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Sample records for alcohol exposure model

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

    PubMed Central

    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. PMID:25910266

  2. Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration

    PubMed Central

    Marshall, Simon Alex; Geil, Chelsea Rhea; Nixon, Kimberly

    2016-01-01

    Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity. PMID:27240410

  3. Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration.

    PubMed

    Marshall, Simon Alex; Geil, Chelsea Rhea; Nixon, Kimberly

    2016-01-01

    Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity. PMID:27240410

  4. Fetal Alcohol Exposure

    MedlinePlus

    ... childhood and last a lifetime. The most profound effects of prenatal alcohol exposure are brain damage and the resulting impairments ... these individuals. Risk Factors 9 The severity of alcohol’s effects on a fetus primarily depends on the following: » ...

  5. Exposure to Alcohol Advertisements and Teenage Alcohol-Related Problems

    PubMed Central

    Dent, Clyde W.; Stacy, Alan W.

    2013-01-01

    OBJECTIVE: This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. METHODS: A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents’ jobs, and parents’ education. RESULTS: Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. CONCLUSIONS: Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence. PMID:23359585

  6. Differential expression of astrocytic connexins in a mouse model of prenatal alcohol exposure.

    PubMed

    Ramani, Meera; Mylvaganam, Shanthini; Krawczyk, Michal; Wang, Lihua; Zoidl, Christiane; Brien, James; Reynolds, James N; Kapur, Bhushan; Poulter, Michael O; Zoidl, Georg; Carlen, Peter L

    2016-07-01

    Maternal alcohol consumption during gestation can cause serious injury to the fetus, and may result in a range of physiological and behavioral impairments, including increased seizure susceptibility, that are collectively termed fetal alcohol spectrum disorder (FASD). The cellular mechanisms underlying increased seizure susceptibility in FASD are not well understood, but could involve altered excitatory coupling of neuronal populations mediated by gap junction proteins. We utilized a mouse model of the prenatal alcohol exposure (PAE) to study the expression pattern of connexin (Cx) major components of gap junctions, and pannexin proteins, which form membrane channels, in the brain of 2-3weeks old PAE and control postnatal offspring. PAE during the first trimester-equivalent period of pregnancy in mice resulted in significant up-regulation of Cx30 mRNA and Cx30 total protein in the hippocampus of PAE animals compared to age-matched controls. Surface level expression of both dimeric and monomeric Cx30 were also found to be significantly up-regulated in both hippocampus and cerebral cortex of PAE animals compared to age-matched controls. On the membrane surface, the fast migrating form of Cx43 was found to be up-regulated in the hippocampus of PAE mice. However, we did not see any up-regulation of the phosphorylated forms of Cx43 on the membrane surface. These results indicate that the expression and processing of astrocytic connexins (Cx30, Cx43) are up-regulated in the brain of PAE offspring, and these changes could play a role in the cerebral hyperexcitability observed in these animals. PMID:26951949

  7. Ethanol Exposure Alters Protein Expression in a Mouse Model of Fetal Alcohol Spectrum Disorders

    PubMed Central

    Mason, Stephen; Anthony, Bruce; Lai, Xianyin; Ringham, Heather N.; Wang, Mu; Witzmann, Frank A.; You, Jin-Sam; Zhou, Feng C.

    2012-01-01

    Alcohol exposure during development can result in variable growth retardation and facial dysmorphology known as fetal alcohol spectrum disorders. Although the mechanisms underlying the disorder are not fully understood, recent progress has been made that alcohol induces aberrant changes in gene expression and in the epigenome of embryos. To inform the gene and epigenetic changes in alcohol-induced teratology, we used whole-embryo culture to identify the alcohol-signature protein profile of neurulating C6 mice. Alcohol-treated and control cultures were homogenized, isoelectrically focused, and loaded for 2D gel electrophoresis. Stained gels were cross matched with analytical software. We identified 40 differentially expressed protein spots (P < 0.01), and 9 spots were selected for LC/MS-MS identification. Misregulated proteins include serotransferrin, triosephosphate isomerase and ubiquitin-conjugating enzyme E2 N. Misregulation of serotransferrin and triosephosphate isomerase was confirmed with immunologic analysis. Alteration of proteins with roles in cellular function, cell cycle, and the ubiquitin-proteasome pathway was induced by alcohol. Several misregulated proteins interact with effectors of the NF-κB and Myc transcription factor cascades. Using a whole-embryo culture, we have identified misregulated proteins known to be involved in nervous system development and function. PMID:22745907

  8. 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

  9. Media Exposure and Marijuana and Alcohol Use Among Adolescents

    PubMed Central

    PRIMACK, BRIAN A.; KRAEMER, KEVIN L.; FINE, MICHAEL J.; DALTON, MADELINE A.

    2010-01-01

    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. PMID:19306219

  10. 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. PMID:19306219

  11. 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. PMID:26992695

  12. 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…

  13. The chick embryo as a model for the effects of prenatal exposure to alcohol on craniofacial development.

    PubMed

    Kiecker, Clemens

    2016-07-15

    Prenatal exposure to ethanol results in fetal alcohol spectrum disorder (FASD), a syndrome characterised by a broad range of clinical manifestations including craniofacial dysmorphologies and neurological defects. The characterisation of the mechanisms by which ethanol exerts its teratogenic effects is difficult due to the pleiotropic nature of its actions. Different experimental model systems have been employed to investigate the aetiology of FASD. Here, I will review studies using these different model organisms that have helped to elucidate how ethanol causes the craniofacial abnormalities characteristic of FASD. In these studies, ethanol was found to impair the prechordal plate-an important embryonic signalling centre-during gastrulation and to negatively affect the induction, migration and survival of the neural crest, a cell population that generates the cartilage and most of the bones of the skull. At the cellular level, ethanol appears to inhibit Sonic hedgehog signalling, alter levels of retionoic acid activity, trigger a Ca(2+)-CamKII-dependent pathway that antagonises WNT signalling, affect cytoskeletal dynamics and increase oxidative stress. Embryos of the domestic chick Gallus gallus domesticus have played a central role in developing a working model for the effects of ethanol on craniofacial development because they are easily accessible and because key steps in craniofacial development are particularly well established in the avian embryo. I will finish this review by highlighting some potential future avenues of fetal alcohol research. PMID:26777098

  14. Socioeconomic Determinants of Exposure to Alcohol Outlets

    PubMed Central

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

    2015-01-01

    Objective: Alcohol outlets tend to be located in lower income areas, exposing lower income populations to excess risks associated with alcohol sales through these establishments. The objective of this study was to test two hypotheses about the etiology of these differential exposures based on theories of the economic geography of retail markets: (a) outlets will locate within or near areas of high alcohol demand, and (b) outlets will be excluded from areas with high land and structure rents. Method: Data from the 2010 National Drug Strategy Household Survey were used to develop a surrogate for alcohol demand (i.e., market potential) at two census geographies for the city of Melbourne, Australia. Bayesian conditional autoregressive Poisson models estimated multilevel spatial relationships between counts of bars, restaurants, and off-premise outlets and market potential, income, and zoning ordinances (Level 1: n = 8,914). Results: Market potentials were greatest in areas with larger older age, male, English-speaking, high-income populations. Independent of zoning characteristics, greater numbers of outlets appeared in areas with greater market potentials and the immediately surrounding areas. Greater income excluded outlets in local and surrounding areas. Conclusions: These findings are consistent with the hypothesis that alcohol outlets are located in areas with high demand and are excluded from high-income areas. These processes appear to take place at relatively small geographic scales, encourage the concentration of outlets in specific low-income areas, and represent a very general economic process likely to take place in communities throughout the world. PMID:25978830

  15. A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.

    PubMed

    Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J

    2016-01-01

    Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID:27268733

  16. Exposure to Alcohol Outlets in Rural Towns

    PubMed Central

    Morrison, Chris

    2014-01-01

    Background Lower income populations are exposed to excess risks related to the presence of greater concentrations of alcohol outlets in their communities. Theory from economic geography suggests this is due to dynamic processes that shape urban retail markets (as outlets are attracted to areas of higher population density due to the increased demand but are excluded from higher income areas due to land and structure rents). This mechanism may explain increased exposure to alcohol outlets for lower income populations in rural areas. This study tests the hypothesis that the distribution of outlets between rural towns will reflect these market dynamics, such that outlets are concentrated in towns with (i) greater resident and temporary populations, (ii) lower income, and (iii) are adjacent to towns with higher income. Method Bayesian conditional autoregressive Poisson models examined counts of bars, restaurants and off-premise outlets within 353 discrete towns of rural Victoria, Australia (mean population = 4,326.0, SD = 15,754.1). Independent variables were each town’s total resident population, net changes to population (due to commuter flow, visitors, and the flow of local residents to other towns (spatial interaction)), and income for the local and adjacent towns. Results Lower local income and increased income in adjacent towns were associated with more outlets of all types. Greater resident populations and greater net population due to commuters also predicted greater numbers of all outlets. Bars and restaurants were positively related to greater net population due to visitors, and negatively related to spatial interaction. Conclusions The economic geographic processes that lead to greater concentrations of alcohol outlets in lower income areas are common to all retail markets. Lower income populations are exposed to increased risk associated with the presence of additional outlets that service demand from non-residents. In rural areas these processes appear

  17. Prenatal Alcohol Exposure and Cellular Differentiation

    PubMed Central

    Veazey, Kylee J.; Muller, Daria; Golding, Michael C.

    2013-01-01

    Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell–cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell’s identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes—the Polycomb and Trithorax proteins—are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder. PMID:24313167

  18. Neuroimmune Function and the Consequences of Alcohol Exposure

    PubMed Central

    Crews, Fulton T.; Sarkar, Dipak K.; Qin, Liya; Zou, Jian; Boyadjieva, Nadka; Vetreno, Ryan P.

    2015-01-01

    Induction of neuroimmune genes by binge drinking increases neuronal excitability and oxidative stress, contributing to the neurobiology of alcohol dependence and causing neurodegeneration. Ethanol exposure activates signaling pathways featuring high-mobility group box 1 and Toll-like receptor 4 (TLR4), resulting in induction of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells, which regulates expression of several cytokine genes involved in innate immunity, and its target genes. This leads to persistent neuroimmune responses to ethanol that stimulate TLRs and/or certain glutamate receptors (i.e., N-methyl-d-aspartate receptors). Alcohol also alters stress responses, causing elevation of peripheral cytokines, which further sensitize neuroimmune responses to ethanol. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of alcohol abuse have identified significant frontal cortical degeneration and loss of hippocampal neurogenesis, consistent with neuroimmune activation pathology contributing to these alcohol-induced, long-lasting changes in the brain. These alcohol-induced long-lasting increases in brain neuroimmune-gene expression also may contribute to the neurobiology of alcohol use disorder. PMID:26695754

  19. Alcohol Exposure In Utero and Child Academic Achievement*

    PubMed Central

    von Hinke Kessler Scholder, Stephanie; Wehby, George L; Lewis, Sarah; Zuccolo, Luisa

    2014-01-01

    We examine the effect of prenatal alcohol exposure on child academic achievement. We use a genetic variant in the maternal alcohol-metabolism gene ADH1B to instrument for alcohol exposure, whilst controlling for the child's genotype on the same variant. We show that the instrument is unrelated to an extensive range of parental characteristics and behaviour. OLS regressions suggest an ambiguous association between alcohol exposure and attainment but there is a strong social gradient in drinking, with mothers in higher socio-economic groups more likely to drink. In contrast to the OLS, the IV estimates show clear negative effects of prenatal alcohol exposure. PMID:25431500

  20. 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…

  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. 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

  3. The Effects of Prenatal Alcohol Exposure on Behavior: Rodent and Primate Studies

    PubMed Central

    Moore, Colleen F.; Adkins, Miriam M.

    2014-01-01

    The use of alcohol by women during pregnancy is a continuing problem. In this review the behavioral effects of prenatal alcohol from animal models are described and related to studies of children and adults with FASD. Studies with monkeys and rodents show that prenatal alcohol exposure adversely affects neonatal orienting, attention and motor maturity, as well as activity level, executive function, response inhibition, and sensory processing later in life. The primate moderate dose behavioral findings fill an important gap between human correlational data and rodent mechanistic research. These animal findings are directly translatable to human findings. Moreover, primate studies that manipulated prenatal alcohol exposure and prenatal stress independently show that prenatal stress exacerbates prenatal alcohol-induced behavioral impairments, underscoring the need to consider stress-induced effects in fetal alcohol research. Studies in rodents and primates show long-term effects of prenatal and developmental alcohol exposure on dopamine system functioning, which could underpin the behavioral effects. PMID:21499982

  4. ADOLESCENT ALCOHOL EXPOSURE: ARE THERE SEPARABLE VULNERABLE PERIODS WITHIN ADOLESCENCE?

    PubMed Central

    Spear, Linda Patia

    2015-01-01

    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

  5. 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

  6. 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…

  7. 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

  8. Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors.

    PubMed

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

    2015-09-01

    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

  9. Evaluation of Furfuryl Alcohol Sensitization Potential Following Dermal and Pulmonary Exposure: Enhancement of Airway Responsiveness

    PubMed Central

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

    2015-01-01

    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. PMID:22003193

  10. Effects of Prenatal Alcohol Exposure and ADHD on Adaptive Functioning

    PubMed Central

    Ware, Ashley L.; Glass, Leila; Crocker, Nicole; Deweese, Benjamin N.; Coles, Claire D.; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2014-01-01

    Background Heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) are associated with adaptive behavior deficits. The present study examined the interaction between these two factors on parent ratings of adaptive behavior. Methods As part of a multisite study, primary caregivers of 317 children (8–16y, M=12.38) completed the Vineland Adaptive Behavior Scales-II (VABS-II). Four groups of subjects were included: children with prenatal alcohol exposure with (AE+, n = 82) and without ADHD (AE−, n = 34), children with ADHD (ADHD, n = 71), and control children (CON, n = 130). VABS-II domain scores (Communication, Daily Living Skills, Socialization) were examined using separate 2 (Alcohol Exposure [AE]) × 2 (ADHD diagnosis) between-subjects ANCOVAs. Results There were significant main effects of AE (p < .001) and ADHD (p < .001) on all VABS-II domains; alcohol-exposed children had lower scores than children without prenatal alcohol exposure and children with ADHD had lower scores than those without ADHD. There was a significant AE × ADHD interaction effect for Communication [F (1, 308) = 7.49, p = .007, partial η2 =.024], but not Daily Living Skills or Socialization domains (ps > .27). Follow up analyses in the Communication domain indicated the effects of ADHD were stronger in comparison subjects (ADHD vs. CON) than exposed subjects (AE+ vs. AE−) and the effects of alcohol exposure were stronger in subjects without ADHD (AE− vs. CON) than in subjects with ADHD (AE+ vs. ADHD). Conclusion As found previously, both prenatal alcohol exposure and ADHD increase adaptive behavior deficits in all domains. However, these two factors interact to cause the greatest impairment in children with both prenatal alcohol exposure and ADHD for communication abilities. These results further demonstrate the deleterious effects of prenatal alcohol exposure and broadens our understanding of how ADHD exacerbates behavioral outcomes in this population

  11. 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

  12. 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

  13. Prenatal Alcohol Exposure and Infant Information Processing Ability.

    ERIC Educational Resources Information Center

    Jacobson, Sandra W.; And Others

    1993-01-01

    A total of 403 black, inner-city infants born to women recruited prenatally on basis of their alcohol consumption during pregnancy were assessed on a battery of tests focusing on information processing and complexity of play. Increased prenatal alcohol exposure was associated with longer fixation duration, a result indicative of less efficient…

  14. Prenatal Alcohol Exposure and the Developing Immune System

    PubMed Central

    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. PMID:26695750

  15. 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

  16. Strengthening the Case: Prenatal Alcohol Exposure is Associated with Increased Risk for Conduct Disorder

    PubMed Central

    Disney, Elizabeth R.; Iacono, William; McGue, Matthew; Tully, Erin; Legrand, Lisa

    2008-01-01

    Objective The purpose of this study was to examine the relationship between alcohol exposure in pregnancy and offspring conduct disorder (CD) symptoms in adolescence, and to examine how much this increasingly well-known association may be mediated by maternal and paternal externalizing diagnoses, including lifetime maternal and paternal alcohol and drug abuse/dependence diagnoses as well as antisocial disorders. Few other studies have examined the contribution of these diagnoses across both parents. Method A population sample of 1252 adolescents (53.8% female; drawn from the Minnesota Twin Family Study) as well as both their parents completed structured diagnostic interviews to generate lifetime psychiatric diagnoses; mothers were also retrospectively interviewed about alcohol and nicotine use during pregnancy. Linear regression models were used to test the effects of prenatal alcohol exposure on adolescents' CD symptoms. Results Prenatal exposure to alcohol was associated with higher levels of CD symptoms in offspring, even after statistically controlling for the effects of parental externalizing disorders (i.e., illicit substance use disorders, alcohol dependence, and antisocial/behavioral disorders), prenatal nicotine exposure, monozygosity, gestational age, and birth weight. Conclusions Prenatal alcohol exposure contributes to increased risk for CD in offspring. PMID:19047223

  17. Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone.

    PubMed

    Besheer, Joyce; Fisher, Kristen R; Lindsay, Tessa G; Cannady, Reginald

    2013-09-01

    Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5-0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

  18. Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus.

    PubMed

    Boschen, K E; Ruggiero, M J; Klintsova, A Y

    2016-06-01

    Aberrant activation of the developing immune system can have long-term negative consequences on cognition and behavior. Teratogens, such as alcohol, activate microglia, the brain's resident immune cells, which could contribute to the lifelong deficits in learning and memory observed in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. The current study investigates the microglial response of the brain 24h following neonatal alcohol exposure (postnatal days (PDs) 4-9, 5.25g/kg/day). On PD10, microglial cell counts and area of cell territory were assessed using unbiased stereology in the hippocampal subfields CA1, CA3 and dentate gyrus (DG), and hippocampal expression of pro- and anti-inflammatory genes was analyzed. A significant decrease in microglial cell counts in CA1 and DG was found in alcohol-exposed and sham-intubated (SI) animals compared to undisturbed suckle controls (SCs), suggesting overlapping effects of alcohol exposure and intubation alone on the neuroimmune response. Cell territory was decreased in alcohol-exposed animals in CA1, CA3, and DG compared to controls, suggesting the microglia have shifted to a more activated state following alcohol treatment. Furthermore, both alcohol-exposed and SI animals had increased levels of pro-inflammatory cytokines IL-1β, TNF-α, CD11b, and CCL4; in addition, CCL4 was significantly increased in alcohol-exposed animals compared to SI as well. Alcohol-exposed animals also showed increased levels of anti-inflammatory cytokine TGF-β compared to both SI and SCs. In summary, the number and activation of microglia in the neonatal hippocampus are both affected in a rat model of FASD, along with increased gene expression of pro- and anti-inflammatory cytokines. This study shows that alcohol exposure during development induces a neuroimmune response, potentially contributing to long-term alcohol-related changes to cognition, behavior and immune function. PMID:26996510

  19. Thermoregulatory deficits following prenatal alcohol exposure: structural correlates.

    PubMed

    Zimmerberg, B

    1989-01-01

    Prenatal exposure to alcohol delays the development of thermoregulation in newborn rats. This study examined two possible physiological correlates of this effect. In the first experiment, the effect of prenatal alcohol exposure on the availability of brown adipose tissue for nonshivering thermogenesis was investigated in rat pups from birth to weanling age. Male and female pups were chosen from independent litters with one of three prenatal treatment histories: 35% ethanol-derived calories (35% EDC), pair-fed control (0% EDC), or lab-chow control (LC). Prenatal alcohol exposure resulted in decreased body weight from postnatal (PN) day 1 to 20 compared to controls. Similarly, alcohol-exposed subjects had lighter interscapular brown adipose tissue pads than controls. However, the proportion of brown adipose tissue to body weight in alcohol-exposed pups was not different from controls. It appears that thermoregulatory deficits at birth due to prenatal alcohol exposure are not due to decreased substrate availability. In the second experiment, the relative growth rate of the tail compared to the growth rate of the body was measured in male and female pups from the three prenatal treatment groups. Five-day-old rat pups exposed to alcohol prenatally had relatively slower tail growth than control pups. Since tail growth rate has been associated with ambient temperature, these results suggest that alcohol-exposed rat pups may be experiencing transient periods of cold stress in the nest because of their thermoregulatory deficiencies, which, in turn, could have important implications for neural and body growth retardation seen in Alcohol Related Birth Defects. PMID:2818842

  20. Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

    PubMed Central

    McCaskill, Michael L.; Romberger, Debra J.; DeVasure, Jane; Boten, Jessica; Sisson, Joseph H.; Bailey, Kristina L.; Poole, Jill A.; Wyatt, Todd A.

