, television, magazine advertisements, songs, and video games) in the past 3 months, and alcohol use in the past 30 days. Structural equation modeling was used to examine cross-lagged associations between media exposure and alcohol use. Results Greater AOD-related media exposure in 7th grade was significantly associated with a higher probability of alcohol use in 8th grade (p=.02), and alcohol use in 7th grade was marginally associated with greater AOD-related media exposure in 8th grade (p=.07). These cross-lagged associations did not statistically differ by ethnicity (Hispanic vs. non-Hispanic white) or gender. Further, there was no evidence that certain types of media exposure were more strongly associated with alcohol use than others. Conclusions Results from this study suggest that AOD-related media effects and media selectively form a reciprocal, mutually influencing process that may escalate adolescent alcohol use over time. Addressing adolescents’ exposure to AOD-related media content and its effects on behavior, such as through media literacy education, may hold promise for improving the efficacy of alcohol prevention efforts for middle school students. PMID:23770074

  13. Rape-Myth Congruent Beliefs in Women Resulting from Exposure to Violent Pornography: Effects of Alcohol and Sexual Arousal

    ERIC Educational Resources Information Center

    Davis, Kelly Cue; Norris, Jeanette; George, William H.; Martell, Joel; Heiman, Julia R.

    2006-01-01

    Previous research findings indicate that women suffer a variety of detrimental effects from exposure to violent pornography. This study used an experimental paradigm to examine the effects of a moderate alcohol dose and alcohol expectancies on women's acute reactions to a violent pornographic stimulus. A community sample of female social drinkers…

  14. Alcohol exposure leads to unrecoverable cardiovascular defects along with edema and motor function changes in developing zebrafish larvae

    PubMed Central

    Li, Xu; Gao, Aiai; Wang, Yanan; Chen, Man; Peng, Jun; Yan, Huaying; Zhao, Xin; Feng, Xizeng

    2016-01-01

    ABSTRACT Maternal alcohol consumption during pregnancy can cause a series of developmental disorders in the fetus called FAS (fetal alcohol syndrome). In the present study we exposed zebrafish embryos to 1% and 2% alcohol and observed the morphology of heart and blood vessels during and after exposure to investigate motor function alterations, and damage and recovery to the cardiovascular system. The results showed that alcohol exposure could induce heart deformation, slower heart rate, and incomplete blood vessels and pericardium. After stopping exposure, larvae exposed to 1% alcohol could recover only in heart morphology, but larvae in 2% alcohol could not recover either morphology or function of cardiovascular system. The edema-like characteristics in the 2% alcohol group became more conspicuous afterwards, with destruction in the dorsal aorta, coarctation in segmental arteries and a decrease in motor function, implying more serious unrecoverable cardiovascular defects in the 2% group. The damaged blood vessels in the 2% alcohol group resulted in an alteration in permeability and a decrease of blood volume, which were the causes of edema in pathology. These findings contribute towards a better understanding of ethanol-induced cardiovascular abnormalities and co-syndrome in patients with FAS, and warns against excessive maternal alcohol consumption during pregnancy. PMID:27422904

  15. Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure.

    PubMed

    Sadrian, B; Lopez-Guzman, M; Wilson, D A; Saito, M

    2014-11-07

    Gestational exposure to alcohol can result in long-lasting behavioral deficiencies generally described as fetal alcohol spectrum disorder (FASD). FASD-modeled rodent studies of acute ethanol exposure typically select one developmental window to simulate a specific context equivalent of human embryogenesis, and study consequences of ethanol exposure within that particular developmental epoch. Exposure timing is likely a large determinant in the neurobehavioral consequence of early ethanol exposure, as each brain region is variably susceptible to ethanol cytotoxicity and has unique sensitive periods in their development. We made a parallel comparison of the long-term effects of single-day binge ethanol at either embryonic day 8 (E8) or postnatal day 7 (P7) in male and female mice, and here demonstrate the differential long-term impacts on neuroanatomy, behavior and in vivo electrophysiology of two systems with very different developmental trajectories. The significant long-term differences in odor-evoked activity, local circuit inhibition, and spontaneous coherence between brain regions in the olfacto-hippocampal pathway that were found as a result of developmental ethanol exposure, varied based on insult timing. Long-term effects on cell proliferation and interneuron cell density were also found to vary by insult timing as well as by region. Finally, spatial memory performance and object exploration were affected in P7-exposed mice, but not E8-exposed mice. Our physiology and behavioral results are conceptually coherent with the neuroanatomical data attained from these same mice. Our results recognize both variable and shared effects of ethanol exposure timing on long-term circuit function and their supported behavior.

  16. Dietary exposure of secondary school students in Hong Kong to benzoic acid in prepackaged non-alcoholic beverages.

    PubMed

    Ma, Ka Ming; Chan, Cheok Man; Chung, Stephen Wai Cheung; Ho, Yuk Yin; Xiao, Ying

    2009-01-01

    This study evaluated the dietary exposure of secondary school students in Hong Kong to benzoic acid from pre-packaged non-alcoholic beverages. Exposure was estimated using local food consumption data of secondary school students obtained by a semi-quantitative food frequency questionnaire in 2000 and the benzoic acid level detected in pre-packaged beverages, including soft drink (both diet/light and regular types), fruit juice, soy milk, Chinese tea and coffee/tea) available locally in late 2006. The estimated dietary exposure to benzoic acid from pre-packaged beverages of average and high consumers (95(th) percentile) was 0.31 and 0.97 mg kg(-1) bw day(-1), respectively. These exposures accounted for 6.1 and 19.3% of the acceptable daily intake (ADI: 0-5 mg kg(-1) bw) of benzoic acid for average and high consumers, respectively. As in other countries, soft drinks contributed most to dietary exposure to benzoic acid from pre-packaged beverages in Hong Kong.

  17. Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea

    PubMed Central

    Hwang, Yunji; Lee, Kyu Eun; Weiderpass, Elisabete; Park, Young Joo; Chai, Young Jun; Kwon, Hyungju; Park, Do Joon; Cho, BeLong; Choi, Ho-Chun; Kang, Daehee; Park, Sue K.

    2016-01-01

    Background This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC). Methods The Thyroid Cancer Longitudinal Study (T-CALOS) included 2,258 DTC patients (449 men and 1,809 women) and 22,580 healthy participants (4,490 men and 18,090 women) who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional regression models. Results While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion) was associated with increased risks in men (OR = 2.22, 95%CI = 1.27–3.87) and women (OR = 3.61, 95%CI = 1.52–8.58) compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31–40 years: OR = 1.58, 95%CI = 1.10–2.28; 41+ years: OR = 3.46, 95%CI = 2.06–5.80) and women (31–40 years: OR = 2.18, 95%CI = 1.62–2.92; 41+ years: OR = 2.71, 95%CI = 1.36–5.05) compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage. Conclusion The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC. PMID:26985827

  18. Ethylglucuronide in maternal hair as a biomarker of prenatal alcohol exposure.

    PubMed

    Gutierrez, Hilda L; Hund, Lauren; Shrestha, Shikhar; Rayburn, William F; Leeman, Lawrence; Savage, Daniel D; Bakhireva, Ludmila N

    2015-09-01

    While direct ethanol metabolites, including ethylglucuronide (EtG), play an important role for the confirmation of prenatal alcohol exposure (PAE), their utility is often limited by their short half-lives in blood and urine. Maternal hair allows for a retrospective measure of PAE for up to several months. This study examined the validity of hair EtG (hEtG) relative to self-reporting and five other biomarkers in 85 pregnant women. Patients were recruited from a UNM prenatal clinic, which provides care to women with substance abuse and addiction disorders. The composite index, which was based on self-reported measures of alcohol use and allowed us to classify subjects into PAE (n = 42) and control (n = 43) groups, was the criterion measure used to estimate the sensitivity and specificity of hEtG. Proximal segments of hair were collected at enrollment (average 22.0 gestational weeks) and analyzed by LC-MS/MS. At the same visit, maternal blood and urine specimens were collected for analysis of GGT, %dCDT, PEth, uEtG, and uEtS. The study population included mostly opioid-dependent (80%) patients, a large proportion of ethnic minorities (75.3% Hispanic/Latina, 8.2% American Indian, 4.7% African-American), and patients with low education (48.2% < high school). The mean maternal age at enrollment was 26.7 ± 4.8 years. Hair EtG demonstrated 19% sensitivity and 86% specificity. The sensitivities of other biomarkers were comparable (5-20%) to hEtG but specificities were higher (98-100%). Hair EtG sensitivity improved when combined with other biomarkers, especially with GGT (32.5%) and PEth (27.5%). In addition, validity of hEtG improved in patients with less frequent shampooing and those who did not use hair dyes/chemical treatments. These data suggest that hEtG alone is not a sufficiently sensitive or specific biomarker to be used separately for the identification of PAE, but might be useful in a battery along with other maternal biomarkers.

  19. Embryonic alcohol exposure promotes long-term effects on cerebral glutamate transport of adult zebrafish.

    PubMed

    Baggio, Suelen; Mussulini, Ben Hur; de Oliveira, Diogo Losch; Zenki, Kamila Cagliari; Santos da Silva, Emerson; Rico, Eduardo Pacheco

    2017-01-01

    Ethanol is a widely consumed substance throughout the world. During development it can substantially damage the human fetus, whereas the developing brain is particularly vulnerable. The brain damage induced by prenatal alcohol exposure may lead to a variety of long-lasting behavioral and neurochemical problems. However, there are no data concerning the effects of developmental ethanol exposure on the glutamatergic system, where extracellular glutamate acts as signaling molecule. Here we investigated the effect of ethanol exposure for 2h (concentrations of 0.0%, 0.1%, 0.25%, 0.50%, and 1.00%) in embryos at 24h post-fertilization (hpf) by measuring the functionality of glutamate transporters in the brain of adult (4 months) zebrafish. However, ethanol 0.1%, 0.25% and 0.50% decreased transport of glutamate to 81.96%, 60.65% and 45.91% respectively, when compared with the control group. Interestingly, 1.00% was able to inhibit the transport activity to 68.85%. In response to the embryonic alcohol exposure, we found impairment in the function of cerebral glutamate transport in adult fish, contributing to long-term alteration in the homeostasis glutamatergic signaling.

  20. Alcohol

    MedlinePlus

    ... parents and other adults use alcohol socially — having beer or wine with dinner, for example — alcohol seems ... besides just hanging out in someone's basement drinking beer all night. Plan a trip to the movies, ...

  1. Prenatal alcohol exposure delays the development of the cortical barrel field in neonatal rats.

    PubMed

    Margret, Cecilia P; Li, Cheng X; Chappell, Tyson D; Elberger, Andrea J; Matta, Shannon G; Waters, Robert S

    2006-06-01

    In-utero alcohol exposure produces sensorimotor developmental abnormalities that often persist into adulthood. The rodent cortical barrel field associated with the representation of the body surface was used as our model system to examine the effect of prenatal alcohol exposure (PAE) on early somatosensory cortical development. In this study, pregnant female rats were intragastrically gavaged daily with high doses of alcohol (6 gm/kg body weight) throughout the first 20 days of pregnancy. Blood alcohol levels were measured in the pregnant dams on gestational days 13 (G13) and G20. The ethanol treated group (EtOH) was compared to the normal control chowfed (CF) group, nutritionally matched pairfed (PF) group, and cross-foster (XF) group. Cortical barrel development was examined in pups across all treatment groups from G25, corresponding to postnatal day 2 (P2), to G32 corresponding to P9. The EtOH and control group pups were weighed, anesthetized, and perfused. Brains were removed and weighed with, and without cerebellum and olfactory bulbs, and neocortex was removed and weighed. Cortices were then flattened, sectioned tangentially, and stained with a metabolic marker, cytochrome oxidase (CO) to reveal the barrel field. Progression of barrel development was distinguished into three categories: (a) absent, (b) cloudy barrel-like pattern, and (c) well-formed barrels with intervening septae. The major findings are: (1) PAE delayed barrel field development by one or more days, (2) the barrel field first appeared as a cloudy pattern that gave way on subsequent days to an adult-like pattern with clearly demarcated intervening septal regions, (3) the barrel field developed differentially in a lateral-to-medial gradient in both alcohol and control groups, (4) PAE delayed birth by one or more days in 53% of the pups, (5) regardless of whether pups were born on G23 (normal expected birth date for non-alcohol controls) or as in the case for the alcohol-delayed pups born as

  2. Alcoholism.

    ERIC Educational Resources Information Center

    Caliguri, Joseph P., Ed.

    This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and…

  3. Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.

    PubMed

    Saito, Atsushi; Taniguchi, Yu; Kim, Sun-Hong; Selvakumar, Balakrishnan; Perez, Gabriel; Ballinger, Michael D; Zhu, Xiaolei; Sabra, James; Jallow, Mariama; Yan, Priscilla; Ito, Koki; Rajendran, Shreenath; Hirotsune, Shinji; Wynshaw-Boris, Anthony; Snyder, Solomon H; Sawa, Akira; Kamiya, Atsushi

    2016-07-01

    Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

  4. White Matter Deficits Mediate Effects of Prenatal Alcohol Exposure on Cognitive Development in Childhood

    PubMed Central

    Fan, Jia; Jacobson, Sandra W.; Taylor, Paul A.; Molteno, Christopher D.; Dodge, Neil C.; Stanton, Mark E.; Jacobson, Joseph L.; Meintjes, Ernesta M.

    2016-01-01

    Fetal alcohol spectrum disorders comprise the spectrum of cognitive, behavioral, and neurological impairments caused by prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) was performed on 54 children (age 10.1 ±1.0 years) from the Cape Town Longitudinal Cohort, for whom detailed drinking histories obtained during pregnancy are available: 26 with full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 15 nonsyndromal heavily exposed (HE), and 13 controls. Using voxelwise analyses, children with FAS/PFAS showed significantly lower fractional anisotropy (FA) in four white matter (WM) regions and higher mean diffusivity (MD) in seven; three regions of FA and MD differences (left inferior longitudinal fasciculus (ILF), splenium, and isthmus) overlapped, and the fourth FA cluster was located in the same WM bundle (right ILF) as an MD cluster. HE children showed lower FA and higher MD in a subset of these regions. Significant correlations were observed between three continuous alcohol measures and DTI values at cluster peaks, indicating that WM damage in several regions is dose dependent. Lower FA in the regions of interest was attributable primarily to increased radial diffusivity rather than decreased axonal diffusivity, suggesting poorer axon packing density and/or myelination. Multiple regression models indicated that this cortical WM impairment partially mediated adverse effects of PAE on information processing speed and eyeblink conditioning. PMID:27219850

  5. Rape-myth congruent beliefs in women resulting from exposure to violent pornography: effects of alcohol and sexual arousal.

    PubMed

    Davis, Kelly Cue; Norris, Jeanette; George, William H; Martell, Joel; Heiman, Julia R

    2006-09-01

    Previous research findings indicate that women suffer a variety of detrimental effects from exposure to violent pornography. This study used an experimental paradigm to examine the effects of a moderate alcohol dose and alcohol expectancies on women's acute reactions to a violent pornographic stimulus. A community sample of female social drinkers (N = 134) read an eroticized rape depiction after completing an alcohol administration protocol. As predicted, intoxicated participants were less likely to label the depicted events as rape than their sober counterparts. A path analytic model illustrated that participants' self-reported sexual arousal to the stimulus, as influenced by alcohol consumption and expectancies, resulted in increased rape myth congruent perceptions of the victim and decreased labeling of the incident as rape. Findings suggest that acute alcohol intoxication during violent pornography exposure may ultimately result in women developing more calloused attitudes toward rape and rape victims.

  6. Differences in cortico-striatal-cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure.

    PubMed

    Diwadkar, Vaibhav A; Meintjes, Ernesta M; Goradia, Dhruman; Dodge, Neil C; Warton, Christopher; Molteno, Christopher D; Jacobson, Sandra W; Jacobson, Joseph L

    2013-08-01

    Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI. Intra-group one-sample t-tests were used to identify activity regions of interest central to verbal working memory including the dorsal prefrontal cortex (dPFC), inferior frontal gyrus, caudate/putamen, parietal cortex, and cerebellar Crus I/lobule VI and lobule VIIB-IX. Whereas groups did not differ in task sensitivity, fMRI analyses suggested different patterns of sub-network recruitment across groups. Controls primarily recruited left inferior frontal gyrus (Broca's area). By contrast, HE primarily recruited an extensive set of fronto-striatal regions, including left dPFC and left caudate, and the FAS/PFAS group relied primarily on two cerebellar subregions and parietal cortex. This study is, to our knowledge, the first to demonstrate differential recruitment of critical brain regions that subserve basic function in children with different fetal alcohol spectrum disorders compared to controls. The distinct activation patterns seen in the two exposed groups may be related to substantial differences in alcohol dose/occasion to which these groups were exposed in utero.

  7. Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells

    PubMed Central

    Srinivasan, Padmanabhan; Nabokina, Svetlana

    2015-01-01

    Thiamin is essential for normal metabolic activity of all mammalian cells, including those of the pancreas. Cells obtain thiamin from their surroundings and enzymatically convert it into thiamin pyrophosphate (TPP) in the cytoplasm; TPP is then taken up by mitochondria via a specific carrier the mitochondrial TPP transporter (MTPPT; product of the SLC25A19 gene). Chronic alcohol exposure negatively impacts the health of pancreatic acinar cells (PAC), but its effect on physiological/molecular parameters of MTPPT is not known. We addressed this issue using mouse pancreatic acinar tumor cell line 266-6 and primary PAC of wild-type and transgenic mice carrying the SLC25A19 promoter that were fed alcohol chronically. Chronic alcohol exposure of 266-6 cells (but not to its nonoxidative metabolites ethyl palmitate and ethyl oleate) led to a significant inhibition in mitochondrial TPP uptake, which was associated with a decreased expression of MTPPT protein, mRNA, and activity of the SLC25A19 promoter. Similarly, chronic alcohol feeding of mice led to a significant inhibition in expression of MTPPT protein, mRNA, heterogeneous nuclear RNA, as well as in activity of SLC25A19 promoter in PAC. While chronic alcohol exposure did not affect DNA methylation of the Slc25a19 promoter, a significant decrease in histone H3 euchromatin markers and an increase in H3 heterochromatin marker were observed. These findings show, for the first time, that chronic alcohol exposure negatively impacts pancreatic MTPPT, and that this effect is exerted, at least in part, at the level of Slc25a19 transcription and appears to involve epigenetic mechanism(s). PMID:26316591

  8. Adolescent Alcohol Exposure Alters GABAA Receptor Subunit Expression in Adult Hippocampus

    PubMed Central

    Centanni, Samuel W.; Teppen, Tara; Risher, Mary-Louise; Fleming, Rebekah L.; Moss, Julia L.; Acheson, Shawn K.; Mulholland, Patrick J.; Pandey, Subhash C.; Chandler, L. Judson; Swartzwelder, H. Scott

    2014-01-01

    Background The long-term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to alcohol during adolescence decreased the amplitude of GABAA receptor-mediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of the present study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on the expression of hippocampal GABAA receptors (GABAARs). Methods We used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by western blots to measure GABAAR protein expression. We also measured mRNA levels of GABAAR subunits using quantitative real-time PCR. Results Although the protein levels of α1-, α4- and δ-GABAAR subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the α5-GABAAR subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30–46, there was a significant reduction in the protein levels of the δ-GABAAR, in the absence of any changes in mRNA levels, at 48 hours and 26 days after the last ethanol exposure. Protein levels of the α4-GABAAR subunit were significantly reduced, but mRNA levels were increased, 26 days (but not 48 hours) after the last AIE exposure. Protein levels of α5-GABAAR were not changed by AIE, but mRNA levels were reduced at 48hrs but normalized 26 days after AIE. In contrast to the effects of AIE, chronic intermittent exposure to ethanol during adulthood (CIE) had no effect on expression of any of the GABAAR subunits examined. Conclusions AIE produced both short- and long-term alterations of GABAAR subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long lasting effects on those measures. The observed reduction of protein

  9. Potential youth exposure to alcohol advertising on the internet: A study of internet versions of popular television programs

    PubMed Central

    Siegel, Michael; Kurland, Rachel P.; Castrini, Marisa; Morse, Catherine; de Groot, Alexander; Retamozo, Cynthia; Roberts, Sarah P.; Ross, Craig S.; Jernigan, David H.

    2015-01-01

    Background No previous paper has examined alcohol advertising on the internet versions of television programs popular among underage youth. Objectives To assess the volume of alcohol advertising on web sites of television networks which stream television programs popular among youth. Methods Multiple viewers analyzed the product advertising appearing on 12 television programs that are available in full episode format on the internet. During a baseline period of one week, six coders analyzed all 12 programs. For the nine programs that contained alcohol advertising, three underage coders (ages 10, 13, and 18) analyzed the programs to quantify the extent of that advertising over a four-week period. Results Alcohol advertisements are highly prevalent on these programs, with nine of the 12 shows carrying alcohol ads, and six programs averaging at least one alcohol ad per episode. There was no difference in alcohol ad exposure for underage and legal age viewers. Conclusions There is a substantial potential for youth exposure to alcohol advertising on the internet through internet-based versions of television programs. The Federal Trade Commission should require alcohol companies to report the underage youth and adult audiences for internet versions of television programs on which they advertise. PMID:27212891

  10. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  11. Prenatal Alcohol Exposure in Rodents As a Promising Model for the Study of ADHD Molecular Basis

    PubMed Central

    Rojas-Mayorquín, Argelia E.; Padilla-Velarde, Edgar; Ortuño-Sahagún, Daniel

    2016-01-01

    A physiological parallelism, or even a causal effect relationship, can be deducted from the analysis of the main characteristics of the “Alcohol Related Neurodevelopmental Disorders” (ARND), derived from prenatal alcohol exposure (PAE), and the behavioral performance in the Attention-deficit/hyperactivity disorder (ADHD). These two clinically distinct disease entities, exhibits many common features. They affect neurological shared pathways, and also related neurotransmitter systems. We briefly review here these parallelisms, with their common and uncommon characteristics, and with an emphasis in the subjacent molecular mechanisms of the behavioral manifestations, that lead us to propose that PAE in rats can be considered as a suitable model for the study of ADHD. PMID:28018163

  12. Pfeiffer-like syndrome with holoprosencephaly: a newborn with maternal smoking and alcohol exposure.

    PubMed

    Su, Pen-Hua; Chen, Jia-Yuh; Lee, Inn-Chi; Ng, Yan-Yan; Hu, Jui-Ming; Chen, Suh-Jen

    2009-10-01

    We report the case of a female infant with Pfeiffer-like syndrome and holoprosencephaly. She had a cloverleaf skull, ocular proptosis, broad thumbs and halluces, and variable accompanying anomalies compatible with Pfeiffer syndrome. She also displayed microcephaly, short palpebral fissures, and a smooth philtrum, which are clinical signs consistent with fetal alcohol syndrome. She suffered from multiple congenital anomalies and died at 41 days of age. Cardio-pulmonary failure, brain abnormalities, prematurity, and multiple complications contributed to her death. The patient displayed normal chromosomal numbers and type. DNA analysis did not reveal fibrobtast growth factor receptor (FGFR) genes FGFR1, FGFR2, FGFR3 or TWIST gene mutations. We review the previous reports of Pfeiffer syndrome and holoprosencephaly and describe our infant patient with Pfeiffer-like syndrome, holoprosencephaly, and heavy in utero maternal alcohol and smoking exposures.

  13. The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

    SciTech Connect

    Nekvasil, N.; Baggio, C. )

    1992-02-26

    Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressure than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.

  14. Paroxysmal Autonomic Instability With Dystonia Managed Using Chemodenervation Including Alcohol Neurolysis and Botulinum Toxin Type A Injection: A Case Report

    PubMed Central

    Lee, Hye-Sun; Oh, Hyun-Seung

    2015-01-01

    Paroxysmal autonomic instability with dystonia (PAID) is a rare complication of brain injury. Symptoms of PAID include diaphoresis, hyperthermia, hypertension, tachycardia, and tachypnea accompanied by hypertonic movement. Herein, we present the case of a 44-year-old female patient, who was diagnosed with paraneoplastic limbic encephalopathy caused by thyroid papillary cancer. The patient exhibited all the symptoms of PAID. On the basis that the symptoms were unresponsive to antispastic medication and her liver function test was elevated, we performed alcohol neurolysis of the musculocutaneous nerve followed by botulinum toxin type A (BNT-A) injection into the biceps brachii and brachialis. Unstable vital signs and hypertonia were relieved after chemodenervation. Accordingly, alcohol neurolysis and BNT-A injection are proposed as a treatment option for intractable PAID. PMID:25932429

  15. Effect of prenatal alcohol exposure on bony craniofacial development: a mouse MicroCT study.

    PubMed

    Shen, Li; Ai, Huisi; Liang, Yun; Ren, Xiaowei; Anthony, Charles Bruce; Goodlett, Charles R; Ward, Richard; Zhou, Feng C

    2013-08-01

    Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI® liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC < CHOW and ALC < PF. While covarying for gender and head size or circumference, the treatment affected the total skull and mandible at P7 (ALC > CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC = 0.967), between ALC and PF (AUC = 0.995), and between PF and CHOW (AUC = 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper

  16. Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive- and Anxiety-Like Behaviors in Male and Female Offspring

    PubMed Central

    Hellemans, Kim G. C.; Verma, Pamela; Yoon, Esther; Yu, Wayne K.; Young, Allan H.; Weinberg, Joanne

    2016-01-01

    Background Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. Results We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. PMID:20102562

  17. Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine.

    PubMed

    Yohn, Nicole L; Bartolomei, Marisa S; Blendy, Julie A

    2015-07-01

    Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse. Specifically, changes found following the administration of alcohol, opioids, cocaine, marijuana, and nicotine will be discussed. In addition, epigenetic modifications to the genome following administration of these drugs will be detailed as well as their potential for transmission to the next generation.

  18. Alcohol Advertising on Boston's Massachusetts Bay Transportation Authority Transit System: An Assessment of Youths' and Adults' Exposure

    PubMed Central

    Nyborn, Justin A.; Wukitsch, Kimberly; Nhean, Siphannay

    2009-01-01

    Objectives. We investigated the frequency with which alcohol advertisements appeared on Massachusetts Bay Transportation Authority (MBTA) transit lines in Boston, MA, and we calculated adult and youths' exposure to the ads. Methods. We measured the nature and extent of alcohol advertisements on 4 Boston transit lines on 2 separate weekdays 1 month apart in June and July of 2008. We calculated weekday ad exposure for all passengers (all ages) and for Boston Public School student passengers (aged 11–18 years). Results. Alcohol ads were viewed an estimated 1 212 960 times across all Boston-area transit passengers during an average weekday, reaching the equivalent of 42.7% of that population. Alcohol ads were viewed an estimated 18 269 times by Boston Public School student transit passengers during an average weekday, reaching the equivalent of 54.1% of that population. Conclusions. Advertisers reached the equivalent of half of all Boston Public School transit passengers aged 11 to 18 years and the equivalent of nearly half of all transit passengers in the Boston area with an alcohol advertisement each day. Because of the high exposure of underage youths to alcohol advertisements, we recommend that the MBTA prohibit alcohol advertising on the Boston transit system. PMID:19890170

  19. Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

    PubMed Central

    Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

    2015-01-01

    Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

  20. Comparison of the deleterious effects of binge drinking-like alcohol exposure in adolescent and adult mice.

    PubMed

    Lacaille, Hélène; Duterte-Boucher, Dominique; Liot, Donovan; Vaudry, Hubert; Naassila, Mickael; Vaudry, David

    2015-03-01

    A major cause of alcohol toxicity is the production of reactive oxygen species generated during ethanol metabolism. The aim of this study was to compare the effect of binge drinking-like alcohol exposure on a panel of genes implicated in oxidative mechanisms in adolescent and adult mice. In adolescent animals, alcohol decreased the expression of genes involved in the repair and protection of oxidative DNA damage such as atr, gpx7, or nudt15 and increased the expression of proapoptotic genes such as casp3. In contrast, in the adult brain, genes activated by alcohol were mainly associated with protective mechanisms that prevent cells from oxidative damage. Whatever the age, iterative binge-like episodes provoked the same deleterious effects as those observed after a single binge episode. In adolescent mice, multiple binge ethanol exposure substantially reduced neurogenesis in the dentate gyrus and impaired short-term memory in the novel object and passive avoidance tests. Taken together, our results indicate that alcohol causes deleterious effects in the adolescent brain which are distinct from those observed in adults. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity. The effects of alcohol exposure were investigated on genes involved in oxidative mechanisms. In adolescent animals, alcohol decreased the expression of genes involved in DNA repair, a potential cause of the observed decrease of neurogenesis. In contrast, in the adult brain, alcohol increased the expression of genes associated with antioxidant mechanisms. Apoptosis was increase in all groups and converged with other biochemical alterations to enhance short-term memory impairment in the adolescent brain. These data contribute to explain the greater sensitivity of the adolescent brain to alcohol toxicity.

  1. The use of a selective serotonin reuptake inhibitor decreases heavy alcohol exposure-induced inflammatory response and tissue damage in rats.

    PubMed

    Hu, Tsung M; Subeq, Yi M; Yang, Fwu L; Hsu, Bang G; Lin, Nien T; Lee, Ru P

    2013-10-01

    Alcohol intoxication and psychiatric medication overdoses, including antidepressants, are common emergency room events. Heavy alcohol and antidepressant exposure are able to induce changes in cytokines disturbing normal physiology. We examined the inflammatory and physiological effects of selective serotonin reuptake inhibitor (SSRI) medication after heavy alcohol exposure. Rats were randomly divided into Alc (EtOH 5g/kg, intravenous infusion for 3 h), SSRI (paroxetine oral intake) and Alc+SSRI groups. Serum samples were collected to measure blood ethanol, aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. Lactate dehydrogenase levels in bronchoalveolar lavage fluid were also examined. Liver, pancreas and lungs were removed after sacrifice and any pathological changes were catalogued. Ethanol infusion resulted in blood levels of ethanol of >100 mg/dL after ethanol infusion. Serum levels of aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, TNF-α and IL-6 in the Alc+SSRI group were lower than in the Alc group. Moreover, pathological damages to the liver, pancreas and lungs were slightly lower in the Alc+SSRI group than in the Alc group. These findings suggested that SSRI is able to decrease the release of pro-inflammatory cytokines and thereby reduce liver and pancreas damage after heavy alcohol exposure.

  2. Changes in health professionals' knowledge, attitudes and practice following provision of educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder.

    PubMed

    Payne, Janet; France, Kathryn; Henley, Nadine; D'Antoine, Heather; Bartu, Anne; O'Leary, Colleen; Elliott, Elizabeth; Bower, Carol

    2011-07-01

    We provided health professionals in Western Australia (WA) with educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder and assessed changes in their knowledge, attitudes and practice concerning fetal alcohol syndrome (FAS) and alcohol consumption in pregnancy. Following our 2002 survey of health professionals in WA, we developed and distributed educational resources to 3348 health professionals in WA in 2007. Six months later we surveyed 1483 of these health professionals. Prevalence rate ratios [PRR] and 95% confidence intervals [CI] were calculated to compare 2007 results with results from the 2002 survey. Of the 1001 responding health professionals, 69.8% had seen the educational resources; of these 77.1% have used them and 48.5% said the resources had assisted them to change their practice or their intention to change their practice. Compared with 2002, there was an increase in the proportion who knew all the essential features of FAS from 11.7% to 15.8% [PRR 1.35; 95% CI 1.09, 1.67] and had diagnosed FAS, from 4.8% to 7.3% [PRR 1.52; 95% CI 1.08, 2.13]. In 2007, 98.1% of health professionals stated they would advise pregnant women to consider not drinking at all or advise them that no alcohol in pregnancy is the safest choice. Health professionals surveyed in 2007 have increased their knowledge, changed their attitudes and practice about FAS, and altered the advice they give to pregnant women about alcohol consumption since our survey in 2002. It is essential that we build on this change and continue to support health professionals' knowledge, attitudes and practice about the prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder. The educational resources for health professionals may be ordered as hard copies and downloaded from the internet http://www.ichr.uwa.edu.au/alcoholandpregnancy.

  3. DEMOGRAPHIC AND HISTORICAL FINDINGS, INCLUDING EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE, IN DOGS WITH CHRONIC COUGH

    PubMed Central

    Hawkins, Eleanor C.; Clay, Latoya D.; Bradley, Julie M.; Davidian, Marie

    2013-01-01

    Background Controlled studies investigating risk factors for the common presenting problem of chronic cough in dogs are lacking. Hypothesis/Objectives To identify demographic and historical factors associated with chronic cough in dogs, and associations between the characteristics of cough and diagnosis. Animals Dogs were patients of an academic internal medicine referral service. Coughing dogs had a duration of cough ≥ 2 months (n=115). Control dogs had presenting problems other than cough (n=104). Methods Owners completed written questionnaires. Demographic information and diagnoses were obtained from medical records. Demographic and historical data were compared between coughing and control dogs. Demographic data and exposure to environmental tobacco smoke (ETS) also were compared with hospital accessions and adult smoking rates, respectively. Characteristics of cough were compared among diagnoses. Results Most coughing dogs had a diagnosis of large airway disease (n=88; 77%). Tracheobronchomalacia was diagnosed in 59 dogs (51%), including 79% of toy breed dogs. Demographic risk factors included older age, smaller body weight, and being toy breed (p<0.001). No association was found between coughing and month (p=0.239) or season (p=0.414) of presentation. Exposure to ETS was not confirmed to be a risk factor (p=0.243). No historical description of cough was unique to a particular diagnosis. Conclusions and clincal importance Associations with age, size, and toy breeds were strong. Tracheobronchomalacia is frequent in dogs with chronic cough, but descriptions of cough should be used cautiously in prioritizing differential diagnoses. The association between exposure to ETS and chronic cough deserves additional study. PMID:20492480

  4. Reduced Toxicity Fuel Satellite Propulsion System Including Fuel Cell Reformer with Alcohols Such as Methanol

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J. (Inventor)

    2001-01-01

    A reduced toxicity fuel satellite propulsion system including a reduced toxicity propellant supply for consumption in an axial class thruster and an ACS class thruster. The system includes suitable valves and conduits for supplying the reduced toxicity propellant to the ACS decomposing element of an ACS thruster. The ACS decomposing element is operative to decompose the reduced toxicity propellant into hot propulsive gases. In addition the system includes suitable valves and conduits for supplying the reduced toxicity propellant to an axial decomposing element of the axial thruster. The axial decomposing element is operative to decompose the reduced toxicity propellant into hot gases. The system further includes suitable valves and conduits for supplying a second propellant to a combustion chamber of the axial thruster, whereby the hot gases and the second propellant auto-ignite and begin the combustion process for producing thrust.

  5. Effect of chronic carbon monoxide exposure on experimental alcoholic liver injury in rats

    SciTech Connect

    Nanji, A.A. ); Jui, L.T.; French, S.W. )

    1989-01-01

    Two groups of experimental animals with pair-fed controls were studied to evaluate the effect of chronic carbon monoxide (CO) exposure on progression of experimental alcoholic liver injury. Eight pairs of male Wistar rats were continuously infused liquid diet and ethanol or isocaloric dextrose for four months. Four pairs were also exposed to CO. Liver damage was followed monthly by serum ALT and morphologic assessment of liver biopsy. Serum levels of ALT were significantly higher in the CO-ethanol group compared to other groups. Electron microscopy revealed a greater degree of cell necrosis in the CO exposed group which explained the significantly higher ALT activity in these animals. Both experimental groups had significantly greater liver damage than controls. Carboxyhemoglobin levels were not different in the ethanol-fed and control group. Our results show that chronic CO exposure enhances liver cell necrosis in ethanol-fed rats thereby lending support to the hypothesis that ethanol and hypoxia enhance cellular disruption in the liver which could be important in the pathogenesis of alcoholic liver disease in rats.

  6. Rigorous tests of gene-environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression.

    PubMed

    LoParo, Devon; Johansson, Ada; Walum, Hasse; Westberg, Lars; Santtila, Pekka; Waldman, Irwin

    2016-07-01

    Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (rGE ), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition. © 2015 Wiley Periodicals, Inc.

  7. Exposure of Children and Adolescents to Alcohol Marketing on Social Media Websites

    PubMed Central

    Winpenny, Eleanor M.; Marteau, Theresa M.; Nolte, Ellen

    2014-01-01

    Aims: In 2011, online marketing became the largest marketing channel in the UK, overtaking television for the first time. This study aimed to describe the exposure of children and young adults to alcohol marketing on social media websites in the UK. Methods: We used commercially available data on the three most used social media websites among young people in the UK, from December 2010 to May 2011. We analysed by age (6–14 years; 15–24 years) and gender the reach (proportion of internet users who used the site in each month) and impressions (number of individual pages viewed on the site in each month) for Facebook, YouTube and Twitter. We further analysed case studies of five alcohol brands to assess the marketer-generated brand content available on Facebook, YouTube and Twitter in February and March 2012. Results: Facebook was the social media site with the highest reach, with an average monthly reach of 89% of males and 91% of females aged 15–24. YouTube had a similar average monthly reach while Twitter had a considerably lower usage in the age groups studied. All five of the alcohol brands studied maintained a Facebook page, Twitter page and YouTube channel, with varying levels of user engagement. Facebook pages could not be accessed by an under-18 user, but in most cases YouTube content and Twitter content could be accessed by those of all ages. Conclusion: The rise in online marketing of alcohol and the high use of social media websites by young people suggests that this is an area requiring further monitoring and regulation. PMID:24293506

  8. Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure

    PubMed Central

    Balaraman, Sridevi; Schafer, Jordan J.; Tseng, Alexander M.; Wertelecki, Wladimir; Yevtushok, Lyubov; Zymak-Zakutnya, Natalya; Chambers, Christina D.; Miranda, Rajesh C.

    2016-01-01

    Fetal alcohol spectrum disorders (FASD) are difficult to diagnose since many heavily exposed infants, at risk for intellectual disability, do not exhibit craniofacial dysmorphology or growth deficits. Consequently, there is a need for biomarkers that predict disability. In both animal models and human studies, alcohol exposure during pregnancy resulted in significant alterations in circulating microRNAs (miRNAs) in maternal blood. In the current study, we asked if changes in plasma miRNAs in alcohol-exposed pregnant mothers, either alone or in conjunction with other clinical variables, could predict infant outcomes. Sixty-eight pregnant women at two perinatal care clinics in western Ukraine were recruited into the study. Detailed health and alcohol consumption histories, and 2nd and 3rd trimester blood samples were obtained. Birth cohort infants were assessed by a geneticist and classified as unexposed (UE), heavily prenatally exposed and affected (HEa) or heavily exposed but apparently unaffected (HEua). MiRNAs were assessed in plasma samples using qRT-PCR arrays. ANOVA models identified 11 miRNAs that were all significantly elevated in maternal plasma from the HEa group relative to HEua and UE groups. In a random forest analysis classification model, a combination of high variance miRNAs, smoking history and socioeconomic status classified membership in HEa and UE groups, with a misclassification rate of 13%. The RFA model also classified 17% of the HEua group as UE-like, whereas 83% were HEa-like, at least at one stage of pregnancy. Collectively our data indicate that maternal plasma miRNAs predict infant outcomes, and may be useful to classify difficult-to-diagnose FASD subpopulations. PMID:27828986

  9. Objective assessment of ADHD core symptoms in children with heavy prenatal alcohol exposure.

    PubMed

    Infante, M Alejandra; Moore, Eileen M; Nguyen, Tanya T; Fourligas, Nikolaos; Mattson, Sarah N; Riley, Edward P

    2015-09-01

    Attention deficits are often observed in children with prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) is commonly diagnosed in this population. This study used an objective assessment tool to examine differences between alcohol-exposed and non-exposed children on core symptoms of ADHD: inattention, impulsivity, and hyperactivity. Two groups of individuals, aged 7-14years, participated in the study: alcohol-exposed children (AE, n=43), and non-exposed children (CON, n=54). Subjects were evaluated with the Quotient ADHD System, which provides objective data on ADHD core symptoms by combining an infrared motion tracking system and a computerized continuous performance task. Twelve separate ANCOVAs controlling for the effects of age and sex, were conducted on attention and motion variables. Results revealed that in comparison to the CON group, the AE group was significantly (p's<.05) less accurate, made an increased number of omission errors, had longer response latencies, and increased variability in response time. Moreover, the AE group spent less time staying still, and made an increased number of head movements, which traveled a larger distance, covered a greater area, and demonstrated a less complex movement pattern. No significant group differences were observed on the number of commission errors and temporal scaling. Our findings provide further support for the notion that inattention is a core deficit in children prenatally exposed to alcohol. Results from this study are also consistent with parent reports of increased hyperactivity. The Quotient ADHD System may be a useful objective measure of ADHD symptomatology in children with FASD.

  10. Different digital paths to the keg? How exposure to peers' alcohol-related social media content influences drinking among male and female first-year college students.

    PubMed

    Boyle, Sarah C; LaBrie, Joseph W; Froidevaux, Nicole M; Witkovic, Yong D

    2016-06-01

    Despite speculation that peers' alcohol-related content on social media sites (SMS) may influence the alcohol use behaviors of SMS frequenting college students, this relationship has not been investigated longitudinally. The current prospective study assesses the relationship between exposure to peers' alcohol-related SMS content and later-drinking among first-year college students. Among 408 first-year students, total exposure to peers' alcohol-related content on Facebook, Instagram, and Snapchat during the initial 6 weeks of college predicted alcohol consumption 6 months later. The rather robust relationship persisted even after students' and close friends drinking were accounted for, indicating that alcohol references on SMS do not simply reflect alcohol use behaviors that would otherwise be observed in the absence of SMS and be predictive of later alcohol use. Findings also illuminate important gender differences in the degree to which peers' alcohol-related SMS content influenced later drinking behavior as well as psychological mediators of this relationship. Among females, enhancement drinking motives and beliefs about the role of alcohol in the college experience fully mediated the relationship between SMS alcohol exposure and later drinking. Males, however, evidenced a much stronger predictive relationship between SMS alcohol exposure and second semester drinking, with this relationship only partially explained by perceptions of drinking norms, enhancement drinking motives, and beliefs about the role of alcohol in the college experience. Implications of these findings for college drinking prevention efforts and directions for future research are discussed.

  11. Spaceflight exposure effects on transcription, activity, and localization of alcohol dehydrogenase in the roots of Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Porterfield, D. M.; Matthews, S. W.; Daugherty, C. J.; Musgrave, M. E.

    1997-01-01

    Although considerable research and speculation have been directed toward understanding a plant's perception of gravity and the resulting gravitropic responses, little is known about the role of gravity-dependent physical processes in normal physiological function. These studies were conducted to determine whether the roots of plants exposed to spaceflight conditions may be experiencing hypoxia. Arabidopsis thaliana (L.) Heynh. plants were grown in agar medium during 6 or 11 d of spaceflight exposure on shuttle missions STS-54 (CHROMEX-03) and STS-68 (CHROMEX-05), respectively. The analysis included measurement of agar redox potential and root alcohol dehydrogenase (ADH) activity, localization, and expression. ADH activity increased by 89% as a result of spaceflight exposure for both CHROMEX-03 and -05 experiments, and ADH RNase protection assays revealed a 136% increase in ADH mRNA. The increase in ADH activity associated with the spaceflight roots was realized by a 28% decrease in oxygen availability in a ground-based study; however, no reduction in redox potential was observed in measurements of the spaceflight bulk agar. Spaceflight exposure appears to effect a hypoxic response in the roots of agar-grown plants that may be caused by changes in gravity-mediated fluid and/or gas behavior.

  12. Spaceflight exposure effects on transcription, activity, and localization of alcohol dehydrogenase in the roots of Arabidopsis thaliana.

    PubMed Central

    Porterfield, D M; Matthews, S W; Daugherty, C J; Musgrave, M E

    1997-01-01

    Although considerable research and speculation have been directed toward understanding a plant's perception of gravity and the resulting gravitropic responses, little is known about the role of gravity-dependent physical processes in normal physiological function. These studies were conducted to determine whether the roots of plants exposed to spaceflight conditions may be experiencing hypoxia. Arabidopsis thaliana (L.) Heynh. plants were grown in agar medium during 6 or 11 d of spaceflight exposure on shuttle missions STS-54 (CHROMEX-03) and STS-68 (CHROMEX-05), respectively. The analysis included measurement of agar redox potential and root alcohol dehydrogenase (ADH) activity, localization, and expression. ADH activity increased by 89% as a result of spaceflight exposure for both CHROMEX-03 and -05 experiments, and ADH RNase protection assays revealed a 136% increase in ADH mRNA. The increase in ADH activity associated with the spaceflight roots was realized by a 28% decrease in oxygen availability in a ground-based study; however, no reduction in redox potential was observed in measurements of the spaceflight bulk agar. Spaceflight exposure appears to effect a hypoxic response in the roots of agar-grown plants that may be caused by changes in gravity-mediated fluid and/or gas behavior. PMID:9085569

  13. 75 FR 64411 - Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ...The Mine Safety and Health Administration (MSHA) proposes to lower miners' exposure to respirable coal mine dust by revising the Agency's existing standards on miners' occupational exposure to respirable coal mine dust. The major provisions of the proposal would lower the existing exposure limit; provide for full-shift sampling; redefine the term ``normal production shift; '' and add......

  14. Kupffer Cell Activation by Ambient Air Particulate Matter Exposure May Exacerbate Non-alcoholic Fatty Liver Disease

    PubMed Central

    Tan, Hui-Hui; Fiel, M. Isabel; Sun, Qinghua; Guo, Jinsheng; Gordon, Ronald E.; Chen, Lung-Chi; Friedman, Scott L.; Odin, Joseph A.; Allina, Jorge

    2009-01-01

    Due to increased obesity, non-alcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the United States. NAFLD is considered a component of metabolic syndrome, a cluster of disorders that also includes diabetes mellitus, dyslipidemia, arteriosclerosis, and hypertension. Exposure to ambient air particulate matter with aerodynamic diameters < 2.5 µm (PM2.5) is a risk factor for arteriosclerosis as well as lung disease, but its effect on NAFLD is unknown. PM2.5 induces pulmonary dysfunction via toll-like receptor activation on alveolar macrophages. Toll-like receptor activation of Kupffer cells, resident hepatic macrophages, and subsequent pro-inflammatory cytokine production have been shown to play a key role in NAFLD progression. We hypothesized that PM2.5 exposure is a significant risk factor for progression of NAFLD. Thus, following exposure of male C57BL/6 mice fed high fat chow to concentrated air particulate matter (CAPs) or filtered air for 6 wk, progression of NAFLD was evaluated by standardized histological assessment of hepatic inflammation and fibrosis. In mice fed high fat chow, the hepatic inflammatory grade (3.00 ± 0.00 vs. 1.50 ± 0.71, p < 0.001) and fibrosis stage (1.00 ± 0.00 vs. 0.60 ± 0.52, p = 0.023) were both significantly higher in mice exposed to CAPs versus filtered air, respectively. Increased numbers of Kupffer cells contained PM in CAPs-exposed mice (2.00 ± 0.94 vs. 0.20 ± 0.42, respectively, p < 0.001). PM exposure increased IL-6 secretion up to seven fold in a dose-dependent manner by isolated wild-type but not TLR4−/− Kupffer cells (p < 0.050). Conclusion: Ambient PM2.5 exposure may be a significant risk factor for NAFLD progression. PMID:19908945

  15. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  16. Alcohol

    MedlinePlus

    ... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...

  17. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  18. Ethanol administration dampens the prolactin response to psychosocial stress exposure in sons of alcohol-dependent fathers.

    PubMed

    Zimmermann, Ulrich S; Buchmann, Arlette F; Spring, Constance; Uhr, Manfred; Holsboer, Florian; Wittchen, Hans-Ulrich

    2009-08-01

    Genetic predisposition and exposure to alcohol and stress increase the risk for alcoholism, possibly by forming a threefold interaction. This is suggested by various aspects of alcohol-induced stress response dampening in offspring of alcoholics. We tested whether such an interaction is also revealed by prolactin secretion, which is predominantly controlled by hypothalamic dopamine. Plasma prolactin was measured during four experimental days in 26 young males with a paternal history of alcoholism (PHA) and in 22 family history negative (FHN) controls. A public speaking stress paradigm was applied on the first 2 days, and a non-stress acoustic startle experiment on the others. Before the tests, subjects drank alcohol (0.6 g/kg) or placebo in a randomized, double-blind crossover design. During placebo experiments, prolactin levels significantly increased after stress, but not after startle, and did not differ between risk groups. Alcohol administration significantly increased prolactin before stress and during startle in both groups, did not alter stress-induced prolactin stimulation in FHN, but significantly attenuated the prolactin stress response in PHA subjects. The alcohol effects on prolactin, cortisol, and adrenocorticotropin stress response were positively interrelated with each other. These data confirm that alcohol specifically dampens the stress response in PHA but not FHN subjects. Since prolactin responses to stress alone and alcohol alone were normal in PHA, we conclude that this genetic effect is not related to altered physiology of the hypothalamic dopaminergic system, but to risk-group specific alcohol effects on hierarchically higher brain areas controlling the stress response in general.

  19. Preformed biomarkers including dialkylphosphates (DAPs) in produce may confound biomonitoring in pesticide exposure and risk assessment.

    PubMed

    Chen, Li; Zhao, Taifeng; Pan, Canping; Ross, John H; Krieger, Robert I

    2012-09-12

    Low levels of pesticides and their metabolites/degradates occur in produce when pesticides are used in conventional or organic crop protection. Human dietary and nonoccupational urine biomonitoring studies may be confounded by preformed pesticide biomarkers in the diet. The extent of formation of putative urine biomarkers, including malathion specific (MMA, MDA; malathion mono- and diacids), organophosphorus generic (DMP, DMTP, DMDTP; dimethyl-, dimethylthio-, and dimethydithiophosphate), pyrethroid generic (3-PBA; 3-phenoxybenzoic acid), and captan-specific metabolites (THPI; tetrahydrophthalimide), was measured in produce samples containing the parent pesticide. Every produce sample of 19 types of fruits and vegetables contained biomarkers of potential human exposure. A total of 134 of 157 (85%) samples contained more molar equivalent biomarkers than parent pesticide. Malathion and fenpropathrin were sprayed (1 lb/A), and the time-dependent formation of pesticide biomarkers in strawberries was investigated under field conditions typical of commercial production in California. Malathion and fenpropathrin residues were always below established residue tolerances. Malathion, MMA, and MDA dissipated, while DMP, DMTP, and DMDTP increased, during a 20 day study period following the preharvest interval. The mole ratios of biomarkers/(malathion + malaoxon) were always greater than 1 and increased from day 4 to day 23 postapplication. Fenpropathrin and 3-PBA also dissipated in strawberries during each monitoring period. The mole ratios of 3-PBA/fenpropathrin were always less than 1 and decreased from day 4 to day 14. The absorption of pesticide biomarkers in produce and excretion in urine would falsely indicate consumer pesticide exposure if used to reconstruct dose for risk characterization.

  20. MODERATE PRENATAL ALCOHOL EXPOSURE AND SEROTONIN GENOTYPE INTERACT TO ALTER CNS SEROTONIN FUNCTION IN RHESUS MONKEYS OFFSPRING

    PubMed Central

    Schneider, Mary L.; Moore, Colleen F.; Barr, Christina S.; Larson, Julie A.; Kraemer, Gary W.

    2010-01-01

    Background Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Methods Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from four groups of females were assessed: (1) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/day alcohol solution on gestational days 0 – 50; (2) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/day alcohol solution on gestational days 50 – 135; (3) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/day alcohol solution on gestational days 0 – 135; and (4) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 – 50, 50 – 135, or 0 – 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l versus homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Results Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, while 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared to monkeys homozygous for the long allele. Conclusion Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle

  1. Transient activation of microglia following acute alcohol exposure in developing mouse neocortex is primarily driven by BAX-dependent neurodegeneration.

    PubMed

    Ahlers, Katelin E; Karaçay, Bahri; Fuller, Leah; Bonthius, Daniel J; Dailey, Michael E

    2015-10-01

    Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in the developing brain in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice, we found that alcohol-induced neuroapoptosis in the neocortex is closely correlated in space and time with the appearance of activated microglia near dead cells. The timing and molecular pattern of microglial activation varied with the level of cell death. Although microglia rapidly mobilized to contact and engulf late-stage apoptotic neurons, apoptotic bodies temporarily accumulated in neocortex, suggesting that in severe cases of alcohol toxicity the neurodegeneration rate exceeds the clearance capacity of endogenous microglia. Nevertheless, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, there was a transient increase in expression of pro-inflammatory factors, TNFα and IL-1β, after severe (5 g/kg) but not moderate (3 g/kg) EtOH levels. Alcohol-induced microglial activation and pro-inflammatory factor expression were largely abolished in BAX null mice lacking neuroapoptosis, indicating that microglial activation is primarily triggered by apoptosis rather than the alcohol. Therefore, acute alcohol exposure in the developing neocortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain.

  2. Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.

    PubMed

    Caldeira, Jerri C; Wu, Yan; Mameli, Manuel; Purdy, Robert H; Li, Pui-Kai; Akwa, Yvette; Savage, Daniel D; Engen, John R; Valenzuela, C Fernando

    2004-09-01

    Neurosteroids are modulators of neuronal function that may play important roles in brain maturation. We determined whether chronic prenatal ethanol exposure altered neurosteroid levels in the developing brain. Rat dams were exposed to: (i) a 5% ethanol-containing liquid diet that produces peak maternal blood alcohol levels near the legal intoxication limit (approximately 0.08 g/dL); (ii) an isocaloric liquid diet containing maltose-dextrin instead of ethanol with pair-feeding; (iii) rat chow ad libitum. Neurosteroid levels were assessed in offspring brains using radioimmunoassay or gas chromatography-mass spectrometry techniques. A prenatal ethanol exposure-induced increase in pregnenolone sulfate levels, but not dehydroepiandrosterone sulfate levels, was evident at the earliest time point studied (embryonic day 14). This effect lasted until post-natal day 5. Levels of other neurosteroids were assessed at embryonic day 20; pregnenolone levels, but not allopregnanolone levels, were elevated. Pregnenolone sulfate levels were not altered in the maternal brain. Neither pregnenolone nor pregnenolone sulfate levels were significantly altered in the fetal liver, placenta and maternal blood, indicating that the effect of ethanol is not secondary to accumulation of peripherally-produced steroids. Fetal ethanol exposure has been shown to decrease both cellular and behavioral responsiveness to neurosteroids, and our findings provide a plausible explanation for this effect.

  3. [Survival of Gram-positive spore-forming bacteria including Bacillus cereus after hand washing using alcohol-based handrub].

    PubMed

    Ogawa, Midori; Takada, Shinichiro; Takahashi, Masao; Yasuda, Etsuko; Watase, Mariko; Taniguchi, Hatsumi

    2006-12-01

    Hand washing is the most fundamental method for preventing infection. Currently, hand washing with an alcohol-based handrub is the international gold standard method. However, in our study we found many samples of ineffective hand washing using an alcohol-based handrub. The rates of ineffective samples were 10.4% (5/48) in 2004 and 34.3% (12/35) in 2005. We examined the morphology by Gram staining and biochemical properties of the bacteria which remained after hand washing in 2005. Their colonies were divided into 3 groups (round colonies, irregular-shaped and diffusive colonies). The round colonies were considered Staphylococcus spp., and the irregular-shaped colonies or diffusive colonies were considered Gram-positive spore-forming bacteria. In the 12 ineffective hand washing samples (more than the same number of bacteria colonies as before hand washing, or > or = 300), there were 3 samples considered to be the result of the survival of Staphylococcus spp., and 9 samples considered to be the result of the survival of Gram-positive spore-forming bacteria including Bacillus cereus. Based on these results, we should take careful measures, such as wearing sterile gloves if necessary. We should never be overconfident regarding the effect of hand washing.

  4. Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration.

    PubMed

    Ryan, S Hunter; Williams, Jennifer K; Thomas, Jennifer D

    2008-10-27

    Despite the harmful effects of fetal alcohol exposure, some pregnant women continue to drink alcohol. Thus, it is imperative to pursue safe, effective treatments for children with fetal alcohol spectrum disorders. Using an animal model, our laboratory has demonstrated that choline, an essential nutrient, effectively reduces the severity of some fetal alcohol effects, even when administered after the ethanol insult is complete. The present study investigated whether there is a critical developmental period when choline is most effective in attenuating ethanol's teratogenic effects. Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol during the third trimester equivalent brain growth spurt (postnatal days (PD) 4-9) via intubation. A non-intubation control group and a sham intubation control group were included. Following ethanol exposure, pups received subcutaneous injections of saline vehicle or choline chloride (100 mg/kg/day) from PD 11-20, PD 21-30, or PD 11-30. Beginning on PD 45, subjects were tested on a Morris water maze spatial learning task. Performance of both the ethanol-exposed group that did not receive choline and the ethanol-exposed group treated with choline from PD 21-30 was significantly impaired compared to controls during acquisition of the Morris water maze task. Performance of ethanol-exposed groups treated with choline from PD 11-20 or PD 11-30 was intermediate, not differing significantly from any other groups. However, during the probe trial, ethanol exposure produced significant deficits in spatial memory which were mitigated by all choline treatments, regardless of the timing of administration. These findings suggest that choline's therapeutic window may be very large, or spans across the two developmental periods examined in this study. Importantly, these findings indicate that choline supplementation may effectively reduce some alcohol-related learning impairments, even when administered in later childhood.

  5. THE INFLUENCE OF EXTRINSIC REINFORCEMENT ON CHILDREN WITH HEAVY PRENATAL ALCOHOL EXPOSURE

    PubMed Central

    Graham, Diana M.; Glass, Leila; Mattson, Sarah N.