    2012-01-01

    Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF), tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon) activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability of the lung to activate PKCε

  1. Alcohol exposure alters mouse lung inflammation in response to inhaled dust.

    PubMed

    McCaskill, Michael L; Romberger, Debra J; DeVasure, Jane; Boten, Jessica; Sisson, Joseph H; Bailey, Kristina L; Poole, Jill A; Wyatt, Todd A

    2012-07-01

    Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF), tracheas and lungs were collected. HDE stimulated a 2-4 fold increase in lung and tracheal PKCε (epsilon) activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability of the lung to activate PKCε

  2. 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. PMID:25913787

  3. 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

  4. 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. PMID:21477057

  5. MODEL DEVELOPMENT - EXPOSURE MODELS

    EPA Science Inventory

    Humans are exposed to mixtures of chemicals from multiple pathways and routes. These exposures may result from a single event or may accumulate over time if multiple exposure events occur. The traditional approach of assessing risk from a single chemical and a single route of e...

  6. [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. PMID:23819941

  7. 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.

  8. 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…

  9. Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets.

    PubMed

    Krahe, Thomas E; Filgueiras, Claudio C; Medina, Alexandre E

    2016-08-01

    Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5g/kg, i.p.), VPA (200mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction. PMID:27208641

  10. White matter microstructure, alcohol exposure, and familial risk for alcohol dependence

    PubMed Central

    Hill, Shirley Y.; Terwilliger, Robert; McDermott, Michael

    2013-01-01

    Offspring from families with alcohol dependence (AD) have been shown to exhibit brain morphological alterations that appear to be related to their familial/genetic risk for AD. Greater susceptibility for developing AD may be related to structural underpinnings of behavioral traits that predispose to AD. We examined white matter (WM) integrity in 81 individuals with either a high density of AD in their families (N=44) or without a family history for either alcohol or drug dependence (N=37). Magnetic resonance images were acquired on a Siemens 3 T scanner with fractional anistropy (FA) and the apparent diffusion coefficient (ADC), along with radial diffusivity (RD) and longitudinal (axial) diffusivity calculated for major white matter tracts in both hemispheres. Extensive personal histories of alcohol and drug use were available from longitudinal collection of data allowing for reliable estimates of alcohol and drug exposure. We found that the interaction of personal exposure to alcohol and familial risk for AD predicts reduction in WM integrity for the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF) in the left hemisphere and the forceps major tract. Only one tract showed a significant difference for exposure alone, the anterior thalamic radiation. PMID:23473988

  11. 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. PMID:18389374

  12. Watching and drinking: Expectancies, prototypes, and peer affiliations mediate the effect of exposure to alcohol use in movies on adolescent drinking

    PubMed Central

    Dal Cin, Sonya; Worth, Keilah A.; Gerrard, Meg; Gibbons, Frederick X.; Stoolmiller, Mike; Wills, Thomas A.; Sargent, James D.

    2009-01-01

    Objective To investigate the psychological processes that underlie the relation between exposure to alcohol use in media with adolescent alcohol use. Design Structural equation modeling analysis of data from four waves of a longitudinal, nationally-representative, random-digit dial telephone survey of adolescents in the United States. Main Outcome Measures Adolescent alcohol consumption and willingness to use alcohol. Tested mediators were alcohol-related norms, prototypes, expectancies, and friends' use. Results Alcohol prototypes, expectancies, willingness, and friends' use of alcohol (but not perceived prevalence of alcohol use among peers) were significant mediators of the relation between movie alcohol exposure and alcohol consumption, even after controlling for demographic, child, and family factors associated with both movie exposure and alcohol consumption. Conclusion Established psychological and interpersonal predictors of alcohol use mediate the effects of exposure to alcohol use in movies on adolescent alcohol consumption. The findings suggest that exposure movie portrayals may operate through similar processes as other social influences, highlighting the importance of considering these exposures in research on adolescent risk behavior. PMID:19594272

  13. 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

  14. Effects of developmental alcohol exposure on potentiation and depression of visual cortex responses

    PubMed Central

    Lantz, Crystal L.; Sipe, Grayson O.; Wong, Elissa L.; Majewska, Ania K.; Medina, Alexandre E.

    2015-01-01

    Background Neuronal plasticity deficits are thought to underlie abnormal neurodevelopment in Fetal Alcohol Spectrum Disorders (FASD) and in animal models of this condition. Previously, we found that alcohol exposure during a period that is similar to the last months of gestation in humans disrupts ocular dominance plasticity (ODP), as measured in superficial cortical layers. We hypothesize that exposure to alcohol can differentially affect the potentiation and depression of responses that are necessary for activity dependent sprouting and pruning of neuronal networks. ODP is an established paradigm that allows the assessment of activity-dependent depression and potentiation of responses in vivo. Methods Mouse pups were exposed to 3.6 – 5g/kg of ethanol in saline daily or every other day between postnatal days 4 and 9. Visual cortex plasticity was then assessed during the critical period for ODP using two techniques that separately record in layers 4 (visual evoked potentials, VEPs) and 2/3 (optical imaging of intrinsic signals, OI). Results We discovered a layer-specific effect of early alcohol exposure. Recording of VEPs, from layer 4, showed that while the potentiation component of ODP (Pc-ODP) was disrupted in animals treated with alcohol when compared to saline controls, the depression component of ODP (Dc-ODP) was unaltered. In contrast, OI, from layers 2/3, showed that Dc-ODP was markedly disrupted in alcohol treated animals when compared to controls. Conclusions Combined with our previous work, these findings strongly suggest that developmental alcohol exposure has a distinct and layer-specific effect on the potentiation and depression of cortical responses after monocular deprivation. PMID:26108422

  15. Long-Term Consequences of Developmental Alcohol Exposure on Brain Structure and Function: Therapeutic Benefits of Physical Activity

    PubMed Central

    Klintsova, Anna Y.; Hamilton, Gillian F.; Boschen, Karen E.

    2012-01-01

    Developmental alcohol exposure both early in life and during adolescence can have a devastating impact on normal brain structure and functioning, leading to behavioral and cognitive impairments that persist throughout the lifespan. This review discusses human work as well as animal models used to investigate the effect of alcohol exposure at various time points during development, as well as specific behavioral and neuroanatomical deficits caused by alcohol exposure. Further, cellular and molecular mediators contributing to these alcohol-induced changes are examined, such as neurotrophic factors and apoptotic markers. Next, this review seeks to support the use of aerobic exercise as a potential therapeutic intervention for alcohol-related impairments. To date, few interventions, behavioral or pharmacological, have been proven effective in mitigating some alcohol-related deficits. Exercise is a simple therapy that can be used across species and also across socioeconomic status. It has a profoundly positive influence on many measures of learning and neuroplasticity; in particular, those measures damaged by alcohol exposure. This review discusses current evidence that exercise may mitigate damage caused by developmental alcohol exposure and is a promising therapeutic target for future research and intervention strategies. PMID:24961305

  16. Prenatal alcohol exposure among Alaska Native/American Indian infants

    PubMed Central

    Khan, Burhan A.; Robinson, Renee F.; Smith, Julia J.; Dillard, Denise A.

    2013-01-01

    Background Recent reports indicate a decline in rates of Fetal Alcohol Syndrome (FAS) among Alaska Native and American Indian (AN/AI) infants. Nevertheless, AN/AI infants remain disproportionately impacted by the effects of prenatal alcohol exposure. Methods AN/AI pregnant women in their 3rd trimester completed a questionnaire on demographic data and the amount and frequency of their alcohol consumption in the month prior to conception and during pregnancy. Differences across demographics and trimesters were tested with the Chi-square, Fisher's exact or McNemar's test as appropriate. Results Of the 125 participants, 56% (n=71) reported no alcohol consumption in the 1st through 3rd trimesters of pregnancy; 30% (n=38) of the 125 participants also reported no alcohol consumption in the month before pregnancy. Of the 43% (n=54) who reported consuming alcohol during pregnancy (1st, 2nd and/or 3rd trimester), most (35%) reported alcohol use only in the 1st trimester. Binge drinking in the 1st or 2nd trimester was reported amongst 20% (n=25) of participants with an additional 18% (n=29) reporting binge drinking in the month prior to pregnancy. Women who reported pre-conception binge drinking were significantly more likely to report binge drinking during their 1st trimester (p<0.0001) and 2nd trimester (p<0.0001). A history of tobacco use (p=0.0403) and cigarette smoking during pregnancy (p<0.0001) were also associated with binge drinking during pregnancy. Conclusion Among study participants, reported use of alcohol was primarily limited to pre-conception and the 1st trimester, with a dramatic decrease in the 2nd and 3rd trimesters. Prevention programmes, such as the Alaska FAS Prevention Project, may have contributed to observed decreases in the 2nd and 3rd trimesters. Additional study and focus on pre-conception, the 1st trimester and binge drinking, as well as tobacco use might augment Fetal Alcohol Spectrum Disorder prevention efforts. PMID:23984278

  17. Association of Attention Deficit Hyperactivity Disorder and Gestational Alcohol Exposure: An Exploratory Study

    ERIC Educational Resources Information Center

    Bhatara, Vinod; Loudenberg, Roland; Ellis, Roland

    2006-01-01

    Objective and methods: To explore association between prevalence of ADHD and levels of risk for gestational alcohol exposure, the authors reviewed the charts of 2,231 youth referred for fetal alcohol spectrum disorders. Participants were categorized into four groups by different levels of risk for gestational alcohol exposure. For each group, the…

  18. Household exposure models

    SciTech Connect

    McKone, T.E.

    1988-01-01

    Human exposure to volatile organic compounds (VOCs) in tap water is often assumed to be dominated by ingestion of drinking water. This paper addresses the relative importance of inhalation and dermal exposures in a typical household. A three-compartment model is used to simulate the 24-h concentration history of VOCs in the shower, bathroom, and remaining household volumes as a result of tap water use. Mass transfers from water to air are derived from measured data for radon and used to estimate mass-transfer properties for VOCs. The model is used to calculate a range of concentrations and human exposures in US dwellings. The estimated ratio of household- inhalation uptake to ingestion uptake is in the range of 1 to 6 for VOCs. We use a dermal absorption model to assess exposure across the skin boundary during baths and showers. The ratio of dermal exposure to ingestion exposure is in the range 0.6 to 1. 24 refs., 1 fig., 7 tabs.

  19. Neonatal Binge Alcohol Exposure Produces Dose Dependent Deficits in Interstimulus Interval Discrimination Eyeblink Conditioning in Juvenile Rats

    PubMed Central

    Brown, Kevin L.; Burman, Michael A.; Duong, Huan B.; Stanton, Mark E.

    2009-01-01

    Alcohol consumption in neonatal rats produces cerebellar damage and is widely used to model 3rd-trimester human fetal alcohol exposure. Neonatal “binge-like” exposure to high doses of alcohol (5 g/kg/day or more) impairs acquisition of eyeblink classical conditioning (EBC), a cerebellar-dependent Pavlovian motor learning task. We have recently found impairments in interstimulus interval (ISI) discrimination – a complex task variant of EBC - in adult rats following postnatal day (PD) 4–9 alcohol exposure at doses of 3, 4, and 5 g/kg/day. Because robust developmental differences in conditioned response (CR) generation and CR latency measures are present between untreated juveniles and adults in this task, we sought to extend alcohol findings to juvenile rats (PD30). Five neonatal treatment groups were used: (1) undisturbed controls, (2) sham intubation controls, (3) 3 g/kg/day of alcohol (blood alcohol concentration {BAC} = 139.9 mg/dl), (4) 4 g/kg/day of alcohol (BAC = 237.3 mg/dl), or (5) 5 g/kg/day of alcohol (BAC = 301.8 mg/dl). Intubations occurred over PD4-9. ISI discrimination training in juveniles (PD30-33) revealed dose-dependent CR deficits in all three alcohol-exposed groups relative to controls. Contrary to expected outcomes, CR latency measures were not significantly affected as a function of neonatal treatment. Comparison of these findings with our recent study in adults suggests that alcohol-induced impairments in ISI discrimination EBC may be greater in adults relative to juveniles. The present findings provide further evidence that ISI discrimination may provide greater sensitivity to functional deficits resulting from moderate levels of neonatal alcohol exposure relative to single-cue EBC paradigms. PMID:19007754

  20. Prenatal alcohol exposure: An assessment strategy for the legal context.

    PubMed

    Brown, Natalie Novick; Burd, Larry; Grant, Therese; Edwards, William; Adler, Richard; Streissguth, Ann

    2015-01-01

    Studies over the last two decades have shown that people with fetal alcohol spectrum disorders (FASD) have the kind of brain damage that increases risk of criminal behavior. Thus, it is generally accepted that FASD is likely to affect a sizable minority of individuals involved in the justice system. Most of these defendants have never been diagnosed because they lack the facial abnormalities and severe intellectual deficiency that would have improved identification and diagnosis in childhood. Despite the fact that an FASD diagnosis and associated cognitive deficits may be directly relevant to offense conduct and post-arrest capacities, screening for prenatal alcohol exposure (PAE) by legal teams remains relatively rare. This article addresses the relatively straightforward screening process with strategies that may be used singly or in combination to produce information that can establish PAE and provide a foundation for diagnostic assessment by medical and mental health experts. PMID:26338492

  1. 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

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

    PubMed

    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 14years. 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

  3. 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

  4. TRANSIENT CORTICAL ASTROGLIOSIS INDUCED BY ALCOHOL EXPOSURE DURING THE NEONATAL BRAIN GROWTH SPURT IN RATS

    EPA Science Inventory

    The astrocyte response to central nervous system injury induced by neonatal alcohol exposure was evaluated using radioimmunoassay and immunocytochemistry of glial fibrillary acidic protein (GFAP). at pups were exposed to alcohol on postnatal days 4 through 9 via artificial rearin...

  5. 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

  6. 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

  7. 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. PMID:16893966

  8. Prenatal alcohol exposure and thermotaxic behavior in neonatal rats.

    PubMed

    Zimmerberg, B; Beckstead, J W; Riley, E P

    1987-01-01

    The effect of prenatal alcohol exposure on thermotaxic behavior was investigated in 5-day-old rat pups. Pregnant dams were administered a liquid diet which contained 35% ethanol-derived calories (35% EDC) on days 6 to 20 of gestation. Two control groups were included: a liquid diet control which was pair-fed and had sucrose substituted for ethanol (0% EDC), and a group fed standard lab chow (LC) throughout pregnancy. Pups from each of these prenatal treatments were tested on a thermal gradient (thermocline). On each of 5 trails, pups were placed in the cool end of the thermocline and their position along the gradient was measured after 10 min. All prenatal treatment groups displayed thermotaxic behavior by moving towards the warm end. However, pups in the 35% EDC treatment group moved significantly further towards the warm end in the later trials. Despite their position on a warmer surface, their body temperature did not rise concurrently. Thermoregulatory deficits caused by prenatal alcohol exposure might account for these results. PMID:3683345

  9. Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure.

    PubMed

    Infante, M Alejandra; Moore, Eileen M; Bischoff-Grethe, Amanda; Migliorini, Robyn; Mattson, Sarah N; Riley, Edward P

    2015-10-22

    Prenatal alcohol exposure can adversely affect brain development, although little is known about the effects of prenatal alcohol exposure on gyrification. Gyrification reflects cortical folding complexity and is a process by which the surface of the brain creates sulci and gyri. Prior studies have shown that prenatal alcohol exposure is associated with reduced gyrification in childhood, but no studies have examined adolescents. Subjects (12-16 years) comprised two age-equivalent groups: 30 adolescents with histories of heavy prenatal alcohol exposure (AE) and 19 non-exposed controls (CON). A T1-weighted image was obtained for all participants. Local gyrification index (LGI) was estimated using FreeSurfer. General linear models were used to determine between group differences in LGI controlling for age and sex. Age-by-group interactions were also investigated while controlling for sex. The AE group displayed reduced LGI relative to CON in the bilateral superior parietal region, right postcentral region, and left precentral and lateral occipital regions (ps<.001). Significant age-by-group interactions were observed in the right precentral and lateral occipital regions, and in the left pars opercularis and inferior parietal regions (ps<.01). The AE group showed age-related reductions in gyrification in all regions whereas the CON group showed increased gyrification with age in the lateral occipital region only. While cross-sectional, the age-related reduction in gyrification observed in the AE group suggests alterations in cortical development throughout adolescence and provides further insight into the pathophysiology and brain maturation of adolescents prenatally exposed to alcohol. PMID:26275919

  10. Simple exposure to alcohol cues causally increases negative implicit attitudes toward lesbians and gay men.

    PubMed

    Greitemeyer, Tobias; Nierula, Carina

    2016-01-01

    Previous research has shown that acute alcohol consumption is associated with negative responses toward outgroup members such as sexual minorities. However, simple alcohol cue exposure without actually consuming alcohol also influences social behavior. Hence, it was reasoned that priming participants with words related to alcohol (relative to neutral words) would promote prejudiced attitudes toward sexual minorities. In fact, an experiment showed that alcohol cue exposure causally led to more negative implicit attitudes toward lesbians and gay men. In contrast, participants' explicit attitudes were relatively unaffected by the priming manipulation. Moreover, participants' typical alcohol use was not related to their attitudes toward lesbians and gay men. In sum, it appears that not only acute alcohol consumption but also the simple exposure of alcohol cues may promote negative views toward lesbians and gay men. PMID:26548738

  11. 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…

  12. Predicting alcohol consumption in adolescence from alcohol-specific and general externalizing genetic risk factors, key environmental exposures and their interaction

    PubMed Central

    Kendler, K. S.; Gardner, C.; Dick, D. M.