    2016-01-01

    Background Prenatal alcohol exposure affects inhibitory control and other aspects of attention and executive function. However, the efficacy of extrinsic reinforcement on these behaviors has not been tested. Methods Alcohol-exposed children (AE; n=34), children with ADHD (ADHD; n=23), and controls (CON; n=31) completed a flanker task with four reward conditions (no reward, reward, reward+occasional response cost, equal probability of reward+response cost). Inhibitory control was tested in the no reward conditions using a 3(group) x 2(flanker type) ANCOVA. Response to reinforcement was tested using 3(group) x 4(reward condition) x 4(flanker type) ANCOVA. Response time (RT) and accuracy were tested independently. Results Groups did not differ on demographic variables. The flanker task was successful in taxing interference control, an aspect of executive attention (i.e., responses to incongruent stimuli were slower than to congruent stimuli) and the AE group demonstrated impaired executive control over the other groups. Overall, the AE group had significantly slower response times compared to the CON and ADHD groups, which did not differ. However, reinforcement improved RT in all groups. While occasional response cost had the greatest benefit in the CON group, the type of reinforcement did not differentially affect the AE and ADHD groups. Accuracy across reward conditions did not differ by group, but was dependent on flanker type and reward condition. Conclusions Alcohol-exposed children, but not children with ADHD, had impaired interference control in comparison to controls, supporting a differential neurobehavioral profile in these two groups. Both clinical groups were equally affected by introduction of reinforcement, although the type of reinforcement did not differentially affect performance as it did in the control group, suggesting that reward or response cost could be used interchangeably to result in the same benefit. PMID:26842253

  6. Influence of prenatal exposure to cimetidine and alcohol on selected morphological parameters of sexual differentiation: a preliminary report.

    PubMed

    McGivern, R F

    1987-01-01

    Pregnant rats were administered ethanol, cimetidine or a combination of both drugs from day 14 of gestation until parturition. Ano-genital (AG) distance measured at birth was significantly reduced in males exposed to cimetidine, but not in males or females exposed to alcohol. AG distance in males exposed to both ethanol and cimetidine also was not reduced, indicating a possible protective influence of ethanol against this effect of cimetidine. Birthweights in both sexes were reduced by prenatal ethanol exposure, both alone and with cimetidine exposure. Prenatal cimetidine exposure, both alone and in combination with ethanol significantly reduced seminal vesicle weights of adult males. However, no long-term effects of ethanol or cimetidine were observed on adrenal, testicular or ovarian weights. These results indicate that when fetal alcohol exposure is restricted to the critical prenatal period for hormonal actions on sexual differentiation, testosterone levels are maintained at an adequate level for normal morphological development of the genitalia.

  7. Multigenerational and Transgenerational Inheritance of Drug Exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine

    PubMed Central

    Yohn, Nicole L.; Bartolomei, Marisa S.; Blendy, Julie A.

    2015-01-01

    Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse. Specifically, changes found following the administration of alcohol, opioids, cocaine, marijuana, and nicotine will be discussed. In addition, epigenetic modifications to the genome following administration of these drugs will be detailed as well as their potential for transmission to the next generation. PMID:25839742

  8. Initial subjective reward: single-exposure conditioned place preference to alcohol in mice

    PubMed Central

    Grisel, Judith E.; Beasley, John B.; Bertram, Emma C.; Decker, Brooke E.; Duan, Chunyu A.; Etuma, Mahder; Hand, Annie; Locklear, Mallory N.; Whitmire, Matthew P.

    2014-01-01

    Most adults consume alcohol with relative impunity, but about 10–20% of users persist (or progress) in their consumption, despite mounting and serious repercussions. Identifying at-risk individuals before neuroadaptative changes associated with chronic use become well ingrained is thus a key step in mitigating and preventing the end stage disease and its devastating impacts. Explaining liability has been impeded, in part, by the absence of animal models for assessing initial sensitivity to the drug's reinforcing properties, an important endophenotype in the trajectory toward excessive drinking. Here we assess the initial rewarding effects of the drug in a novel application of the conditioned place preference paradigm. In contrast to previous studies that have all employed repeated drug administration, we demonstrated a robust preference for a context paired with a single exposure to 1.5 g/kg EtOH in male and female subjects of three strains. This model validates an assay of initial sensitivity to the subjective rewarding effects of alcohol, a widely used drug with multifarious impacts on both brain and society, and provides a new tool for theory-driven endophenotypic pharmacogenetic approaches to understanding and treating addiction. PMID:25408633

  9. Alcohol exposure in utero leads to enhanced prepubertal mammary development and alterations in mammary IGF and estradiol systems.

    PubMed

    Polanco, Tiffany A; Crismale-Gann, Catina; Cohick, Wendie S

    2011-08-01

    Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life.

  10. A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.

    PubMed

    Linderborg, Klas; Salaspuro, Mikko; Väkeväinen, Satu

    2011-09-01

    The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure.

  11. Does exposure to domestic wastewater effluent (including steroid estrogens) harm fish populations in the UK?

    PubMed

    Johnson, Andrew C; Chen, Yihong

    2017-07-01

    Historic fisheries data collected from locations across the UK over several years were compared with predicted estrogen exposure derived from the resident human population. This estrogen exposure could be viewed as a proxy for general sewage (wastewater) exposure. With the assistance of the Environment Agency in the UK, fisheries abundance data for Rutilis rutilis (roach), Alburnus alburnus (bleak), Leuciscus leuciscus (dace) and Perca fluviatilis (perch) from 38 separate sites collected over 7 to 17year periods were retrieved. From these data the average density (fish/m(2)/year) were compared against average and peak predicted estrogen (wastewater) exposure for these sites. Estrogen concentrations were predicted using the LF2000-WQX model. No correlation between estrogen/wastewater exposure and fish density could be found for any of the species. Year on year temporal changes in roach population abundance at 3 sites on the middle River Thames and 4 sites on the Great Ouse were compared against estrogen exposure over the preceding year. In this case the estrogen prediction was calculated based on the upstream human population providing the estrogen load and the daily flow value allowing concentration to be estimated over time. At none of the sites on these rivers were temporal declines in abundance associated with preceding estrogen (effluent) exposure. The results indicate that, over the past decade, wastewater and estrogen exposure has not led to a catastrophic decline in these four species of cyprinid fish.

  12. Withdrawal from chronic intermittent alcohol exposure increases dendritic spine density in the lateral orbitofrontal cortex of mice.

    PubMed

    McGuier, Natalie S; Padula, Audrey E; Lopez, Marcelo F; Woodward, John J; Mulholland, Patrick J

    2015-02-01

    Alcohol use disorders (AUDs) are associated with functional and morphological changes in subfields of the prefrontal cortex. Clinical and preclinical evidence indicates that the orbitofrontal cortex (OFC) is critical for controlling impulsive behaviors, representing the value of a predicted outcome, and reversing learned associations. Individuals with AUDs often demonstrate deficits in OFC-dependent tasks, and rodent models of alcohol exposure show that OFC-dependent behaviors are impaired by chronic alcohol exposure. To explore the mechanisms that underlie these impairments, we examined dendritic spine density and morphology, and NMDA-type glutamate receptor expression in the lateral OFC of C57BL/6J mice following chronic intermittent ethanol (CIE) exposure. Western blot analysis demonstrated that NMDA receptors were not altered immediately following CIE exposure or after 7 days of withdrawal. Morphological analysis of basal dendrites of layer II/III pyramidal neurons revealed that dendritic spine density was also not affected immediately after CIE exposure. However, the total density of dendritic spines was significantly increased after a 7-day withdrawal from CIE exposure. The effect of withdrawal on spine density was mediated by an increase in the density of long, thin spines with no change in either stubby or mushroom spines. These data suggest that morphological neuroadaptations in lateral OFC neurons develop during alcohol withdrawal and occur in the absence of changes in the expression of NMDA-type glutamate receptors. The enhanced spine density that follows alcohol withdrawal may contribute to the impairments in OFC-dependent behaviors observed in CIE-treated mice.

  13. Analytic Strategies to Evaluate the Association of Time-Varying Exposures to HIV-Related Outcomes: Alcohol Consumption as an Example

    PubMed Central

    Cook, Robert L.; Kelso, Natalie E.; Brumback, Babette A.; Chen, Xinguang

    2016-01-01

    Background As persons with HIV are living longer, there is a growing need to investigate factors associated with chronic disease, rate of disease progression and survivorship. Many risk factors for this high-risk population change over time, such as participation in treatment, alcohol consumption and drug abuse. Longitudinal datasets are increasingly available, particularly clinical data that contain multiple observations of health exposures and outcomes over time. Several analytic options are available for assessment of longitudinal data; however, it can be challenging to choose the appropriate analytic method for specific combinations of research questions and types of data. The purpose of this review is to help researchers choose the appropriate methods to analyze longitudinal data, using alcohol consumption as an example of a time-varying exposure variable. When selecting the optimal analytic method, one must consider aspects of exposure (e.g. timing, pattern, and amount) and outcome (fixed or time-varying), while also addressing minimizing bias. In this article, we will describe several analytic approaches for longitudinal data, including developmental trajectory analysis, generalized estimating equations, and mixed effect models. For each analytic strategy, we describe appropriate situations to use the method and provide an example that demonstrates the use of the method. Clinical data related to alcohol consumption and HIV are used to illustrate these methods. PMID:26511345

  14. Abuse Liability Assessment of Tobacco Products Including Potential Reduced Exposure Products (PREPs)

    PubMed Central

    Carter, Lawrence P.; Stitzer, Maxine L.; Henningfield, Jack E.; O'Connor, Rich J.; Cummings, K. Michael; Hatsukami, Dorothy K.

    2009-01-01

    The harm produced by tobacco products is a result of frequent use of a highly toxic product. Reducing the adverse public health impact of tobacco products might be most effectively achieved by reducing the likelihood of their use and the toxicity of the products. Products that retain some characteristics of cigarettes, but have been altered with the intention of reducing toxicity have been referred to as modified risk tobacco products or potential reduced exposure products (MRTP/PREPS). Evaluation of their content, emission, and toxicity is discussed in other articles in this special issue. Here, we discuss the methodology that has been used to examine the likelihood of abuse or addiction. Abuse liability assessment (ALA) methodology has been used by the Food and Drug Administration (FDA) and other drug regulatory agencies world-wide for decades to assess the risks posed by a wide variety of pharmacologically active substances. ALA is routinely required among other evaluations of safety during the premarket assessment of new drugs, and is continually adapted to meet the challenges posed by new drug classes and drug formulations. In the 2009 law giving FDA regulation over tobacco products, FDA is now required to evaluate new tobacco products including MRTP/PREPs to determine their risk for abuse and toxicity at the population level. This paper describes the traditional tools and methods of ALA that can be used to evaluate new tobacco and nicotine products including MRTP/PREPs. Such ALA data could contribute to the scientific foundation on which future public policy decisions are based. PMID:19959676

  15. Abuse liability assessment of tobacco products including potential reduced exposure products.

    PubMed

    Carter, Lawrence P; Stitzer, Maxine L; Henningfield, Jack E; O'Connor, Rich J; Cummings, K Michael; Hatsukami, Dorothy K

    2009-12-01

    The harm produced by tobacco products is a result of frequent use of a highly toxic product. Reducing the adverse public health impact of tobacco products might be most effectively achieved by reducing the likelihood of their use and the toxicity of the products. Products that retain some characteristics of cigarettes but have been altered with the intention of reducing toxicity have been referred to as modified risk tobacco products or potential reduced exposure products (MRTP/PREP). Evaluation of their content, emission, and toxicity is discussed in other articles in this special issue. Here, we discuss the methodology that has been used to examine the likelihood of abuse or addiction. Abuse liability assessment (ALA) methodology has been used by the Food and Drug Administration (FDA) and other drug regulatory agencies world-wide for decades to assess the risks posed by a wide variety of pharmacologically active substances. ALA is routinely required among other evaluations of safety during the pre-market assessment of new drugs, and is continually adapted to meet the challenges posed by new drug classes and drug formulations. In the 2009 law giving FDA regulation over tobacco products, FDA is now required to evaluate new tobacco products including MRTP/PREPs to determine their risk for abuse and toxicity at the population level. This article describes the traditional tools and methods of ALA that can be used to evaluate new tobacco and nicotine products including MRTP/PREPs. Such ALA data could contribute to the scientific foundation on which future public policy decisions are based.

  16. Is Prenatal Alcohol Exposure Related to Inattention and Hyperactivity Symptoms in Children? Disentangling the Effects of Social Adversity

    ERIC Educational Resources Information Center

    Rodriguez, A.; Olsen, J.; Kotimaa, A. J.; Kaakinen, M.; Moilanen, I.; Henriksen, T. B.; Linnet, K. M.; Miettunen, J.; Obel, C.; Taanila, A.; Ebeling, H.; Jarvelin, M. R.

    2009-01-01

    Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting…

  17. Behavioral Effects of Pre- and Postnatal Exposure to Smoking, Alcohol, and Caffeine in 5-Month-Old Infants.

    ERIC Educational Resources Information Center

    Dowler, Jeffrey K.; Jacobson, Sandra W.

    This study examined the behavioral effects of prenatal and postnatal exposure to smoking, alcohol, and caffeinated beverages on 5-month-old infants. The sample consisted of 179 Caucasian infants and their mothers. All mothers were 19 years of age or older and had at least a tenth-grade education. Mental and motor portions of the Bayley Scales of…

  18. Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure

    PubMed Central

    March, Samanta M.; Culleré, Marcela E.; Abate, Paula; Hernández, José I.; Spear, Norman E.; Molina, Juan C.

    2013-01-01

    Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life. PMID:23785319

  19. Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure.

    PubMed

    March, Samanta M; Culleré, Marcela E; Abate, Paula; Hernández, José I; Spear, Norman E; Molina, Juan C

    2013-01-01

    Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life.

  20. Human exposure to fluorotelomer alcohols, perfluorooctane sulfonate and perfluorooctanoate via house dust in Bavaria, Germany.

    PubMed

    Xu, Zhenlan; Fiedler, Stefan; Pfister, Gerd; Henkelmann, Bernhard; Mosch, Christine; Völkel, Wolfgang; Fromme, Hermann; Schramm, Karl-Werner

    2013-01-15

    This study aimed at investigating the presence and distribution of fluorotelomer alcohols (FTOHs), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in house dust to evaluate human exposure to these compounds via dust ingestion. 31 house dust samples were collected from Bavaria, Germany and analyzed for 4:2, 6:2, 8:2 and 10:2 FTOH, PFOS and PFOA. PFOA was the dominant compound in 79% of the dust samples, followed by PFOS and 8:2 FTOH, while 4:2 FTOH was not detected in any samples. The total concentration of per- and polyfluorinated compounds (PFCs) varied from 32.2 to 2456 ng/g. In addition, the total ingestion rate for PFCs was 0.4-135 ng/d for adults and 5.1-246 ng/d for toddlers, and the highest 8:2 FTOH-based PFOA intake via indoor dust was 0.24 ng/d for adults and 0.44 ng/d for toddlers. Overall, the results of this study demonstrate that dust ingestion is a minor pathway for human exposure to these PFCs; the PFC ingestion via indoor dust is generally low, and only under a worst scenario high intakes have to be expected for toddlers.

  1. Prenatal Alcohol Exposure Affects Progenitor Cell Numbers in Olfactory Bulbs and Dentate Gyrus of Vervet Monkeys

    PubMed Central

    Burke, Mark W.; Inyatkin, Alexey; Ptito, Maurice; Ervin, Frank R.; Palmour, Roberta M.

    2016-01-01

    Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation. PMID:27801790

  2. Alcohol tolerance in large-conductance, calcium-activated potassium channels of CNS terminals is intrinsic and includes two components: decreased ethanol potentiation and decreased channel density.

    PubMed

    Pietrzykowski, Andrzej Z; Martin, Gilles E; Puig, Sylvie I; Knott, Thomas K; Lemos, Jose R; Treistman, Steven N

    2004-09-22

    Tolerance is an important element of drug addiction and provides a model for understanding neuronal plasticity. The hypothalamic-neurohypophysial system (HNS) is an established preparation in which to study the actions of alcohol. Acute application of alcohol to the rat neurohypophysis potentiates large-conductance calcium-sensitive potassium channels (BK), contributing to inhibition of hormone secretion. A cultured HNS explant from adult rat was used to explore the molecular mechanisms of BK tolerance after prolonged alcohol exposure. Ethanol tolerance was intrinsic to the HNS and consisted of: (1) decreased BK potentiation by ethanol, complete within 12 min of exposure, and (2) decreased current density, which was not complete until 24 hr after exposure, indicating that the two components of tolerance represent distinct processes. Single-channel properties were not affected by chronic exposure, suggesting that decreased current density resulted from downregulation of functional channels in the membrane. Indeed, we observed decreased immunolabeling against the BK alpha-subunit on the surface of tolerant terminals. Analysis using confocal microscopy revealed a reduction of BK channel clustering, likely associated with the internalization of the channel.

  3. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci

    PubMed Central

    Gelernter, J; Kranzler, HR; Sherva, R; Almasy, L; Koesterer, R; Smith, AH; Anton, R; Preuss, UW; Ridinger, M; Rujescu, D; Wodarz, N; Zill, P; Zhao, H; Farrer, LA

    2014-01-01

    We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus, showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P = 1.17 × 10−31; AAs: Arg369Cys, P = 6.33 × 10−17) and ADH1C in AAs (Thr151Thr, P = 4.94 × 10−10), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P = 2.63 × 10−11), PDLIM5 in EAs (P = 2.01 × 10−8), and METAP in AAs (P = 3.35 × 10−8). We also identified a novel GWS association (1.17 × 10−10) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits. PMID:24166409

  4. The Potential Impact of a “No-Buy” List on Youth Exposure to Alcohol Advertising on Cable Television

    PubMed Central

    Ross, Craig S.; Brewer, Robert D.; Jernigan, David H.

    2016-01-01

    Objective: The purpose of this study was to outline a method to improve alcohol industry compliance with its self-regulatory advertising placement guidelines on television with the goal of reducing youth exposure to noncompliant advertisements. Method: Data were sourced from Nielsen (The Nielsen Company, New York, NY) for all alcohol advertisements on television in the United States for 2005–2012. A “no-buy” list, that is a list of cable television programs and networks to be avoided when purchasing alcohol advertising, was devised using three criteria: avoid placements on programs that were noncompliant in the past (serially noncompliant), avoid placements on networks at times of day when youth make up a high proportion of the audience (high-risk network dayparts), and use a “guardbanded” (or more restrictive) composition guideline when placing ads on low-rated programs (low rated). Results: Youth were exposed to 15.1 billion noncompliant advertising impressions from 2005 to 2012, mostly on cable television. Together, the three no-buy list criteria accounted for 99% of 12.9 billion noncompliant advertising exposures on cable television for youth ages 2–20 years. When we evaluated the no-buy list criteria sequentially and mutually exclusively, serially noncompliant ads accounted for 67% of noncompliant exposure, high-risk network-daypart ads accounted for 26%, and low rated ads accounted for 7%. Conclusions: These findings suggest that the prospective use of the no-buy list criteria when purchasing alcohol advertising could eliminate most noncompliant advertising exposures and could be incorporated into standard post-audit procedures that are widely used by the alcohol industry in assessing exposure to television advertising. PMID:26751350

  5. Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex.

    PubMed

    Ferrario, Daniele; Gribaldo, Laura; Hartung, Thomas

    2016-03-01

    Increasing evidence suggests that inorganic arsenic, a major environmental pollutant, exerts immunosuppressive effects in epidemiological, in vitro, and animal models. The mechanisms, however, remain unclear, and little is known about variation in susceptibilities due to age and sex. We performed a review of the experimental and epidemiologic evidence on the association of arsenic exposure and immune diseases. The majority of the studies described arsenic as a potent immunosuppressive compound, though others have reported an increase in allergy and autoimmune diseases, suggesting that arsenic may also act as an immune system stimulator, depending on the dose or timing of exposure. Limited information, due to either the high concentrations of arsenic used in in vitro studies or the use of non-human data for predicting human risks, is available from experimental studies. Moreover, although there is emerging evidence that health effects of arsenic manifest differently between men and women, we found limited information on sex differences on the immunotoxic effects of arsenic. In conclusion, preliminary data show that chronic early-life exposure to arsenic might impair immune responses, potentially leading to increased risk of infections and inflammatory-like diseases during childhood and in adulthood. Further investigation to evaluate effects of arsenic exposure on the developing immune system of both sexes, particularly in human cells and using concentrations relevant to human exposure, should be a research priority.

  6. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    SciTech Connect

    Chen Bo; Xia Jing; Li Guangxing; Zhou Yifeng

    2010-03-15

    Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

  7. Military sexual trauma, combat exposure, and negative urgency as independent predictors of PTSD and subsequent alcohol problems among OEF/OIF veterans.

    PubMed

    Hahn, Austin M; Tirabassi, Christine K; Simons, Raluca M; Simons, Jeffrey S

    2015-11-01

    This study tested a path model of relationships between military sexual trauma (MST), combat exposure, negative urgency, posttraumatic stress disorder (PTSD) symptoms, and alcohol use and related problems. The sample consisted of 86 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans who reported drinking at least one alcoholic beverage per week. PTSD mediated the relationships between MST and alcohol-related problems, negative urgency and alcohol-related problems, and combat exposure and alcohol-related problems. In addition, negative urgency had a direct effect on alcohol problems. These results indicate that MST, combat exposure, and negative urgency independently predict PTSD symptoms and PTSD symptoms mediate their relationship with alcohol-related problems. Findings support previous literature on the effect of combat exposure and negative urgency on PTSD and subsequent alcohol-related problems. The current study also contributes to the limited research regarding the relationship between MST, PSTD, and alcohol use and related problems. Clinical interventions aimed at reducing emotional dysregulation and posttraumatic stress symptomology may subsequently improve alcohol-related outcomes.

  8. Military Sexual Trauma, Combat Exposure, and Negative Urgency as Independent Predictors of PTSD and Subsequent Alcohol Problems among OEF/OIF Veterans

    PubMed Central

    Tirabassi, Christine K.; Simons, Raluca M.; Simons, Jeffrey S.

    2015-01-01

    This study tested a path model of relationships between military sexual trauma (MST), combat exposure, negative urgency, posttraumatic stress disorder (PTSD) symptoms, and alcohol use and related problems. The sample consisted of 86 OEF/OIF veterans who reported drinking at least one alcoholic beverage per week. PTSD mediated the relationships between MST and alcohol-related problems, negative urgency and alcohol-related problems, as well as combat exposure and alcohol-related problems. In addition, negative urgency had a direct effect on alcohol problems. These results indicate that MST, combat exposure, and negative urgency independently predict PTSD symptoms and PTSD symptoms mediate their relationship with alcohol-related problems. Findings support previous literature on the effect of combat exposure and negative urgency on PTSD and subsequent alcohol-related problems. The current study also contributes to the limited research regarding the relationship between MST, PSTD, and alcohol use and related problems. Clinical interventions aimed at reducing emotional dysregulation and posttraumatic stress symptomology may subsequently improve alcohol related outcomes. PMID:26524279

  9. Prenatal coke: what's behind the smoke? Prenatal cocaine/alcohol exposure and school-age outcomes: the SCHOO-BE experience.

    PubMed

    Delaney-Black, V; Covington, C; Templin, T; Ager, J; Martier, S; Compton, S; Sokol, R

    1998-06-21

    Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgement of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be

  10. Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain.

    PubMed

    D'Addario, Claudio; Caputi, Francesca F; Rimondini, Roberto; Gandolfi, Ottavio; Del Borrello, Elia; Candeletti, Sanzio; Romualdi, Patrizia

    2013-05-01

    Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5 g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence.

  11. Exposure to tobacco, alcohol and drugs of abuse during pregnancy. A study of prevalence among pregnant women in Malaga (Spain).

    PubMed

    Blasco-Alonso, Marta; González-Mesa, Ernesto; Gálvez Montes, Milagros; Lozano Bravo, Isabel; Merino Galdón, Federico; Cuenca Campos, Francisco; Marín Schiaffino, Gema; Pérez Torres, Sergio; Herrera Peral, José; Bellido Estévez, Inmaculada

    2015-06-17

    The prevalence of substance abuse in women who become pregnant is similar to that of the general population, resulting in a high fetal exposure rate during the most vulnerable period regarding neurodevelopment and organogenesis. The present study was intended to assess the level of prenatal exposure to tobacco, alcohol or illicit drugs in the city of Málaga (Spain). It was designed as a cross-sectional study, and based on the anonymous self-reports of participants. A total of 451 pregnant women were recruited in the first, second or third trimester. The prevalence in each of the quarters respectively was 21.2%, 18.5% and 13.3% for smoking, 40.7%, 23.1% and 17.1% for alcohol and 4.8%, 1.9% and 1.2% for cannabis. We also found that a higher educational level was associated with a lower consumption of tobacco (RR 0.659 [0.537-0.810] p<0.0001) and greater exposure to alcohol (RR 1.87 [1.30-2.69] p<0.0007). These results, particularly in regard to alcohol intake, are sufficiently alarming to alert obstetric care providers about the need to implement preventive measures.

  12. Blood lactate concentration after exposure to conducted energy weapons (including TASER® devices): is it clinically relevant?

    PubMed

    Jauchem, James R

    2013-09-01

    In previous studies, blood lactate concentration (BLac) consistently increased in anesthetized animals and in human subjects after exposures to TASER(®) conducted energy weapons (CEWs). Some have suggested the increased BLac would have detrimental consequences. In the current review, the following are evaluated: (a) the nature of muscle contractions due to CEWs, (b) general aspects of increased BLac, (c) previous studies of conventional neuromuscular electrical stimulation and CEW exposures, and (d) BLac in disease states. On the basis of these analyses, one can conclude that BLac, per se (independent of acidemia), would not be clinically relevant immediately after short-duration CEW applications, due to the short time course of any increase.

  13. Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar-to-ductal metaplasia through PI3K/Akt/IKK

    PubMed Central

    HUANG, XIN; LI, XUQI; MA, QINGYONG; XU, QINHONG; DUAN, WANXING; LEI, JIANJUN; ZHANG, LUN; WU, ZHENG

    2015-01-01

    Pancreatic acinar-to-ductal metaplasia (ADM) has been identified as an initiating event that can progress to pancreatic intraepithelial neoplasia (PanIN) or pancreatic ductal adenocarcinoma (PDAC). Acini transdifferentiation can be induced by persistent inflammation. Notably, compelling evidence has emerged that chronic alcohol exposure may trigger an inflammatory response of macrophages/monocytes stimulated by endotoxins. In the present study, we aimed to evaluate the role of inflammation induced by chronic alcohol and lipopolysaccharide (LPS) exposure in the progression of pancreatic ADM, as well as to elucidate the possible mechanisms involved. For this purpose, cultured macrophages were exposed to varying doses of alcohol for 1 week prior to stimulation with LPS. Tumor necrosis factor-α (TNF-α) and regulated upon activation, normal T cell expression and secreted (RANTES) expression were upregulated in the intoxicated macrophages with activated nuclear factor-κB (NF-κB). Following treatment with the supernatant of intoxicated macrophages, ADM of primary acinar cells was induced. Furthermore, the expression of TNF-α and RANTES, as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B(Akt)/inhibitory κB kinase (IKK) signaling pathway have been proven to be involved in the ADM of acinar cells. Moreover, Sprague-Dawley (SD) rats were employed to further explore the induction of pancreatic ADM by chronic alcohol and LPS exposure in vivo. At the end of the treatment period, a number of physiological parameters, such as body weight, liver weight and pancreatic weight were reduced in the exposed rats. Plasma alcohol concentrations and oxidative stress levels in the serum, as well as TNF-α and RANTES expression in monocytes were also induced following chronic alcohol and LPS exposure. In addition, pancreatic ADM was induced through the PI3K/Akt/IKK signaling pathway by the augmented TNF-α and RANTES expression levels in the exposed rats. Overall, we

  14. Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation

    PubMed Central

    Sanchez-Marin, Laura; Pavon, Francisco J.; Decara, Juan; Suarez, Juan; Gavito, Ana; Castilla-Ortega, Estela; Rodriguez de Fonseca, Fernando; Serrano, Antonia

    2017-01-01

    Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain. Alcohol-exposed rats exhibited anxiogenic-like responses and impaired recognition memory but no motor alterations. There were brain region-dependent changes in the mRNA levels of the ECS and molecular signals compared with control rats. Thus, overall, alcohol-exposed rats expressed higher mRNA levels of endocannabinoid synthetic enzymes (N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipases) in the medial-prefrontal cortex (mPFC) but lower mRNA levels in the amygdala. Furthermore, we observed lower mRNA levels of receptors CB1 CB2 and peroxisome proliferator-activated receptor-α in the striatum. Regarding neuropeptide signaling, alcohol-exposed rats displayed lower mRNA levels of the neuropeptide Y signaling, particularly NPY receptor-2, in the amygdala and hippocampus and higher mRNA levels of corticotropin-releasing factor in the hippocampus. Additionally, we observed changes of several neuroinflammation-related factors. Whereas, the mRNA levels of toll-like receptor-4, tumor necrosis factor-α, cyclooxygenase-2 and glial fibrillary acidic protein were significantly increased in the mPFC, the mRNA levels of cyclooxygenase-2 and glial fibrillary acidic protein were decreased in the striatum and hippocampus. However, nuclear factor-κβ mRNA levels were lower in the mPFC and striatum and allograft inflammatory factor-1

  15. Effects of Intermittent Alcohol Exposure on Emotion and Cognition: A Potential Role for the Endogenous Cannabinoid System and Neuroinflammation.

    PubMed

    Sanchez-Marin, Laura; Pavon, Francisco J; Decara, Juan; Suarez, Juan; Gavito, Ana; Castilla-Ortega, Estela; Rodriguez de Fonseca, Fernando; Serrano, Antonia

    2017-01-01

    Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain. Alcohol-exposed rats exhibited anxiogenic-like responses and impaired recognition memory but no motor alterations. There were brain region-dependent changes in the mRNA levels of the ECS and molecular signals compared with control rats. Thus, overall, alcohol-exposed rats expressed higher mRNA levels of endocannabinoid synthetic enzymes (N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipases) in the medial-prefrontal cortex (mPFC) but lower mRNA levels in the amygdala. Furthermore, we observed lower mRNA levels of receptors CB1 CB2 and peroxisome proliferator-activated receptor-α in the striatum. Regarding neuropeptide signaling, alcohol-exposed rats displayed lower mRNA levels of the neuropeptide Y signaling, particularly NPY receptor-2, in the amygdala and hippocampus and higher mRNA levels of corticotropin-releasing factor in the hippocampus. Additionally, we observed changes of several neuroinflammation-related factors. Whereas, the mRNA levels of toll-like receptor-4, tumor necrosis factor-α, cyclooxygenase-2 and glial fibrillary acidic protein were significantly increased in the mPFC, the mRNA levels of cyclooxygenase-2 and glial fibrillary acidic protein were decreased in the striatum and hippocampus. However, nuclear factor-κβ mRNA levels were lower in the mPFC and striatum and allograft inflammatory factor-1

  16. Growing up with Parental Alcohol Abuse: Exposure to Childhood Abuse, Neglect, and Household Dysfunction.

    ERIC Educational Resources Information Center

    Dube, Shanta R.; Anda, Robert F.; Felitti, Vincent J.; Croft, Janet B.; Edwards, Valerie J.; Giles, Wayne H.

    2001-01-01

    A study involving 8,629 adults examined the association between parental alcohol abuse and child abuse, neglect, and other household dysfunction. Compared to households without alcohol abuse, the adjusted odds ratio for each category of adverse childhood experience was 2 to 13 times higher if parents abused alcohol. (Contains references.) (CR)

  17. Alcohol's Collateral Damage: Childhood Exposure to Problem Drinkers and Subsequent Adult Mortality Risk.

    PubMed

    Rogers, Richard G; Lawrence, Elizabeth M; Montez, Jennifer Karas

    2016-12-07

    The importance of childhood circumstances, broadly defined, for shaping adult health and longevity is well-established. But the significance of one of the most prevalent childhood adversities-exposure to problem drinkers-has been understudied from a sociological perspective and remains poorly understood. We address this gap by drawing on cumulative inequality theory, using data from the 1988-2011 National Health Interview Survey-Linked Mortality Files, and estimating Cox proportional hazards models to examine the relationship between exposure to problem drinkers in childhood and adult mortality risk. Childhood exposure to problem drinkers is common (nearly 1 in 5 individuals were exposed) and elevates adult overall and cause-specific mortality risk. Compared to individuals who had not lived with a problem drinker during childhood, those who had done so suffered 17 percent higher risk of death (p<.001) over the follow-up period, net of age, sex, and race/ethnicity. We find compelling evidence that the duration, source, and intensity of exposure to problem drinkers in childhood contributes to inequality in adult mortality risk. Favorable socioeconomic status in adulthood does not ameliorate the consequences of childhood exposure to problem drinkers. The primary intervening mechanisms are risky behaviors, including adult drinking and smoking. The findings-which reveal that the influence of problem drinking is far-reaching and long-term-should inform policies to improve childhood circumstances, reduce detrimental effects of problem drinking, and increase life expectancy.

  18. Olfactory exposure to males, including men, causes stress and related analgesia in rodents.

    PubMed

    Sorge, Robert E; Martin, Loren J; Isbester, Kelsey A; Sotocinal, Susana G; Rosen, Sarah; Tuttle, Alexander H; Wieskopf, Jeffrey S; Acland, Erinn L; Dokova, Anastassia; Kadoura, Basil; Leger, Philip; Mapplebeck, Josiane C S; McPhail, Martina; Delaney, Ada; Wigerblad, Gustaf; Schumann, Alan P; Quinn, Tammie; Frasnelli, Johannes; Svensson, Camilla I; Sternberg, Wendy F; Mogil, Jeffrey S

    2014-06-01

    We found that exposure of mice and rats to male but not female experimenters produces pain inhibition. Male-related stimuli induced a robust physiological stress response that results in stress-induced analgesia. This effect could be replicated with T-shirts worn by men, bedding material from gonadally intact and unfamiliar male mammals, and presentation of compounds secreted from the human axilla. Experimenter sex can thus affect apparent baseline responses in behavioral testing.

  19. Poly(vinyl alcohol) hydrogel coatings with tunable surface exposure of hydroxyapatite.

    PubMed

    Moreau, David; Villain, Arthur; Ku, David N; Corté, Laurent

    2014-01-01

    Insufficient bone anchoring is a major limitation of artificial substitutes for connective osteoarticular tissues. The use of coatings containing osseoconductive ceramic particles is one of the actively explored strategies to improve osseointegration and strengthen the bone-implant interface for general tissue engineering. Our hypothesis is that hydroxyapatite (HA) particles can be coated robustly on specific assemblies of PVA hydrogel fibers for the potential anchoring of ligament replacements. A simple dip-coating method is described to produce composite coatings made of microscopic hydroxyapatite (HA) particles dispersed in a poly(vinyl alcohol) (PVA) matrix. The materials are compatible with the requirements for implant Good Manufacturing Practices. They are applied to coat bundles of PVA hydrogel fibers used for the development of ligament implants. By means of optical and electronic microscopy, we show that the coating thickness and surface state can be adjusted by varying the composition of the dipping solution. Quantitative analysis based on backscattered electron microscopy show that the exposure of HA at the coating surface can be tuned from 0 to over 55% by decreasing the weight ratio of PVA over HA from 0.4 to 0.1. Abrasion experiments simulating bone-implant contact illustrate how the coating cohesion and wear resistance increase by increasing the content of PVA relative to HA. Using pullout experiments, we find that these coatings adhere well to the fiber bundles and detach by propagation of a crack inside the coating. These results provide a guide to select coated implants for anchoring artificial ligaments.

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

    PubMed

    Washburn, Shannon E; Sawant, Onkar B; Lunde, Emilie R; Wu, Guoyao; Cudd, Timothy A

    2013-09-01

    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.

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

    PubMed Central

    Washburn, Shannon E.; Sawant, Onkar B.; Lunde, Emilie R.; Wu, Guoyao; Cudd, Timothy A.

    2013-01-01

    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. PMID:23315157

  2. Neonatal screening for prenatal alcohol exposure: assessment of voluntary maternal participation in an open meconium screening program.

    PubMed

    Zelner, Irene; Shor, Sarit; Lynn, Hazel; Roukema, Henry; Lum, Lisa; Eisinga, Kirsten; Koren, Gideon

    2012-05-01

    Meconium fatty acid ethyl esters (FAEEs) are validated biomarkers of fetal alcohol exposure. Meconium FAEE testing can potentially be used as a screen by health-care professionals to identify neonates at-risk for Fetal Alcohol Spectrum Disorder, thereby permitting diagnostic follow-up of these children and early intervention in those who develop disabilities. The purpose of this study was to assess whether women would willingly partake in a screening program of this nature. This was determined by launching a pilot screening program for prenatal alcohol exposure in a high-risk obstetric unit previously shown to have a high prevalence of FAEE-positive meconium via anonymous meconium testing. The program involved voluntary testing of meconium for FAEEs and long-term developmental follow-up of positive cases through an existing public health program. The participation rate in the screening program was significantly lower than when testing was conducted anonymously (78% vs. 95%, respectively; p < 0.05), and the positivity rate was 3% in contrast to 30% observed under anonymous conditions (p < 0.001). These low rates suggest that the majority of mothers who consumed alcohol in pregnancy refused to participate. We conclude that despite the potential benefits of such screening programs, maternal unwillingness to consent, likely due to fear, embarrassment, and guilt, may limit the effectiveness of meconium testing for population-based open screening, highlighting the need for public education and social marketing efforts for such programs to be of benefit.

  3. Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors.

    PubMed

    Retson, T A; Reyes, B A; Van Bockstaele, E J

    2015-01-02

    Understanding the neurobiological bases for sex differences in alcohol dependence is needed to help guide the development of individualized therapies for alcohol abuse disorders. In the present study, alcohol-induced adaptations in (1) anxiety-like behavior, (2) patterns of c-Fos activation and (3) subcellular distribution of corticotropin releasing factor receptor in locus coeruleus (LC) neurons was investigated in male and female Sprague-Dawley rats that were chronically exposed to ethanol using a liquid diet. Results confirm and extend reports by others showing that chronic ethanol exposure produces an anxiogenic-like response in both male and female subjects. Ethanol-induced sex differences were observed with increased c-Fos expression in LC neurons of female ethanol-treated subjects compared to controls or male subjects. Results also reveal sex differences in the subcellular distribution of the CRFr in LC-noradrenergic neurons with female subjects exposed to ethanol exhibiting a higher frequency of plasmalemmal CRFrs. These adaptations have implications for LC neuronal activity and its neural targets across the sexes. Considering the important role of the LC in ethanol-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis, the present results indicate important sex differences in feed-forward regulation of the HPA axis that may render alcohol dependent females more vulnerable to subsequent stress exposure.

  4. Epidemiological Trends Strongly Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer's Disease, Diabetes Mellitus, and Non-Alcoholic Steatohepatitis

    PubMed Central

    de la Monte, Suzanne M.; Neusner, Alexander; Chu, Jennifer; Lawton, Margot

    2015-01-01

    Nitrosamines mediate their mutagenic effects by causing DNA damage, oxidative stress, lipid peroxidation, and pro-inflammatory cytokine activation, which lead to increased cellular degeneration and death. However, the very same pathophysiological processes comprise the “unbuilding” blocks of aging and insulin-resistance diseases including, neurodegeneration, diabetes mellitus (DM), and non-alcoholic steatohepatitis (NASH). Previous studies demonstrated that experimental exposure to streptozotocin, a nitrosamine-related compound, causes NASH, and diabetes mellitus Types 1, 2 and 3 (Alzheimer (AD)-type neurodegeneration). Herein, we review evidence that the upwardly spiraling trends in mortality rates due to DM, AD, and Parkinson's disease typify exposure rather than genetic-based disease models, and parallel the progressive increases in human exposure to nitrates, nitrites, and nitrosamines via processed/preserved foods. We propose that such chronic exposures have critical roles in the pathogenesis of our insulin resistance disease pandemic. Potential solutions include: 1) eliminating the use of nitrites in food; 2) reducing nitrate levels in fertilizer and water used to irrigate crops; and 3) employing safe and effective measures to detoxify food and water prior to human consumption. Future research efforts should focus on refining our ability to detect and monitor human exposures to nitrosamines and assess early evidence of nitrosamine-mediated tissue injury and insulin resistance. PMID:19363256

  5. Isopropyl alcohol intoxication in a neonate through chronic dermal exposure: a complication of a culturally-based umbilical care practice.

    PubMed

    Vivier, P M; Lewander, W J; Martin, H F; Linakis, J G

    1994-04-01

    A 21-day-old boy presented to our emergency department hypotonic, lethargic, and intermittently unresponsive to pain. A workup for ketoacidosis, sepsis, and central nervous system hemorrhage was negative. A urine drug screen collected eight hours after hospitalization showed 39 mg/dl of isopropyl alcohol and 76 mg/dl of acetone. The first serum drug analysis was not performed until 18 hours after admission, at a time when there had been clinical improvement. The isopropyl alcohol concentration was 8 mg/dl, and the acetone concentration was 203 mg/dl. Management was supportive, and the patient stabilized. He was discharged from the hospital in good health in three days. A further review of the history showed no evidence for an oral exposure to isopropyl alcohol. However, since leaving the maternity hospital the mother had been applying gauze pads or cotton balls soaked with isopropyl alcohol to the umbilicus with every diaper change. We conclude that the child suffered from an isopropyl alcohol intoxication that occurred by absorption through the umbilical area.

  6. Overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure.

    PubMed

    Paul, A P; Medina, A E

    2012-09-27

    Neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF-) or control Green Fluorescent Protein (GFP). After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF- or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD.

  7. Alcohol Consumption Has a Protective Effect against Hematological Malignancies: a Population-Based Study in Sweden Including 420,489 Individuals with Alcohol Use Disorders12345

    PubMed Central

    Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2014-01-01

    BACKGROUND: It has been suggested that alcohol consumption is associated with increased risk of a few solid cancers, although studies that examined the association with hematological malignancies have shown inconsistent results. In this study, we examined the risk of hematological malignancies among individuals who had alcohol use disorders (AUDs) in Sweden. METHODS: Individuals with AUDs were identified from the nationwide Swedish Hospital Discharge Register and Outpatient Register, the Crime Register, and the Prescription Drug Register, and they were linked to the Swedish Cancer Registry to calculate standardized incidence ratios (SIRs) of hematological malignancies, using those Swedes without AUDs as a reference. In addition, we used a quasi-experimental sibling design to investigate the odds ratios among sibling pairs who were discordant with AUDs. RESULTS: A total of 420,489 individuals were identified with AUDs. After more than 15 million person-years of follow-up, a total of 1755 individuals developed hematological malignancies demonstrating a low risk, i.e., SIR = 0.60 (95% confidence interval = 0.57-0.63). People with AUDs had low risks for developing specific types of malignancies. The lowest risk (0.51) was for leukemia, followed by myeloma (0.52), non-Hodgkin lymphoma (0.65), and Hodgkin disease (0.71). The risk was lower among AUDs identified at an older age. The low risks of hematological malignancies were also noted using sibling analysis. CONCLUSIONS: Our data suggest that alcohol consumption has a protective effect against hematological malignancies. However, further studies are needed to identity the underlying mechanisms of the protective effect of alcohol consumption against hematological malignancies. PMID:24783999

  8. Establishment of the South-Eastern Norway Regional Health Authority Resource Center for Children with Prenatal Alcohol/Drug Exposure

    PubMed Central

    Løhaugen, Gro C. C.; Flak, Marianne Møretrø; Gerstner, Thorsten; Sundberg, Cato; Lerdal, Bjørn; Skranes, Jon

    2015-01-01

    This paper presents a new initiative in the South-Eastern Health Region of Norway to establish a regional resource center focusing on services for children and adolescents aged 2–18 years with prenatal exposure to alcohol or other drugs. In Norway, the prevalence of fetal alcohol spectrum (FAS) is not known but has been estimated to be between 1 and 2 children per 1000 births, while the prevalence of prenatal exposure to illicit drugs is unknown. The resource center is the first of its kind in Scandinavia and will have three main objectives: (1) provide hospital staff, community health and child welfare personnel, and special educators with information, educational courses, and seminars focused on the identification, diagnosis, and treatment of children with a history of prenatal alcohol/drug exposure; (2) provide specialized health services, such as diagnostic services and intervention planning, for children referred from hospitals in the South-Eastern Health Region of Norway; and (3) initiate multicenter studies focusing on the diagnostic process and evaluation of interventions. PMID:26692762

  9. Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

  10. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    PubMed

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.

  11. Cancer risks related to low-level RF/MW exposures, including cell phones.

    PubMed

    Szmigielski, Stanislaw

    2013-09-01

    For years, radiofrequency (RF) and microwave (MW) radiations have been applied in the modern world. The rapidly increasing use of cellular phones called recent attention to the possible health risks of RF/MW exposures. In 2011, a group of international experts organized by IARC (International Agency for Research on Cancer in Lyon) concluded that RF/MW radiations should be listed as a possible carcinogen (group 2B) for humans. Three meta-analyses of case-control studies have concluded that using cell phones for more than ten years was associated with an increase in the overall risk of developing a brain tumor. The Interphone Study, the largest health-related case-control international study of use of cell phones and head and neck tumors, showed no statistically significant increases in brain cancers related to higher amounts of cell phone use, but excess risk in a small subgroup of more heavily exposed users associated with latency and laterality was reported. So far, the published studies do not show that mobile phones could for sure increase the risk of cancer. This conclusion is based on the lack of a solid biological mechanism, and the fact that brain cancer rates are not going up significantly. However, all of the studies so far have weaknesses, which make it impossible to entirely rule out a risk. Mobile phones are still a new technology and there is little evidence about effects of long-term use. For this reason, bioelectromagnetic experts advise application of a precautionary resources. It suggests that if people want to use a cell phone, they can choose to minimize their exposure by keeping calls short and preferably using hand-held sets. It also advises discouraging children from making non essential calls as well as also keeping their calls short.

  12. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    PubMed

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

  13. Increased DNA double-strand break was associated with downregulation of repair and upregulation of apoptotic factors in rat hippocampus after alcohol exposure.

    PubMed

    Suman, Shubhankar; Kumar, Santosh; N'Gouemo, Prosper; Datta, Kamal

    2016-08-01

    Binge drinking is known to cause damage in critical areas of the brain, including the hippocampus, which is important for relational memory and is reported to be sensitive to alcohol toxicity. However, the roles of DNA double-strand break (DSB) and its repair pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) in alcohol-induced hippocampal injury remain to be elucidated. The purpose of this first study was to assess alcohol-induced DNA DSB and the mechanism by which alcohol affects DSB repair pathways in rat hippocampus. Male Sprague-Dawley rats (8-10 weeks old) were put on a 4-day binge ethanol treatment regimen. Control animals were maintained under similar conditions but were given the vehicle without ethanol. All animals were humanely euthanized 24 h after the last dose of ethanol administration and the hippocampi were dissected for immunoblot and immunohistochemistry analysis. Ethanol exposure caused increased 4-hydroxynonenal (4-HNE) staining as well as elevated γH2AX and 53BP1 foci in hippocampal cells. Immunoblot analysis showed decreased Mre11, Rad51, Rad50, and Ku86 as well as increased Bax and p21 in samples from ethanol-treated rats. Additionally, we also observed increased activated caspase3 staining in hippocampal cells 24 h after ethanol withdrawal. Taken together, our data demonstrated that ethanol concurrently induced DNA DSB, downregulated DSB repair pathway proteins, and increased apoptotic factors in hippocampal cells. We believe these findings will provide the impetus for further research on DNA DSB and its repair pathways in relation to alcohol toxicity in brain.

  14. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation.

    PubMed

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay. AML-12 cells were pretreated with AA (5, 10, 20 μM), or AICAR (500 μM), GW3965 (1 μM), SRT1720 (6 μM), Nicotinamide (20 mM) for 2 h, respectively, and then following treated with EtOH (200 mM) and lipopolysaccharide (LPS) (10 ng/ml) for additional 48 h. Cell protein and mRNA were collected for western blot and RT-PCR. Cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) release were detected by ELISA assay. Results: It was found that AA significantly decreased acute ethanol-induced increasing of the serum ALT/AST, LDH, ALP levels, and hepatic and serum triglyceride levels, and reduced fat droplets accumulation in mice liver. AA significantly suppressed the levels of sterol regulatory element binding protein 1 (SREBP-1), cytochrome P4502E1 (CYP2E1), IL-1β, and caspase-1 induced by ethanol. Furthermore, a significant decline of sirtuin 1 (Sirt1) and liver X receptors (LXRs) levels was observed in EtOH group, compared with normal group mice. And AA pretreatment increased the Sirt1 and LXRs levels, and also ameliorated phosphorylation of liver kinase B-1 (LKB-1), adenosine monophosphate-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC) proteins, compared with EtOH group. However, the levels of peroxisome proliferator activated receptor -α or -γ (PPAR-α or PPAR-γ) induced by acute ethanol were reversed by AA. In EtOH/LPS cultivated AML-12 cells, AA decreased IL-1β and TNF-α levels, lipid

  15. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation

    PubMed Central

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay. AML-12 cells were pretreated with AA (5, 10, 20 μM), or AICAR (500 μM), GW3965 (1 μM), SRT1720 (6 μM), Nicotinamide (20 mM) for 2 h, respectively, and then following treated with EtOH (200 mM) and lipopolysaccharide (LPS) (10 ng/ml) for additional 48 h. Cell protein and mRNA were collected for western blot and RT-PCR. Cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) release were detected by ELISA assay. Results: It was found that AA significantly decreased acute ethanol-induced increasing of the serum ALT/AST, LDH, ALP levels, and hepatic and serum triglyceride levels, and reduced fat droplets accumulation in mice liver. AA significantly suppressed the levels of sterol regulatory element binding protein 1 (SREBP-1), cytochrome P4502E1 (CYP2E1), IL-1β, and caspase-1 induced by ethanol. Furthermore, a significant decline of sirtuin 1 (Sirt1) and liver X receptors (LXRs) levels was observed in EtOH group, compared with normal group mice. And AA pretreatment increased the Sirt1 and LXRs levels, and also ameliorated phosphorylation of liver kinase B-1 (LKB-1), adenosine monophosphate-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC) proteins, compared with EtOH group. However, the levels of peroxisome proliferator activated receptor -α or -γ (PPAR-α or PPAR-γ) induced by acute ethanol were reversed by AA. In EtOH/LPS cultivated AML-12 cells, AA decreased IL-1β and TNF-α levels, lipid

  16. The Activation Effects of Low Level Isopropyl Alcohol Exposure on Arterial Blood Pressures Are Associated with Decreased 5-Hydroxyindole Acetic Acid in Urine

    PubMed Central

    Zhao, Zhiqiang; Liu, Xinxia; Xing, Xiumei; Lu, Yao; Sun, Yi; Ou, Xiaoyan; Su, Xiaolin; Jiang, Jun; Yang, Yarui; Chen, Jingli; Shen, Biling; He, Yun

    2016-01-01

    Purposes The objectives of this paper are to study the impact of low level isopropyl alcohol exposure on blood pressure and to explore its potential mechanism. Methods This cross-sectional study was based on a prospective occupational cohort in south China, which focusing on occupational risk factors related cardiovascular health problems. A total of 283 participants (200 low isopropyl alcohol exposed workers and 83 controls) was finally enrolled in this study. Linear regression models were used to analyze the relationship between arterial blood pressures and low level isopropyl alcohol exposure. We used mediation method to explore possible mediated roles of neurogenic factors. Results Systolic blood pressure (SBP, 123±10 vs. 118±11), diastolic blood pressure (DBP, 79±7 vs. 74±7) and mean blood pressure (MBP, 93±8 vs. 89±9) were different between the exposed group and the control group (p < 0.01). After adjusting for covariates, the difference was still significant. Besides, isopropyl alcohol and smoking had an interactive effect on DBP and MBP (p < 0.05). Furthermore, we observed a mediated effect of 5-hydroxyindole acetic acid (5-HIAA) on isopropyl alcohol exposure induced arterial blood pressure increase, which accounted for about 25%. Conclusions Our results suggest that low level isopropyl alcohol exposure is a potential risk factor for the increased arterial blood pressure and 5-HIAA partly mediates the association between low level isopropyl alcohol exposure and arterial blood pressures. PMID:27622502

  17. Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity

    PubMed Central

    McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F.; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

    2016-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the HPA or stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5–18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA. PMID:27286932

  18. Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity.

    PubMed

    McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

    2016-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5-18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA.

  19. Poly(vinyl alcohol) hydrogel coatings with tunable surface exposure of hydroxyapatite

    PubMed Central

    Moreau, David; Villain, Arthur; Ku, David N; Corté, Laurent

    2014-01-01

    Insufficient bone anchoring is a major limitation of artificial substitutes for connective osteoarticular tissues. The use of coatings containing osseoconductive ceramic particles is one of the actively explored strategies to improve osseointegration and strengthen the bone-implant interface for general tissue engineering. Our hypothesis is that hydroxyapatite (HA) particles can be coated robustly on specific assemblies of PVA hydrogel fibers for the potential anchoring of ligament replacements. A simple dip-coating method is described to produce composite coatings made of microscopic hydroxyapatite (HA) particles dispersed in a poly(vinyl alcohol) (PVA) matrix. The materials are compatible with the requirements for implant Good Manufacturing Practices. They are applied to coat bundles of PVA hydrogel fibers used for the development of ligament implants. By means of optical and electronic microscopy, we show that the coating thickness and surface state can be adjusted by varying the composition of the dipping solution. Quantitative analysis based on backscattered electron microscopy show that the exposure of HA at the coating surface can be tuned from 0 to over 55% by decreasing the weight ratio of PVA over HA from 0.4 to 0.1. Abrasion experiments simulating bone-implant contact illustrate how the coating cohesion and wear resistance increase by increasing the content of PVA relative to HA. Using pullout experiments, we find that these coatings adhere well to the fiber bundles and detach by propagation of a crack inside the coating. These results provide a guide to select coated implants for anchoring artificial ligaments. PMID:25482413

  20. Molecular changes during neurodevelopment following second-trimester binge ethanol exposure in a mouse model of fetal alcohol spectrum disorder: from immediate effects to long-term adaptation.

    PubMed

    Mantha, Katarzyna; Laufer, Benjamin I; Singh, Shiva M

    2014-01-01

    Fetal alcohol spectrum disorder (FASD) is an umbrella term that refers to a wide range of behavioral and cognitive deficits resulting from prenatal alcohol exposure. It involves changes in brain gene expression that underlie lifelong FASD symptoms. How these changes are achieved from immediate to long-term effects, and how they are maintained, is unknown. We have used the C57BL/6J mouse to assess the dynamics of genomic alterations following binge alcohol exposure. Ethanol-exposed fetal (short-term effect) and adult (long-term effect) brains were assessed for gene expression and microRNA (miRNA) changes using Affymetrix mouse arrays. We identified 48 and 68 differentially expressed genes in short- and long-term groups, respectively. No gene was common between the 2 groups. Short-term (immediate) genes were involved in cellular compromise and apoptosis, which represent ethanol's toxic effects. Long-term genes were involved in various cellular functions, including epigenetics. Using quantitative RT-PCR, we confirmed the downregulation of long-term genes: Camk1g, Ccdc6, Egr3, Hspa5, and Xbp1. miRNA arrays identified 20 differentially expressed miRNAs, one of which (miR-302c) was confirmed. miR-302c was involved in an inverse relationship with Ccdc6. A network-based model involving altered genes illustrates the importance of cellular redox, stress and inflammation in FASD. Our results also support a critical role of apoptosis in FASD, and the potential involvement of miRNAs in the adaptation of gene expression following prenatal ethanol exposure. The ultimate molecular footprint involves inflammatory disease, neurological disease and skeletal and muscular disorders as major alterations in FASD. At the cellular level, these processes represent abnormalities in redox, stress and inflammation, with potential underpinnings to anxiety.

  1. Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

    PubMed

    Helland, Arne; Lydersen, Stian; Lervåg, Lone-Eirin; Jenssen, Gunnar D; Mørland, Jørg; Slørdal, Lars

    2016-09-01

    Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies.

  2. Effects of prenatal tobacco, alcohol and marijuana exposure on processing speed, visual-motor coordination, and interhemispheric transfer.

    PubMed

    Willford, Jennifer A; Chandler, Lynette S; Goldschmidt, Lidush; Day, Nancy L

    2010-01-01

    Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual-motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n=320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTE and PME were associated with deficits in visual-motor coordination. There were no interactions between PAE, PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT.

  3. Effects of Prenatal Tobacco, Alcohol and Marijuana Exposure on Processing Speed, Visual-Motor Coordination, and Interhemispheric Transfer

    PubMed Central

    Willford, Jennifer A.; Chandler, Lynette S.; Goldschmidt, Lidush; Day, Nancy L.

    2010-01-01

    Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual-motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n=320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTEand PME were associated with deficits in visual motor coordination. There were no interactions between PAE, PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT. PMID:20600845

  4. Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

    PubMed

    Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2016-05-15

    Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety.

  5. Biomechanical analysis of a salt-modified polyvinyl alcohol hydrogel for knee meniscus applications, including comparison with human donor samples.

    PubMed

    Hayes, Jennifer C; Curley, Colin; Tierney, Paul; Kennedy, James E

    2016-03-01

    The primary objective of this research was the biomechanical analysis of a salt-modified polyvinyl alcohol hydrogel, in order to assess its potential for use as an artificial meniscal implant. Aqueous polyvinyl alcohol (PVA) was treated with a sodium sulphate (Na2SO4) solution to precipitate out the polyvinyl alcohol resulting in a pliable hydrogel. The freeze-thaw process, a strictly physical method of crosslinking, was employed to crosslink the hydrogel. Development of a meniscal shaped mould and sample housing unit allowed the production of meniscal shaped hydrogels for direct comparison to human meniscal tissue. Results obtained show that compressive responses were slightly higher in PVA/Na2SO4 menisci, displaying maximum compressive loads of 2472N, 2482N and 2476N for samples having undergone 1, 3 and 5 freeze-thaw cycles respectively. When compared to the human meniscal tissue tested under the same conditions, an average maximum load of 2467.5N was observed. This suggests that the PVA/Na2SO4 menisci are mechanically comparable to the human meniscus. Biocompatibility analysis of PVA/Na2SO4 hydrogels revealed no acute cytotoxicity. The work described herein has innovative potential in load bearing applications, specifically as an alternative to meniscectomy as replacement of critically damaged meniscal tissue in the knee joint where repair is not viable.