    2011-01-01

    Background Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development. Method Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood. Analysis by linear mixed models. Results The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15–17 years and then declined slowly. Alcohol-specific genetic risk factors increased slowly in influence through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs. Conclusions The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects on alcohol use are more pronounced when social constraints are minimized (e.g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e.g. high alcohol availability or peer deviance). Gene–environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns. PMID:20942993

  13. Effects of heavy prenatal alcohol exposure and iron deficiency anemia on child growth and body composition through age 9 years

    PubMed Central

    Carter, R. Colin; Jacobson, Joseph L.; Molteno, Christopher D.; Jiang, Hongyu; Meintjes, Ernesta M.; Jacobson, Sandra W.; Duggan, Christopher

    2012-01-01

    BACKGROUND Prenatal alcohol exposure has been associated with pre- and postnatal growth restriction, but little is known about the natural history of this restriction throughout childhood or the effects of prenatal alcohol on body composition. OBJECTIVE To examine the effects of heavy prenatal alcohol exposure on longitudinal growth and body composition. DESIGN 85 heavy drinking pregnant women (≥ 2 drinks/day or ≥ 4 drinks/occasion) and 63 abstaining and light-drinking controls (< 1 drink/day, no binging) were recruited at initiation of prenatal care in an urban obstetrical clinic in Cape Town, South Africa, and prospectively interviewed during pregnancy about alcohol, smoking, drug use, and demographics. Among their children, length/height, weight, and head circumference were measured at 6.5 and 12 months and at 5 and 9 years. Percent body fat was estimated at age 9 years using bioelectric impedance analysis. RESULTS In multiple regression models with repeated measures (adjusted for confounders), heavy alcohol exposure was associated with reductions in weight (0.6 SD), length/height (0.5 SD), and head circumference (0.9 cm) from 6.5 months to 9 years that were largely determined at birth. These effects were exacerbated by iron deficiency in infancy but were not modified by iron deficiency or measures of food security at 5 years. An alcohol-related postnatal delay in weight gain was seen at 12 months. Effects on head circumference were greater at age 9 than at other age points. Although heavy alcohol exposure was not associated with changes in body composition, children with fetal alcohol syndrome (FAS) and partial FAS (PFAS) had lower % body fat than heavy exposed nonsyndromal and control children. CONCLUSIONS Heavy prenatal alcohol exposure is related to prenatal growth restriction that persists through age 9 years and an additional delay in weight gain during infancy. FAS and PFAS diagnoses are associated with leaner body composition in later childhood. PMID

  14. 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

  15. Adolescent Intermittent Alcohol Exposure: Persistence of Structural and Functional Hippocampal Abnormalities into Adulthood

    PubMed Central

    Risher, Mary-Louise; Fleming, Rebekah L.; Risher, Christopher; Miller, K. M.; Klein, Rebecca C.; Wills, Tiffany; Acheson, Shawn K.; Moore, Scott D.; Wilson, Wilkie A.; Eroglu, Cagla; Swartzwelder, H. S.

    2015-01-01

    Background Human adolescence is a crucial stage of neurological development during which ethanol (EtOH) consumption is often at its highest. Alcohol abuse during adolescence may render individuals at heightened risk for subsequent alcohol abuse disorders, cognitive dysfunction, or other neurological impairments by irreversibly altering long-term brain function. To test this possibility, we modeled adolescent alcohol abuse (i.e., intermittent EtOH exposure during adolescence [AIE]) in rats to determine whether adolescent exposure to alcohol leads to long-term structural and functional changes that are manifested in adult neuronal circuitry. Methods We specifically focused on hippocampal area CA1, a brain region associated with learning and memory. Using electrophysiological, immunohistochemical, and neuroanatomical approaches, we measured post-AIE changes in synaptic plasticity, dendritic spine morphology, and synaptic structure in adulthood. Results We found that AIE-pretreated adult rats manifest robust long-term potentiation, induced at stimulus intensities lower than those required in controls, suggesting a state of enhanced synaptic plasticity. Moreover, AIE resulted in an increased number of dendritic spines with characteristics typical of immaturity. Immunohistochemistry-based analysis of synaptic structures indicated a significant decrease in the number of co-localized pre- and postsynaptic puncta. This decrease is driven by an overall decrease in 2 postsynaptic density proteins, PSD-95 and SAP102. Conclusions Taken together, these findings reveal that repeated alcohol exposure during adolescence results in enduring structural and functional abnormalities in the hippocampus. These synaptic changes in the hippocampal circuits may help to explain learning-related behavioral changes in adult animals preexposed to AIE. PMID:25916839

  16. EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS)

    EPA Science Inventory

    The Exposure Analysis Modeling System (EXAMS), first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals--pesti...

  17. 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…

  18. 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…

  19. 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

  20. Optogenetics in animal model of alcohol addiction

    NASA Astrophysics Data System (ADS)

    Nalberczak, Maria; Radwanska, Kasia

    2014-11-01

    Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.

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

    PubMed Central

    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.

    2010-01-01

    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 to 15), 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 (CON group). Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally, and 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 IQ (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. Further, 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. PMID:20237258

  2. 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

  3. 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. PMID:26053323

  4. Brief and Extended Alcohol Cue Exposure Effects on Craving and Attentional Bias

    PubMed Central

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

    2015-01-01

    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 (Group Short Exposure [SE], two 3-min blocks) or to a group that received a long exposure period (Group Long Exposure [LE], six 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 female participants in the LE Group. Implications for treatments that aim to reduce craving or attentional bias are discussed. PMID:26053323

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

    PubMed

    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

  6. 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

  7. 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. PMID:27151262

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

    PubMed

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

    2014-11-01

    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. PMID:25241068

  9. Type of alcohol drink and exposure to violence: an emergency department study.

    PubMed

    Chavira, Cynthia; Bazargan-Hejazi, Shahrzad; Lin, Johnny; del Pino, Homero E; Bazargan, Mohsen

    2011-08-01

    We compared the prevalence of exposure to violence across different types of alcohol consumed and the association between the type of alcohol consumed and exposure to violence. A cross-sectional analysis of data collected from a sample of 295 Emergency Department (ED) patients identified as having an alcohol problem. Outcome measure include exposure to violence, and the main study predictor was "type of alcoholic drink" including: malt liquor beer (MLB), regular beer, wine cooler, wine, fortified wine or hard liquor. Using logistic regression analysis, ED patients who drank MLB in combination with other types of alcohol increased their odds of being both threatened and physically attacked by 8.5 compared to ED patients who drank other types of alcohol. Being female increased the odds of being both threatened and physically attacked by 2.5 and using illicit drugs increased the odds by 3.8. Analysis of covariance and estimated marginal means revealed that ED patients who only drank MLB had a higher exposure to violence compared to non-MLB drinkers, and that female illicit drug users who drank MLB in combination with other types of alcohol had the highest exposure to violence. MLB was identified as a predictor of the amount of exposure to violence and in particular, that the use of malt liquor beer in combination with other types of alcohol increased the risk of being both threatened and physically attacked. Implications for ED and community interventions are suggested. PMID:21170574

  10. 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. PMID:26524279

  11. 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

  12. Modeling exposure to particulate matter.

    PubMed

    Moschandreas, Demetrios J; Saksena, Sumeet

    2002-12-01

    Exposure assessment, a component of risk assessment, links sources of pollution with health effects. Exposure models are scientific tools used to gain insights into the processes affecting exposure assessment. The purpose of this paper is to review the process and methodology of estimating inhalation exposure to particulate matter (PM) using various types of models. Three types of models are discussed in the paper. Indirect type of models are physical models that employ inventories of outdoor and indoor sources and their emission rates to identify major sources contributing to exposure to PM, and use fate and transport and indoor air quality models to estimate PM concentrations at receptor sites. PM concentrations and time spent by a subject at each receptor site are input variables to the conventional exposure model that estimates the desired exposure levels. Direct type models use measured exposure or exposure concentrations in conjunction with information obtained from questionnaires to formulate exposure regression models. Stochastic models use exposure measurements, estimates can also be used, to formulate exposure population distributions and investigate associated uncertainty and variability. Since models developed using databases from western countries are not necessarily applicable in developing countries, the difference in requirements among western and developing countries is highlighted in the paper. Employment of exposure modeling methods in developing countries requires development of local information. Such information includes local outdoor and indoor source inventories, local or regional meteorological conditions, adjustment of indoor models to reflect local building construction conditions, and use of questionnaires to obtain local time budget and activity patterns of the subject population. PMID:12492168

  13. White matter deficits mediate effects of prenatal alcohol exposure on cognitive development in childhood.

    PubMed

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

    2016-08-01

    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. Hum Brain Mapp 37:2943-2958, 2016. © 2016 Wiley Periodicals, Inc. PMID:27219850

  14. Rodent models for compulsive alcohol intake

    PubMed Central

    Hopf, F. Woodward; Lesscher, Heidi M.B.

    2014-01-01

    Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction. PMID:24731992

  15. Rodent models for compulsive alcohol intake.

    PubMed

    Hopf, F Woodward; Lesscher, Heidi M B

    2014-05-01

    Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction. PMID:24731992

  16. 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

  17. Determining the best population-level alcohol consumption model and its impact on estimates of alcohol-attributable harms

    PubMed Central

    2012-01-01

    Background The goals of our study are to determine the most appropriate model for alcohol consumption as an exposure for burden of disease, to analyze the effect of the chosen alcohol consumption distribution on the estimation of the alcohol Population- Attributable Fractions (PAFs), and to characterize the chosen alcohol consumption distribution by exploring if there is a global relationship within the distribution. Methods To identify the best model, the Log-Normal, Gamma, and Weibull prevalence distributions were examined using data from 41 surveys from Gender, Alcohol and Culture: An International Study (GENACIS) and from the European Comparative Alcohol Study. To assess the effect of these distributions on the estimated alcohol PAFs, we calculated the alcohol PAF for diabetes, breast cancer, and pancreatitis using the three above-named distributions and using the more traditional approach based on categories. The relationship between the mean and the standard deviation from the Gamma distribution was estimated using data from 851 datasets for 66 countries from GENACIS and from the STEPwise approach to Surveillance from the World Health Organization. Results The Log-Normal distribution provided a poor fit for the survey data, with Gamma and Weibull distributions providing better fits. Additionally, our analyses showed that there were no marked differences for the alcohol PAF estimates based on the Gamma or Weibull distributions compared to PAFs based on categorical alcohol consumption estimates. The standard deviation of the alcohol distribution was highly dependent on the mean, with a unit increase in alcohol consumption associated with a unit increase in the mean of 1.258 (95% CI: 1.223 to 1.293) (R2 = 0.9207) for women and 1.171 (95% CI: 1.144 to 1.197) (R2 = 0. 9474) for men. Conclusions Although the Gamma distribution and the Weibull distribution provided similar results, the Gamma distribution is recommended to model alcohol consumption from population

  18. AIR TOXICS HUMAN EXPOSURE MODELING

    EPA Science Inventory

    This project aims to improve the scientific basis for the Environmental Protection Agency's (EPA's) assessments of human exposures to air toxics by developing improved human exposure models. The research integrates the major components of the exposure paradigm, i.e., sources, tr...

  19. 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. PMID:16943763

  20. 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. PMID:24284473

  1. The new disease model of alcoholism.

    PubMed Central

    Wallace, J

    1990-01-01

    The new biopsychosocial disease model of alcoholism is examined from the perspective of recent biologic research. Studies of animal and human genetic predispositions suggest the presence of genetic influences over drinking behavior as well as biologic risk factors related to deficiencies in various neurochemicals. Ethanol affects the fluidity of cell membrane lipids, eventually causing membrane dysfunction. It also adversely affects the activity of two enzymes, monoamine oxidase and adenylate cyclase, that have important functions in the information processing system of the brain. Research on condensation products formed in the brain after alcohol consumption has provided clues to the development of alcoholism, but many questions remain unanswered. Alcoholism is clearly a multidimensional phenomenon in which biologic, psychological, and sociocultural factors interact to produce illness. PMID:2190417

  2. 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…

  3. State Alcohol Advertising Laws: Current Status and Model Policies.

    ERIC Educational Resources Information Center

    2003

    The concern about alcohol marketing and underage drinking has been heightened by recent findings in the scientific research community. Studies have established that alcohol advertising exposure influences a young person's beliefs about alcohol and his/her intention to drink. They also suggest that advertising may have a direct impact on youth…

  4. 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

  5. Increased Exposure to Alcohol and Cannabis Education and Changes in Use Patterns.

    ERIC Educational Resources Information Center

    Smart, Reginald G.

    1989-01-01

    Used data from Ontario Alcohol and Drug Use Among Students survey (N=4,267) to determine how reported alcohol and cannabis (marijuana) use changed with increased exposure to drug education. Concluded drug education had stronger influence on younger students and lighter drinkers but little impact on heavy drinkers. Found decrease in cannabis use…

  6. 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…

  7. 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…

  8. The effect of intimate exposure to alcohol abuse on the acquisition of knowledge about drinking.

    PubMed

    Rainer, J P

    1994-01-01

    This study explored how an alcohol education program might be structured to effectively educate college students about the consequences of alcohol use. The primary hypothesis tested stated that individuals would vary significantly in the amount of knowledge learned from a structured alcohol education workshop, based on the degree of familial or social exposure s/he has had to alcohol abuse. Social learning variables of locus of control, dogmatism, and expectancy for risk were tested for interaction with degree of exposure, to determine their influence on learning. A pretest-posttest control group was employed with a sample of 66 undergraduate college students. A four hour alcohol education program was administered to teach cognitive information and fact about alcohol, with a goal of facilitating responsible use/nonuse of alcohol. The Student Drinking Questionnaire measured acquisition of knowledge. The Adult Nowicki-Strickland Internal/External Scale measured locus of control, and Schultze's Short Dogmatism Scale measured dogmatism. The researcher developed an instrument for expectancy for risk. Multiple regression analyses yielded prediction equations for the variables under study. For the sample group, results demonstrated that a significant portion of the variance in the residualized posttest scores was accounted for by level of exposure and dogmatism. When the sample was blocked according to intimate or social exposure, dogmatism was the only construct entering the regression equation at a significant level for the intimate exposure group. None of the constructs were able to predict any of the residualized posttest scores for the social exposure group. It was concluded that: (1) Students in the sample learned differentially based on the degree of intimate exposure of alcohol; (2) Dogmatism is a moderating variable with acquisition of knowledge for those intimately exposed to alcohol abuse, but locus of control and expectancy for risk are not; and (3) Further

  9. 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.

  10. 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. PMID:20445483

  11. 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…

  12. MULTIMEDIA EXPOSURE ASSESSMENT MODEL (MULTIMED)

    EPA Science Inventory

    The Multimedia Exposure Assessment Model (MULTIMED) for exposure assessment simulates the movement of contaminants leaching from a waste disposal facility. The model consists of a number of modules which predict concentrations at a receptor due to transport in the subsurface, sur...

  13. 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

  14. 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

  15. A Multidimensional Model of Mothers’ Perceptions of Parent Alcohol Socialization and Adolescent Alcohol Misuse

    PubMed Central

    Ennett, Susan T.; Jackson, Christine; Cole, Veronica T.; Haws, Susan; Foshee, Vangie A.; Reyes, Heathe Luz McNaughton; Burns, Alison Reimuller; Cox, Melissa J.; Cai, Li

    2015-01-01

    We assessed a multidimensional model of parent alcohol socialization in which key socialization factors were considered simultaneously to identify combinations of factors that increase or decrease risk for development of adolescent alcohol misuse. Of interest was the interplay between putative risk and protective factors, such as whether the typically detrimental effects on youth drinking of parenting practices tolerant of some adolescent alcohol use are mitigated by an effective overall approach to parenting and parental modeling of modest alcohol use. The sample included 1,530 adolescents and their mothers; adolescents’ mean age was 13.0 (SD = .99) at the initial assessment. Latent profile analysis was conducted of mothers’ reports of their attitude toward teen drinking, alcohol-specific parenting practices, parental alcohol use and problem use, and overall approach to parenting. The profiles were used to predict trajectories of adolescent alcohol misuse from early to middle adolescence. Four profiles were identified: two profiles reflected conservative alcohol-specific parenting practices and two reflected alcohol-tolerant practices, all in the context of other attributes. Alcohol misuse accelerated more rapidly from grade 6 through 10 in the two alcohol-tolerant compared with conservative profiles. Results suggest that maternal tolerance of some youth alcohol use, even in the presence of dimensions of an effective parenting style and low parental alcohol use and problem use, is not an effective strategy for reducing risky adolescent alcohol use. PMID:26415053

  16. A multidimensional model of mothers' perceptions of parent alcohol socialization and adolescent alcohol misuse.

    PubMed

    Ennett, Susan T; Jackson, Christine; Cole, Veronica T; Haws, Susan; Foshee, Vangie A; Reyes, Heathe Luz McNaughton; Burns, Alison Reimuller; Cox, Melissa J; Cai, Li

    2016-02-01

    We assessed a multidimensional model of parent alcohol socialization in which key socialization factors were considered simultaneously to identify combinations of factors that increase or decrease risk for development of adolescent alcohol misuse. Of interest was the interplay between putative risk and protective factors, such as whether the typically detrimental effects on youth drinking of parenting practices tolerant of some adolescent alcohol use are mitigated by an effective overall approach to parenting and parental modeling of modest alcohol use. The sample included 1,530 adolescents and their mothers; adolescents' mean age was 13.0 (SD = .99) at the initial assessment. Latent profile analysis was conducted of mothers' reports of their attitude toward teen drinking, alcohol-specific parenting practices, parental alcohol use and problem use, and overall approach to parenting. The profiles were used to predict trajectories of adolescent alcohol misuse from early to middle adolescence. Four profiles were identified: 2 profiles reflected conservative alcohol-specific parenting practices and 2 reflected alcohol-tolerant practices, all in the context of other attributes. Alcohol misuse accelerated more rapidly from Grade 6 through 10 in the 2 alcohol-tolerant compared with conservative profiles. Results suggest that maternal tolerance of some youth alcohol use, even in the presence of dimensions of an effective parenting style and low parental alcohol use and problem use, is not an effective strategy for reducing risky adolescent alcohol use. (PsycINFO Database Record PMID:26415053

  17. Social Behavior of Offspring Following Prenatal Cocaine Exposure in Rodents: A Comparison with Prenatal Alcohol

    PubMed Central

    Sobrian, Sonya K.; Holson, R. R.