  6. Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

    PubMed Central

    Sluyter, Frans; Jamot, Laure; Bertholet, Jean-Yves; Crusio, Wim E

    2005-01-01

    Background The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J). Results Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age. Conclusion Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models. PMID:15916699

  7. Short-term exposure to alcohol in rats affects brain levels of anandamide, other N-acylethanolamines and 2-arachidonoyl-glycerol.

    PubMed

    Rubio, Marina; McHugh, Douglas; Fernández-Ruiz, Javier; Bradshaw, Heather; Walker, J Michael

    2007-06-29

    Chronic alcohol exposure leads to significant changes in the levels of endocannabinoids and their receptors in the brains of humans and laboratory animals, as well as in cultured neuronal cells. However, little is known about the effects of short-term periods of alcohol exposure. In the present study, we examined the changes in endocannabinoid levels (anandamide and 2-arachidonoylglycerol), as well as four additional N-acylethanolamines, in four brain regions of rats exposed to alcohol through the liquid diet for a period of 24h. The levels of N-acylethanolamines were diminished 24h after the onset of alcohol exposure. This was particularly evident for anandamide in the hypothalamus, amygdala and caudate-putamen, for N-palmitoylethanolamine in the caudate-putamen, for N-oleoylethanolamine in the hypothalamus, caudate-putamen and prefrontal cortex, and for N-stearoylethanolamine in the amygdala. The only exception was N-linoleoylethanolamine for which the levels increased in the amygdala after the exposure to alcohol. The levels of the other major endocannabinoid, 2-arachidonoylglycerol, were also reduced with marked effects in the prefrontal cortex. These results support the notion that short-term alcohol exposure reduces endocannabinoid levels in the brain accompanied by a reduction in several related N-acylethanolamines.

  8. Third Trimester Equivalent Alcohol Exposure Reduces Modulation of Glutamatergic Synaptic Transmission by 5-HT1A Receptors in the Rat Hippocampal CA3 Region

    PubMed Central

    Morton, Russell A.; Valenzuela, C. Fernando

    2016-01-01

    Fetal alcohol exposure has been associated with many neuropsychiatric disorders that have been linked to altered serotonin (5-hydroxytryptamine; 5-HT) signaling, including depression and anxiety. During the first 2 weeks of postnatal life in rodents (equivalent to the third trimester of human pregnancy) 5-HT neurons undergo significant functional maturation and their axons reach target regions in the forebrain (e.g., cortex and hippocampus). The objective of this study was to identify the effects of third trimester ethanol (EtOH) exposure on hippocampal 5-HT signaling. Using EtOH vapor inhalation chambers, we exposed rat pups to EtOH for 4 h/day from postnatal day (P) 2 to P12. The average serum EtOH concentration in the pups was 0.13 ± 0.04 g/dl (legal intoxication limit in humans = 0.08 g/dl). We used brain slices to assess the modulatory actions of 5-HT on field excitatory postsynaptic potentials in the hippocampal CA3 region at P13-P15. Application of the GABAA/glycine receptor antagonist, picrotoxin, caused broadening of field excitatory postsynaptic potentials (fEPSPs), an effect that was reversed by application of 5-HT in slices from air exposed rats. However, this effect of 5-HT was absent in EtOH exposed animals. In slices from naïve animals, application of a 5-HT1A receptor antagonist blocked the effect of 5-HT on the fEPSPs recorded in presence of picrotoxin, suggesting that third trimester ethanol exposure acts by inhibiting the function of these receptors. Studies indicate that 5-HT1A receptors play a critical role in the development of hippocampal circuits. Therefore, inhibition of these receptors by third trimester ethanol exposure could contribute to the pathophysiology of fetal alcohol spectrum disorders. PMID:27375424

  9. Therapy or threat? Inadvertent exposure to alcohol and illicit drug cues in the neighbourhoods of sober living homes.

    PubMed

    Heslin, Kevin C; Singzon, Trudy K; Farmer, Melissa; Dobalian, Aram; Tsao, Jennie; Hamilton, Alison B

    2013-09-01

    Alcohol retail outlets and other environmental cues can contribute to relapse among individuals recovering from substance abuse. Sober living homes are residences designed to strengthen abstinence from substances, in part by helping residents develop skills for coping with cues and other stressors. Between January 2009 and March 2010, we conducted 10 focus groups with 68 adults aged 18 and over who lived in or operated any of 35 sober living homes in Los Angeles County, California. A stratified purposive sampling strategy was used to recruit sober living home residents and operators. The study aim was to assess how residents responded to the neighbourhood alcohol and drug cues they encountered in their daily lives. The focus group transcripts were analysed using the constructs of 'approach coping' and 'avoidance coping'. Findings suggest that the sober living homes helped residents cope with cue exposure through social rules and processes such as chaperones and evening curfews, as well as the presence of peer support for managing the conflictive thoughts and emotions that result from cue exposure. The examples of 'avoidance coping' and 'approach coping' identified in the transcripts were more often behavioural than cognitive. For example, residents described efforts they made to increase their physical distance from (i.e. avoid) neighbours who used substances. Whereas some participants believed that living in areas with high levels of drug use and trafficking was 'a time bomb' for relapse, others suggested that cue exposure could actually strengthen their ability to remain abstinent ('approach coping'). The approach/avoidance coping construct did not account for the experiences of all residents. Several participants expressed indifference towards cues while performing daily routines and pursuing important recovery goals. The threat of alcohol and drug cues may be mitigated by recovery-oriented homes that support coping on an individualised, as-needed basis.

  10. Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test.

    PubMed

    Desikan, Anita; Wills, Derek N; Ehlers, Cindy L

    2014-07-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the "adolescent phenotype" to be retained into adulthood. However, the "adolescent phenotype" has not been studied for a number of behavioral tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and forced swim test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to test whether they retained the "adolescent phenotype" in these behavioral tests. Three age groups of rats were tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the forced swim test no clear developmental pattern emerged. The results of the light/dark box and the forced swim test do not support the hypothesis that adolescent ethanol vapor exposure can "lock-in" all adolescent phenotypes. However, data from the open field conflict test suggest that the adolescent and the AIE rats both engaged in more "disinhibited" and food motivated behaviors. These data suggest that, in some behavioral tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence.

  11. Volume changes and brain-behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure.

    PubMed

    Gautam, Prapti; Lebel, Catherine; Narr, Katherine L; Mattson, Sarah N; May, Philip A; Adnams, Colleen M; Riley, Edward P; Jones, Kenneth L; Kan, Eric C; Sowell, Elizabeth R

    2015-06-01

    Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ~2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group-by-age interactions and group-score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group-score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain-behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE.

  12. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    SciTech Connect

    Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup -}) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH{sup -} and hepatic ADH-normal (ADH{sup +}) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was {approx} 1.5-fold greater in ADH{sup -} vs. ADH{sup +} deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH{sup -} deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  13. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol.

    PubMed

    Kaphalia, Bhupendra S; Bhopale, Kamlesh K; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J; Ansari, G A Shakeel

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH(-)) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH(-) and hepatic ADH-normal (ADH(+)) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼1.5-fold greater in ADH(-) vs. ADH(+) deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH(-) deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  14. Older Adults and Alcohol

    MedlinePlus

    ... Alcohol Exposure Support & Treatment Alcohol Policy Special Populations & Co-occurring Disorders Publications & Multimedia Brochures & Fact Sheets NIAAA ... are here Home » Alcohol & Your Health » Special Populations & Co-occurring Disorders » Older Adults In this Section Underage ...

  15. Fetal Alcohol Syndrome

    MedlinePlus

    ... The diagnosis of fetal alcohol syndrome. Deutsches Arztebaltt International. 2013;110:703. Ungerer M, et al. In utero alcohol exposure, epigenetic changes and their consequences. Alcohol Research: Current Reviews. 2013;35:37. Coriale G, et al. ...

  16. Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

    PubMed

    Gaztañaga, Mirari; Aranda-Fernández, P Ezequiel; Chotro, M Gabriela

    2015-09-01

    Rat fetuses can perceive chemosensory stimuli derived from their mother's diet, and they may learn about those stimuli. In previous studies we have observed that prenatal exposure to alcohol during the last days of gestation increases the acceptance and liking of an alcohol flavor in infant and adolescent rats. While these results were not found after prenatal exposure to vanilla, cineole or anise, suggesting that the pharmacological properties of alcohol, mediated by the opioid system, underlie the effects observed with this drug. Considering that other studies report enhanced acceptance of non-alcohol flavors experienced prenatally when subjects were tested before infancy, we explore the possibility of observing similar results if testing 1-day old rats exposed prenatally to vanilla. Using an "odor-induced crawling" testing procedure, it was observed that neonates exposed prenatally to vanilla or alcohol crawl for a longer distance towards the experienced odor than to other odors or than control pups. Blocking mu, but not kappa opioid receptors, reduced the attraction of vanilla odor to neonates exposed to vanilla in utero, while the response to alcohol in pups exposed prenatally to this drug was affected by both antagonists. Results confirm that exposure to a non-alcohol odor enhances postnatal responses to it, observable soon after birth, while also suggesting that the mu opioid receptor system plays an important role in generating this effect. The results also imply that with alcohol exposure, the prenatal opioid system is wholly involved, which could explain the longer retention of the enhanced attraction to alcohol following prenatal experience with the drug.

  17. Stress and Alcohol

    PubMed Central

    Keyes, KM.; Hatzenbuehler, ML.; Grant, Bridget F.; Hasin, Deborah S.

    2012-01-01

    Exposure to stress often is psychologically distressing. The impact of stress on alcohol use and the risk of alcohol use disorders (AUDs) depends on the type, timing during the life course, duration, and severity of the stress experienced. Four important categories of stressors that can influence alcohol consumption are general life stress, catastrophic/fateful stress, childhood maltreatment, and minority stress. General life stressors, including divorce and job loss, increase the risk for AUDs. Exposure to terrorism or other disasters causes population-level increases in overall alcohol consumption but little increase in the incidence of AUDs. However, individuals with a history of AUDs are more likely to drink to cope with the traumatic event. Early onset of drinking in adolescence, as well as adult AUDs, are more common among people who experience childhood maltreatment. Finally, both perceptions and objective indicators of discrimination are associated with alcohol use and AUDs among racial/ethnic and sexual minorities. These observations demonstrate that exposure to stress in many forms is related to subsequent alcohol consumption and AUDs. However, many areas of this research remain to be studied, including greater attention to the role of various stressors in the course of AUDs and potential risk moderators when individuals are exposed to stressors. PMID:23584105

  18. The Role of Arsenic Speciation in Dietary Exposure Assessment and the Need to Include Bioaccessibility and Biotransformation

    EPA Science Inventory

    Chemical form specific exposure assessment for arsenic has long been identified as a source of uncertainty in estimating the risk associated with the aggregate exposure for a population. Some speciation based assessments document occurrence within an exposure route; however, the...

  19. Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood.

    PubMed

    Willoughby, Karen A; Sheard, Erin D; Nash, Kelly; Rovet, Joanne

    2008-11-01

    Children with prenatal alcohol exposure (PAE) show deficits in verbal learning and spatial memory, as well as abnormal hippocampal development. The relationship between their memory and neuroanatomic impairments, however, has not been directly explored. Given that the hippocampus is integral for the synthesis and retrieval of learned information and is particularly vulnerable to the teratogenic effects of alcohol, we assessed whether reduced learning and recall abilities in children with fetal alcohol spectrum disorders (FASDs) are associated with abnormal hippocampal volumes. Nineteen children with FASDs and 18 typically developing controls aged 9 to 15 years were assessed for verbal learning and verbal and spatial recall and underwent structural magnetic resonance imaging. Images were analyzed for total intracranial volume and for right and left hippocampal volumes. Results revealed smaller left hippocampi and poorer verbal learning and verbal and spatial recall performance in children with FASDs than controls, as well as positive correlations between selective memory indices and hippocampal volumes only in the FASD group. Additionally, hippocampal volumes increased significantly with age in controls only, suggesting that PAE may be associated with long-term abnormalities in hippocampal development that may contribute to impaired verbal learning and verbal and spatial recall.

  20. Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

    PubMed Central

    Wang, G; Bieberich, E

    2010-01-01

    Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol. PMID:21364652

  1. Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development.

    PubMed

    Wang, G; Bieberich, E

    2010-05-27

    Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol.

  2. Human alcohol-related neuropathology

    PubMed Central

    Kril, Jillian J.

    2015-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  3. The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models

    PubMed Central

    Marquardt, Kristin; Brigman, Jonathan L.

    2016-01-01

    Fetal Alcohol Spectrum Disorders (FASD) are characterized by deficits in working memory, response inhibition, and behavioral flexibility. However, the combination and severity of impairments are highly dependent upon maternal ethanol consumption patterns, which creates a complex variety of manifestations. Rodent models have been essential in identifying behavioral endpoints of prenatal alcohol exposure (PAE). However, experimental model outcomes are extremely diverse based on level, pattern, timing, and method of ethanol exposure, as well as the behavioral domain assayed and paradigm used. Therefore, comparisons across studies are difficult and there is currently no clear comprehensive behavioral phenotype of PAE. This lack of defined cognitive and behavioral phenotype is a contributing factor to the difficulty in identifying FASD individuals. The current review aims to critically examine preclinical behavioral outcomes in the social, cognitive, and affective domains in terms of the PAE paradigm, with a special emphasis on dose, timing, and delivery, to establish a working model of behavioral impairment. In addition, this review identifies gaps in our current knowledge and proposes future areas of research that will advance knowledge in the field of PAE outcomes. Understanding the complex behavioral phenotype, which results from diverse ethanol consumption will allow for development of better diagnostic tools and more critical evaluation of potential treatments for FASD. PMID:26992695

  4. The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models.

    PubMed

    Marquardt, Kristin; Brigman, Jonathan L

    2016-03-01

    Fetal Alcohol Spectrum Disorders (FASD) are characterized by deficits in working memory, response inhibition, and behavioral flexibility. However, the combination and severity of impairments are highly dependent upon maternal ethanol consumption patterns, which creates a complex variety of manifestations. Rodent models have been essential in identifying behavioral endpoints of prenatal alcohol exposure (PAE). However, experimental model outcomes are extremely diverse based on level, pattern, timing, and method of ethanol exposure, as well as the behavioral domain assayed and paradigm used. Therefore, comparisons across studies are difficult and there is currently no clear comprehensive behavioral phenotype of PAE. This lack of defined cognitive and behavioral phenotype is a contributing factor to the difficulty in identifying FASD individuals. The current review aims to critically examine preclinical behavioral outcomes in the social, cognitive, and affective domains in terms of the PAE paradigm, with a special emphasis on dose, timing, and delivery, to establish a working model of behavioral impairment. In addition, this review identifies gaps in our current knowledge and proposes future areas of research that will advance knowledge in the field of PAE outcomes. Understanding the complex behavioral phenotype, which results from diverse ethanol consumption will allow for development of better diagnostic tools and more critical evaluation of potential treatments for FASD.

  5. Effect of gestational ethanol exposure on parvalbumin and calretinin expressing hippocampal neurons in a chick model of fetal alcohol syndrome.

    PubMed

    Marshall, Audrey G; McCarthy, Molly M; Brishnehan, Kirk M; Rao, Venugopal; Batia, Lyn M; Gupta, Madhul; Das, Srijit; Mitra, Nilesh K; Chaudhuri, Joydeep D

    2009-03-01

    Fetal alcohol syndrome (FAS), a condition occurring in some children of mothers who have consumed alcohol during pregnancy, is characterized by physical deformities and learning and memory deficits. The chick hippocampus, whose functions are controlled by interneurons expressing calcium-binding proteins parvalbumin (PV) and calretinin (CR), is involved in learning and memory mechanisms. Effects on growth and development and hippocampal morphology were studied in chick embryos exposed to 5% and 10% ethanol volume/volume (vol/vol) for 2 or 8 days of gestation. There was a significant dose-dependent reduction (P<.05) in body weight and mean number per section of PV and CR expressing hippocampal neurons in ethanol-exposed chicks, without alterations in neuronal nuclear size or hippocampal volume, compared appropriate controls. Moreover, when chicks exposed to 5% ethanol for 2 and 8 days of gestation were compared, no significant differences were found in body parameters or neuronal counts. Similarly, exposure to 10% ethanol did not induce any significant changes in chicks exposed for 2 or 8 gestational days. Thus, these results suggest that gestational ethanol exposure induces a reduction in the mean number per section of PV and CR expressing hippocampal neurons, and could be a possible mechanism responsible for learning and memory disorders in FAS.

  6. Effects of alcohol exposure during development on play behavior and c-Fos expression in response to play behavior

    PubMed Central

    Lawrence, R. Charles; Bonner, H. Cale; Newsom, Ryan J.; Kelly, Sandra J.

    2008-01-01

    Developmental exposure to alcohol can produce characteristic physiological and cognitive deficits, often termed Fetal Alcohol Spectrum Disorder (FASD). More recently, social deficits have been shown to occur both in FASD and animal models of FASD; the behavioral and neural bases of these deficits remain to be determined. It was hypothesized that changes in sensory processing may in part underlie the social deficits seen in FASD. This study used a rat model of FASD and social play, a behavior critical to adult social functioning, to begin to examine this hypothesis. Somatosensory cues from dorsal contact to the nape of the neck, critical to the initiation of pinning, were systematically degraded by administration of different doses of xylocaine, a topical anesthetic. Neuronal activity after one hour of play was assessed by measurement of c-Fos immunoreactivity (IR) in different brain regions. Ethanol-exposed rats showed an increase frequency of pinning during social play and were more sensitive to the degradation of somatosensory cues compared to the control groups, suggesting difficulties in processing somatosensory cues. Neuronal activity in the somatosensory cortex induced by play was significantly decreased in the ethanol-exposed group compared to the non-treated group. The c-Fos IR in the nucleus accumbens was altered in a sexually dimorphic manner in the ethanol-exposed group. Thus, the behavioral and brain measures are consistent with the hypothesis that ethanol exposure during development induces alterations in social play via deficits in processing somatosensory cues that are important to social play. PMID:18160143

  7. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

    PubMed Central

    Gershkovich, Pavel; Wasan, Kishor M; Ribeyre, Charles; Ibrahim, Fady; McNeill, John H

    2015-01-01

    Purpose: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored. PMID:26322116

  8. Effects of short deprivation and re-exposure intervals on the ethanol drinking behavior of selectively bred high alcohol-consuming rats.

    PubMed

    Bell, Richard L; Rodd, Zachary A; Schultz, Jonathon A; Peper, Caron L; Lumeng, Lawrence; Murphy, James M; McBride, William J

    2008-08-01

    Alcoholics generally display cycles of excessive ethanol intake, abstinence and relapse behavior. Using an animal model of relapse-like drinking, the alcohol deprivation effect (ADE), our laboratory has shown that repeated 2-week cycles of ethanol deprivation and re-exposure, following an initial 6-week access period, result in a robust ADE by alcohol-preferring (P) and high alcohol-drinking (HAD-1 and HAD-2) rats. These rat lines have been selectively bred to prefer a 10% ethanol solution over water. The present study examined whether P and HAD rats would display an ADE using much shorter ethanol deprivation and re-exposure intervals. Rats were given either continuous or periodic concurrent access to multiple concentrations (10%, 20%, and 30% [vol/vol]) of ethanol. The periodic protocol involved access to ethanol for 12 days followed by four cycles of 4 days of deprivation and 4 days of re-exposure to ethanol access. High-alcohol-drinking rats displayed a robust 24-h ADE upon first re-exposure (HAD-1: approximately 5 vs. 8g/kg/day; HAD-2: approximately 6 vs. 9g/kg/day, baseline vs. re-exposure), whereas P rats ( approximately 7 vs. 8g/kg/day) displayed a modest, nonsignificant, increase in 24-h intake. In a separate group of rats, ethanol intake and blood alcohol concentrations after the first hour of the fourth re-exposure cycle were HAD-1: 2.0g/kg and 97 mg%, HAD-2: 2.3g/kg and 73 mg%, and P: 1.2g/kg and 71 mg%; with all three lines displaying a robust first hour ADE. These findings suggest that (a) an ADE may be observed with short ethanol deprivation and re-exposure intervals in HAD rats, and (b) the genetic make-up of the P and HAD rats influences the expression of this ADE.

  9. Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats.

    PubMed

    Loxton, David; Canales, Juan J

    2017-03-06

    A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure.

  10. Intermittent binge alcohol exposure during the periadolescent period induces spatial working memory deficits in young adult rats.

    PubMed

    Schulteis, Gery; Archer, Clay; Tapert, Susan F; Frank, Lawrence R

    2008-09-01

    Human and animal studies suggest adolescence is a period of heightened sensitivity to adverse cognitive sequelae of alcohol exposure. The present study assessed the effects of intermittent binge ethanol intoxication during the periadolescent period of Wistar rats on subsequent performance in a Morris water maze spatial navigation task. On postnatal days 32-56, rats were exposed to ethanol or air 3 days/week via vapor inhalation chambers. Acquisition of spatial navigation was assessed beginning 5 days after the final day of exposure, with 3 days of training in the Morris Water maze (four trials per day spaced at 90-s intertrial intervals [ITIs]). Rats were placed into the water maze at one of four positions along the perimeter, with a different release position to begin each trial. A probe trial assessed retention of platform location on the day after the final set of training trials. Four days after this probe trial, rats entered a working memory phase in which the platform was in a new location each day and a variable ITI of 1, 2, or 4 h was inserted between Trials 1 and 2; Trials 3 and 4 followed at 90-s intervals after Trial 2 on each day. The "savings" in latency to find the platform and distance traveled before finding it from Trial 1 to Trial 2 on each day served as an index of working memory. Ethanol-exposed rats showed similar acquisition of spatial navigation as control rats during training, as well as similar retention of platform location during the probe trial. However, rats exposed to average blood alcohol level (BAL) >200 mg% showed accelerated forgetting, with decreased retention of platform location at the 2-h ITI (P < .05), compared to control rats. Therefore, a 4-week history of intermittent ethanol exposure at BAL in excess of 200 mg% during periadolescence led to a working memory deficit in young adult rats, demonstrated by accelerated forgetting of novel information. These behavioral data are consistent with findings from adolescent human

  11. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats.

    PubMed

    Allen, Camryn D; Lee, Soon; Koob, George F; Rivier, Catherine

    2011-06-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration.

  12. Receptivity to alcohol marketing predicts initiation of alcohol use

    PubMed Central

    Henriksen, Lisa; Feighery, Ellen C.; Schleicher, Nina C.; Fortmann, Stephen P.

    2008-01-01

    Purpose This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Methods Data were obtained from in-class surveys of 6th, 7th, and 8th graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n=1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. Results At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity) and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Conclusions Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents’ receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors’ marketing tactics. PMID:18155027

  13. Slowing the Tide of Alcohol Use Disorders.

    PubMed

    Chamsi-Pasha, Hassan; Chamsi-Pasha, Majed; Albar, Mohammed Ali

    2016-09-28

    Alcohol use disorders (AUDs)-a spectrum including at-risk drinking, alcohol abuse, dependence, and addiction-is a highly prevalent problem worldwide with a substantial economic impact. The toll of alcohol on individual health and healthcare systems is devastating. Alcohol is estimated to be the fifth leading risk factor for global disability-adjusted life years. Tackling the problem of AUD requires a comprehensive strategy that includes solid action on price, availability, and marketing of alcohol. Restricting or banning alcohol advertising may reduce exposure to the risk posed by alcohol at the individual and general population level. Warning labels about the cancer risks associated with drinking have a high degree of public support and may be an inexpensive and acceptable way to educate the public. Religiosity may reduce risk behaviors and contribute to health decision making related to alcohol use.

  14. Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function.

    PubMed

    Gautam, P; Nuñez, S C; Narr, K L; Kan, E C; Sowell, E R

    2014-01-01

    Prenatal alcohol exposure can cause a wide range of deficits in executive function that persist throughout life, but little is known about how changes in brain structure relate to cognition in affected individuals. In the current study, we predicted that the rate of white matter volumetric development would be atypical in children with fetal alcohol spectrum disorders (FASD) when compared to typically developing children, and that the rate of change in cognitive function would relate to differential white matter development between groups. Data were available for 103 subjects [49 with FASD, 54 controls, age range 6-17, mean age = 11.83] with 153 total observations. Groups were age-matched. Participants underwent structural magnetic resonance imaging (MRI) and an executive function (EF) battery. Using white matter volumes measured bilaterally for frontal and parietal regions and the corpus callosum, change was predicted by modeling the effects of age, intracranial volume, sex, and interactions with exposure status and EF measures. While both groups showed regional increases in white matter volumes and improvement in cognitive performance over time, there were significant effects of exposure status on age-related relationships between white matter increases and EF measures. Specifically, individuals with FASD consistently showed a positive relationship between improved cognitive function and increased white matter volume over time, while no such relationships were seen in controls. These novel results relating improved cognitive function with increased white matter volume in FASD suggest that better cognitive outcomes could be possible for FASD subjects through interventions that enhance white matter plasticity.

  15. Intrauterine Exposure to Drugs and Alcohol: How Do the Children Fare?

    PubMed

    Budden

    1996-10-01

    The increasing use of drugs and alcohol by pregnant women has resulted in a population of children with unique neurodevelopmental behaviors. Of 223 children evaluated in a multidisciplinary child-development program in Portland, Oregon, 188 required long-term follow-up because of neurodevelopmental and/or behavioral problems; 153 had been polydrug-exposed in utero and 35 were born with fetal alcohol syndrome (FAS). Evaluations of the polydrug-exposed children revealed that 13% had severe speech and language disorders, 10% had significant cognitive deficits, and 81% had behavior problems after the age of 3 years. These deficits could not be attributed to social/environmental factors alone and probably reflect the effect of toxins on the developing brain. While polydrug-exposed children had learning problems related to impaired neurodevelopment and attention deficits, their IQs were normal. Among children with FAS, however, 67% had some degree of mental retardation.

  16. The Relationship Between Population-Level Exposure to Alcohol Advertising on Television and Brand-Specific Consumption Among Underage Youth in the US

    PubMed Central

    Ross, Craig S.; Maple, Emily; Siegel, Michael; DeJong, William; Naimi, Timothy S.; Padon, Alisa A.; Borzekowski, Dina L.G.; Jernigan, David H.

    2015-01-01

    Aims: We investigated the population-level relationship between exposure to brand-specific advertising and brand-specific alcohol use among US youth. Methods: We conducted an internet survey of a national sample of 1031 youth, ages 13–20, who had consumed alcohol in the past 30 days. We ascertained all of the alcohol brands respondents consumed in the past 30 days, as well as which of 20 popular television shows they had viewed during that time period. Using a negative binomial regression model, we examined the relationship between aggregated brand-specific exposure to alcohol advertising on the 20 television shows [ad stock, measured in gross rating points (GRPs)] and youth brand-consumption prevalence, while controlling for the average price and overall market share of each brand. Results: Brands with advertising exposure on the 20 television shows had a consumption prevalence about four times higher than brands not advertising on those shows. Brand-level advertising elasticity of demand varied by exposure level, with higher elasticity in the lower exposure range. The estimated advertising elasticity of 0.63 in the lower exposure range indicates that for each 1% increase in advertising exposure, a brand's youth consumption prevalence increases by 0.63%. Conclusions: At the population level, underage youths' exposure to brand-specific advertising was a significant predictor of the consumption prevalence of that brand, independent of each brand's price and overall market share. The non-linearity of the observed relationship suggests that youth advertising exposure may need to be lowered substantially in order to decrease consumption of the most heavily advertised brands. PMID:25754127

  17. The effects of binge alcohol exposure in the 2nd trimester on the estimated density of cerebral microvessels in near-term fetal sheep.

    PubMed

    Simon, Katherine E; Mondares, Robin L; Born, Donald E; Gleason, Christine A

    2008-09-22

    Heavy fetal alcohol exposure is associated with a spectrum of neurological abnormalities, although the mechanism of injury is largely unknown. We previously reported attenuated cerebral blood flow response to hypoxia in fetal and newborn sheep which were exposed to alcohol earlier in pregnancy. One possible mechanism for this effect of alcohol on the developing cerebral vasculature is a decrease in cerebral microvessel density, similar to its effect on developing neurons. Therefore, we tested the hypothesis that prenatal alcohol exposure decreases cerebral microvessel density. Pregnant ewes received intravenous infusions of ethanol or saline during days 60-84 of gestation (term=150 days) and at 125 days of gestation we obtained the fetal brains for study. We immunohistochemically labeled vessels of the left cerebral forebrain hemispheres with antibody to endothelial nitric oxide synthase and then obtained unbiased stereological estimates of cerebral microvessel density using a modified optical fractionator method. We studied 20 fetal brains of which 9 were alcohol-exposed, 11 were saline-controls, and all were products of a twin gestation. Although brain and body weights were not different between groups, the alcohol-exposed group had significantly lower brain weight as a percentage of body weight. Estimates of cerebral microvessel density were not significantly different between alcohol-exposed and saline-control groups: 12.7+/-8.7 and 9.1+/-2.8 microvessels per mm(3), respectively (mean+/-SD, p=0.32). Since there is no change in estimated cerebral microvessel density after prenatal alcohol exposure, we conclude that decreased cerebral microvessel density is not a likely explanation for attenuated cerebral blood flow in response to hypoxia.

  18. Commercial Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Testing is not Vulnerable to Incidental Alcohol Exposure in Pregnant Women

    PubMed Central

    Beatty, Jessica R.; Rosano, Thomas G.; Strickler, Ronald C.; Graham, Amy E.; Sokol, Robert J.

    2016-01-01

    Background Ethyl Glucoronide (EtG) and Ethyl Sulfate (EtS) have shown promise as biomarkers for alcohol and may be sensitive enough for use with pregnant women in whom even low-level alcohol use is important. However, there have been reports of over-sensitivity of EtG and EtS to incidental exposure to sources such as alcohol-based hand sanitizer. Further, few studies have evaluated these biomarkers among pregnant women, in whom the dynamics of these metabolites may differ. Objectives This study evaluated whether commercial EtG-EtS testing was vulnerable to high levels of environmental exposure to alcohol in pregnant women. Methods Two separate samples of five nurses—one pregnant and the other postpartum, all of whom reported high levels of alcohol-based hand sanitizer use—provided urine samples before and 4–8 hours after rinsing with alcohol-based mouthwash and using hand sanitizer. The five pregnant nurses provided urine samples before, during, and after an 8-hour nursing shift, during which they repeatedly cleansed with alcohol-based hand sanitizer (mean 33.8 uses). The five postpartum nurses used hand sanitizer repeatedly between baseline and follow-up urine samples. Results No urine samples were positive for EtG-EtS at baseline or follow-up, despite use of mouthwash and—in the pregnant sample—heavy use of hand sanitizer (mean of 33.8 uses) throughout the 8-hour shift. Conclusions/Importance Current, commercially available EtG-EtS testing does not appear vulnerable to even heavy exposure to incidental sources of alcohol among pregnant and postpartum women. PMID:26771303

  19. Alcohol and pregnancy

    MedlinePlus

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... group of defects in the baby known as fetal alcohol syndrome. Symptoms can include: Behavior and attention problems Heart ...

  20. The epigenetic landscape of alcoholism.

    PubMed

    Krishnan, Harish R; Sakharkar, Amul J; Teppen, Tara L; Berkel, Tiffani D M; Pandey, Subhash C

    2014-01-01

    Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, hold great therapeutic potential in the treatment and prevention of alcoholism.

  1. The Epigenetic Landscape of Alcoholism

    PubMed Central

    Krishnan, Harish R.; Sakharkar, Amul J.; Teppen, Tara L.; Berkel, Tiffani D.M.; Pandey, Subhash C.

    2015-01-01

    Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure, but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, holds great therapeutic potential in the treatment and prevention of alcoholism. PMID:25131543

  2. Physical Activity- and Alcohol-dependent Association Between Air Pollution Exposure and Elevated Liver Enzyme Levels: An Elderly Panel Study

    PubMed Central

    Kim, Kyoung-Nam; Lee, Hyemi; Kim, Jin Hee; Jung, Kweon; Lim, Youn-Hee; Hong, Yun-Chul

    2015-01-01

    Objectives: The deleterious effects of air pollution on various health outcomes have been demonstrated. However, few studies have examined the effects of air pollution on liver enzyme levels. Methods: Blood samples were drawn up to three times between 2008 and 2010 from 545 elderly individuals who regularly visited a community welfare center in Seoul, Korea. Data regarding ambient air pollutants (particulate matter ≤2.5 μm [PM2.5], nitrogen dioxide [NO2], ozone [O3], carbon monoxide, and sulfur dioxide) from monitoring stations were used to estimate air pollution exposure. The effects of the air pollutants on the concentrations of three liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltranspeptidase [γ-GTP)]) were evaluated using generalized additive and linear mixed models. Results: Interquartile range increases in the concentrations of the pollutants showed significant associations of PM2.5 with AST (3.0% increase, p=0.0052), ALT (3.2% increase, p=0.0313), and γ-GTP (5.0% increase, p=0.0051) levels; NO2 with AST (3.5% increase, p=0.0060) and ALT (3.8% increase, p=0.0179) levels; and O3 with γ-GTP (5.3% increase, p=0.0324) levels. Significant modification of these effects by exercise and alcohol consumption was found (p for interaction <0.05). The effects of air pollutants were greater in non-exercisers and heavy drinkers. Conclusions: Short-term exposure to air pollutants such as PM2.5, NO2, and O3 is associated with increased liver enzyme levels in the elderly. These adverse effects can be reduced by exercising regularly and abstinence from alcohol. PMID:26081652

  3. Treatment of co-occurring PTSD-AUD: Effects of exposure-based and non-trauma focused psychotherapy on alcohol and trauma cue-reactivity

    PubMed Central

    Nosen, Elizabeth; Littlefield, Andrew K.; Schumacher, Julie A.; Stasiewicz, Paul R.; Coffey, Scott F.

    2014-01-01

    Laboratory studies have shown that exposure to trauma memories increases both craving and salivation responses to alcohol cues among individual with co-occurring posttraumatic stress disorder (PTSD) and alcohol dependence (AD). The purpose of the present study was to examine 1) whether this cue reactivity is dampened following exposure-based treatment for PTSD and 2) how changes in reactivity to trauma cues correspond to changes in alcohol cue-reactivity. Adults with current PTSD and AD (N=120) were randomly assigned to 9–12 sessions of either Trauma-focused Exposure Therapy (EXP) for PTSD or Health & Lifestyles (HLS, a non-trauma focused comparison treatment), concurrent with 6-week residential AD treatment-asusual. Participants completed trauma and alcohol cue-reactivity laboratory sessions before and after treatment. Compared to HLS, individuals receiving EXP showed significantly greater reductions in negative affect elicited by trauma cues following treatment. Both treatments demonstrated similar, moderate to large reductions in craving and salivary reactivity over time. Interestingly, latent change in trauma cue-elicited distress over the course of treatment predicted latent change in both trauma cue-elicited alcohol craving and salivation. Overall, findings highlight the utility of integrating trauma-focused therapies like EXP into substance use treatment in the interests of reducing PTSD symptoms and distress associated with trauma cues. PMID:25127178

  4. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

    PubMed Central

    2009-01-01

    Background The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. Methods Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. Results NDEA and HFD ± NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. Conclusions Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics. PMID:20034403

  5. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  6. Relationship between Methyl Tertiary Butyl Ether Exposure and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Petrol Station Attendants in Southern China

    PubMed Central

    Yang, Jianping; Wei, Qinzhi; Peng, Xiaochun; Peng, Xiaowu; Yuan, Jianhui; Hu, Dalin

    2016-01-01

    Methyl tertiary butyl ether (MTBE)—A well known gasoline additive substituting for lead alkyls—causes lipid disorders and liver dysfunctions in animal models. However, whether MTBE exposure is a risk factor for non-alcoholic fatty liver disease (NAFLD) remains uncertain. We evaluate the possible relationship between MTBE exposure and the prevalence of NAFLD among 71 petrol station attendants in southern China. The personal exposure concentrations of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS. NAFLD was diagnosed by using abdominal ultrasonography according to the guidelines for the diagnosis and treatment of NAFLD suggested by the Chinese Hepatology Association. Demographic and clinical characteristics potentially associated with NAFLD were investigated. Mutivariate logistic regression analysis was applied to measure odds ratios and 95% confidence intervals (CI). The result showed that the total prevalence of NAFLD was 15.49% (11/71) among the study subjects. The average exposure concentrations of MTBE were 292.98 ± 154.90 μg/m3 and 286.64 ± 122.28 μg/m3 in NAFLD and non-NAFLD groups, respectively, and there was no statistically significant difference between them (p > 0.05). After adjusting for age, gender, physical exercise, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), white blood cell (WBC), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), the odds ratios were 1.31 (95% CI: 0.85–1.54; p > 0.05), 1.14 (95% CI: 0.81–1.32; p > 0.05), 1.52 (95% CI: 0.93–1.61; p > 0.05) in the groups (including men and women) with exposure concentrations of MTBE of 100–200 μg/m3, 200–300 μg/m3, and ≥300 μg/m3, respectively, as compared to the group (including men and women) ≤100 μg/m3. Our investigation indicates that exposure to MTBE does not seem to be a significant risk factor for the prevalence of

  7. Neuroimaging and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

  8. Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters

    PubMed Central

    Yang, J.Y.; Kwak, H.S.; Choi, J.S.; Ahn, H.K.; Oh, Y.J.; Velázquez-Armenta, E.Y.; Nava-Ocampo, A.A.

    2015-01-01

    Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week. PMID:26691866

  9. Prenatal Exposure to Alcohol, Caffeine, Tobacco, and Aspirin: Effects on Fine and Gross Motor Preformance in 4-Year-Old Children.

    ERIC Educational Resources Information Center

    Barr, Helen M.; And Others

    1990-01-01

    Multiple regression analyses of data from 449 children indicated statistically significant relationships between moderate levels of prenatal alcohol exposure and increased errors, increased latency, and increased total time on the Wisconsin Fine Motor Steadiness Battery and poorer balance on the Gross Motor Scale. (RH)

  10. Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

    PubMed Central

    Han, Mingda

    2016-01-01

    Background Embryonic acute exposure to ethanol (EtOH), lithium, and homocysteine (HCy) induces cardiac defects at the time of exposure; folic acid (FA) supplementation protects normal cardiogenesis (Han et al., 2009, 2012; Serrano et al., 2010). Our hypothesis is that EtOH exposure and FA protection relate to lipid and FA metabolism during mouse cardiogenesis and placentation. Methods On the morning of conception, pregnant C57BL/6J mice were placed on either of two FA‐containing diets: a 3.3 mg health maintenance diet or a high FA diet of 10.5 mg/kg. Mice were injected a binge level of EtOH, HCy, or saline on embryonic day (E) 6.75, targeting gastrulation. On E15.5, cardiac and umbilical blood flow were examined by ultrasound. Embryonic cardiac tissues were processed for gene expression of lipid and FA metabolism; the placenta and heart tissues for neutral lipid droplets, or for medium chain acyl‐dehydrogenase (MCAD) protein. Results EtOH exposure altered lipid‐related gene expression on E7.5 in comparison to control or FA‐supplemented groups and remained altered on E15.5 similarly to changes with HCy, signifying FA deficiency. In comparison to control tissues, the lipid‐related acyl CoA dehydrogenase medium length chain gene and its protein MCAD were altered with EtOH exposure, as were neutral lipid droplet localization in the heart and placenta. Conclusion EtOH altered gene expression associated with lipid and folate metabolism, as well as neutral lipids, in the E15.5 abnormally functioning heart and placenta. In comparison to controls, the high FA diet protected the embryo and placenta from these effects allowing normal development. Birth Defects Research (Part A) 106:749–760, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27296863

  11. Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method validation and implementation of a screening program for prenatal drug exposure.

    PubMed

    Hastedt, Martin; Krumbiegel, Franziska; Gapert, René; Tsokos, Michael; Hartwig, Sven

    2013-09-01

    Alcohol consumption during pregnancy is a widespread problem and can cause severe fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the implementation of a reliable marker for alcohol consumption during pregnancy into meconium drug screening programs would be invaluable. A previously published gas chromatography mass spectrometry method for the detection of fatty acid ethyl esters (FAEEs) as alcohol markers in meconium was optimized and newly validated for a sample size of 50 mg. This method was applied to 122 cases from a drug-using population. The meconium samples were also tested for common drugs of abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the samples tested positive for FAEEs at levels indicating significant alcohol exposure. Consequently, alcohol was found to be the third most frequently abused substance within the study group. This re-validated method provides an increase in testing sensitivity, is reliable and easily applicable as part of a drug screening program. It can be used as a non-invasive tool to detect high alcohol consumption in the last trimester of pregnancy. The introduction of FAEEs testing in meconium screening was found to be of particular use in a drug-using population.

  12. The different effects on cranial and trunk neural crest cell behaviour following exposure to a low concentration of alcohol in vitro.

    PubMed

    Czarnobaj, Joanna; Bagnall, Keith M; Bamforth, J Steven; Milos, Nadine C

    2014-05-01

    Embryonic neural crest cells give rise to large regions of the face and peripheral nervous system. Exposure of these cells to high alcohol concentrations leads to cell death in the craniofacial region resulting in facial defects. However, the effects of low concentrations of alcohol on neural crest cells are not clear. In this study, cranial neural crest cells from Xenopus laevis were cultured in an ethanol concentration approximately equivalent to one drink. Techniques were developed to study various aspects of neural crest cell behaviour and a number of cellular parameters were quantified. In the presence of alcohol, a significant number of cranial neural crest cells emigrated from the explant on fibronectin but the liberation of individual cells was delayed. The cells also remained close to the explant and their morphology changed. Cranial neural crest cells did not grow on Type 1 collagen. For the purposes of comparison, the behaviour of trunk neural crest cells was also studied. The presence of alcohol correlated with increased retention of single cells on fibronectin but left other parameters unchanged. The behaviour of trunk neural crest cells growing on Type 1 collagen in the presence of alcohol did not differ from controls. Low concentrations of alcohol therefore significantly affected both cranial and trunk neural crest cells, with a wider variety of effects on cells from the cranial as opposed to the trunk region. The results suggest that low concentrations of alcohol may be more detrimental to early events in organ formation than currently suspected.

  13. The Relationship between Exposure to Brand-Specific Alcohol Advertising and Brand-Specific Consumption among Underage Drinkers—United States, 2011-2012

    PubMed Central

    Siegel, Michael; Ross, Craig S.; Albers, Alison B.; DeJong, William; King, Charles; Naimi, Timothy S.; Jernigan, David H.

    2015-01-01

    Background Marketing is increasingly recognized as a potentially important contributor to youth drinking, yet few studies have examined the relationship between advertising exposure and alcohol consumption among underage youth at the brand level. Objectives To examine the relationship between brand-specific exposure to alcohol advertising among underage youth and the consumption prevalence of each brand in a national sample of underage drinkers. Methods We analyzed the relationship between population-level exposure of underage youth ages 12-20 to brand-specific alcohol advertising in national magazines and television programs and the 30-day consumption prevalence—by brand—among a national sample of underage drinkers ages 13-20. Underage youth exposure to alcohol advertising by brand for each month in 2011, measured in gross rating points (GRPs), was obtained from GfK MRI and Nielsen for all measured national issues of magazines and all national television programs, respectively. The 30-day consumption prevalence for each brand was obtained from a national survey of 1,031 underage drinkers conducted between December 2011 and May 2012. Results Underage youth were more than five times more likely to consume brands that advertise on national television and 36% more likely to consume brands that advertise in national magazines. The consumption prevalence of a brand increased by 36% for each 1.5 standard deviation (50 GRPs) increase in television adstock among underage youth and by 23% for each 1.5 standard deviation (10 GRPs) increase in magazine adstock. Conclusion These findings suggest that alcohol advertising influences an important aspect of drinking behavior— brand choice—among youth who consume alcohol. PMID:26479468

  14. Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise.

    PubMed

    Hamilton, G F; Hernandez, I J; Krebs, C P; Bucko, P J; Rhodes, J S

    2017-04-06

    Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. Male C57BL/6J mice received either saline or 5g/kg ethanol (two doses, two hours apart) on PD5, 7, and 9. On PD35, animals received a running wheel or remained sedentary for 48days before behavioral testing and perfusion on PD83. The number of PV+ interneurons was stereologically measured in three separate mPFC subregions: infralimbic, prelimbic and anterior cingulate cortices (ACC). Neonatal alcohol exposure decreased number of PV+ interneurons and volume of the ACC, but the other regions of the mPFC were spared. Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.

  15. Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats.

    PubMed

    Bowen, Michael T; Carson, Dean S; Spiro, Adena; Arnold, Jonathon C; McGregor, Iain S

    2011-01-01

    Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33-42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A "booster" shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

  16. Nothing good ever happens after midnight: observed exposure and alcohol use during weekend nights among young male drivers carrying passengers in a late licensing country.

    PubMed

    Houwing, Sjoerd; Twisk, Divera

    2015-02-01

    Similar to other countries, also in the Netherlands young male drivers (ages between 18 and 24 years) are overrepresented in crashes during weekend nights, thereby fatally injuring one or more of their passengers. This overrepresentation may be due to two contributing factors: (a) a higher exposure-to-risk because of dangerous trip condition, and (b) a higher tendency to take risks. Studies on these factors, mostly carried out in jurisdictions where youngsters are licensed at an earlier age than in Europe, suggest a strong -often negative- influence from peer-aged passengers. Given that in adolescence susceptibility to peer pressure reduces with age, these findings may not be applicable to late licensing countries, such as in Europe. In the Netherlands -a late licensing country- youngsters are licensed after the age of 18 years, followed by a 5 year probation period with a legal alcohol limit of 0.2g/L. Further, designated driver schemes are in place since 2001, alcohol limits are enforced by random breath testing schemes, and no passenger and night time restrictions are in force. Against this background, we examined the incidence of dangerous trip conditions and risk taking among young male drivers and compared those with a reference group with a low passenger fatality rate. To that end, data on trip conditions and risk behavior were obtained from a data base on 18,608 randomly selected drivers during weekend nights in 2010, between 22:00 and 06:00. This data base held information for each randomly selected on breath alcohol concentration (BAC), license status, driver characteristics (age and gender), number of passengers, time of night, and level of urbanization. Binary logistic regression analysis confirmed the overrepresentation of young male drivers in traffic, carrying more frequently passengers than the reference group, especially after midnight. Urbanization level was not a modifying factor, but 'time of night' was, with riskier conditions after midnight in

  17. Fetal Alcohol Spectrum Disorders: Neuropsychological and Behavioral Features

    PubMed Central

    Mattson, Sarah N.; Crocker, Nicole; Nguyen, Tanya T.

    2012-01-01

    Heavy prenatal alcohol exposure can cause alterations to the developing brain. The resulting neurobehavioral deficits seen following this exposure are wide-ranging and potentially devastating and, therefore, are of significant concern to individuals, families, communities, and society. These effects occur on a continuum, and qualitatively similar neuropsychological and behavioral features are seen across the spectrum of effect. The term fetal alcohol spectrum disorders (FASD) has been used to emphasize the continuous nature of the outcomes of prenatal alcohol exposure, with fetal alcohol syndrome (FAS) representing one point on the spectrum. This paper will provide a comprehensive review of the neuropsychological and behavioral effects of heavy prenatal alcohol exposure, including a discussion of the emerging neurobehavioral profile. Supporting studies of lower levels of exposure, brain-behavior associations, and animal model systems will be included when appropriate. PMID:21503685

  18. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

    PubMed

    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

  19. Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats.

    PubMed

    Allen, Gregg C; Farnell, Yuhua Z; Maeng, Ji-ung; West, James R; Chen, Wei-Jung A; Earnest, David J

    2005-10-01

    In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid brain growth produces structural damage in some brain regions that often persists into adulthood and thus may have long-term consequences in the neural regulation of behavior. Because recent findings indicate that the circadian clock located in the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during development, the present study examined the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior in adult rats. Rat pups were exposed to alcohol (3.0, 4.5, or 6.0 g x kg(-1) x day(-1)) or isocaloric milk formula on postnatal days 4-9 using artificial-rearing methods. At 2 months of age, animals were housed individually and circadian wheel-running behavior was continuously analyzed to determine the effects of neonatal alcohol treatment on the rate of reentrainment to a 6-h advance in the 12-h light:12-h dark photoperiod and the phase-shifting properties of free-running rhythms in response to discrete light pulses on a background of constant darkness. For all doses, neonatal alcohol exposure had a significant effect in reducing the time for reentrainment such that EtOH-treated rats required four to five fewer days than control animals for stable realignment of the activity rhythm to the shifted light-dark cycle. Coupled with the accelerated rate of reentrainment, the amplitude of light-evoked phase delays at circadian time 14 and advances at circadian time 22 in the 4.5 and 6.0 g x kg(-1) x day(-1) EtOH groups was almost twofold greater than that observed in control animals. The present observations indicate that the mechanisms by which photic signals regulate circadian behavior are permanently altered following alcohol exposure during the period of rapid brain development. These long-term alterations in the photic regulation of circadian rhythms may account, at least partially, for some neurobehavioral consequences of prenatal

  20. Alcoholism and Minority Populations.

    ERIC Educational Resources Information Center

    Watts, Thomas D.; Wright, Roosevelt, Jr.

    1991-01-01

    Briefly discusses some aspects of the role of the state and the position of minorities in respect to alcoholism policies and services. Includes case study of a Black alcoholic. Refers readers to studies on Black alcoholism, Native American alcoholism, Hispanic alcoholism, and Asian-American alcoholism. (Author/NB)

  1. Alcoholic and non-alcoholic steatohepatitis

    PubMed Central

    Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

    2015-01-01

    This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  2. Alcoholic and non-alcoholic steatohepatitis.

    PubMed

    Neuman, Manuela G; French, Samuel W; French, Barbara A; Seitz, Helmut K; Cohen, Lawrence B; Mueller, Sebastian; Osna, Natalia A; Kharbanda, Kusum K; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J; McKillop, Iain H; Kirpich, Irina A; McClain, Craig J; Bataller, Ramon; Nanau, Radu M; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomes, Paul G; Ganesan, Murali; Malnick, Steve

    2014-12-01

    This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  3. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.

    PubMed

    Pavón, Francisco Javier; Marco, Eva María; Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  4. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

    PubMed Central

    Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    2016-01-01

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  5. Including exposure variability in the life cycle impact assessment of indoor chemical emissions: the case of metal degreasing.

    PubMed

    Golsteijn, Laura; Huizer, Daan; Hauck, Mara; van Zelm, Rosalie; Huijbregts, Mark A J

    2014-10-01

    The present paper describes a method that accounts for variation in indoor chemical exposure settings and accompanying human toxicity in life cycle assessment (LCA). Metal degreasing with dichloromethane was used as a case study to show method in practice. We compared the human toxicity related to the degreasing of 1m(2) of metal surface in different exposure scenarios for industrial workers, professional users outside industrial settings, and home consumers. The fraction of the chemical emission that is taken in by exposed individuals (i.e. the intake fraction) was estimated on the basis of operational conditions (e.g. exposure duration), and protective measures (e.g. local exhaust ventilation). The introduction of a time-dependency and a correction for protective measures resulted in reductions in the intake fraction of up to 1.5 orders of magnitude, compared to application of existing, less advanced models. In every exposure scenario, the life cycle impacts for human toxicity were mainly caused by indoor exposure to metal degreaser (>60%). Emissions released outdoors contributed up to 22% of the life cycle impacts for human toxicity, and the production of metal degreaser contributed up to 19%. These findings illustrate that human toxicity from indoor chemical exposure should not be disregarded in LCA case studies. Particularly when protective measures are taken or in the case of a short duration (1h or less), we recommend the use of our exposure scenario-specific approach.

  6. Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa)

    PubMed Central

    Zuccolo, Luisa; DeRoo, Lisa A.; Wills, Andrew K.; Davey Smith, George; Suren, Pål; Roth, Christine; Stoltenberg, Camilla; Magnus, Per

    2016-01-01

    Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999–2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy. PMID:28008975

  7. The Use of Open- and Closed-Loop Control During Goal-Directed Force Responses by Children with Heavy Prenatal Alcohol Exposure

    PubMed Central

    Simmons, Roger W.; Nguyen, Tanya T.; Thomas, Jennifer D.; Riley, Edward P.

    2015-01-01

    Background Many daily functional activities involve goal-directed responses based on open-loop and closed-loop motor control, yet little is known about how children with heavy prenatal alcohol-exposure organize and regulate these two types of control systems when completing a goal-directed force response. Methods Children with (n = 19) or without (n = 23) heavy prenatal alcohol exposure were required to match a target force (25% and 50% of maximum voluntary force) in a specified target time (200 ms, 800 ms, and 2000 ms). Target force and produced force were visually displayed on a computer monitor. The analog force-time record was parsed into two segments: the period beginning from force initiation to the first reversal in force was designated the open-loop phase, and the remainder of the response was the closed-loop phase. Results Compared to controls, alcohol-exposed children produced a significantly shorter duration of open-loop control, a higher open-loop phase rate of force development, a shorter time to reach maximum force during the closed-loop phase and greater absolute target force error. Increasing target force magnitude did not differentially alter the performance of the clinical group. Conclusions The results indicate that alcohol-exposed children experience deficits in completing goal-directed force responses that likely stem from an alcohol related insult to the CNS. Therapeutic exercises should be designed to re-calibrate internal timing systems and improve visuomotor integration. PMID:26248225

  8. Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa).

    PubMed

    Zuccolo, Luisa; DeRoo, Lisa A; Wills, Andrew K; Davey Smith, George; Suren, Pål; Roth, Christine; Stoltenberg, Camilla; Magnus, Per

    2016-12-23

    Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

  9. Phthalates in plastic bottled non-alcoholic beverages from China and estimated dietary exposure in adults.

    PubMed

    Yang, Ji-Feng; Yang, Li-Ming; Zheng, Li-Ying; Ying, Guang-Guo; Liu, Cheng-Bin; Luo, Sheng-Lian

    2017-03-01

    Concentrations of six phthalates were determined in 69 plastic bottled non-alcoholic beverages collected from marketplaces in China. Di-n-butyl phthalate (DBP) and di-(2-ethylhexyl)-phthalate (DEHP) were the most detected compounds with frequencies of 100%. Dimethyl phthalate was found less, with a mean frequency of almost 34%. The samples were divided into seven groups. The frequencies of phthalates in these groups ranged from 6.67% to 100%, which indicated that different types of beverages were differently contaminated by phthalates. DEHP contained the highest mean and median concentrations (1.60 ng g(-1) and 0.62 ng g(-1)), followed by DBP (1.34 ng g(-1) and 0.27 ng g(-1)). For DBP, the highest phthalate concentration of 14.3 ng g(-1) was measured. The results of estimated daily intake (EDI) showed that the risk of Chinese adults exposed to these 6 phthalates in beverages examined was lower than the reference doses as suggested by the United States Environmental Protection Agency. The range of EDI values was between 1.77 × 10(-)(4) μg kg-bw(-1) day(-1) and 0.478 μg kg-bw(-1) day(-1).

  10. Alcohol brand references in U.S. popular music, 2009-2011.

    PubMed

    Siegel, Michael; Johnson, Renee M; Tyagi, Keshav; Power, Kathryn; Lohsen, Mark C; Ayers, Amanda J; Jernigan, David H

    2013-12-01

    This study aimed to assess the prevalence and context of alcohol brand references in popular music. Billboard Magazine year-end charts from 2009 to 2011 were used to identify the most popular songs in four genres: Urban, Pop, Country, and Rock. Of the 720 songs, 23% included an alcohol mention, and 6.4% included an alcohol brand mention. Songs classified as Urban had the highest percentage of alcohol mentions and alcohol brand mentions. The context associated with alcohol brand mentions was almost uniformly positive or neutral. Public health efforts may be necessary to reduce youth exposure to these positive messages about alcohol use.

  11. Alcohol Brand References in U.S. Popular Music, 2009–2011

    PubMed Central

    Siegel, Michael; Johnson, Renee M.; Tyagi, Keshav; Power, Kathryn; Lohsen, Mark C.; Ayers, Amanda J.; Jernigan, David H.

    2013-01-01

    This study aimed to assess the prevalence and context of alcohol brand references in popular music. Billboard Magazine year-end charts from 2009–2011 were used to identify the most popular songs in four genres: Urban, Pop, Country, and Rock. Of the 720 songs, 23% included an alcohol mention, and 6.4% included an alcohol brand mention. Songs classified as Urban had the highest percentage of alcohol mentions and alcohol brand mentions. The context associated with alcohol brand mentions was almost uniformly positive or neutral. Public health efforts may be necessary to reduce youth exposure to these positive messages about alcohol use. PMID:23971875

  12. Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy L.; Bodnar, Tamara; Yu, Wayne K.; Weinberg, Joanne; Galea, Liisa A. M.

    2014-01-01

    Rationale Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Methods Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. Results PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. Conclusions PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD. PMID:25420606

  13. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    PubMed Central

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Falkner, K. Cameron; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; States, J. Christopher; Cave, Matthew C.

    2014-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. PMID:24998970

  14. Enhancement of placental antioxidative function and P-gp expression by sodium ferulate mediated its protective effect on rat IUGR induced by prenatal tobacco/alcohol exposure.