    2011-01-01

    Clinical and experimental reports suggest that prenatal cocaine exposure (PCE) alters the offsprings’ social interactions with caregivers and conspecifics. Children exposed to prenatal cocaine show deficits in caregiver attachment and play behavior. In animal models, a developmental pattern of effects that range from deficits in play and social interaction during adolescence, to aggressive reactions during competition in adulthood is seen. This review will focus primarily on the effects of PCE on social behaviors involving conspecifics in animal models. Social relationships are critical to the developing organism; maternally directed interactions are necessary for initial survival. Juvenile rats deprived of play behavior, one of the earliest forms of non-mother directed social behaviors in rodents, show deficits in learning tasks and sexual competence. Social behavior is inherently complex. Because the emergence of appropriate social skills involves the interplay between various conceptual and biological facets of behavior and social information, it may be a particularly sensitive measure of prenatal insult. The social behavior surveyed include social interactions, play behavior/fighting, scent marking, and aggressive behavior in the offspring, as well as aspects of maternal behavior. The goal is to determine if there is a consensus of results in the literature with respect to PCE and social behaviors, and to discuss discrepant findings in terms of exposure models, the paradigms, and dependent variables, as well as housing conditions, and the sex and age of the offspring at testing. As there is increasing evidence that deficits in social behavior may be sequelae of developmental exposure alcohol, we compare changes in social behaviors reported for prenatal alcohol with those reported for prenatal cocaine. Shortcomings in the both literatures are identified and addressed in an effort to improve the translational value of future experimentation. PMID:22144967

  18. Adult Children of Alcoholics: A Counseling Model.

    ERIC Educational Resources Information Center

    Crawford, Robert L.; Phyfer, Ann Quinn

    1988-01-01

    Notes that adult children of alcoholics attending college present unique problems and opportunities to the college counselor. Presents a treatment model for serving such students which identifies four survivor roles and their manifestations, and suggests counseling techniques for each role. (Author/NB)

  19. Postdependent state in rats as a model for medication development in alcoholism.

    PubMed

    Meinhardt, Marcus W; Sommer, Wolfgang H

    2015-01-01

    Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review. PMID:25403107

  20. 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…

  1. 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…

  2. Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester.

    PubMed

    Birch, Sharla M; Lenox, Mark W; Kornegay, Joe N; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R; Cudd, Tim A; Washburn, Shannon E

    2015-11-01

    Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker

  3. Context-induced relapse to alcohol seeking after punishment in a rat model

    PubMed Central

    Marchant, Nathan J.; Khuc, Thi N.; Pickens, Charles L.; Bonci, Antonello; Shaham, Yavin

    2012-01-01

    Background Rat studies have demonstrated that exposure to environments associated with alcohol intake reinstates alcohol seeking after extinction of alcohol-reinforced responding in a different context. However, extinction is limited as an abstinence model because humans typically abstain because of negative consequences associated with excessive drinking. It is currently unknown whether alcohol-associated contexts can provoke relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences in a different context. Methods Alcohol-preferring P rats were first given home-cage access to 20% ethanol. Next, they were trained to self-administer 20% ethanol in one context (context A). Subsequently, all rats continued to self-administer alcohol in a different context (context B). For one group, 50% of alcohol-reinforced responses were punished by mild footshock; two other groups either received non-contingent shocks or no shock. A fourth group was given extinction training in context B. All rats were then tested for relapse to alcohol seeking under extinction conditions in contexts A and B. Results In Context B, alcohol-taking behavior was suppressed by contingent shock (punishment) and extinction training but not by non-contingent shock. In Context A, relapse to alcohol seeking was reliably observed in the punished and extinction groups; a context switch had no effect on alcohol seeking in the no-shock or non-contingent shock groups. Conclusions Our data indicate that punishment-induced suppression of alcohol-taking behavior is context-dependent. We propose that our procedure can be used to explore mechanisms of context-induced relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences. PMID:22883434

  4. A covariance structure model test of antecedents of adolescent alcohol misuse and a prevention effort.

    PubMed

    Dielman, T E; Shope, J T; Butchart, A T; Campanelli, P C; Caspar, R A

    1989-01-01

    As part of an alcohol misuse prevention evaluation, questionnaires were administered to 4,157 junior high school students to determine levels of alcohol misuse, exposure to peer use and misuse of alcohol, susceptibility to peer pressure, internal health locus of control, and self-esteem. A conceptual model of the antecedents of adolescent alcohol misuse and the effectiveness of a prevention effort was tested using covariance structure modeling techniques. The factor loadings for the model were all moderate to high, indicating that the observed variables served well as measurement instruments for the latent variables. The hypothesized structural relationships among the latent variables of alcohol misuse, exposure to peer use and misuse of alcohol, susceptibility to peer pressure, internal health locus of control, and self-esteem were supported by the data. The full model explained 45 percent of the variance in alcohol misuse in the analysis based on the total sample. The direct effect of the intervention on alcohol misuse was small but significant in the hypothesized direction. The direct effects of the intervention on susceptibility to peer pressure and internal health locus of control were not significant. The model was tested separately for groups of students who had high versus low scores on susceptibility to peer pressure in order to test the interaction between susceptibility to peer pressure and exposure to peer use and misuse of alcohol. The percentage of variance accounted for in alcohol misuse did not increase upon testing the model separately for students who had high versus low scores on susceptibility to peer pressure. Observed differences in the significance of the parameter estimates between the high and low susceptibility to peer pressure groups suggest that different approaches to the design and evaluation of substance abuse prevention programs may be necessary for different subgroups of students. PMID:2621540

  5. Effects of prenatal alcohol exposure on the developmental pattern of temperature preference in a thermocline.

    PubMed

    Zimmerberg, B; Tomlinson, T M; Glaser, J; Beckstead, J W

    1993-01-01

    Prenatal alcohol exposure is associated with a variety of impairments in neonatal state regulatory systems. Since prenatal alcohol exposure causes thermoregulatory deficits in response to both heat and cold stress in rats, body temperature set-point might be altered in alcohol-exposed offspring. The effect of prenatal alcohol exposure on behavior in a thermocline was investigated in 10-, 15-, and 125-day-old male and female rats from three prenatal treatment conditions: alcohol liquid diet, pair-fed liquid diet control, or standard control. Subjects were placed in the thermocline in the cold, hot, or middle start positions and observed for 60 min. Subjects exposed to alcohol prenatally had a wider "preference zone" than control subjects at 10 and 15 days of age, but did not as adults. This widening of the temperature set-point in young subjects prenatally exposed to alcohol may represent a developmental lag in the development of body temperature set-point or a central compensatory process allowing the animal to adapt to alternating experiences of heat and cold stress. PMID:8216888

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

    PubMed

    2013-11-01

    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. PMID:24196664

  7. 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

  8. 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. PMID:26906760

  9. Sex Differences in Adolescent Depression: Stress Exposure and Reactivity Models

    ERIC Educational Resources Information Center

    Hankin, Benjamin L.; Mermelstein, Robin; Roesch, Linda

    2007-01-01

    Stress exposure and reactivity models were examined as explanations for why girls exhibit greater levels of depressive symptoms than boys. In a multiwave, longitudinal design, adolescents' depressive symptoms, alcohol usage, and occurrence of stressors were assessed at baseline, 6, and 12 months later (N=538; 54.5% female; ages 13-18, average…

  10. Children with Heavy Prenatal Alcohol Exposure Experience Reduced Control of Isotonic Force

    PubMed Central

    Nguyen, Tanya T.; Levy, Susan S.; Riley, Edward P.; Thomas, Jennifer D.; Simmons, Roger W.

    2013-01-01

    Background Heavy prenatal alcohol exposure can result in diverse and extensive damage to the central nervous system, including the cerebellum, basal ganglia, and cerebral cortex. Given that these brain regions are involved in the generation and maintenance of motor force, we predicted that prenatal alcohol exposure would adversely affect this parameter of motor control. We previously reported that children with gestational alcohol exposure experience significant deficits in regulating isometric (i.e., constant) force. The purpose of the present study was to determine if these children exhibit similar deficits when producing isotonic (i.e., graded) force. Methods Children with heavy prenatal alcohol exposure and typically developing children completed a series of isotonic force contractions by exerting force on a load cell to match a criterion target force displayed on a computer monitor. Two levels of target force (5% or 20% of maximum voluntary force) were investigated in combination with varying levels of visual feedback. Results Compared to controls, children with heavy prenatal alcohol exposure generated isotonic force signals that were less accurate, more variable, and less complex in the time domain compared to control children. Specifically, interactions were found between group and visual feedback for response accuracy and signal complexity, suggesting that these children have greater difficulty altering their motor output when visual feedback is low. Conclusions These data suggest that prenatal alcohol exposure produces deficits in regulating isotonic force, which presumably result from alcohol-related damage to developing brain regions involved in motor control. These children will most likely experience difficulty performing basic motor skills and daily functional skills that require coordination of finely graded force. Therapeutic strategies designed to increase feedback and, consequently, facilitate visual-motor integration could improve isotonic force

  11. Early Adolescent Exposure to Alcohol Advertising and Its Relationship to Underage Drinking

    PubMed Central

    Collins, Rebecca L.; Ellickson, Phyllis L.; McCaffrey, Daniel; Hambarsoomians, Katrin

    2009-01-01

    Purpose To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Methods Two in-school surveys of 1,786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during sixth grade, and drinking intentions and behavior at seventh grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. Results After adjusting for covariates, the joint effect of exposure to advertising from all six sources at Grade 6 was strongly predictive of Grade 7 drinking and Grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Conclusions Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence. PMID:17531759

  12. 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. PMID:27017477

  13. 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. PMID:25709101

  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. Effects of alcohol on thermoregulation during mild heat exposure in humans.

    PubMed

    Yoda, Tamae; Crawshaw, Larry I; Nakamura, Mayumi; Saito, Kumiko; Konishi, Aki; Nagashima, Kei; Uchida, Sunao; Kanosue, Kazuyuki

    2005-07-01

    We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during mild heat exposure in humans. Eight healthy men participated in this study. Experiments were conducted twice for each subject at a room temperature of 33 degrees C. After a 30-min resting period, the subject drank either 15% alcohol (alcohol session) at a dose of 0.36 g/kg body weight or equal volume of water (control session). Skin blood flow and chest sweat rate in the alcohol session significantly increased over those in controls 10 min after drinking. Deep body temperature in the alcohol session started to decrease 20 min after the onset of sweating and eventually fell 0.3 degrees C lower than in the controls. Whole body hot sensation transiently increased after alcohol drinking, whereas it changed little after water drinking. The increased "hot" sensation would presumably cause cool-seeking behavior, if permitted. Thus, alcohol influences thermoregulation so that body core temperature is lowered not only by automatic mechanisms (sweating and skin vasodilation) but also behaviorally. These results suggest that decreases in body temperature after alcohol drinking are not secondary to skin vasodilation, a well-known effect of alcohol, but rather result from a decrease in the regulated body temperature evidenced by the coordinated modulation of various effectors of thermoregulation and sensation. PMID:16377461

  16. Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

    PubMed

    Fish, E W; Holloway, H T; Rumple, A; Baker, L K; Wieczorek, L A; Moy, S S; Paniagua, B; Parnell, S E

    2016-09-15

    Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers. PMID:27185739

  17. MULTIMEDIA EXPOSURE MODELING

    EPA Science Inventory

    This task addresses a number of issues that arise in multimedia modeling with an emphasis on interactions among the atmosphere and multiple other environmental media. Approaches for working with multiple types of models and the data sets are being developed. Proper software tool...

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

    PubMed

    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

  19. 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

  20. Middle and High School Students’ Exposure to Alcohol- and Smoking-Related Media: A Pilot Study Using Ecological Momentary Assessment

    PubMed Central

    Scharf, Deborah M.; Martino, Steven C.; Setodji, Claude M.; Staplefoote, B. Lynette; Shadel, William G.

    2013-01-01

    The goals of this study were to assess the feasibility of using Ecological Momentary Assessment (EMA) to measure adolescents’ exposure to alcohol and smoking-related media. A sample of 20 middle and high school students completed a two-week EMA protocol in which they monitored exposures to alcohol and smoking-related media. Results showed that adolescents were highly compliant with the study protocol. A total of 255 exposures to alcohol (67%) and smoking (33%) were captured, representing an average of 8.50 (5.82) alcohol-related media exposures and 4.25 (SD = 3.67) smoking-related media exposures and an average of per participant during the study period. Exposures tended to occur in the afternoon (52% alcohol; 54% smoking), at point of sale (44% alcohol; 65% smoking) and on days leading up to the weekend (57% alcohol; 57% smoking). Exposures were also likely in the presence of family (69% alcohol; 56% smoking). Overall, results of this small pilot provide preliminary evidence that EMA is a useful tool for tracking and characterizing middle and high school students’ real-world exposures to alcohol and smoking-related media. Future studies may suggest mechanisms by which media exposures lead to youth uptake of drinking and smoking behaviors. PMID:23772763

  1. Dietary Exposure Potential Model

    EPA Science Inventory

    Existing food consumption and contaminant residue databases, typically products of nutrition and regulatory monitoring, contain useful information to characterize dietary intake of environmental chemicals. A PC-based model with resident database system, termed the Die...

  2. Alcohol Induced Facial Dysmorphology in C57BL/6 Mouse Models of Fetal Alcohol Spectrum Disorder

    PubMed Central

    Anthony, Bruce; Vinci-Booher, Sophia; Wetherill, Leah; Ward, Richard; Goodlett, Charles; Zhou, Feng C.

    2010-01-01

    Alcohol consumption during pregnancy causes Fetal Alcohol Spectrum Disorder (FASD), which includes a range of developmental deficits. Fetal alcohol syndrome (FAS) is the most severe form of FASD and can be diagnosed with pathognomonic facial features (smooth philtrum, short palpebral fissure, and thin upper vermilion). However, many children with developmental damage due to prenatal alcohol exposure exhibit no, or only a subset, of the above features, making diagnosis difficult. This study explored novel analyses to quantify the effect of a known dose of alcohol on specific facial measurements in sub-strains C57BL/B6J (B6J) and C57BL/6NHsd (B6N) mice. Mouse dams were provided alcohol (Alc) consisting of 4.8% (v/v) alcohol in a liquid diet for 16 days pre-pregnancy, chow and water diet during mating, and the alcohol liquid diet reinstated on gestational days 7(E7) to E17. Treatment controls included a pair-fed (PF) group given matched volumes of an alcohol-free liquid diet made isocalorically, and a group given ad lib access to lab chow and water (Chow). Maternal diet intake (Alc and PF), blood alcohol concentrations (BACs), embryo weights, and 15 morphometric facial measurements for E17 embryos were analyzed. B6N dams drank more alcohol during pregnancy and generated higher BAC than B6J dams. Both the Alc and PF treatments induced significant reductions in embryo weights relative to Chow in both sub-strains. Alcohol treatments produced significant changes, relative to controls, in four of the 15 facial measures for the B6N sub-strain, but only in two measures for the B6J sub-strain. Discriminant analysis demonstrated successful classification of the B6N alcohol-exposed versus non-alcohol exposed embryos with high sensitivity (86%), and specificity (80%), and overall classification (total correct 83%), while, B6J mice yielded sensitivity of 80%, specificity 78%, and overall correct classification in 79%. In addition, B6N mice showed significantly more effects of

  3. 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. PMID:26616173

  4. Prenatal Alcohol Exposure is Associated with Regionally Thinner Cortex During the Preadolescent Period.

    PubMed

    Robertson, Frances C; Narr, Katherine L; Molteno, Christopher D; Jacobson, Joseph L; Jacobson, Sandra W; Meintjes, Ernesta M

    2016-07-01

    Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neurobehavioral deficits, and reduced brain volume. Studies of cortical thickness in FASD have yielded contradictory findings, with 3 reporting thicker cerebral cortex in frontal and temporal brain regions and 2 showing thinner cortex across multiple regions. All 5 studies included subjects spanning a broad age range, and none have examined continuous measures of prenatal alcohol exposure. We investigated the relation of extent of in utero alcohol exposure to cortical thickness in 78 preadolescent children with FASD and controls within a narrow age range. A whole-brain analysis using FreeSurfer revealed no significant clusters where cortical thickness differed by FASD diagnostic group. However, alcohol dose/occasion during pregnancy was inversely related to cortical thickness in 3 regions-right cuneus/pericalcarine/superior parietal lobe, fusiform/lingual gyrus, and supramarginal/postcentral gyrus. The effect of prenatal alcohol exposure on IQ was mediated by cortical thickness in the right occipitotemporal region. It is noteworthy that a continuous measure of maternal alcohol consumption during pregnancy was more sensitive than FASD diagnosis and that the effect on cortical thickness was most evident in relation to a measure of maternal binge drinking. PMID:26088967

  5. Alcohol

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Alcohol KidsHealth > For Teens > Alcohol Print A A A ... you can make an educated choice. What Is Alcohol? Alcohol is created when grains, fruits, or vegetables ...

  6. The relationship between duration of initial alcohol exposure and persistence of molecular tolerance is markedly nonlinear.

    PubMed

    Velázquez-Marrero, Cristina; Wynne, Patricia; Bernardo, Alexandra; Palacio, Stephanie; Martin, Gilles; Treistman, Steven N

    2011-02-16

    The neuronal calcium- and voltage-activated BK potassium channel is modulated by ethanol, and plays a role in behavioral tolerance in vertebrates and invertebrates. We examine the influence of temporal parameters of alcohol exposure on the characteristics of BK molecular tolerance in the ventral striatum, an important component of brain reward circuitry. BK channels in striatal neurons of C57BL/6J mice exhibited molecular tolerance whose duration was a function of exposure time. After 6 h exposure to 20 mm (0.09 mg%) ethanol, alcohol sensitivity was suppressed beyond 24 h after withdrawal, while after a 1 or 3 h exposure, sensitivity had significantly recovered after 4 h. This temporally controlled transition to persistent molecular tolerance parallels changes in BK channel isoform profile. After withdrawal from 6 h, but not 3 h alcohol exposure, mRNA levels of the alcohol-insensitive STREX (stress axis-regulated exon) splice variant were increased. Moreover, the biophysical properties of BK channels during withdrawal from 6 h exposure were altered, and match the properties of STREX channels exogenously expressed in HEK 293 cells. Our results suggest a temporally triggered shift in BK isoform identity. Once activated, the transition does not require the continued presence of alcohol. We next determined whether the results obtained using cultured striatal neurons could be observed in acutely dissociated striatal neurons, after alcohol administration in the living mouse. The results were in remarkable agreement with the striatal culture data, showing persistent molecular tolerance after injections producing 6 h of intoxication, but not after injections producing only 3 h of intoxication. PMID:21325511

  7. NEUROPSYCHOLOGICAL DEFICITS ASSOCIATED WITH HEAVY PRENATAL ALCOHOL EXPOSURE ARE NOT EXACERBATED BY COMORBID ADHD

    PubMed Central

    Glass, Leila; Ware, Ashley L.; Crocker, Nicole; Deweese, Benjamin N.; Coles, Claire D.; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2013-01-01

    Objective: Neuropsychological functioning of individuals with attention-deficit/hyperactivity disorder (ADHD) or heavy prenatal alcohol exposure has been well documented independently. This study examined the interaction between both factors on cognitive performance in children. Method: As part of a multisite study, 344 children (8-16y, M=12.28, SD=2.52) completed a comprehensive neuropsychological battery. Four subject groups were tested: children with histories of heavy prenatal alcohol exposure (AE) and ADHD (AE+, n=90), alcohol-exposed without ADHD, (AE−, n=38), non-exposed with ADHD (ADHD, n=80), and non-exposed without ADHD (CON, n=136). Results: Separate 2(AE) × 2(ADHD) MANCOVAs revealed significant main and interactive effects of ADHD and AE on overall WISC-IV, D-KEFS, and CANTAB performance. Individual ANOVAs revealed significant interactions on 2 WISC-IV indices [Verbal Comprehension (VCI), Perceptual Reasoning (PRI)], and four D-KEFS and CANTAB subtests [Design Fluency, Verbal Fluency, Trail Making, Spatial Working Memory]. Follow-up analyses demonstrated no difference between AE+ and AE− groups on any measures. The combined AE+/− group demonstrated more severe impairment than the ADHD group on VCI and PRI, but there were no other differences between clinical groups. Conclusions: These results support a combined AE+/− group for neuropsychological research and indicate that, in some cases, the neuropsychological effects seen in ADHD are altered by prenatal alcohol exposure. The effects of alcohol exposure on verbal comprehension and perceptual reasoning were greater than those related to having ADHD without alcohol exposure, although both conditions independently resulted in cognitive impairment compared to controls. Clinically, these findings demonstrate task-dependent patterns of impairment across clinical disorders. PMID:24040921

  8. The development of thermoregulation after prenatal exposure to alcohol in rats.

    PubMed

    Zimmerberg, B; Ballard, G A; Riley, E P

    1987-01-01

    The effect of prenatal exposure to alcohol on the development of thermoregulation and behavioral thermogenesis was assessed in rats. Pups at 5, 10, 15, and 20 days of age were chosen from litters with one of three prenatal treatment histories: liquid diet with 35% ethanol-derived-calories (35% EDC), pair-fed control (0% EDC), or lab chow control (LC). Subjects were removed from the home nest and had their initial rectal temperatures recorded before placement alone in the center of an observational chamber in a testing room maintained at 23-24 degrees C. Rectal temperatures were recorded again every hour for the next 4 h. Speed to reach the wall for behavioral thermogenesis (wall-huddling) was also measured at each hourly interval. With increasing age, all pups displayed increasing ability to maintain their initial core temperature, but prenatal exposure to alcohol had a significant effect in retarding the development of thermoregulation. At 5 and 10 days of age, alcohol-exposed pups had significantly lower rectal temperatures at 1-4 h out of the nest compared to control pups. In addition, the speed to reach the wall was slower in 35% EDC pups than in pups from the two control groups, suggesting a deficit in behavioral thermogenesis as well. These results agree with others demonstrating alcohol-induced development delays, and may have implications for other behavioral deficits seen after prenatal exposure to alcohol. PMID:3108928

  9. 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

  10. 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.

  11. Effects of alcohol on autonomic responses and thermal sensation during cold exposure in humans.

    PubMed

    Yoda, Tamae; Crawshaw, Larry I; Saito, Kumiko; Nakamura, Mayumi; Nagashima, Kei; Kanosue, Kazuyuki

    2008-05-01

    We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during cold exposure in humans. Eight healthy men (mean age 22.3+/-0.7 year) participated in this study. Experiments were conducted twice for each subject at a room temperature of 18 degrees C. After a 30-min resting period, the subject drank either 15% alcohol at a dose of 0.36 g/kg body weight (alcohol session) or an equal volume of distilled water (control session), and remained in a sitting position for another 60 min. Mean skin temperature continued to decrease and was similar in control and alcohol sessions. Metabolic rate was lower in the alcohol session, but the difference did not affect core temperature, which decreased in a similar manner in both alcohol and control sessions (from 36.9+/-0.1 degrees C to 36.6+/-0.1 degrees C). Whole body sensations of cold and thermal discomfort became successively stronger in the control session, whereas these sensations were both greatly diminished after drinking alcohol. In a previous study we performed in the heat, using a similar protocol, alcohol produced a definite, coordinated effect on all autonomic and sentient heat loss effectors. In the current study in the cold, as compared to responses in the heat, alcohol intake was followed by lesser alterations in autonomic effector responses, but increased changes in sensations of temperature and thermal discomfort. Overall, our results indicate that although alcohol influences thermoregulation in the cold as well as in the heat, detailed aspects of the influence are quite different. PMID:18420115

  12. Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

    PubMed Central

    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.

    2014-01-01

    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 PAE1, 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. PMID:25549080

  13. 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

    2014-01-01

    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. PMID:25549080

  14. Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring

    PubMed Central

    Murugan, Sengottuvelan; Zhang, Changqing; Mojtahedzadeh, Sepideh; Sarkar, Dipak K.

    2013-01-01

    Background Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined if any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol exposed male rats during the adult period. Methods Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed), pair-fed with isocaloric liquid diet (pair-fed), or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostate of these animals were processed for determination of biochemical changes and histopathologies. Results Prostates of non-carcinogen treated animals which were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatally alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia primarily in the ventral prostate, whereas control animals showed only low-grade prostatic intraepithelial neoplasia. Prenatally ethanol-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. Conclusions These results suggest for the first time that prenatal ethanol exposures induces histophysiological changes in the prostate as well as

  15. 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

  16. 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

  17. Chronic alcohol exposure alters gene expression in HepG2 cells

    PubMed Central

    Pochareddy, Sirisha; Edenberg, Howard J.

    2011-01-01

    Background Liver is the primary site of alcohol metabolism and is highly vulnerable to injuries due to chronic alcohol abuse. Several molecular mechanisms, including oxidative stress and altered cellular metabolism, have been implicated in the development and progression of alcoholic liver disease. We sought to gain further insight into the molecular pathogenesis by studying the effects of ethanol exposure on global gene expression in HepG2 cells. Methods HepG2 cells were cultured in the presence or absence of 75 mM ethanol for nine days, with fresh media daily. Global gene expression changes were studied using Affymetrix GeneChip® Human Exon 1.0 ST Arrays. Gene expression differences were validated for thirteen genes by quantitative real-time RT-PCR. To identify biological pathways affected by ethanol treatment, differentially expressed genes were analyzed by Ingenuity Pathway Analysis software. Results Long term ethanol exposure altered the expression of 1093 genes (FDR ≤ 3%); many of these changes were modest. Long term ethanol exposure affected several pathways, including acute phase response, amino acid metabolism, carbohydrate metabolism and lipid metabolism. Conclusions Global measurements of gene expression show that a large number of genes are affected by chronic ethanol, although most show modest effect. These data provide insight into the molecular pathology resulting from extended alcohol exposure. PMID:22150570

  18. 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…

  19. 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…

  20. 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

  1. 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. PMID:23785319

  2. Alcohol

    MedlinePlus

    ... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

  3. 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 ...

  4. Is it important to prevent early exposure to drugs and alcohol among adolescents?

    PubMed

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

    2008-10-01

    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

  5. 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

  6. Toxic effects of prenatal exposure to alcohol, tobacco and other drugs.

    PubMed

    Scott-Goodwin, A C; Puerto, M; Moreno, I

    2016-06-01

    Tobacco, alcohol, cannabis and cocaine are the most consumed psychoactive drugs throughout the population. Prenatal exposure to these drugs could alter normal foetal development and could threaten future welfare. The main changes observed in prenatal exposure to tobacco are caused by nicotine and carbon monoxide, which can impede nutrient and oxygen exchange between mother and foetus, restricting foetal growth. Memory, learning processes, hearing and behaviour can also be affected. Alcohol may cause physical and cognitive alterations in prenatally exposed infants, fundamentally caused by altered NMDAR and GABAR activity. Tetrahydrocannabinol, the psychoactive compound of cannabis, is capable of activating CB1R, inducing connectivity deficits during the foetal brain development. This fact could be linked to behavioural and cognitive deficits. Many of the effects from prenatal cocaine exposure are caused by altered cell proliferation, migration, differentiation and dendritic growth processes. Cocaine causes long term behavioural and cognitive alterations and also affects the uteroplacental unit. PMID:27037188

  7. Motor Response Programming and Movement Time in Children with Heavy Prenatal Alcohol Exposure

    PubMed Central

    Simmons, Roger W.; Thomas, Jennifer D.; Levy, Susan S.; Riley, Edward P.

    2010-01-01

    The present experiment assessed motor response programming and movement time in children with histories of heavy prenatal alcohol exposure. Alcohol-exposed children between the ages of 7 and 17 years were classified into two groups: Fetal Alcohol Syndrome (FAS: n = 9) and children with prenatal alcohol exposure (PEA: n = 19) but who did not have the defining characteristics of FAS. The FAS and PEA children were compared to non-alcohol exposed children (NC: n = 23) when completing two tasks: a simple reaction time task (RT alone condition) and a reaction plus movement task (RT + Move condition). The movement involved responding to an imperative stimulus signal and depressing three target buttons in a set sequence. Participants completed 24 trials each for the RT alone and RT + Move response conditions. Results indicated no significant differences in performance among FAS, PEA and NC groups during the RT alone condition. However, during the RT + Move condition, the FAS group produced significantly longer and more variable reaction times than either the PEA and NC groups, which produced comparable reaction times. The FAS group also produced significantly slower movement times when moving to all three targets, whereas movement time variability did not significantly differ as a function of group. The observed results indicate children with FAS experience deficits in response programming and movement time production. PMID:20598488

  8. Alcohol Abuse and Alcoholism Prevention Model Learning Systems: Preliminary Designs. Final Report.

    ERIC Educational Resources Information Center

    Jacobs, Saul H.

    The final report on a project designed to develop a model learning system for alcohol abuse and alcoholism prevention contains format details of four specific programs. Each program is geared to obtain maximum success in reinforcing responsible behavior, to change learner behavior, and to insure effective implementation in a variety of…

  9. 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. PMID:25138642

  10. Alcohol advertising, consumption and abuse: a covariance-structural modelling look at Strickland's data.

    PubMed

    Adlaf, E M; Kohn, P M

    1989-07-01

    Re-analysis employing covariance-structural models was conducted on Strickland's (1983) survey data on 772 drinking students from Grades 7, 9 and 11. These data bear on the relations among alcohol consumption, alcohol abuse, association with drinking peers and exposure to televised alcohol advertising. Whereas Strickland used a just-identified model which, therefore, could not be tested for goodness of fit, our re-analysis tested several alternative models, which could be contradicted by the data. One model did fit his data particularly well. Its major implications are as follows: (1) Symptomatic consumption, negative consequences and self-rated severity of alcohol-related problems apparently reflect a common underlying factor, namely alcohol abuse. (2) Use of alcohol to relieve distress and frequency of intoxication, however, appear not to reflect abuse, although frequent intoxication contributes substantially to it. (3). Alcohol advertising affects consumption directly and abuse indirectly, although peer association has far greater impact on both consumption and abuse. These findings are interpreted as lending little support to further restrictions on advertising. PMID:2758148

  11. Alcohol

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Alcohol KidsHealth > For Kids > Alcohol Print A A A Text Size What's in ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  12. Fate Analysis of Adult Hippocampal Progenitors in a Murine Model of Fetal Alcohol Spectrum Disorder (FASD)

    PubMed Central

    Kajimoto, Kenta; Allan, Andrea; Cunningham, Lee Anna

    2013-01-01

    Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreERT2/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access “drinking-in-the-dark” model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A–B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population. PMID:24040071

  13. Fate analysis of adult hippocampal progenitors in a murine model of fetal alcohol spectrum disorder (FASD).

    PubMed

    Kajimoto, Kenta; Allan, Andrea; Cunningham, Lee Anna

    2013-01-01

    Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreER(T2)/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access "drinking-in-the-dark" model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A-B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population. PMID:24040071

  14. Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

    PubMed

    Wang, He Joe; Murray, Gary J; Jung, Mary Katherine

    2015-01-01

    Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed. PMID:26293978

  15. 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

  16. The Male Role, Alcohol Use, and Alcohol Problems: A Structural Modeling Examination in Adult Women and Men.

    ERIC Educational Resources Information Center

    McCreary, Donald R.; Newcomb, Michael D.; Sadava, Stanley W.

    1999-01-01

    Utilizes structural model to examine relationships between three male-role variables, alcohol consumption, and alcohol-related problems in sample of men and women. For men, traditional attitudes led to more alcohol consumption, whereas agentic traits protected them from experiencing alcohol-related problems and from experiencing masculine…

  17. Effects of childhood exposure to familial alcoholism and family violence on adolescent substance use, conduct problems, and self-esteem.

    PubMed

    Ritter, Jennifer; Stewart, Michael; Bernet, Christine; Coe, Michael; Brown, Sandra A

    2002-04-01

    Exposure to familial alcoholism has been associated with many behavioral and emotional difficulties among offspring. However, few studies have examined environmental risks that often coexist with familial alcoholism, and which may influence the development of offspring psychosocial problems. This study examined potential additive and interactive effects of childhood exposure to family violence and childhood exposure to familial alcoholism on adolescent functioning. Three domains of adolescent functioning were examined in a high-risk community sample of 109 families: lifetime levels of substance use, conduct disorder behaviors, and self-esteem. Results indicated that both childhood exposure to familial alcoholism and childhood exposure to family violence were associated with psychosocial functioning of offspring during adolescence, although the relations differ according to domain of functioning and gender. PMID:12013062

  18. Preconception care: caffeine, smoking, alcohol, drugs and other environmental chemical/radiation exposure

    PubMed Central

    2014-01-01

    Introduction As providing health education, optimizing nutrition, and managing risk factors can be effective for ensuring a healthy outcome for women and her yet un-conceived baby, external influences play a significant role as well. Alcohol, smoking, caffeine use and other similar lifestyle factors, have now become an integral part of the daily life of most men and women, who use/misuse one or more of these harmful substances regularly despite knowledge of their detrimental effects. The adverse health outcomes of these voluntary and involuntary exposures are of even greater concern in women of child bearing age where the exposure has the potential of inflicting harm to two generations. This paper is examining the available literature for the possible effects of caffeine consumption, smoking, alcohol or exposure to chemicals may have on the maternal, newborn and child health (MNCH). Methods A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception usage of caffeine, tobacco, alcohol and other illicit drugs; and exposure to environmental chemicals and radiant on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Results Heavy maternal preconception caffeine intake of >300mg/d significantly increase the risk of a subsequent fetal loss by 31% (95% CI: 8-58%). On the other hand, preconception alcohol consumption leads to non-significant 30% increase in spontaneous abortion (RR 1.30; 95% CI: 0.85-1.97). Preconception counselling can lead to a significant decrease in the consumption of alcohol during the first trimester (OR 1.79; 95% CI: 1.08-2.97). Periconception smoking, on the other hand, was found to be associated with an almost 3 times increased risk of congenital heart defects

  19. Trauma exposure, posttraumatic stress disorder and risk for alcohol, nicotine, and marijuana dependence in Israel

    PubMed Central

    Walsh, Kate; Elliott, Jennifer C.; Shmulewitz, Dvora; Aharonovich, Efrat; Strous, Rael; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah

    2014-01-01

    Background Substance dependence is more common among trauma-exposed individuals; however, most studies suggest that Posttraumatic Stress Disorder (PTSD) accounts for the link between trauma exposure (TE) and substance dependence. Objectives This study examined associations between TE and substance dependence (alcohol, nicotine, and marijuana), and whether PTSD accounted for this association. Method 1,317 Jewish Israeli household residents completed in-person structured interviews assessing TE, PTSD, and substance (alcohol, nicotine, marijuana) dependence between 2007–2009. Regression analyses examined associations among TE, PTSD, and substance dependence. Results In the full sample, mean number of traumatic events was 2.7 (sd=2.2), with 83.7% experiencing at least one event. In the full sample, mean number of PTSD symptoms was 2.5 (sd=3.4), with 13.5% meeting PTSD diagnostic criteria. Prevalence of alcohol dependence was 13.4%; nicotine dependence 52.8%; and marijuana dependence 12.1%. Number of traumatic events was associated with increased odds of alcohol (OR=1.3; 95% CI=1.2–1.4) and nicotine (OR=1.2; 95% CI=1.1–1.3) dependence. Similarly, any traumatic event exposure was associated with increased odds of alcohol (OR= 3.1; 95% CI= 1.6–6.0) and nicotine (OR=1.9; 95% CI=1.2–2.9) dependence. PTSD symptoms were associated with increased odds of alcohol (OR=1.2; 95% CI=1.1–1.3), nicotine (OR=1.1; 95% CI=1.1–1.2), and marijuana (OR=1.1; 95% CI=1.04–1.2) dependence; similarly, a PTSD diagnosis was associated with increased odds of alcohol (OR=3.4; 95% CI=2.1–5.5), nicotine (OR=2.2; 95% CI = 1.4–3.4), and marijuana (OR=2.6; 95% CI=1.2–5.9) dependence. PTSD symptoms accounted for a sizeable proportion of the TE effect on alcohol (46%) and nicotine dependence (31%). Conclusion Individuals with more traumatic events had heightened risk for alcohol and nicotine dependence, and PTSD symptoms partially accounted for this risk. However, marijuana

  20. 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

  1. 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. PMID:21349236

  2. 75 FR 859 - Exposure Modeling Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-06

    ... AGENCY Exposure Modeling Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Cancellation and Rescheduling of meeting. SUMMARY: This notice announces that the Exposure Modeling Public... Facility telephone number is (703) 305-5805. II. Background The purpose of the Exposure Modeling...

  3. Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma

    PubMed Central

    Purohit, Vishnudutt; Rapaka, Rao; Kwon, Oh Sang; Song, B. J.