    PubMed

    Li, Yan; Yan, You-E; Wang, Hui

    2011-11-01

    This study was aimed to explore the therapeutic effect of sodium ferulate (SF) on rats with intrauterine growth retardation (IUGR), and then to clarify the corresponding mechanism. Pregnant rats were divided into normal group, tobacco/alcohol exposure group, and tobacco/alcohol+SF groups. Fetal developmental indices, placental weight, histological alteration, oxidative and antioxidative-function (e.g. MDA, SOD, CAT) and Mdr1 levels were assayed. Results showed exposure to tobacco/alcohol resulted in reduced fetal developmental indices and placental histological alteration, as well as the increased MDA content, decreased SOD and CAT activities and decreased Mdr1a level. After SF treatment, fetal developmental indices, and placental weight, histological alteration, oxidative and antioxidative-function and mdr1a levels were reversed. Our study indicated SF may be effective in reversing IUGR production, and its underlying mechanism may be due to enhanced placental antioxidative function and P-gp expression, which may be related to IUGR formation by tobacco/alcohol exposure.

  15. Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.

    PubMed

    Mouton, Alan J; Ninh, Van K; El Hajj, Elia C; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

    2016-08-01

    Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III

  16. Prenatal alcohol exposure alters response of kisspeptin-ir neurons to estradiol and progesterone in adult female rats

    PubMed Central

    Sliwowska, Joanna H.; Bodnar, Tamara S.; Weinberg, Joanne

    2014-01-01

    BACKGROUND Prenatal alcohol exposure (PAE) has adverse effects on reproductive function and hypothalamic-pituitary-gonadal (HPG) activity. Kisspeptin neurons play a role in mediating feedback effects of estradiol (E2) and progesterone (P4) on the HPG axis. We hypothesized that PAE will have long-term effects on the response of kisspeptin neurons to E2 and P4. METHODS Adult female rats (53–58 days) from prenatal ad libitum-fed control (C), pair-fed (PF), and alcohol-exposed (PAE) groups were subjected to Sham ovariectomy (OVX) or OVX without or with replacement with low or high physiological levels of E2 and P4, and terminated under basal conditions. E2 and P4 levels, and the response of kisspeptin-ir neurons in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei to these hormones, were measured. As the E2 signal is conveyed to kisspeptin neurons via estrogen receptor-α (ERα), we investigated PAE effects on the number of kisspetin-ir/ERα-ir neurons. To determine if PAE alters interactions between kisspeptin and gonadotropin releasing hormone (GnRH) neurons, close contacts between kisspeptin-ir fibers and GnRH-ir cell bodies were examined. RESULTS Our data present the novel finding that kisspeptin-ir neurons in the ARC of PAE females show differential responses to E2 and to the combined treatment with E2 and P4 compared to controls: 1) OVX increased the number of kisspeptin-ir neurons in C and PF, but not PAE females compared to their Sham counterparts; 2) E2 replacement restored kisspeptin-ir cell numbers to Sham levels in C and PF females but caused a robust downregulation of kisspeptin-ir neurons below Sham levels in PAE females; 3) OVX and replacement with high physiological concentrations of E2 resulted in fewer kisspeptin-ir cells in PAE than C females; 4) OVX and replacement with high levels of both E2 and P4 markedly decreased the number of kisspeptin-ir neurons, below levels observed following E2 alone, in PF and C females, but had no

  17. Trends in toxic alcohol exposures in the United States from 2000 to 2013: a focus on the use of antidotes and extracorporeal treatments.

    PubMed

    Ghannoum, Marc; Hoffman, Robert S; Mowry, James B; Lavergne, Valery

    2014-01-01

    Morbidity and mortality from toxic alcohols like ethylene glycol and methanol remain prevalent worldwide. The introduction of fomepizole, a potent blocker of alcohol dehydrogenase, has modified current practice over the last 15 years. The aim of the study was to describe the characteristics of toxic alcohol poisoning reported to US poison centers, the trends in the incidence of antidote use and hemodialysis treatment, as well as the related mortality. A retrospective study of all electronic entries from the AAPCC National Poison Data System database, from the years 2000 to 2013 was reviewed. When considering all exposures, the great majority of patients had a benign outcome. Major effects (e.g., life threatening) occurred in 2.1% and 4.9% of methanol and ethylene glycol cases, respectively. Mortality rates were similar for both toxic alcohols, approximately 0.6%. When only considering ingestions reported to healthcare facilities, a major effect was reported in 9.5% and 20.5%, and the mortality rate was 2.9% and 2.4% for methanol and ethylene glycol exposures, respectively, and remained constant over time. The use of fomepizole increased statistically over the study period while that of ethanol decreased, until it became proportionally negligible by 2012-2013. The use of hemodialysis significantly decreased in "Early" ethylene glycol exposures during the study period. Similar to other reports, it appears that the use of fomepizole has largely supplanted ethanol as the antidote of choice in toxic alcohol exposures and may decrease the requirements for hemodialysis in patients poisoned with ethylene glycol who have no acidosis and normal kidney function.

  18. Fetal exposure to alcohol as evidenced by fatty acid ethyl esters in meconium in the absence of maternal drinking history in pregnancy.

    PubMed

    Chan, Daphne; Klein, Julia; Karaskov, Tatyana; Koren, Gideon

    2004-10-01

    The detection of fatty acid ethyl esters (FAEE) in neonatal meconium has been proposed as a novel screening method for intrauterine exposure to alcohol. We investigated the potential use of meconium FAEE screening in a high-risk neonatal population in the absence of maternal drinking history. One hundred forty-two meconium samples of neonates suspected of intrauterine illicit substance exposure and referred to the Motherisk Laboratory were analyzed for the existence of drugs by enzyme-linked immunosorbent assay (ELISA) and FAEE by gas chromatography-flame ionization detection (GC-FID). A positive FAEE test was previously defined as a cumulative measurement of 7 individual FAEE > or = 2 nmol/g. Seventy-one percent of the samples tested positive for at least 1 illicit drug, with cannabis being the most prevalent (52.3%). Fourteen percent of all samples tested positive for prenatal alcohol exposure, as evidenced by cumulative meconium FAEE > or = 2 nmol/g. Ethyl oleate, linoleate, palmitate, and arachidonate were detected most often and at the highest levels. At least 3 individual FAEE were detected in 95% of all positive samples, and none could be identified by the use of 1 selected FAEE. Significantly elevated levels of FAEE above the baseline and the presence of multiple FAEE species in meconium are exclusive to neonates who have likely been exposed to excessive amounts of alcohol in utero. Babies born to mothers who are suspected to use illicit drugs in pregnancy are at elevated risk for exposure also to alcohol in utero. Meconium FAEE are emerging biologic markers that can potentially facilitate earlier diagnosis and intervention for less apparent forms of alcohol-related disabilities that cannot be confirmed in the absence of maternal drinking history.

  19. Adult and adolescent exposure to tobacco and alcohol content in contemporary YouTube music videos in Great Britain: a population estimate

    PubMed Central

    Cranwell, Jo; Opazo-Breton, Magdalena; Britton, John

    2016-01-01

    Background We estimate exposure of British adults and adolescents to tobacco and alcohol content from a sample of popular YouTube music videos. Methods British viewing figures were generated from 2 representative online national surveys of adult and adolescent viewing of the 32 most popular videos containing content. 2068 adolescents aged 11–18 years (1010 boys, 1058 girls), and 2232 adults aged 19+years (1052 male, 1180 female) completed the surveys. We used the number of 10 s intervals in the 32 most popular videos containing content to estimate the number of impressions. We extrapolated gross and per capita impressions for the British population from census data and estimated numbers of adults and adolescents who had ever watched the sampled videos. Results From video release to the point of survey, the videos delivered an estimated 1006 million gross impressions of alcohol (95% CI 748 to 1264 million), and 203 million of tobacco (95% CI 151 to 255 million), to the British population. Per capita exposure was around 5 times higher for alcohol than for tobacco, and nearly 4 times higher in adolescents, who were exposed to an average of 52.1 (95% CI 43.4 to 60.9) and 10.5 (95% CI 8.8 to 12.3) alcohol and tobacco impressions, respectively, than in adults (14.1 (95% CI 10.2 to 18.1) and 2.9 (95% CI 2.1 to 3.6)). Exposure rates were higher in girls than in boys. Conclusions YouTube music videos deliver millions of gross impressions of alcohol and tobacco content. Adolescents are exposed much more than adults. Music videos are a major global medium of exposure to such content. PMID:26767404

  20. Intrauterine exposure to alcohol and tobacco use and childhood IQ: findings from a parental-offspring comparison within the Avon Longitudinal Study of Parents and Children.

    PubMed

    Alati, Rosa; Macleod, John; Hickman, Matthew; Sayal, Kapil; MAY, Margaret; Smith, George Davey; Lawlor, Debbie A

    2008-12-01

    This study aims to test the hypothesis that moderate maternal alcohol and tobacco use in pregnancy is associated with intelligent quotient (IQ) scores in childhood through intrauterine mechanisms. We conducted parental-offspring comparisons between the associations of tobacco and alcohol consumption with child's IQ in the Avon Longitudinal Study of Parents and Children. Analyses were conducted on 4332 participants with complete data on maternal and paternal use of alcohol and tobacco at 18 wk gestation, child's IQ and a range of confounders. IQ was measured at child age 8 with the Weschler Intelligence Scale for Children (WISC-III). We used multivariable linear and logistic regression to estimate mean differences and 95% confidence intervals in IQ scores across the exposure categories and computed f statistics to compare maternal and paternal associations. In fully adjusted models, there was no strong statistical evidence that maternal alcohol and tobacco consumption during pregnancy were associated with childhood IQ with any greater magnitude than paternal alcohol and tobacco consumption (also assessed during their partners' pregnancy). Our findings suggest that the relationship between maternal moderate alcohol and tobacco use in early pregnancy and childhood IQ may not be explained by intrauterine mechanisms.

  1. Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

    PubMed

    Swartzwelder, H Scott; Acheson, Shawn K; Miller, Kelsey M; Sexton, Hannah G; Liu, Wen; Crews, Fulton T; Risher, Mary-Louise

    2015-01-01

    The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

  2. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    SciTech Connect

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  3. Including non-dietary sources into an exposure assessment of the European Food Safety Authority: The challenge of multi-sector chemicals such as Bisphenol A.

    PubMed

    von Goetz, N; Pirow, R; Hart, A; Bradley, E; Poças, F; Arcella, D; Lillegard, I T L; Simoneau, C; van Engelen, J; Husoy, T; Theobald, A; Leclercq, C

    2017-04-01

    In the most recent risk assessment for Bisphenol A for the first time a multi-route aggregate exposure assessment was conducted by the European Food Safety Authority. This assessment includes exposure via dietary sources, and also contributions of the most important non-dietary sources. Both average and high aggregate exposure were calculated by source-to-dose modeling (forward calculation) for different age groups and compared with estimates based on urinary biomonitoring data (backward calculation). The aggregate exposure estimates obtained by forward and backward modeling are in the same order of magnitude, with forward modeling yielding higher estimates associated with larger uncertainty. Yet, only forward modeling can indicate the relative contribution of different sources. Dietary exposure, especially via canned food, appears to be the most important exposure source and, based on the central aggregate exposure estimates, contributes around 90% to internal exposure to total (conjugated plus unconjugated) BPA. Dermal exposure via thermal paper and to a lesser extent via cosmetic products may contribute around 10% for some age groups. The uncertainty around these estimates is considerable, but since after dermal absorption a first-pass metabolism of BPA by conjugation is lacking, dermal sources may be of equal or even higher toxicological relevance than dietary sources.

  4. Is it time to ban alcohol advertising?

    PubMed

    Anderson, Peter

    2009-04-01

    Children and adolescents are particularly vulnerable to the harmful effects of alcohol, with heavy drinking risking impaired brain development and future alcohol dependence. Advertisements increase expectancies about alcohol, leading to a greater likelihood of drinking. A systematic review of 13 longitudinal studies of over 38,000 young people found convincing evidence of an impact of media exposure and alcohol advertising on subsequent alcohol use, including initiation of drinking and heavier drinking among existing drinkers. All European countries, with the exception of the UK, have a ban on one or more types of advertising. Since self-regulation is reported as failing to prevent marketing which has an impact on younger people, and since advertising commonly crosses country borders, there is an argument to approximate advertising rules across Europe banning alcohol advertising targeted at young people, a highly cost-effective measure to reduce harmful alcohol use, and one supported by European citizens and case law.

  5. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    PubMed

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

  6. Fetal alcohol syndrome

    MedlinePlus

    ... resources for information on alcoholism: Alcoholics Anonymous -- www.aa.org Al-Anon Family Groups -- www.al-anon. ... exposures to the fetus. In: Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ...

  7. Breath gas concentrations mirror exposure to sevoflurane and isopropyl alcohol in hospital environments in non-occupational conditions.

    PubMed

    Castellanos, Mar; Xifra, Gemma; Fernández-Real, José Manuel; Sánchez, Juan M

    2016-01-29

    Anaesthetic gases and disinfectants are a primary source of air contamination in hospitals. A highly sensitive sorbent-trap methodology has been used to analyse exhaled breath samples with detection limits in the pptv range, which allows volatile organic compounds (VOCs) to be detected at significantly lower levels (5-6 orders of magnitude below) than the recommended exposure limits by different organizations. Two common VOCs used in hospital environments, isopropyl alcohol (IPA) and sevoflurane, have been evaluated. Forced-expiratory breath samples were obtained from 100 volunteers (24 hospital staff, 45 hospital visitors and 31 external controls). Significant differences for IPA were found between samples from volunteers who had not been in contact with hospital environments (mean value of 8.032 ppbv) and people staying (20.981 ppbv, p  =  0.0002) or working (19.457 ppbv, p  =  0.000 09) in such an environment. Sevoflurane, an anaesthetic gas routinely used as an inhaled anaesthetic, was detected in all samples from volunteers in the hospital environment but not in volunteers who had not been in recent contact with a hospital environment. The levels of sevoflurane were significantly higher (p  =  0.000 24) among staff members (0.522 ppbv) than among visitors to the hospital (0.196 ppbv). We conclude that highly sensitive methods are required to detect anaesthetic gas contamination in hospital environments.

  8. Community violence exposure, coping, and problematic alcohol and drug use among urban, female caregivers: A prospective study

    PubMed Central

    Kliewer, Wendy; Zaharakis, Nikola

    2013-01-01

    Victimization is associated with substance use in women, but less is known about linkages between witnessing community violence and substance use, even though more women witness versus directly experience violence. Further, factors that contribute to or protect against women’s problematic substance use are less well understood. Urban female caregivers (N = 318; > 92% African American/black) living in low-income communities were interviewed annually for three waves regarding exposure to community violence, coping behaviors, substance use, and protective factors. Path analyses revealed that lifetime witnessing of violence, but not victimization, assessed at baseline, was associated with changes in avoidant coping, but not active coping, one year later; avoidant coping, in turn, was related to changes in and higher levels of problematic drug use the following year. Victimization was directly related to problematic drug use, but not to alcohol use. Regression analyses indicated that high levels of religious commitment and social support at baseline were prospectively associated with lower levels of avoidant coping. Because caregivers are important role models for their children, it is important to attend to the factors that contribute to their substance use and abuse. PMID:24039324

  9. Community violence exposure, coping, and problematic alcohol and drug use among urban, female caregivers: A prospective study.

    PubMed

    Kliewer, Wendy; Zaharakis, Nikola

    2013-08-01

    Victimization is associated with substance use in women, but less is known about linkages between witnessing community violence and substance use, even though more women witness versus directly experience violence. Further, factors that contribute to or protect against women's problematic substance use are less well understood. Urban female caregivers (N = 318; > 92% African American/black) living in low-income communities were interviewed annually for three waves regarding exposure to community violence, coping behaviors, substance use, and protective factors. Path analyses revealed that lifetime witnessing of violence, but not victimization, assessed at baseline, was associated with changes in avoidant coping, but not active coping, one year later; avoidant coping, in turn, was related to changes in and higher levels of problematic drug use the following year. Victimization was directly related to problematic drug use, but not to alcohol use. Regression analyses indicated that high levels of religious commitment and social support at baseline were prospectively associated with lower levels of avoidant coping. Because caregivers are important role models for their children, it is important to attend to the factors that contribute to their substance use and abuse.

  10. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt.

    PubMed

    Helfer, Jennifer L; Goodlett, Charles R; Greenough, William T; Klintsova, Anna Y

    2009-10-19

    Exposure to alcohol during the brain growth spurt results in impaired cognition and learning in adulthood. This impairment is accompanied by permanent structural changes in the hippocampal formation. Exercise improves performance on hippocampal-dependent learning and memory tasks and increases adult neurogenesis in the rat hippocampal dentate gyrus. The present study examined the effects of wheel running during adolescence on dentate gyrus cell proliferation and neurogenesis after postnatal binge-like alcohol exposure. On postnatal days (PD) 4-9, pups were either intubated with alcohol in a binge-like manner, sham intubated, or reared normally. On PD30-42, all animals were randomly assigned to two adolescent conditions: wheel running or inactive control. Animals were injected with BrdU every day between PD32 and PD42 and perfused on PD42 or PD72. In inactive control animals at both PD42 and PD72, cell proliferation and neurogenesis did not differ between postnatal treatment groups. Wheel running significantly increased the number of BrdU-labeled cells on PD42 in all three postnatal treatments. On PD72, only the normal controls showed significant increases in survival of newly generated cells resulting from the wheel running. These results indicate that adolescent wheel running can induce comparable increases in cell proliferation and neurogenesis in alcohol-exposed and control rats, but the long-term survival of those newly generated cells is impaired relative normal controls. Exercise may provide a means to stimulate neurogenesis, with implications for amelioration of hippocampal-dependent learning impairments associated with alcohol exposure. However, benefits requiring long-lasting survival of the newly generated cells will depend on identifying ways to promote survival.

  11. The contribution of childhood parental rejection and early androgen exposure to impairments in socio-cognitive skills in intimate partner violence perpetrators with high alcohol consumption.

    PubMed

    Romero-Martínez, Ángel; Lila, Marisol; Catalá-Miñana, Alba; Williams, Ryan K; Moya-Albiol, Luis

    2013-08-20

    Alcohol consumption, a larger history of childhood parental rejection, and high prenatal androgen exposure have been linked with facilitation and high risk of recidivism in intimate partner violence (IPV) perpetrators. Participants were distributed into two groups according to their alcohol consumption scores as high (HA) and low (LA). HA presented a higher history of childhood parental rejection, prenatal masculinization (smaller 2D:4D ratio), and violence-related scores than LA IPV perpetrators. Nonetheless, the former showed poor socio-cognitive skills performance (cognitive flexibility, emotional recognition and cognitive empathy). Particularly in HA IPV perpetrators, the history of childhood parental rejection was associated with high hostile sexism and low cognitive empathy. Moreover, a masculinized 2D:4D ratio was associated with high anger expression and low cognitive empathy. Parental rejection during childhood and early androgen exposure are relevant factors for the development of violence and the lack of adequate empathy in adulthood. Furthermore, alcohol abuse plays a key role in the development of socio-cognitive impairments and in the proneness to violence and its recidivism. These findings contribute to new coadjutant violence intervention programs, focused on the rehabilitation of basic executive functions and emotional decoding processes and on the treatment of alcohol dependence.

  12. The Contribution of Childhood Parental Rejection and Early Androgen Exposure to Impairments in Socio-Cognitive Skills in Intimate Partner Violence Perpetrators with High Alcohol Consumption

    PubMed Central

    Romero-Martínez, Ángel; Lila, Marisol; Catalá-Miñana, Alba; Williams, Ryan K.; Moya-Albiol, Luis

    2013-01-01

    Alcohol consumption, a larger history of childhood parental rejection, and high prenatal androgen exposure have been linked with facilitation and high risk of recidivism in intimate partner violence (IPV) perpetrators. Participants were distributed into two groups according to their alcohol consumption scores as high (HA) and low (LA). HA presented a higher history of childhood parental rejection, prenatal masculinization (smaller 2D:4D ratio), and violence-related scores than LA IPV perpetrators. Nonetheless, the former showed poor socio-cognitive skills performance (cognitive flexibility, emotional recognition and cognitive empathy). Particularly in HA IPV perpetrators, the history of childhood parental rejection was associated with high hostile sexism and low cognitive empathy. Moreover, a masculinized 2D:4D ratio was associated with high anger expression and low cognitive empathy. Parental rejection during childhood and early androgen exposure are relevant factors for the development of violence and the lack of adequate empathy in adulthood. Furthermore, alcohol abuse plays a key role in the development of socio-cognitive impairments and in the proneness to violence and its recidivism. These findings contribute to new coadjutant violence intervention programs, focused on the rehabilitation of basic executive functions and emotional decoding processes and on the treatment of alcohol dependence. PMID:23965927

  13. Effects of exercise and environmental complexity on deficits in trace and contextual fear conditioning produced by neonatal alcohol exposure in rats.

    PubMed

    Schreiber, W B; St Cyr, S A; Jablonski, S A; Hunt, P S; Klintsova, A Y; Stanton, M E

    2013-07-01

    In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9 followed by either free access to a running wheel on PD 30-41 and housing in a complex environment on PD 42-72 (wheel-running plus environmental complexity; WREC) or conventional social housing (SHSH) from PD 30 to 72. Adult rats (PD 80 ± 5) received 5 trials/day of a 10-s flashing-light conditioned stimulus (CS) paired with .8 mA footshock either immediately (delay conditioning) or after a 10-s trace interval (trace conditioning) for 2 days. Neonatal alcohol exposure impaired context and trace conditioning, but not short-delay conditioning. The WREC intervention did not reverse these deficits, despite increasing context-related freezing in ethanol-exposed and SI animals.

  14. Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling

    PubMed Central

    Spoelder, Marcia; Tsutsui, Kimberly T; Lesscher, Heidi M B; Vanderschuren, Louk J M J; Clark, Jeremy J

    2015-01-01

    Adolescent alcohol use remains a major public health concern due in part to well-established findings implicating the age of onset in alcohol use in the development of alcohol use disorders and persistent decision-making deficits in adults. We have previously demonstrated that moderate adolescent alcohol consumption in rats promotes suboptimal decision making and an associated perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent incentive learning processes are an integral component of value-based decision making and a fundamental element to many theoretical accounts of addiction. Thus we tested the hypothesis that adolescent alcohol use selectively alters incentive learning processes through perturbation of mesolimbic dopamine systems. To assess incentive learning, behavioral and neurochemical measurements were made during the acquisition, maintenance, extinction, and reacquisition of a Pavlovian conditioned approach procedure in adult rats with a history of adolescent alcohol consumption. We show that moderate adolescent alcohol consumption potentiates stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan cyclic voltammetry, in adulthood and biases individuals toward a dopamine-dependent incentive learning strategy. Moreover, we demonstrate that animals exposed to alcohol in adolescence are more sensitive to an unexpected variation in reward outcomes. This pattern of phasic dopamine signaling and the associated bias in learning may provide a mechanism for the well-documented vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood. PMID:25971592

  15. Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling.

    PubMed

    Spoelder, Marcia; Tsutsui, Kimberly T; Lesscher, Heidi M B; Vanderschuren, Louk J M J; Clark, Jeremy J

    2015-12-01

    Adolescent alcohol use remains a major public health concern due in part to well-established findings implicating the age of onset in alcohol use in the development of alcohol use disorders and persistent decision-making deficits in adults. We have previously demonstrated that moderate adolescent alcohol consumption in rats promotes suboptimal decision making and an associated perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent incentive learning processes are an integral component of value-based decision making and a fundamental element to many theoretical accounts of addiction. Thus we tested the hypothesis that adolescent alcohol use selectively alters incentive learning processes through perturbation of mesolimbic dopamine systems. To assess incentive learning, behavioral and neurochemical measurements were made during the acquisition, maintenance, extinction, and reacquisition of a Pavlovian conditioned approach procedure in adult rats with a history of adolescent alcohol consumption. We show that moderate adolescent alcohol consumption potentiates stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan cyclic voltammetry, in adulthood and biases individuals toward a dopamine-dependent incentive learning strategy. Moreover, we demonstrate that animals exposed to alcohol in adolescence are more sensitive to an unexpected variation in reward outcomes. This pattern of phasic dopamine signaling and the associated bias in learning may provide a mechanism for the well-documented vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood.

  16. Alcohol Consumption Patterns among Adolescents are Related to Family Structure and Exposure to Drunkenness within the Family: Results from the SEYLE Project

    PubMed Central

    Rüütel, Erik; Sisask, Merike; Värnik, Airi; Värnik, Peeter; Carli, Vladimir; Wasserman, Camilla; Hoven, Christina W.; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Bobes, Julio; Brunner, Romuald; Corcoran, Paul; Cosman, Doina; Haring, Christian; Iosue, Miriam; Kaess, Michael; Kahn, Jean-Pierre; Poštuvan, Vita; Sáiz, Pilar A.; Wasserman, Danuta

    2014-01-01

    There is expedient evidence showing that differences in adolescent alcohol consumption and other risk-behaviour depend on both family structure and family member drunkenness exposure. Data were obtained among adolescents (N = 12,115, mean age 14.9 ± 0.89) in Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain within the European Union’s 7th Framework Programme funded project, ‘Saving and Empowering Young Lives in Europe (SEYLE)’. The current study reveals how adolescents’ alcohol consumption patterns are related to their family structure and having seen their family member drunk. The results revealed statistically significant differences in adolescent alcohol consumption depending on whether the adolescent lives in a family with both birth parents, in a single-parent family or in a family with one birth parent and one step-parent. The study also revealed that the abstaining from alcohol percentage among adolescents was greater in families with both birth parents compared to other family types. The study also showed that the more often adolescents see their family member drunk the more they drink themselves. There is no difference in adolescent drinking patterns whether they see their family member drunk once a month or once a week. This study gives an insight on which subgroups of adolescents are at heightened risk of alcohol abuse and that decrease of family member drunkenness may have positive effects on the drinking habits of their children. PMID:25493392

  17. Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle.

    PubMed

    Khayrullin, Andrew; Smith, Lauren; Mistry, Dhwani; Dukes, Amy; Pan, Y Albert; Hamrick, Mark W

    2016-10-21

    Muscle wasting is estimated to affect 40-60% of alcoholics, and is more common than cirrhosis among chronic alcohol abusers. The molecular and cellular mechanisms underlying alcohol-related musculoskeletal dysfunction are, however, poorly understood. Muscle-specific microRNAs (miRNAs) referred to as myoMirs are now known to play a key role in both myogenesis and muscle atrophy. Yet, no studies have investigated a role for myoMirs in alcohol-related skeletal muscle damage. We developed a zebrafish model of chronic ethanol exposure to better define the mechanisms mediating alcohol-induced muscle atrophy. Adult fish maintained at 0.5% ethanol for eight weeks demonstrated significantly reduced muscle fiber cross-sectional area (∼12%, P < 0.05) compared to fish housed in normal water. Zebrafish miRNA microarray revealed marked changes in several miRNAs with ethanol treatment. Importantly, miR-140, a miRNA that shows 100% sequence homology with miR-140 from both mouse and human, is decreased 10-fold in ethanol treated fish. miR-140 targets several members of the Notch signaling pathway such as DNER, JAG1, and Hey1, and PCR data show that both Hey1 and Notch 1 are significantly up-related (3-fold) in muscle of ethanol treated fish. In addition, miR-146a, which targets the Notch antagonist Numb, is elevated in muscle from ethanol-treated fish. Upregulation of Notch signaling suppresses myogenesis and maintains muscle satellite cell quiescence. These data suggest that miRNAs targeting Notch are likely to play important roles in alcohol-related myopathy. Furthermore, zebrafish may serve as a useful model for better understanding the role of microRNAs in alcohol-related tissue damage.

  18. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus.

  19. Assessment of Nanoparticle Exposure in Nanosilica Handling Process: Including Characteristics of Nanoparticles Leaking from a Vacuum Cleaner

    PubMed Central

    KIM, Boowook; KIM, Hyunwook; YU, Il Je

    2013-01-01

    Nanosilica is one of the most widely used nanomaterials across the world. However, their assessment data on the occupational exposure to nanoparticles is insufficient. The present study performed an exposure monitoring in workplace environments where synthetic powders are prepared using fumed nanosilica. Furthermore, after it was observed during exposure monitoring that nanoparticles were emitted through leakage in a vacuum cleaner (even with a HEPA-filter installed in it), the properties of the leaked nanoparticles were also investigated. Workers were exposed to high-concentration nanosilica emitted into the air while pouring it into a container or transferring the container. The use of a vacuum cleaner with a leak (caused by an inadequate sealing) was found to be the origin of nanosilica dispersion in the indoor air. While the particle size of the nanosilica that emitted into the air (during the handling of nanosilica by a worker) was mostly over 100 nm or several microns (µm) due to the coagulation of particles, the size of nanosilica that leaked out of vacuum cleaner was almost similar to the primary size (mode diameter 11.5 nm). Analysis of area samples resulted in 20% (60% in terms of peak concentration) less than the analysis of the personals sample. PMID:24366536

  20. Assessment of nanoparticle exposure in nanosilica handling process: including characteristics of nanoparticles leaking from a vacuum cleaner.