    2013-01-01

    The purpose of this report is to summarize the roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma (HCC). Chronic heavy alcohol exposure is a major risk factor for HCC, which is the most frequent type of liver cancer. Alcohol ingestion may initiate and or promote the development of HCC by: 1) acetaldehyde-DNA adduct formation; 2) cytochrome P4502E1-associated reactive oxygen species (ROS) generation, lipid peroxidation, p53 mutation, and conversion of pro-carcinogens to carcinogens; 3) iron accumulation that leads to ROS generation, lipid peroxidation, p53 mutation, and initiation of inflammatory cascade via nuclear factor-KappaB (NF-kB) activation; 4) glutathione depletion leading to oxidative stress; 5) s-adenosylmethionine (SAM) depletion and associated DNA hypomethylation of oncogenes ; 6) retinoic acid depletion and resultant hepatocyte proliferation via up-regulation of activator protein-1 (AP-1); 7) initiating an inflammatory cascade through increased transfer of endotoxin from intestine to liver, Kupffer cell activation via CD14/toll-like receptor-4 (TLR-4), oxidative stress, NF-kB or early growth response-1(Egr-1) activation, and generation of inflammatory cytokines and chemokines; 8) induction of liver fibrosis; and 9) decreasing the number and/or function of Natural Killer cells. Tobacco exposure is also a risk factor for HCC. It may contribute to the initiation and promotion of HCC due the presence of mutagenic and carcinogenic compounds as well as by causing oxidative stress due to generation of ROS and depletion of endogenous antioxidants. Simultaneous exposure to alcohol and tobacco is expected to promote the development of HCC in an additive and/or synergistic manner. PMID:23123447

  4. 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

  5. Chronic alcohol exposure affects the cell components involved in membrane traffic in neuronal dendrites.

    PubMed

    Romero, Ana M; Renau-Piqueras, Jaime; Marín, M Pilar; Esteban-Pretel, Guillermo

    2015-01-01

    The specific traffic of the membrane components in neurons is a major requirement to establish and maintain neuronal domains-the axonal and the somatodendritic domains-and their polarized morphology. Unlike axons, dendrites contain membranous organelles, which are involved in the secretory pathway, including the endoplasmic reticulum, the Golgi apparatus and post-Golgi apparatus carriers, the cytoskeleton, and plasma membrane. A variety of molecules and factors are also involved in this process. Previous studies have shown that chronic alcohol exposure negatively affects several of these cell components, such as the Golgi apparatus or cytoskeleton in neurons. Yet very little information is available on the possible effects of this exposure on the remaining cell elements involved in intracellular trafficking in neurons, particularly in dendrites. By qualitative and quantitative electron microscopy, immunofluorescence and immunoblotting, we herein show that chronic exposure to moderate levels (30 mM) of ethanol in cultured neurons reduces the volume and surface density of the rough endoplasmic reticulum, and increases the levels of GRP78, a chaperone involved in endoplasmic reticulum stress. Ethanol also significantly diminishes the proportion of neurons that show an extension of Golgi into dendrites and dendritic Golgi outposts, a structure present exclusively in longer, thicker apical dendrites. Both Golgi apparatus types were also fragmented into a large number of cells. We also investigated the effect of alcohol on the levels of microtubule-based motor proteins KIF5, KIF17, KIFC2, dynein, and myosin IIb, responsible for transporting different cargoes in dendrites. Of these, alcohol differently affects several of them by lowering dynein and raising KIF5, KIFC2, and myosin IIb. These results, together with other previously published ones, suggest that practically all the protein trafficking steps in dendrites are altered to a greater or lesser extent by chronic

  6. 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. PMID:27405361

  7. Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

    PubMed Central

    May, Christina E.; Haun, Harold L.; Griffin, William C.

    2015-01-01

    Introduction Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol) on conditioned taste aversion, ataxia and locomotor activity after repeated exposure. Methods Four groups of mice were exposed by oral gavage twice daily to vehicle, ethanol (4 g/kg), caffeine (15 mg/kg), or the ethanol/caffeine combination. Conditioned taste aversion to saccharin and ataxia in the parallel rod task were evaluated after 8 or 16 gavages, respectively, using ethanol (1–3 g/kg) or ethanol/caffeine (3mg/kg + 2 g/kg) challenges. In addition, locomotor activity was evaluated initially and after repeated exposure to oral gavage of these drugs and doses. Results Repeated oral gavage of ethanol produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/ethanol combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated ethanol exposure, there was significant tolerance to ethanol in the conditioned taste aversion and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced ethanol-induced conditioned taste aversion. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/ethanol combination and appeared to reduce the ataxic response to high doses of ethanol. Conclusion The data support the general hypothesis that repeated exposure to caffeine influences the response to ethanol. Together with previously published work, these data indicate

  8. 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

  9. Alcohol

    MedlinePlus

    ... as well as injuries, liver disease, heart disease, cancer, and other health problems. It can also cause problems at home, at work, and with friends. NIH: National Institute on Alcohol Abuse and Alcoholism

  10. Tracking Adolescents with GPS-enabled Cell Phones to Study Contextual Exposures and Alcohol and Marijuana Use: A Pilot Study

    PubMed Central

    Byrnes, Hilary F.; Miller, Brenda A.; Wiebe, Douglas J.; Morrison, Christopher N.; Remer, Lillian G.; Wiehe, Sarah E.

    2015-01-01

    Purpose Measuring activity spaces, places adolescents spend time, provides information about relations between contextual exposures and risk behaviors. We studied whether contextual exposures in adolescents’ activity spaces differ from contextual risks present in residential contexts and examined relationships between contextual exposures in activity spaces and alcohol/marijuana use. Methods Adolescents (N=18) aged 16–17 carried GPS-enabled smartphones for one week, with locations tracked. Activity spaces were created by connecting GPS points sequentially and adding buffers. Contextual exposure data (e.g., alcohol outlets) were connected to routes. Adolescents completed texts regarding behaviors. Results Adolescent activity spaces intersected 24.3 census tracts and contained 9 times more alcohol outlets than residential census tracts. Outlet exposure in activity spaces was related to drinking. Low SES exposure was related to marijuana use. Conclusions Findings suggest substantial differences between activity spaces and residential contexts, and suggest that activity spaces are relevant for adolescent risk behaviors. PMID:26206448

  11. Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus

    PubMed Central

    Farnell, Yuhua Z.; Allen, Gregg C.; Neuendorff, Nichole; West, James R.; Wei-Jung, A. Chen; Earnest, David J.

    2010-01-01

    Neonatal alcohol exposure produces long-term changes in the suprachiasmatic nucleus (SCN) that are presumably responsible for disturbances in the light–dark regulation of circadian behavior in adult rats, including the pattern of photoentrainment, rate of re-entrainment to shifted light–dark cycles, and phase-shifting responses to light. Because SCN neurons containing vasoactive intestinal polypeptide (VIP) receive direct photic input via the retinohypothalamic tract and thus play an important role in the circadian regulation of the SCN clock mechanism by light, the present study examined the long-term effects of neonatal alcohol exposure on VIP neuronal populations within the SCN of adult rats. Male Sprague-Dawley rat pups were exposed to alcohol (EtOH; 3.0, 4.5, or 6.0 g/kg/day) or isocaloric milk formula (gastrostomy control; GC) on postnatal days 4–9 using artificial-rearing methods. At 2–3 months of age, animals from the suckle control (SC), GC, and EtOH groups were exposed to constant darkness (DD) and SCN tissue was harvested for subsequent analysis of either VIP mRNA expression by quantitative polymerase chain reaction (PCR) and in situ hybridization or of VIP-immunoreactive (ir) neurons using stereological methods. Neonatal alcohol exposure had no impact on VIP mRNA expression but dramatically altered immunostaining of neurons containing this peptide within the SCN of adult rats. The relative abundance of VIP mRNA and anatomical distribution of neurons expressing this transcript were similar among all control- and EtOH-treated groups. However, the total number and density of VIP-ir neurons within the SCN were significantly decreased by about 35% in rats exposed to alcohol at a dose of 6.0 g/kg/day relative to that observed in both control groups. These results demonstrate that VIP neuronal populations in the SCN are vulnerable to EtOH-induced insult during brain development. The observed alterations in SCN neurons containing VIP may have an impact

  12. 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…

  13. 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

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

    PubMed

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

    2016-01-01

    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. 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. PMID:25583378

  16. 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…

  17. Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

    PubMed Central

    Crabbe, John C.

    2016-01-01

    The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking

  18. Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence.

    PubMed

    Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A; Young, Emily A; Helpenstell, Lily K; Schuette, Lindsey M; Fidler, Tara L; Kosten, Therese A; Ryabinin, Andrey E

    2015-10-01

    An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies. PMID:26051399

  19. 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

  20. Rates of fetal alcohol exposure among newborns in a high-risk obstetric unit.

    PubMed

    Goh, Y Ingrid; Hutson, Janine R; Lum, Lisa; Roukema, Henry; Gareri, Joey; Lynn, Hazel; Koren, Gideon

    2010-01-01

    Meconium fatty acid ethyl esters (FAEEs) are sensitive and specific biomarkers for prenatal alcohol exposure (PAE) in pregnancy. We recently reported a 2.5% rate of FAEE positive meconium in a general population sample of infants born in the region of Grey-Bruce, Ontario. Women in this region with high-risk pregnancies are transferred to a tertiary care facility in London, Ontario. The objective of this study was to determine, in a population-based sample, whether high-risk pregnancies are associated with an increased risk of in utero alcohol exposure. Grey-Bruce residents transferred to the high-risk obstetric unit of St. Joseph's Health Care in London, Ontario were identified and consented to this anonymous prevalence study. Meconium was collected and analyzed for FAEE using gas chromatography with mass spectrometry. The prevalence of FAEE positive meconium was compared with the population-based prevalence in the Grey-Bruce. Fifty meconium specimens were collected from August 1, 2006 to July 31, 2007. Fifteen (30%) specimens tested positive for FAEE. The results indicate that infants born in the high-risk obstetric unit had a 12-fold higher risk of screening positive for second and third trimester alcohol exposure compared with infants born in the general population of Grey-Bruce (relative risk=12.04, 95% confidence interval=6.40-22.65, P<.0001). These results suggest that the high-risk pregnancies should be screened for PAE and followed-up for potential diagnosis of fetal alcohol spectrum disorder. PMID:20584588

  1. Drinking beyond a lifetime: New and emerging insights into paternal alcohol exposure on subsequent generations

    PubMed Central

    Finegersh, Andrey; Rompala, Gregory R.; Martin, David I. K.; Homanics, Gregg E.

    2015-01-01

    Alcohol-use disorder (AUD) is prevalent and associated with substantial socioeconomic costs. While heritability estimates of AUD are ~50%, identifying specific gene variants associated with risk for AUD has proven challenging despite considerable investment. Emerging research into heritability of complex diseases has implicated transmission of epigenetic variants in the development of behavioral phenotypes, including drug preference and drug-induced behavior. Several recent rodent studies have specifically focused on paternal transmission of epigenetic variants, which is especially relevant because sires are not present for offspring rearing and changes to offspring phenotype are assumed to result from modifications to the sperm epigenome. While considerable interest in paternal transmission of epigenetic variants has emerged recently, paternal alcohol exposures have been studied for 30+ years with interesting behavioral and physiologic effects noted on offspring. However, only recently, with improvements in technology to identify epigenetic modifications in germ cells, has it been possible to identify mechanisms by which paternal ethanol exposure alters offspring behavior. This review presents an overview of epigenetic inheritance in the context of paternal ethanol exposure and suggests future studies to identify specific effects of paternal ethanol exposure on offspring behavior and response to ethanol. PMID:25887183

  2. Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse

    PubMed Central

    Carnicella, Sebastien; Ron, Dorit; Barak, Segev

    2014-01-01

    One of the major challenges in preclinical studies of alcohol abuse and dependence remains the development of paradigms that will elicit high ethanol intake and mimic the progressive transition from low or moderate social drinking to excessive alcohol consumption. Exposure of outbred rats to repeated cycles of free-choice ethanol intake and withdrawal with the use of intermittent access to 20% ethanol in a 2-bottle choice procedure (IA2BC) has been shown to induce a gradual escalation of voluntary ethanol intake and preference, eventually reaching ethanol consumption levels of 5–6 g/kg/24 h, and inducing pharmacologically relevant blood ethanol concentrations (BECs). This procedure has recently been gaining popularity due to its simplicity, high validity, and reliable outcomes. Here we review experimental and methodological data related to IA2BC, and discuss the usefulness and advantages of this procedure as a valuable pre-training method for initiating operant ethanol self-administration of high ethanol intake, as well as conditioned place preference (CPP). Despite some limitations, we provide evidence that IA2BC and related operant procedures provide the possibility to operationalize multiple aspects of alcohol abuse and addiction in a rat model, including transition from social-like drinking to excessive alcohol consumption, binge drinking, alcohol seeking, relapse, and neuroadaptations related to excessive alcohol intake. Hence, IA2BC appears to be a useful and relevant procedure for preclinical evaluation of potential therapeutic approaches against alcohol abuse disorders. PMID:24721195

  3. Chapter three: methodology of exposure modeling.

    PubMed

    Moschandreas, Demetrios J; Watson, John; D'Abreton, Peter; Scire, Joseph; Zhu, Tan; Klein, Werner; Saksena, Sumeet

    2002-12-01

    In this chapter, the concept of exposure assessment and its evolution is introduced, and evaluated by critically appraising the pertinent literature as it applies to exposures to Particulate Matter (PM). Exposure measurement or estimation methodologies and models are reviewed. Three exposure/measurement methodologies are assessed. Estimation methods focus on source evaluation and attribution, sources include those outdoors and indoors as well as in occupational and in-transit environments. Fate and transport models and their inputs are addressed to estimate concentrations outdoors and indoors; source attribution techniques help focus on the contributing sources. Activity pattern techniques are also reviewed and their use in exposure models to estimate inhalation exposure to PM is presented. Deterministic, regression and other stochastic models of exposure to PM are reviewed and evaluated. Strengths, limitations, assumptions and affirmations of the use of exposure assessment as an integral component of risk assessment and risk management are discussed in the conclusions and discussions section of this work. PMID:12492158

  4. EPA CENTER FOR EXPOSURE ASSESSMENT MODELING (CEAM)

    EPA Science Inventory

    The EPA Center for Exposure Assessment Modeling (CEAM) supports the Agency and professional community in environmental, risk-based decision-making by expanding their applications expertise for quantitatively assessing pollutant exposure via aquatic, terrestrial, and multimedia pa...

  5. Effects of alcohol exposure during development on play behavior and c-Fos expression in response to play behavior.

    PubMed

    Charles Lawrence, R; Cale Bonner, H; Newsom, Ryan J; Kelly, Sandra J

    2008-03-17

    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 1h of play was assessed by measurement of c-Fos immunoreactivity (IR) in different brain regions. Ethanol-exposed rats showed an increased 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

  6. EXPOSURE MODELING OF ACID AEROSOLS

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) is conducting an intensive characterization and human exposure monitoring program of acid species and related air pollutants in an urban environment. he EPA's Atmospheric Research and Exposure Assessment Laboratory (AREAL) in coopera...

  7. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    PubMed Central

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  8. DIETARY EXPOSURE METHODS AND MODELS

    EPA Science Inventory

    The research reported in this task description constitutes the MCEARD base dietary exposure research program and is conducted to complement the NERL aggregate and cumulative exposure program. Its purpose is to reduce the level of uncertainty in exposure assessment by improving N...

  9. A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.

    PubMed

    Meintjes, E M; Narr, K L; van der Kouwe, A J W; Molteno, C D; Pirnia, T; Gutman, B; Woods, R P; Thompson, P M; Jacobson, J L; Jacobson, S W

    2014-01-01

    Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent. PMID:25057467

  10. Animal models and their results in gastrointestinal alcohol research.

    PubMed

    Siegmund, Soren V; Haas, Stephan; Singer, Manfred V

    2005-01-01

    Alcohol-induced diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the precise pathophysiological mechanisms are still largely unknown. Alcohol research depends essentially on animal models due to the fact that controlled experimental studies of ethanol-induced diseases in humans are unethical. Animal models have already been successfully applied to disclose and analyze molecular mechanisms in alcohol-induced diseases, partially by using knockout technology. Because of a lack of transferability of some animal models to the human condition, results have to be interpreted cautiously. For some alcohol-related diseases like chronic alcoholic pancreatitis, the ideal animal model does not yet exist. Here we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the findings based on animal models as well as the current concepts of pathophysiological mechanisms involved in acute and chronic alcoholic damage of the esophagus, stomach, small and large intestine, pancreas and liver. PMID:16508282

  11. MODERATE LEVEL PRENATAL ALCOHOL EXPOSURE ENHANCES ACOUSTIC STARTLE MAGNITUDE AND DISRUPTS PREPULSE INHIBITION IN ADULT RHESUS MONKEYS

    PubMed Central

    Schneider, Mary L.; Larson, Julie A.; Rypstat, Craig W.; Resch, Leslie M.; Roberts, Andrew; Moore, Colleen F.

    2013-01-01

    Background Prenatal alcohol exposure can contribute to a wide range of neurodevelopmental impairments in children and adults including behavioral and neuropsychiatric disorders. In rhesus monkeys we examined whether moderate level prenatal alcohol exposure would alter acoustic startle responses and prepulse inhibition of the acoustic startle (PPI). PPI is a highly quantifiable measure of inhibitory neural processes or sensorimotor gating associated with neuropsychiatric disorders. Methods Acoustic startle and PPI of the acoustic startle was tested in 37 adult rhesus monkeys (Macaca mulatta) from four experimental conditions: (a) moderate level prenatal alcohol-exposed, (b) prenatally-stressed, (c) moderate level prenatal alcohol-exposed + prenatally-stressed, and (d) sucrose controls. Results Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher HPA-axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI. Conclusion Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is one effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the co-morbidity between FASD and mental health conditions. PMID:23763712

  12. Strain-specific vulnerability to alcohol exposure in utero via hippocampal parent-of-origin expression of deiodinase-III

    PubMed Central

    Sittig, Laura J.; Shukla, Pradeep K.; Herzing, Laura B. K.; Redei, Eva E.

    2011-01-01

    Prenatal exposure to alcohol is thought to be the most prevalent nongenetic cause of a wide range of neurodevelopmental deficits. Insufficient thyroid hormone levels are one mechanism that hampers development of the alcohol-exposed brain, and we hypothesized that altered dosage of the imprinted thyroid hormone-inactivating gene deiodinase-III (Dio3) is responsible. To follow parent-of-origin allelic expression of Dio3 in the fetal and adult offspring of alcohol-consuming and control dams, we reciprocally crossed 2 polymorphic rat strains. In the frontal cortex, prenatal alcohol exposure altered imprinting patterns and total expression of Dio3 in the fetus and produced a permanent hypothyroid milieu in the adult. In the hippocampus, alcohol affected the paternal and total expression of Dio3 in the fetus and in the adult male, where thyroid hormone levels were concomitantly increased. Hippocampus-dependent behavioral deficits were identified exclusively in males, suggesting they are dependent on aberrant allelic Dio3 expression. None of these effects were observed in offspring of the reciprocal cross. Thus, genetic background and sex modify vulnerability to prenatal alcohol via brain region-specific expression of Dio3. This finding implies that phenotypic heterogeneity in human fetal alcohol spectrum disorder can be linked to genetic vulnerability in affected brain regions.—Sittig, L. J., Shukla, P. K., Herzing, L. B. K., Redei, E. E. Strain-specific vulnerability to alcohol exposure in utero via hippocampal parent-of-origin expression of deiodinase-III. PMID:21429942

  13. Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2016-07-01

    Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28-53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking. PMID:25950618

  14. 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

  15. 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

  16. 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. PMID:25033032

  17. 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.

  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. PMID:25489875

  19. Social Disadvantage and Exposure to Lower Priced Alcohol in Off-Premise Outlets

    PubMed Central

    Morrison, Christopher; Ponicki, William R; Smith, Karen

    2015-01-01

    Introduction and Aims Greater concentrations of off-premise alcohol outlets are found in areas of social disadvantage, exposing disadvantaged populations to excess risk for problems such as assault, child abuse and intimate partner violence. This study examines whether the outlets to which they are exposed also sell cheaper alcohol, potentially further contributing to income-related health disparities. Design and Methods We conducted unobtrusive observations in 295 off-premise outlets in Melbourne, Australia, randomly selected using a spatial sample frame. In semi-logged linear regression models we related the minimum purchase price for a 750ml bottle of wine to a national index of socio-economic advantage for the Census areas in which the outlets were located. Other independent variables characterised outlet features (e.g., volume, chain management) and conditions of the local alcohol market (adjacent outlet characteristics, neighbourhood characteristics). Results A one decile increase in socio-economic advantage was related to a 1.3% increase in logged price. Larger outlets, chains, outlets adjacent to chains, outlets in greater proximity to the nearest neighbouring outlet, those located in areas with more students also had cheaper alcohol. Discussion and Conclusions Not only are disadvantaged populations exposed to more outlets, the outlets to which they are exposed sell cheaper alcohol. This finding appears to be consistent with the spatial dynamics of typical retail markets. PMID:25808717

  20. PRENATAL ALCOHOL EXPOSURE ALTERS STEADY-STATE AND ACTIVATED GENE EXPRESSION IN THE ADULT RAT BRAIN

    PubMed Central

    Stepien, Katarzyna A.; Lussier, Alexandre A.; Neumann, Sarah M.; Pavlidis, Paul; Kobor, Michael S.; Weinberg, Joanne

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression

  1. 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. PMID:25556946

  2. Gestational Alcohol Exposure and Other Factors Associated With Continued Teenage Drinking.

    PubMed

    Cornelius, Marie D; Goldschmidt, Lidush; Day, Nancy L

    2016-08-01

    Purpose A longitudinal cohort of adolescents who initiated drinking before age 15 were studied to determine which factors distinguished between early initiators who continued to drink (persisters) from those who stopped drinking (desisters). There were 308 early initiators in the total sample (n = 917); 247 were persisters, and 61 were desisters. Method A stepwise discriminant analysis identified differences between the two groups. Considered risk/protective factors were parenting practices, peer drinking, child and maternal depression, child behavior, prenatal alcohol exposure, home environment, and demographic factors. Results Desistence was significantly related to African American race and more parental strictness. Exposure to ≥1 drink/day during pregnancy and high levels of autonomy from parents were significant predictors of persistent drinking. Conclusions Early initiation places adolescents at risk for continued and heavier drinking. Identifying characteristics of those who start early but do or do not continue drinking can inform education programs to better target the most appropriate adolescents. PMID:27405800

  3. Alcohol exposure during the first two trimesters-equivalent alters the development of corpus callosum projection neurons in the rat.

    PubMed

    Livy, Daniel J; Elberger, Andrea J

    2008-06-01

    Children exposed prenatally to alcohol can display a variety of neural deficits, including an altered development of the corpus callosum (CC), the largest interhemispheric axon pathway in the brain. Furthermore, these children show functional abnormalities that are related to brain regions with significant numbers of CC connections. Little is known about how alcohol imparts influence on CC development, but one possible mechanism is by affecting the corpus callosum projection neurons (CCpn) directly. The purpose of this study was to quantify the effects of prenatal alcohol exposure on the number, size, and distribution of CCpn within the visual cortex. The visual cortex was selected specifically due to the many vision-related deficits noted in fetal alcohol exposed children and because the critical role of the CC in visual cortex development is well documented. Sprague-Dawley rat pups received one of four alcohol dosages during gestational days (G) 1-20, or reared as nutritional or untreated control animals. Each litter was categorized according to the peak blood alcohol concentration experienced. Pups were removed from each litter on days equivalent to G29, G36, G43, and G50, for histology and measurement. Callosal axons were labeled retrogradely to their CCpn using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and the CCpn were then examined using confocal laser scanning microscopy. Differences between alcohol-exposed and control animals were observed in CCpn cell body size, number, and location with the cortex. This was particularly true of animals exposed to high doses of alcohol. In addition, some trends of CCpn development were found to be unchanged as a result of prenatal alcohol exposure. The results demonstrate clear differences in the development of CCpn in the visual cortex between alcohol-exposed and control animals and suggest that this development is particularly affected in those animals exposed to high doses of alcohol

  4. 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. PMID:18670372

  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. Prenatal alcohol exposure alters synaptic activity of adult hippocampal dentate granule cells under conditions of enriched environment.

    PubMed

    Kajimoto, Kenta; Valenzuela, C Fernando; Allan, Andrea M; Ge, Shaoyu; Gu, Yan; Cunningham, Lee Anna

    2016-08-01

    Prenatal alcohol exposure (PAE) results in fetal alcohol spectrum disorder (FASD), which is characterized by a wide range of cognitive and behavioral deficits that may be linked to impaired hippocampal function and adult neurogenesis. Preclinical studies in mouse models of FASD indicate that PAE markedly attenuates enrichment-mediated increases in the number of adult-generated hippocampal dentate granule cells (aDGCs), but whether synaptic activity is also affected has not been studied. Here, we utilized retroviral birth-dating coupled with whole cell patch electrophysiological recordings to assess the effects of PAE on enrichment-mediated changes in excitatory and inhibitory synaptic activity as a function of DGC age. We found that exposure to an enriched environment (EE) had no effect on baseline synaptic activity of 4- or 8-week-old aDGCs from control mice, but significantly enhanced the excitatory/inhibitory ratio of synaptic activity in 8-week-old aDGCs from PAE mice. In contrast, exposure to EE significantly enhanced the excitatory/inhibitory ratio of synaptic activity in older pre-existing DGCs situated in the outer dentate granule cell layer (i.e., those generated during embryonic development; dDGCs) in control mice, an effect that was blunted in PAE mice. These findings indicate distinct electrophysiological responses of hippocampal DGCs to behavioral challenge based on cellular ontogenetic age, and suggest that PAE disrupts EE-mediated changes in overall hippocampal network activity. These findings may have implications for future therapeutic targeting of hippocampal dentate circuitry in clinical FASD. © 2016 Wiley Periodicals, Inc. PMID:27009742

  7. 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. PMID:24918069

  8. 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

  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. PMID:25447751

  10. PM POPULATION EXPOSURE AND DOSE MODELS

    EPA Science Inventory

    The overall objective of this study is the development of a refined probabilistic exposure and dose model for particulate matter (PM) suitable for predicting PM10 and PM2.5 population exposures. This modeling research will be conducted both in-house by EPA scientists and through...

  11. NEXT GENERATION MULTIMEDIA/MULTIPATHWAY EXPOSURE MODELING

    EPA Science Inventory

    The Stochastic Human Exposure and Dose Simulation model for pesticides (SHEDS-Pesticides) supports the efforts of EPA to better understand human exposures and doses to multimedia, multipathway pollutants. It is a physically-based, probabilistic computer model that predicts, for u...

  12. 75 FR 22401 - Exposure Modeling Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-28

    ... AGENCY Exposure Modeling Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: An Exposure Modeling Public Meeting (EMPM) will be held for one day on July 27, 2010. This notice... to the meeting, to give EPA as much time as possible to process your request. ADDRESSES: The...

  13. 76 FR 365 - Exposure Modeling Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... AGENCY Exposure Modeling Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: An Exposure Modeling Public Meeting (EMPM) will be held for one day on January 11, 2011. This... meeting, to give EPA as much time as possible to process your request. ] ADDRESSES: The meeting will...

  14. 78 FR 60870 - Exposure Modeling Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... AGENCY Exposure Modeling Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of public meeting. SUMMARY: An Exposure Modeling Public Meeting (EMPM) will be held for 1 day on October 8... days prior to the meeting, to give EPA as much time as possible to process your request. ADDRESSES:...

  15. 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. PMID:26250573

  16. 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)

  17. Prognosis and Prognostic Scoring Models for Alcoholic Liver Disease and Acute Alcoholic Hepatitis.

    PubMed

    Gholam, Pierre M

    2016-08-01

    Multiple prognostic scoring systems have been developed to predict mortality from acute alcoholic hepatitis. Some systems, such as the modified discriminant function, are specific to alcoholic hepatitis. Others, such as the model for end-stage liver disease, apply to a broad range of liver diseases. Prognostic factors are better at predicting patients who are likely to survive rather than die of this condition at 30 and 90 days. This important shortcoming may be improved by combining scores for better prediction accuracy. PMID:27373611

  18. A model system for QTL analysis: Effects of alcohol dehydrogenase genotype on alcohol pharmacokinetics

    SciTech Connect

    Martin, N.G.; Nightingale, B.; Whitfield, J.B.

    1994-09-01

    There is much interest in the detection of quantitative trait loci (QTL) - major genes which affect quantitative phenotypes. The relationship of polymorphism at known alcohol metabolizing enzyme loci to alcohol pharmacokinetics is a good model system. The three class I alcohol dehydrogenase genes are clustered on chromosome 4 and protein electrophoresis has revealed polymorphisms at the ADH2 and ADH3 loci. While different activities of the isozymes have been demonstrated in vitro, little work has been done in trying to relate ADH polymorphism to variation in ethanol metabolism in vivo. We previously measured ethanol metabolism and psychomotor reactivity in 206 twin pairs and demonstrated that most of the repeatable variation was genetic. We have now recontacted the twins to obtain DNA samples and used PCR with allele specific primers to type the ADH2 and ADH3 polymorphisms in 337 individual twins. FISHER has been used to estimate fixed effects of typed polymorphisms simultaneously with remaining linked and unlinked genetic variance. The ADH2*1-2 genotypes metabolize ethanol faster and attain a lower peak blood alcohol concentration than the more common ADH2*1-1 genotypes, although less than 3% of the variance is accounted for. There is no effect of ADH3 genotype. However, sib-pair linkage analysis suggests that there is a linked polymorphism which has a much greater effect on alcohol metabolism that those typed here.

  19. Modeling Particle Exposure in US Trucking Terminals

    PubMed Central

    Davis, ME; Smith, TJ; Laden, F; Hart, JE; Ryan, LM; Garshick, E

    2007-01-01

    Multi-tiered sampling approaches are common in environmental and occupational exposure assessment, where exposures for a given individual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the US trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States sampled between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and sampling at two indoor work locations and an outdoor “background” location. Using the SEM method, we predict: 1) personal exposures as a function of work related exposure and smoking status; 2) work related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions; and 3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the sampling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling. PMID:16856739

  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

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

    1992-09-01

    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. 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. PMID:26835604

  2. Perceived physical availability of alcohol at work and workplace alcohol use and impairment: testing a structural model.

    PubMed

    Frone, Michael R; Trinidad, Jonathan R

    2014-12-01

    This study develops and tests a new conceptual model of perceived physical availability of alcohol at work that provides unique insight into 3 dimensions of workplace physical availability of alcohol and their direct and indirect relations to workplace alcohol use and impairment. Data were obtained from a national probability sample of 2,727 U.S. workers. The results support the proposed conceptual model and provide empirical support for a positive relation of perceived physical availability of alcohol at work to workplace alcohol use and 2 dimensions of workplace impairment (workplace intoxication and workplace hangover). Ultimately, the findings suggest that perceived physical availability of alcohol at work is a risk factor for alcohol use and impairment during the workday, and that this relation is more complex than previously hypothesized. PMID:25243831

  3. Withdrawal symptoms in a long-term model of voluntary alcohol drinking in Wistar rats.

    PubMed

    Hölter, S M; Linthorst, A C; Reul, J M; Spanagel, R

    2000-05-01

    Long-term voluntary alcohol drinking with repeated alcohol deprivation episodes has been suggested as animal model for some aspects of alcoholism. Using a radiotelemetric system, the present study investigated the occurrence of withdrawal symptoms in long-term voluntarily alcohol drinking Wistar rats with (repeated alcohol deprivation group) and without (first alcohol deprivation group) prior alcohol deprivation experience. Six days after transmitter implantation, alcohol bottles were removed, and returned 4 days later. Alcohol deprivation induced hyperlocomotion in both groups. In the repeated alcohol deprivation group, hyperlocomotion was increased at the beginning of the alcohol deprivation phase and decreased during the following dark phase, suggesting that removal of the alcohol bottles might have become a conditioned withdrawal stimulus for this group. Both groups showed an enhanced alcohol intake after representation of alcohol bottles compared to preabstinence intakes (alcohol deprivation effect). However, alcohol intake of the repeated alcohol deprivation group was significantly increased compared to the first alcohol deprivation group at the end of the experiment. It is concluded that repeated alcohol deprivation experience might promote the development of alcohol addiction because of its latent stimulating effect on alcohol drinking that can be unveiled by (presumably mildly stressful) experimental situations. PMID:10837854

  4. The NIfETy Method for Environmental Assessment of Neighborhood-level Indicators of Violence, Alcohol, and Other Drug Exposure

    PubMed Central

    Furr-Holden, C. D. M.; Smart, M. J.; Pokorni, J. L.; Ialongo, N. S.; Leaf, P. J.; Holder, H. D.; Anthony, J. C.

    2010-01-01

    There are limited validated quantitative assessment methods to measure features of the built and social environment that might form the basis for environmental preventive interventions. This study describes a model approach for epidemiologic assessment of suspected environmental determinants of violence, alcohol and other drug (VAOD) exposure and fills this gap in current research. The investigation sought to test the feasibility of a systematic and longitudinal assessment of residential block characteristics related to physical and social disorder and indicators of VAOD exposure. Planometric data were used to establish a stratified random sample of street segments within defined neighborhoods of an urban metropolitan area. Field rater assessments of these neighborhood street segments were conducted using the Neighborhood Inventory for Environmental Typology (NIfETy). This report provides a detailed description of the NIfETy Method, including metric properties of the NIfETy Instrument and outcomes of training procedures and quality control measures. Also presented are block-level characteristics and estimates of observable signs of VAOD activity. This work is a first step toward developing future community-level environmental preventive interventions geared to reduce community VAOD exposure among youthful urban populations and may prove to be useful to other public health research groups as well. PMID:18931911

  5. College Students' Drinking and Posting About Alcohol: Forwarding a Model of Motivations, Behaviors, and Consequences.

    PubMed

    Thompson, Charee M; Romo, Lynsey K

    2016-06-01

    College drinking continues to remain a public health problem that has been exacerbated by alcohol-related posts on social networking sites (SNSs). Although existing research has linked alcohol consumption, alcohol posts, and adverse consequences to one another, comprehensive explanations for these associations have been largely unexplored. Thus, we reasoned that students' personal motivations (i.e., espousing an alcohol identity, needing entertainment, and adhering to social norms) influence their behaviors (i.e., alcohol consumption and alcohol-related posting on SNSs), which can lead to alcohol problems. Using structural equation modeling, we analyzed data from 364 undergraduate students and found general support for our model. In particular, espousing an alcohol identity predicted alcohol consumption and alcohol-related SNS posting, needing entertainment predicted alcohol consumption but not alcohol-related SNS posting, and adhering to social norms predicted alcohol-related SNS posting but not alcohol consumption. In turn, alcohol consumption and alcohol-related SNS posting predicted alcohol problems. It is surprising that alcohol-related SNS posting was a stronger predictor of alcohol problems than alcohol consumption. We discuss the findings within their applied applications for college student health. PMID:27186824

  6. 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. PMID:19243891

  7. 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

  8. Urinary 1-hydroxypyrene in coke oven workers relative to exposure, alcohol consumption, and metabolic enzymes

    PubMed Central

    Zhang, J; Ichiba, M; Hara, K; Zhang, S; Hanaoka, T; Pan, G; Yamano, Y; Takahashi, K; Tomokuni, K

    2001-01-01

    OBJECTIVES—To investigate the influence of personal lifestyle—such as smoking and alcohol consumption—on urinary 1-hydroxypyrene (1-OHP) concentrations in coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) and to evaluate the association of 1-OHP concentrations with the genetic polymorphism of several metabolic enzymes including cytochrome P-450 (CYP) 1A1 and glutathione S-tranferases (GSTs).
METHODS—The study population contained 162 coke oven workers and 58 controls employed at the largest iron and steel factory in China. Personal data were collected at the interview. 1-OHP in urine was measured with high performance liquid chromatography with fluorescence detection. Genetic polymorphisms were identified by the polymerase chain reaction (PCR) method.
RESULTS—A positive association between excretion of urinary 1-OHP and the levels of exposure to PAHs was confirmed. Those people who consumed ⩾50 g/day ethanol had significantly higher 1-OHP excretion than did other coke oven workers (p<0.01). No significant difference in urinary 1-OHP was found between smokers and non-smokers, in both controls and exposed subjects. The variant homozygotes at exon 7 of the CYP1A1 gene had significantly higher urinary 1-OHP concentrations than other CYP1A1 genotypes among the exposed workers (p=0.03). There was less association between the concentrations of 1-OHP and the GSTM1, GSTP1, or GSTT1 polymorphism.
CONCLUSIONS—The present study confirmed that urinary 1-OHP is a good biomarker for exposure to PAHs. Alcohol consumption affected urinary 1-OHP excretion. The variant genotypes of the CYP1A1 gene may result in the enhancement of PAH metabolites. It is helpful to understand the role of individual susceptibility on metabolism of carcinogens. These findings suggest that the modulating effect of individual lifestyle factors or genetic nature should be considered in future studies on occupational exposure to PAHs and in evaluating the health risk

  9. Visual Defects in a Mouse Model of Fetal Alcohol Spectrum Disorder

    PubMed Central

    Lantz, Crystal L.; Pulimood, Nisha S.; Rodrigues-Junior, Wandilson S.; Chen, Ching-Kang; Manhaes, Alex C.; Kalatsky, Valery A.; Medina, Alexandre Esteves

    2014-01-01

    Alcohol consumption during pregnancy can lead to a multitude of neurological problems in offspring, varying from subtle behavioral changes to severe mental retardation. These alterations are collectively referred to as Fetal Alcohol Spectrum Disorders (FASD). Early alcohol exposure can strongly affect the visual system and children with FASD can exhibit an amblyopia-like pattern of visual acuity deficits even in the absence of optical and oculomotor disruption. Here, we test whether early alcohol exposure can lead to a disruption in visual acuity, using a model of FASD to mimic alcohol consumption in the last months of human gestation. To accomplish this, mice were exposed to ethanol (5 g/kg i.p.) or saline on postnatal days (P) 5, 7, and 9. Two to three weeks later we recorded visually evoked potentials to assess spatial frequency detection and contrast sensitivity, conducted electroretinography (ERG) to further assess visual function and imaged retinotopy using optical imaging of intrinsic signals. We observed that animals exposed to ethanol displayed spatial frequency acuity curves similar to controls. However, ethanol-treated animals showed a significant deficit in contrast sensitivity. Moreover, ERGs revealed a market decrease in both a- and b-waves amplitudes, and optical imaging suggest that both elevation and azimuth maps in ethanol-treated animals have a 10–20° greater map tilt compared to saline-treated controls. Overall, our findings suggest that binge alcohol drinking restricted to the last months of gestation in humans can lead to marked deficits in visual function. PMID:25346924

  10. Visual defects in a mouse model of fetal alcohol spectrum disorder.

    PubMed

    Lantz, Crystal L; Pulimood, Nisha S; Rodrigues-Junior, Wandilson S; Chen, Ching-Kang; Manhaes, Alex C; Kalatsky, Valery A; Medina, Alexandre Esteves

    2014-01-01

    Alcohol consumption during pregnancy can lead to a multitude of neurological problems in offspring, varying from subtle behavioral changes to severe mental retardation. These alterations are collectively referred to as Fetal Alcohol Spectrum Disorders (FASD). Early alcohol exposure can strongly affect the visual system and children with FASD can exhibit an amblyopia-like pattern of visual acuity deficits even in the absence of optical and oculomotor disruption. Here, we test whether early alcohol exposure can lead to a disruption in visual acuity, using a model of FASD to mimic alcohol consumption in the last months of human gestation. To accomplish this, mice were exposed to ethanol (5 g/kg i.p.) or saline on postnatal days (P) 5, 7, and 9. Two to three weeks later we recorded visually evoked potentials to assess spatial frequency detection and contrast sensitivity, conducted electroretinography (ERG) to further assess visual function and imaged retinotopy using optical imaging of intrinsic signals. We observed that animals exposed to ethanol displayed spatial frequency acuity curves similar to controls. However, ethanol-treated animals showed a significant deficit in contrast sensitivity. Moreover, ERGs revealed a market decrease in both a- and b-waves amplitudes, and optical imaging suggest that both elevation and azimuth maps in ethanol-treated animals have a 10-20° greater map tilt compared to saline-treated controls. Overall, our findings suggest that binge alcohol drinking restricted to the last months of gestation in humans can lead to marked deficits in visual function. PMID:25346924

  11. Neuroplastic alterations in the limbic system following cocaine or alcohol exposure.

    PubMed

    Stuber, Garret D; Hopf, F Woodward; Tye, Kay M; Chen, Billy T; Bonci, Antonello

    2010-01-01

    Neuroplastic changes in the CNS are thought to be a fundamental component of learning and memory. While pioneering studies in the hippocampus and cerebellum have detailed many of the basic mechanisms that can lead to alterations in synaptic transmission based on previous activity, only more recently has synaptic plasticity been monitored after behavioral manipulation or drug exposure. In this chapter, we review evidence that drugs of abuse are powerful modulators of synaptic plasticity. Both the dopaminergic neurons of the ventral tegmental area as well medium spiny neurons in nucleus accumbens show enhanced excitatory synaptic strength following passive or active exposure to drugs such as cocaine and alcohol. In the VTA, both the enhancement of excitatory synaptic strength and the acquisition of drug-related behaviors depend on signaling through the N-methyl-D: -aspartate receptors (NMDARs) which are mechanistically thought to lead to increased synaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Synaptic insertion of AMPARs by drugs of abuse can be long lasting, depending on the route of administration, number of drug exposures, or whether the drugs are received passively or self-administered. PMID:21161748

  12. Electrostatic model for hydrogen bonds in alcohols

    SciTech Connect

    Giguere, P.A.; Pigeon-Gosselin, M.