    PubMed

    Kim, Boowook; Kim, Hyunwook; Yu, Il Je

    2014-01-01

    Nanosilica is one of the most widely used nanomaterials across the world. However, their assessment data on the occupational exposure to nanoparticles is insufficient. The present study performed an exposure monitoring in workplace environments where synthetic powders are prepared using fumed nanosilica. Furthermore, after it was observed during exposure monitoring that nanoparticles were emitted through leakage in a vacuum cleaner (even with a HEPA-filter installed in it), the properties of the leaked nanoparticles were also investigated. Workers were exposed to high-concentration nanosilica emitted into the air while pouring it into a container or transferring the container. The use of a vacuum cleaner with a leak (caused by an inadequate sealing) was found to be the origin of nanosilica dispersion in the indoor air. While the particle size of the nanosilica that emitted into the air (during the handling of nanosilica by a worker) was mostly over 100 nm or several microns (µm) due to the coagulation of particles, the size of nanosilica that leaked out of vacuum cleaner was almost similar to the primary size (mode diameter 11.5 nm). Analysis of area samples resulted in 20% (60% in terms of peak concentration) less than the analysis of the personals sample.

  1. A Comparison of Brunt Criteria, the Non Alcoholic Fatty Liver Disease Activity Score (NAS) & a Proposed NAS-including fibrosis as Valid Diagnostic Scores for NASH

    PubMed Central

    Santiago-Rolón, Amarilys; Purcell, Dagmary; Rosado, Kathia; Toro, Doris H.

    2016-01-01

    Objective Non-alcoholic steatohepatitis (NASH) can result in cirrhosis and end stage liver disease. It is of utmost importance to differentiate NASH from simple steatosis. The aim of this study is to determine the prevalence of NASH in Latino veterans with metabolic syndrome and compare histologic grading using Brunt Criteria, the NAFLD activity score (NAS), and a proposed NAS score including fibrosis. Methods Veterans with metabolic syndrome, hepatic steatosis and elevation of ALT/AST who underwent a liver biopsy from 2004-2010 were included in this study. Biopsies were evaluated by a single blinded Hepatopathologist. Steatosis, lobular inflammation, ballooning and fibrosis were graded per specimen. Each biopsy was evaluated using Brunt criteria, NAS and NAS plus fibrosis. Results Sixty patients were included in this study, 88.3% men with a mean age of 50.4 (± 12.8). 50.0% met criteria for NASH according to the Brunt system. When classifying biopsies using NAS, only 30.0% (18/60) had a score ≥5, while when adding fibrosis, the number of patients with a score ≥5 increased to 33 (55.0%). When evaluating the predictive ability of the two scoring systems, we found that NAS including fibrosis had a higher sensitivity than NAS (86.7% vs. 40.0%) and a lower specificity (76.7% vs. 80.0%). Conclusion In our population with metabolic syndrome and altered liver function tests, about 50-55% had steatohepatitis. There were significant differences between the scoring systems. When using NAS-plus-fibrosis more patients were recognized and the sensitivity increased. Further validation studies are required to evaluate this proposed NAS scoring System. PMID:26602577

  2. The Role of Neuropeptide Y (NPY) in Uncontrolled Alcohol Drinking and Relapse Behavior Resulting from Exposure to Stressful Events

    DTIC Science & Technology

    2007-01-01

    et al. 2000; Liu and Weiss 2002; Merlo Pich et al. 1995; Overstreet et al. 2004; Rassnick et al. 1993; Stewart 2004; Valdez et al. 2002). While the...rats. Alcohol 32: 101-11 Koob GF, Heinrichs SC, Pich EM, Menzaghi F, Baldwin H, Miczek K, Britton KT (1993) The role of corticotropin-releasing...Mendleson, M.D. (1972) Drinking patterns during work-contigent and noncontigent alcohol alcohol acquistion. Psychosom Med 34: 139-164 Merlo Pich E

  3. Prenatal exposure of a girl with autism spectrum disorder to 'horsetail' (Equisetum arvense) herbal remedy and alcohol: a case report

    PubMed Central

    2011-01-01

    Introduction Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences are thought to play a causal role. In humans, throughout embryonic and fetal life, brain development is exquisitely susceptible to injury caused by exposure to toxic chemicals present in the environment. Although the use of herbal supplements during pregnancy is relatively common, little information is available on their association with fetal neurodevelopment. This is, to the best of our knowledge, the first report in the literature to associate a new plausible mechanism of neurodevelopmental toxicity with a case of autism spectrum disorder through a vitamin deficiency potentiated by concomitant use of herbal supplements and ethanol exposure. Case presentation We describe the pediatric environmental history of a three-year-old Caucasian girl with an autism spectrum disorder. We utilized her pediatric environmental history to evaluate constitutional, genetic, and environmental factors pertinent to manifestation of neurodevelopment disorders. Both parents reported prenatal exposure to several risk factors of interest. A year prior to conception the mother began a weight loss diet and ingested 1200 mg/day of 'horsetail' (Equisetum arvense) herbal remedies containing thiaminase, an enzyme that with long-term use can lead to vitamin deficiency. The mother reported a significant weight loss during the pregnancy and a deficiency of B-complex vitamins. Thiamine (vitamin B1) deficiency could have been potentiated by the horsetail's thiaminase activity and ethanol exposure during pregnancy. No other risk factors were identified. Conclusions A detailed and careful pediatric environmental history, which includes daily intake, herbal remedies and ethanol exposure, should be obtained from all patients with autism spectrum disorder. Maternal consumption of ethanol and of herbal supplements with suspected or potential toxicity should be

  4. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress.

    PubMed

    Uban, Kristina A; Comeau, Wendy L; Ellis, Linda A; Galea, Liisa A M; Weinberg, Joanne

    2013-10-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine (DA) systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24h following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control

  5. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy; Ellis, Linda A.; Galea, Liisa A. M.; Weinberg, Joanne

    2013-01-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic dopamine activity. However, effects of PAE on the interaction between HPA and dopamine (DA) systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and dopamine systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24 hours following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor (MR) mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared

  6. A State of Double Jeopardy: Impact of Prenatal Alcohol Exposure and Adverse Environments on the Social Communicative Abilities of School-Age Children with Fetal Alcohol Spectrum Disorder

    ERIC Educational Resources Information Center

    Coggins, Truman E.; Timler, Geralyn R.; Olswang, Lesley B.

    2007-01-01

    Purpose: This article is a retrospective examination of environmental risk, language performance, and narrative discourse data from a clinical database of school-age children with fetal alcohol spectrum disorder (FASD). Method: A case-defined diagnostic approach for measuring and reporting the full spectrum of disabilities in children with…

  7. Validation of brief questionnaire measures of sun exposure and skin pigmentation against detailed and objective measures including vitamin D status.

    PubMed

    Cargill, Jessica; Lucas, Robyn M; Gies, Peter; King, Kerryn; Swaminathan, Ashwin; Allen, Martin W; Banks, Emily

    2013-01-01

    Self-reported sun exposure is commonly used in research, but how well this represents actual sun exposure is poorly understood. From February to July 2011, a volunteer sample (n = 47) of older adults (≥45 years) in Canberra, Australia, answered brief questions on time outdoors (weekdays and weekends) and natural skin color. They subsequently maintained a sun diary and wore an ultraviolet radiation (UVR) digital dosimeter for 7 days. Melanin density was estimated using reflectance spectrophotometry; lifetime sun damage was assessed using silicone casts of the back of the hand; and serum 25-hydroxyvitamin D (25(OH)D) concentration was assayed. Questionnaire-reported time outdoors correlated significantly with diary-recorded time outdoors (Spearman correlation r(s) = 0.66; 95% CI 0.46, 0.80; P < 0.001) and UVR dosimeter dose (r(s ) = 0.46; 95% CI 0.18, 0.68; P = 0.003), but not 25(OH)D concentration (r(s) = 0.24; 95% CI -0.05, 0.50; P = 0.10). Questionnaire-reported untanned skin color correlated significantly with measured melanin density at the inner upper arm (r(s) = 0.49; 95% CI 0.24, 0.68; P < 0.001). In a multiple linear regression model, statistically significant predictors of 25(OH)D concentration were self-reported frequency of physical activity, skin color and recent osteoporosis treatment (R(2) = 0.54). In this study, brief questionnaire items provided valid rankings of sun exposure and skin color, and enabled the development of a predictive model for 25(OH)D concentration.

  8. Low self–esteem in women with eating disorders and alcohol abuse as a psycho–social factor to be included in their psychotherapeutic approach

    PubMed Central

    2010-01-01

    Author have analyzed the psycho–social peculiarities of the women from Romania who are affected by eating disorders and alcohol excessive consumption, and studied the manner of the link between these disease and the psycho–sexual. 120 participants at the study (Oltenia district) were divided into 2 groups: 60 healthy women, 30 with eating disorders and 30 alcohol dependent women. In all subjects were applied the following tests: Scale for compulsive appetite (SCA) and Scale of interest for own weight, both for eating disorders, CAGE questionnaire for alcohol dependence and two scales for determining: the gender–role ambivalence (O'Neil and Caroll Scale) and the masculinity and feminity index (A. Chelcea). The results obtained in both lots of Romanian women with pathologic behavior (food and/or alcohol consumption) have indicated a low psycho–sexual identity versus control group but no correlation with masculinity/feminity index. PMID:21254749

  9. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  10. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish

    PubMed Central

    Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

  11. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    PubMed

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  12. Neurobiology of alcohol dependence: focus on motivational mechanisms.

    PubMed

    Gilpin, Nicholas W; Koob, George F

    2008-01-01

    Alcoholism is a debilitating disorder for the individual and very costly for society. A major goal of alcohol research is to understand the neural underpinnings associated with the transition from alcohol use to alcohol dependence. Positive reinforcement is important in the early stages of alcohol use and abuse. Negative reinforcement can be important early in alcohol use by people self-medicating coexisting affective disorders, but its role likely increases following the transition to dependence. Chronic exposure to alcohol induces changes in neural circuits that control motivational processes, including arousal, reward, and stress. These changes affect systems utilizing the signaling molecules dopamine, opioid peptides, γ-aminobutyric acid, glutamate, and serotonin, as well as systems modulating the brain's stress response. These neuroadaptations produce changes in sensitivity to alcohol's effects following repeated exposure (i.e., sensitization and tolerance) and a withdrawal state following discontinuation of alcohol use. Chronic alcohol exposure also results in persistent neural deficits, some of which may fully recover following extended periods of abstinence. However, the organism remains susceptible to relapse, even after long periods of abstinence. Recent research focusing on brain arousal, reward, and stress systems is accelerating our understanding of the components of alcohol dependence and contributing to the development of new treatment strategies.

  13. Detailed diesel exhaust characteristics including particle surface area and lung deposited dose for better understanding of health effects in human chamber exposure studies

    NASA Astrophysics Data System (ADS)

    Wierzbicka, Aneta; Nilsson, Patrik T.; Rissler, Jenny; Sallsten, Gerd; Xu, Yiyi; Pagels, Joakim H.; Albin, Maria; Österberg, Kai; Strandberg, Bo; Eriksson, Axel; Bohgard, Mats; Bergemalm-Rynell, Kerstin; Gudmundsson, Anders

    2014-04-01

    Several diesel exhaust (DE) characteristics, comprising both particle and gas phase, recognized as important when linking with health effects, are not reported in human chamber exposure studies. In order to understand effects of DE on humans there is a need for better characterization of DE when performing exposure studies. The aim of this study was to determine and quantify detailed DE characteristics during human chamber exposure. Additionally to compare to reported DE properties in conducted human exposures. A wide battery of particle and gas phase measurement techniques have been used to provide detailed DE characteristics including the DE particles (DEP) surface area, fraction and dose deposited in the lungs, chemical composition of both particle and gas phase such as NO, NO2, CO, CO2, volatile organic compounds (including aldehydes, benzene, toluene) and polycyclic aromatic hydrocarbons (PAHs). Eyes, nose and throat irritation effects were determined. Exposure conditions with PM1 (<1 μm) mass concentration 280 μg m-3, number concentration 4 × 105 cm-3 and elemental to total carbon fraction of 82% were generated from a diesel vehicle at idling. When estimating the lung deposited dose it was found that using the size dependent effective density (in contrast to assuming unity density) reduced the estimated respiratory dose by 132% by mass. Accounting for agglomerated structure of DEP prevented underestimation of lung deposited dose by surface area by 37% in comparison to assuming spherical particles. Comparison of DE characteristics reported in conducted chamber exposures showed that DE properties vary to a great extent under the same DEP mass concentration and engine load. This highlights the need for detailed and standardized approach for measuring and reporting of DE properties. Eyes irritation effects, most probably caused by aldehydes in the gas phase, as well as nose irritation were observed at exposure levels below current occupational exposure limit

  14. OVERVIEW OF EXPOSURE TO DIOXIN-LIKE COMPOUNDS AND PCBS ON DEVELOPMENTAL, IMMUNOSUPPRESSIVE, AND HORMONE-RELATED EFFECTS IN MAMMALS, INCLUDING HUMANS

    EPA Science Inventory

    Exposure to TCDD and related compounds leads to a plethora of effects in multiple species, tissues and stages of development. The response spectrum ranges from simple biochemical alterations to overtly toxic responses, including lethality. Many of the effects of TCDD and relate...

  15. Genetic and epigenetic insights into fetal alcohol spectrum disorders

    PubMed Central

    2010-01-01

    The magnitude of the detrimental effects following in utero alcohol exposure, including fetal alcohol syndrome and other fetal alcohol spectrum disorders (FASD), is globally underestimated. The effects include irreversible cognitive and behavioral disabilities as a result of abnormal brain development, pre- and postnatal growth retardation and facial dysmorphism. Parental alcohol exposure and its effect on offspring has been recognized for centuries, but only recently have we begun to gain molecular insight into the mechanisms involved in alcohol teratogenesis. Genetic attributes (susceptibility and protective alleles) of the mother and the fetus contribute to the risk of developing FASD and specific additional environmental conditions, including malnutrition, have an important role. The severity of FASD depends on the level of alcohol exposure, the developmental stage at which exposure occurs and the nature of the exposure (chronic or acute), and although the most vulnerable period is during the first trimester, damage can occur throughout gestation. Preconception alcohol exposure can also have a detrimental effect on the offspring. Several developmental pathways are affected in FASD, including nervous system development, growth and remodeling of tissues, as well as metabolic pathways that regulate glucocorticoid signaling and balanced levels of retinol, insulin and nitric oxide. A body of knowledge has accumulated to support the role of environmentally induced epigenetic remodeling during gametogenesis and after conception as a key mechanism for the teratogenic effects of FASD that persist into adulthood. Transgenerational effects are likely to contribute to the global burden of alcohol-related disease. FASD results in lifelong disability and preventative programs should include both maternal alcohol abstention and preconception alcohol avoidance. PMID:20423530

  16. An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

    PubMed Central

    2012-01-01

    Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696 PMID:22676069

  17. Exposure to perfluorinated compounds in Catalonia, Spain, through consumption of various raw and cooked foodstuffs, including packaged food.

    PubMed

    Jogsten, Ingrid Ericson; Perelló, Gemma; Llebaria, Xavier; Bigas, Esther; Martí-Cid, Roser; Kärrman, Anna; Domingo, José L

    2009-07-01

    In this study, the role that some food processing and packaging might play as a source of perfluorinated compounds (PFCs) through the diet was assessed. The levels of PFCs were determined in composite samples of veal steak (raw, grilled, and fried), pork loin (raw, grilled, and fried), chicken breast (raw, grilled, and fried), black pudding (uncooked), liver lamb (raw), marinated salmon (home-made and packaged), lettuce (fresh and packaged), pate of pork liver, foie gras of duck, frankfurt, sausages, chicken nuggets (fried), and common salt. Among the 11 PFCs analyzed, only PFHxS, PFOS, PFHxA, and PFOA were detected in at least one composite sample, while the levels of the remaining PFCs (PFBuS, PFHpA, PFNA, PFDA, PFUnDA, and PFDoDA) were under their respective detection limits. PFOS was the compound most frequently detected, being found in 8 of the 20 food items analyzed, while PFHxA was detected in samples of raw veal, chicken nuggets, frankfurt, sausages, and packaged lettuce. According to the results of the present study, it is not sufficiently clear if cooking with non-stick cookware, or packaging some foods, could contribute to a higher human exposure to PFCs.

  18. The developmental psychopathology of alcohol use and alcohol disorders: Research achievements and future directions

    PubMed Central

    CHASSIN, LAURIE; SHER, KENNETH J.; HUSSONG, ANDREA; CURRAN, PATRICK

    2013-01-01

    The last 25 years have seen significant advances in our conceptualization of alcohol use and alcohol use disorders within a developmental framework, along with advances in our empirical understanding that have been potentiated by advances in quantitative methods. These include advances in understanding the heterogeneity of trajectories of alcohol outcomes; new insights about early childhood antecedents, and adolescence and emerging adulthood as important developmental periods for alcohol outcomes; a more nuanced understanding of the influences of developmental transitions, and their timing and contexts; a greater appreciation for the importance of considering multiple levels of analysis (including an increasing number of genetically informative studies); a continuing focus on studying multiple pathways underlying alcohol outcomes; and an increasing focus on studying the effects of alcohol exposure on future development. The current paper reviews these advances and suggests directions for future study. PMID:24342856

  19. Physiologically based pharmacokinetic model for ethyl tertiary-butyl ether and tertiary-butyl alcohol in rats: Contribution of binding to α2u-globulin in male rats and high-exposure nonlinear kinetics to toxicity and cancer outcomes.

    PubMed

    Borghoff, Susan J; Ring, Caroline; Banton, Marcy I; Leavens, Teresa L

    2017-05-01

    In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat-specific protein α2u-globulin, which plays a role in the ETBE and TBA kidney response observed in male rats. Metabolism of ETBE and TBA was described as a single, saturable pathway in the liver. The model predicted similar kidney AUC0-∞ for TBA for various exposure scenarios from ETBE and TBA cancer bioassays, supporting a male-rat-specific mode of action for TBA-induced kidney tumors. The model also predicted nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm, based on blood AUC0-∞ for ETBE and TBA. The shift from linear to nonlinear kinetics at exposure concentrations below the concentration associated with liver tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates under nonlinear kinetics following chronic exposure and is not relevant for assessing human risk. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

  20. Television: Alcohol's Vast Adland.

    ERIC Educational Resources Information Center

    2002

    Concern about how much television alcohol advertising reaches underage youth and how the advertising influences their attitudes and decisions about alcohol use has been widespread for many years. Lacking in the policy debate has been solid, reliable information about the extent of youth exposure to television alcohol advertising. To address this…

  1. 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.

    PubMed

    Topper, Lauren A; Valenzuela, C Fernando

    2014-12-01

    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.

  2. PERFLUOROOCTANOIC ACID AND PERFLUORONONANOIC ACID IN FETAL AND NEONATAL MICE FOLLOWING IN UTERO EXPOSURE TO 8-2 FLUOROTELOMER ALCOHOL

    EPA Science Inventory

    8-2 fluorotelomer alcohol (FTOH) and its metabolites, perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), are developmental toxicants, but metabolism and distribution during pregnancy is not known. To examine this, timed-pregnant mice received a single gavage dose (...

  3. Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats

    PubMed Central

    Uban, Kristina A.; Sliwowska, Joanna H.; Lieblich, Stephanie; Ellis, Linda A.; Yu, Wayne L.; Weinberg, Joanne; Galea, Liisa A. M.

    2010-01-01

    Prenatal alcohol exposure (PAE) alters adult neurogenesis and the neurogenic response to stress in male rats. As the effects of stress on neurogenesis are sexually dimorphic, the present study investigated the effects of PAE on adult hippocampal neurogenesis under both non-stressed and stressed conditions in female rats. Pregnant females were assigned to one of three prenatal treatments: 1) Alcohol (PAE) - liquid alcohol (ethanol) diet ad libitum (36% ethanol-derived calories); 2) Pair-fed - isocaloric liquid diet, with maltose-dextrin substituted for ethanol, in the amount consumed by a PAE partner (g/kg body wt/day of gestation); and 3) Control - lab chow ad libitum. Female offspring were assigned to either non-stressed (undisturbed) or stressed (repeated restraint stress for 9 days) conditions. On day 10, all rats were injected with bromodeoxyuridine (BrdU) and perfused either 24 hours (cell proliferation) or 3 weeks (cell survival) later. We found that PAE did not significantly alter cell proliferation or survival, whereas females from the Pair-fed condition exhibited elevated levels of cell survival compared to Control females. Importantly, however, the proportion of both new neurons and new glial cells in the hippocampal dentate gyrus was reduced in PAE compared to Control females. Exposure to stress did not alter neurogenesis in any of the prenatal treatment groups. In summary, compared to females from the Control condition, prenatal dietary restriction enhanced the survival of new neurons, whereas PAE altered the differentiation of newly produced cells in the adult dentate gyrus. Alterations in hippocampal neurogenesis following PAE may contribute to learning and memory deficits seen in individuals with fetal alcohol spectrum disorders. PMID:20736015

  4. Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats.

    PubMed

    Uban, Kristina A; Sliwowska, Joanna H; Lieblich, Stephanie; Ellis, Linda A; Yu, Wayne K; Weinberg, Joanne; Galea, Liisa A M

    2010-11-01

    Prenatal alcohol exposure (PAE) alters adult neurogenesis and the neurogenic response to stress in male rats. As the effects of stress on neurogenesis are sexually dimorphic, the present study investigated the effects of PAE on adult hippocampal neurogenesis under both nonstressed and stressed conditions in female rats. Pregnant females were assigned to one of three prenatal treatments: (1) alcohol (PAE)-liquid alcohol (ethanol) diet ad libitum (36% ethanol-derived calories); (2) pair-fed-isocaloric liquid diet, with maltose-dextrin substituted for ethanol, in the amount consumed by a PAE partner (g/kg body wt/day of gestation); and (3) control-lab chow ad libitum. Female offspring were assigned to either nonstressed (undisturbed) or stressed (repeated restraint stress for 9 days) conditions. On day 10, all rats were injected with bromodeoxyuridine (BrdU) and perfused either 24 hours (cell proliferation) or 3 weeks (cell survival) later. We found that PAE did not significantly alter cell proliferation or survival, whereas females from the pair-fed condition exhibited elevated levels of cell survival compared to control females. Importantly, however, the proportion of both new neurons and new glial cells in the hippocampal dentate gyrus was reduced in PAE compared to control females. Exposure to stress did not alter neurogenesis in any of the prenatal treatment groups. In summary, compared to females from the control condition, prenatal dietary restriction enhanced the survival of new neurons, whereas PAE altered the differentiation of newly produced cells in the adult dentate gyrus. Alterations in hippocampal neurogenesis following PAE may contribute to learning and memory deficits seen in individuals with fetal alcohol spectrum disorders.

  5. Exposure to cold and draught, alcohol consumption, and the NS-phenotype are associated with chronic bronchitis: an epidemiological investigation of 3387 men aged 53-75 years: the Copenhagen Male Study

    PubMed Central

    Suadicani, P; Hein, H; Meyer, H; Gyntelberg, F

    2001-01-01

    OBJECTIVES—This study was performed to estimate the strength of association between chronic bronchitis and lifetime exposure to occupational factors, current lifestyle, and the NS-phenotype in the MNS blood group among middle aged and elderly men.
METHODS—The study was carried out within the frameworks of the Copenhagen Male Study. Of 3387 men 3331 men with a mean age of 63 (range 53-75) years could be classified by prevalence of chronic bronchitis. As well as the completion of a large questionnaire on health, lifestyle, and working conditions, all participants had a thorough examination, including measurements of height and weight and blood pressure and a venous blood sample was taken for the measurement of serum cotinine and MNS typing; 16.5% of the men had the NS-phenotype. Chronic bronchitis was defined as cough and phlegm lasting 3 months or more for at least 2 years; 14.6% had chronic bronchitis.
RESULTS—Smoking and smoke inhalation were the factors most strongly associated with prevalence of chronic bronchitis. There were three major new findings: (a) long term (>5 years) occupational exposure to cold and draught was associated with a significantly increased prevalence of chronic bronchitis; compared with others, and adjusted for confounders, the odds ratio (OR) with 95% confidence interval (95% CI) was 1.4 (1.1 to 1.7), p=0.004; (b) a significant J shaped association existed between alcohol use and bronchitis, p<0.001, with the lowest prevalence found among moderate users; (c) a significant gene by environment association existed between smoking and the NS-phenotype in the MNS blood group; only among smokers was the NS-phenotype associated with a significantly decreased risk of chronic bronchitis, OR 0.67 (0.47-0.97), p=0.02. Other well known associations between dust, fumes, and even exposure to solvents and bronchitis were confirmed.
CONCLUSION—The results emphasise the multifactorial nature of chronic bronchitis, and show some

  6. Effects of Early Postnatal Alcohol Exposure on the Developing Retinogeniculate Projections in C57BL/6 Mice

    PubMed Central

    Dursun, İlknur; Jakubowska-Doğru, Ewa; Birsen, Elibol-Can; van der List, Deborah; Chapman, Barbara; Qi, Lihong; Berman, Robert F.

    2013-01-01

    Previous studies on the adverse effects of perinatal exposure to ethanol on the developing visual system mainly focused on retinal and optic nerve morphology. The aim of the present study was to investigate whether earlier reported retinal and optic nerve changes are accompanied by anomalies in eye-specific fiber segregation in the dorsal lateral geniculate nucleus (dLGN). C57BL/6 mice pups were exposed to ethanol by intragastric intubation at either 3 or 4 g/kg from postnatal days (PD) 3-10, the third trimester equivalent to human gestation. Control (C) and intubation control (IC) groups not exposed to ethanol were included. On PD9 retinogeniculate projections, were labeled by intraocular microinjections of cholera toxin-β (CTB) either conjugated to Alexa 488 (green) or 594 (red) administrated to the left and right eye, respectively. Pups were sacrificed 24 h after the last CTB injection. The results showed that ethanol exposure decreased the total number of dLGN neurons and significantly reduced the total dLGN projection as well as the contralateral and ipsilateral projection areas. PMID:23402901

  7. Vapor inhalation of alcohol in rats.

    PubMed

    Gilpin, Nicholas W; Richardson, Heather N; Cole, Maury; Koob, George F

    2008-07-01

    Alcohol dependence constitutes a neuroadaptive state critical for understanding alcoholism, and various methods have been utilized to induce alcohol dependence in animals, one of which is alcohol vapor exposure. Alcohol vapor inhalation provides certain advantages over other chronic alcohol exposure procedures that share the ultimate goal of producing alcohol dependence in rats. Chronic alcohol vapor inhalation allows the experimenter to control the dose, duration, and pattern of alcohol exposure. Also, this procedure facilitates testing of somatic and motivational aspects of alcohol dependence. Chronic exposure to alcohol vapor produces increases in alcohol-drinking behavior, increases in anxiety-like behavior, and reward deficits in rats. Alcohol vapor inhalation as a laboratory protocol is flexible, and the parameters of this procedure can be adjusted to accommodate the specific aims of different experiments. This unit describes the options available to investigators using this procedure for dependence induction, when different options are more or less appropriate, and the implications of each.

  8. Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors

    PubMed Central

    Keyes, Katherine M.; Hatzenbuehler, Mark L.; Hasin, Deborah S.

    2013-01-01

    Background Exposure to stress is potentially important in the pathway to alcohol use and alcohol use disorders. Stressors occur at multiple time points across the life course, with varying degrees of chronicity and severity. Method We review evidence from epidemiologic studies on the relationship between four different stressors (fateful/catastrophic events, child maltreatment, common adult stressful life events in interpersonal, occupational, financial, and legal domains, and minority stress) and alcohol consumption and alcohol use disorders. Results Studies generally demonstrate an increase in alcohol consumption in response to exposure to terrorism or other disasters. Research has demonstrated little increase in incident alcohol use disorders, but individuals with a history of alcohol use disorders are more likely to report drinking to cope with the traumatic event. Childhood maltreatment is a consistent risk factor for early onset of drinking in adolescence and adult alcohol use disorders, and accumulating evidence suggests that specific polymorphisms may interact with child maltreatment to increase risk for alcohol consumption and disorder. Stressful life events such as divorce and job loss increase the risk of alcohol disorders, but epidemiologic consensus on the specificity of these associations across gender has not been reached. Finally, both perceptions of discrimination and objective indicators of discrimination are associated with alcohol use and alcohol use disorders among racial/ethnic and sexual minorities. Conclusion Taken together, these literatures demonstrate that exposure to stress is an important component in individual differences in risk for alcohol consumption and alcohol use disorders. However, many areas of this research remain to be studied, including greater attention to the role of various stressors in the course of alcohol use disorders and potential risk moderators when individuals are exposed to stressors. PMID:21373787

  9. Glutamatergic targets for new alcohol medications

    PubMed Central

    Spanagel, Rainer; Krystal, John H.

    2013-01-01

    Rationale An increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol’s intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism. Objectives We discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters. Results Chronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol. Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new

  10. Apollo MEED mycology revisited and reviewed, including the Trichophyton terrestre keratinophilic growth at splashdown and 23 years after exposure to space parameters.

    PubMed

    Volz, P A; Long, J D; Veselenak, J M

    1995-01-01

    Keratinophilic Trichophyton terrestre conidia were exposed to selected parameters of space flight including 254, 280 and 300 nm UV light, full light and total darkness of space. Phenotypic isolates were grown on human hair collected from one source at years 1 and 23 after splashdown. The patterns of