    1988-11-01

    The authors have measured the Raman spectra of liquid methanol at temperatures between 50/sup 0/ and -77/sup 0/C. The weak O-H stretching bands appear, under amplification, more and more asymmetric as the temperature is lowered. They can be decomposed into three Gaussian components centered at about 3220, 3310, and 3400 cm/sup -1/. The former, predominant at low temperature, corresponds to single, linear hydrogen bonds (LHB) between two molecules. The other two are assigned to branched hydrogen bonds, respectively bifurcated (BHB), between three molecules, and trifurcated (THB), between four molecules. They conclude that the molecular structure of liquid alcohols is not chain-like, as presumed so far, but a three-dimensional network featuring a mixture of single (LBH), and multiple hydrogen bonds (BHB, and THB). They are mainly electrostatic in nature, their relative proportions and geometry governed by the packing conditions for minimum energy. They form distinct trimers and tetramers in dilute solutions of alcohols in inert solvents and frozen matrices, and the latter even in the vapor.

  13. The interaction between manganese exposure and alcohol on neurobehavioral outcomes in welders.

    PubMed

    Ellingsen, Dag G; Kusraeva, Zarina; Bast-Pettersen, Rita; Zibarev, Evgenij; Chashchin, Maxim; Thomassen, Yngvar; Chashchin, Valery

    2014-01-01

    Neurobehavioral functions were studied in 137 welders exposed to the geometric mean (GM) air concentration of 214 μg/m(3) (range 1-3230) of manganese (Mn) based on the individual mean from two days of air sampling. Only 22 μg/m(3) (GM) was soluble in the artificial lung fluid Hatch solution. The welders were compared to 137 referents (turner/fitters) recruited from the same plants. The GM concentrations of Mn in whole blood (B-Mn) and urine (U-Mn) were 12.8 μg/L and 0.36 μg/g creatinine versus 8.0 μg/L and 0.07 μg/g creatinine in the referents. Alcohol consumption was assessed by measuring carbohydrate deficient transferrin in serum (sCDT). The welders had poorer performance than the referents on the Grooved Pegboard, Finger Tapping, Simple Reaction Time (SRT) and possibly the Maximum Frequency tests. They also reported more subjective symptoms. Welders with sCDT above the upper reference limit had substantially poorer performances on the Grooved Pegboard test, Finger Tapping test and SRT than welders with sCDT below this level. No effect of high sCDT was observed in the referents, indicating an interaction between high sCDT and exposure to Mn for these tests. Self-reported alcohol consumption had no impact on these neurobehavioral test results. A statistically significant difference in the SRT and Grooved Pegboard test results remained after excluding all subjects with sCDT above the normal level, but the difference in test scores between the groups was smaller. These welders also reported more subjective symptoms than the referents. The results suggest that sCDT should be measured in neurobehavioral studies of occupationally Mn exposed populations for a more precise estimation of high alcohol consumption. PMID:24263125

  14. A BEHAVIORAL ECONOMIC MODEL OF ALCOHOL ADVERTISING AND PRICE

    PubMed Central

    SAFFER, HENRY; DAVE, DHAVAL; GROSSMAN, MICHAEL

    2016-01-01

    SUMMARY This paper presents a new empirical study of the effects of televised alcohol advertising and alcohol price on alcohol consumption. A novel feature of this study is that the empirical work is guided by insights from behavioral economic theory. Unlike the theory used in most prior studies, this theory predicts that restriction on alcohol advertising on TV would be more effective in reducing consumption for individuals with high consumption levels but less effective for individuals with low consumption levels. The estimation work employs data from the National Longitudinal Survey of Youth, and the empirical model is estimated with quantile regressions. The results show that advertising has a small positive effect on consumption and that this effect is relatively larger at high consumption levels. The continuing importance of alcohol taxes is also supported. Education is employed as a proxy for self-regulation, and the results are consistent with this assumption. The key conclusion is that restrictions on alcohol advertising on TV would have a small negative effect on drinking, and this effect would be larger for heavy drinkers. PMID:25919364

  15. A Behavioral Economic Model of Alcohol Advertising and Price.

    PubMed

    Saffer, Henry; Dave, Dhaval; Grossman, Michael

    2016-07-01

    This paper presents a new empirical study of the effects of televised alcohol advertising and alcohol price on alcohol consumption. A novel feature of this study is that the empirical work is guided by insights from behavioral economic theory. Unlike the theory used in most prior studies, this theory predicts that restriction on alcohol advertising on TV would be more effective in reducing consumption for individuals with high consumption levels but less effective for individuals with low consumption levels. The estimation work employs data from the National Longitudinal Survey of Youth, and the empirical model is estimated with quantile regressions. The results show that advertising has a small positive effect on consumption and that this effect is relatively larger at high consumption levels. The continuing importance of alcohol taxes is also supported. Education is employed as a proxy for self-regulation, and the results are consistent with this assumption. The key conclusion is that restrictions on alcohol advertising on TV would have a small negative effect on drinking, and this effect would be larger for heavy drinkers. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25919364

  16. Higher functioning children with prenatal alcohol exposure: is there a specific neurocognitive profile?

    PubMed

    Quattlebaum, Justin L; O'Connor, Mary J

    2013-01-01

    Recent attempts to identify a neurocognitive profile of children with prenatal alcohol exposure (PAE) have led to an emerging "generalized deficit" conceptualization marked by diffuse information processing and integration difficulties as opposed to a specific profile. This study examines whether this conceptualization can be extended to higher functioning children with PAE who are without intellectual disability and addresses several limitations of previous research. One hundred twenty-five children aged 6-12 years with social skills deficits, 97 of whom met diagnostic criteria for a Fetal Alcohol Spectrum Disorder (FASD), underwent a comprehensive, multi-informant assessment of neurocognitive, emotional, social, behavioral, and adaptive functioning. Multivariate analyses of variance examined differences in functioning between the PAE group and a nonexposed comparison group with and without controlling for child IQ. Results indicated that the PAE group returned significantly poorer scores than the nonexposed group on every construct assessed, including executive functioning, attention, working/visuospatial memory, linguistic abstraction, adaptive behavior, emotional/behavioral functioning, and social cognition. These differences largely maintained after controlling for IQ and were similar regardless of informant, although teachers reported somewhat fewer group differences. Within the PAE group, no differences were found across FASD subtypes. These results provide evidence extending the emerging generalized deficit conceptualization of children with PAE to those higher functioning individuals without global intellectual disability. PMID:22905880

  17. 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. PMID:26960969

  18. Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Proposed DSM-5 Diagnosis.

    PubMed

    Kable, Julie A; O'Connor, Mary J; Olson, Heather Carmichael; Paley, Blair; Mattson, Sarah N; Anderson, Sally M; Riley, Edward P

    2016-04-01

    Over the past 40 years, a significant body of animal and human research has documented the teratogenic effects of prenatal alcohol exposure (PAE). Neurobehavioral Disorder associated with PAE is proposed as a new clarifying term, intended to encompass the neurodevelopmental and mental health symptoms associated with PAE. Defining this disorder is a necessary step to adequately characterize these symptoms and allow clinical assessment not possible using existing physically-based diagnostic schemes. Without appropriate diagnostic guidelines, affected individuals are frequently misdiagnosed and treated inappropriately (often to their considerable detriment) by mental health, educational, and criminal justice systems. Three core areas of deficits identified from the available research, including neurocognitive, self-regulation, and adaptive functioning impairments, are discussed and information regarding associated features and disorders, prevalence, course, familial patterns, differential diagnosis, and treatment of the proposed disorder are also provided. PMID:26202432

  19. In silico Models of Alcohol Dependence and Treatment.

    PubMed

    Kovatchev, Boris; Breton, Marc; Johnson, Bankole

    2012-01-01

    In this paper we view alcohol dependence and the response to treatment as a recurrent bio-behavioral process developing in time and propose formal models of this process combining behavior and biology in silico. The behavioral components of alcohol dependence and treatment are formally described by a stochastic process of human behavior, which serves as an event generator challenging the metabolic system. The biological component is driven by the biochemistry of alcohol intoxication described by deterministic models of ethanol pharmacodynamics and pharmacokinetics to enable simulation of drinking addiction in humans. Derived from the known physiology of ethanol and the literature of both ethanol intoxication and ethanol absorption, the different models are distilled into a minimal model (as simple as the complexity of the data allows) that can represent any specific patient. We use these modeling and simulation techniques to explain responses to placebo and ondansetron treatment observed in clinical studies. Specifically, the response to placebo was explained by a reduction of the probability of environmental reinforcement, while the effect of ondansetron was explained by a gradual decline in the degree of ethanol-induced neuromodulation. Further, we use in silico experiments to study critical transitions in blood alcohol levels after specific average number of drinks per day, and propose the existence of two critical thresholds in the human - one at 5 and another at 11 drinks/day - at which the system shifts from stable to critical and to super critical state indicating a state of alcohol addiction. The advantages of such a model-based investigation are that (1) the process of instigation of alcohol dependence and its treatment can be deconstructed into meaningful steps, which allow for individualized treatment tailoring, and (2) physiology and behavior can be quantified in different (animal or human) studies and then the results can be integrated in silico. PMID

  20. 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

  1. Differences in Attitudes About HIV Pre-Exposure Prophylaxis Use Among Stimulant Versus Alcohol Using Men Who Have Sex with Men.

    PubMed

    Oldenburg, Catherine E; Mitty, Jennifer A; Biello, Katie B; Closson, Elizabeth F; Safren, Steven A; Mayer, Kenneth H; Mimiaga, Matthew J

    2016-07-01

    Alcohol and stimulant use are independently associated with increased HIV acquisition among men who have sex with men (MSM). We assessed differences in acceptability and perceived barriers to uptake of pre-exposure prophylaxis (PrEP) among stimulant and alcohol-using MSM in Boston. From September 2012-2013, a quantitative assessment was conducted with 254 MSM respondents who reported recent condomless sex in the context of concurrent stimulant (crack/cocaine and crystal methamphetamine; n = 132) or alcohol use (n = 122). Thirteen (5.1  %) reported previous PrEP use. In multivariable models, stimulant users were more likely to be concerned that substance use would affect PrEP adherence (aRR = 2.79, 95  % CI 1.63-4.77), and were less concerned about HIV stigma as a barrier to PrEP uptake (aRR = 0.52, 95  % CI 0.30-0.90) compared to alcohol users. Barriers to PrEP uptake and adherence differ by type of substance used. Different strategies may be required for PrEP implementation among MSM who use stimulants and alcohol. PMID:26462669

  2. A statistical model of hydrogen bond networks in liquid alcohols

    NASA Astrophysics Data System (ADS)

    Sillrén, Per; Bielecki, Johan; Mattsson, Johan; Börjesson, Lars; Matic, Aleksandar

    2012-03-01

    We here present a statistical model of hydrogen bond induced network structures in liquid alcohols. The model generalises the Andersson-Schulz-Flory chain model to allow also for branched structures. Two bonding probabilities are assigned to each hydroxyl group oxygen, where the first is the probability of a lone pair accepting an H-bond and the second is the probability that given this bond also the second lone pair is bonded. The average hydroxyl group cluster size, cluster size distribution, and the number of branches and leaves in the tree-like network clusters are directly determined from these probabilities. The applicability of the model is tested by comparison to cluster size distributions and bonding probabilities obtained from Monte Carlo simulations of the monoalcohols methanol, propanol, butanol, and propylene glycol monomethyl ether, the di-alcohol propylene glycol, and the tri-alcohol glycerol. We find that the tree model can reproduce the cluster size distributions and the bonding probabilities for both mono- and poly-alcohols, showing the branched nature of the OH-clusters in these liquids. Thus, this statistical model is a useful tool to better understand the structure of network forming hydrogen bonded liquids. The model can be applied to experimental data, allowing the topology of the clusters to be determined from such studies.

  3. A statistical model of hydrogen bond networks in liquid alcohols.

    PubMed

    Sillrén, Per; Bielecki, Johan; Mattsson, Johan; Börjesson, Lars; Matic, Aleksandar

    2012-03-01

    We here present a statistical model of hydrogen bond induced network structures in liquid alcohols. The model generalises the Andersson-Schulz-Flory chain model to allow also for branched structures. Two bonding probabilities are assigned to each hydroxyl group oxygen, where the first is the probability of a lone pair accepting an H-bond and the second is the probability that given this bond also the second lone pair is bonded. The average hydroxyl group cluster size, cluster size distribution, and the number of branches and leaves in the tree-like network clusters are directly determined from these probabilities. The applicability of the model is tested by comparison to cluster size distributions and bonding probabilities obtained from Monte Carlo simulations of the monoalcohols methanol, propanol, butanol, and propylene glycol monomethyl ether, the di-alcohol propylene glycol, and the tri-alcohol glycerol. We find that the tree model can reproduce the cluster size distributions and the bonding probabilities for both mono- and poly-alcohols, showing the branched nature of the OH-clusters in these liquids. Thus, this statistical model is a useful tool to better understand the structure of network forming hydrogen bonded liquids. The model can be applied to experimental data, allowing the topology of the clusters to be determined from such studies. PMID:22401459

  4. 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. PMID:21641957

  5. Effect of Prenatal Alcohol Exposure on Childhood Academic Outcomes: Contrasting Maternal and Paternal Associations in the ALSPAC Study

    PubMed Central

    Alati, Rosa; Davey Smith, George; Lewis, Sarah J.; Sayal, Kapil; Draper, Elizabeth S.; Golding, Jean; Fraser, Robert; Gray, Ron

    2013-01-01

    Background The impact of low-to-moderate levels of alcohol consumption during pregnancy on child cognitive outcomes has been of recent concern. This study has tested the hypothesis that low-to-moderate maternal alcohol use in pregnancy is associated with lower school test scores at age 11 in the offspring via intrauterine mechanisms. Methods We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study based in the South West of England. Analyses were conducted on 7062 participants who had complete data on: maternal and paternal patterns of alcohol use in the first trimester and at 18 weeks' gestation, child's academic outcomes measured at age 11, gender, maternal age, parity, marital status, ethnicity, household crowding, home ownership status and parental education. We contrasted the association of mother's alcohol consumption during pregnancy with child's National Curriculum Key Stage 2 (KS2) test scores with the association for father's alcohol consumption (during the time the mother was pregnant) with child's National Curriculum Key Stage 2 (KS2) test scores. We used multivariate linear regression to estimate mean differences and 95% confidence intervals [CI] in KS2 scores across the exposure categories and computed f statistics to compare maternal and paternal associations. Findings and conclusions Drinking up to 1 unit of alcohol a day during pregnancy was not associated with lower test scores. However, frequent prenatal consumption of 4 units (equivalent to 32 grams of alcohol) on each single drinking occasion was associated with reduced educational attainment [Mean change in offspring KS2 score was −0.68 (−1.03, −0.33) for maternal alcohol categories compared to 0.27 (0.07, 0.46) for paternal alcohol categories]. Frequent consumption of 4 units of alcohol during pregnancy may adversely affect childhood academic outcomes via intrauterine mechanisms. PMID:24130672

  6. Alcohol exposure during late ovine gestation alters fetal liver iron homeostasis without apparent dysmorphology.

    PubMed

    Sozo, Foula; Dick, Anna M; Bensley, Jonathan G; Kenna, Kelly; Brien, James F; Harding, Richard; De Matteo, Robert

    2013-06-15

    High levels of alcohol (ethanol) exposure during fetal life can affect liver development and can increase susceptibility to infection after birth. Our aim was to determine the effects of a moderate level of ethanol exposure in late gestation on the morphology, iron status, and inflammatory status of the ovine fetal liver. Pregnant ewes were chronically catheterized at 91 days of gestation (DG; term ~145 DG) for daily intravenous infusion of ethanol (0.75 g/kg maternal body wt; n = 8) or saline (n = 7) over 1 h from 95 to 133 DG. At necropsy (134 DG), fetal livers were collected for analysis. Liver weight, general liver morphology, hepatic cell proliferation and apoptosis, perivascular collagen deposition, and interleukin (IL)-1β, IL-6, or IL-8 mRNA levels were not different between groups. However, ethanol exposure led to significant decreases in hepatic content of ferric iron and gene expression of the iron-regulating hormone hepcidin and tumor necrosis factor (TNF)-α (all P < 0.05). In the placenta, there was no difference in transferrin receptor, divalent metal transporter 1, and ferritin mRNA levels; however, ferroportin mRNA levels were increased in ethanol-exposed animals (P < 0.05), and ferroportin protein tended to be increased (P = 0.054). Plasma iron concentration was not different between control and ethanol-exposed groups; control fetuses had significantly higher iron concentrations than their mothers, whereas maternal and fetal iron concentrations were similar in ethanol-exposed animals. We conclude that daily ethanol exposure during the third-trimester-equivalent in sheep does not alter fetal liver morphology; however, decreased fetal liver ferric iron content and altered hepcidin and ferroportin gene expression indicate that iron homeostasis is altered. PMID:23594612

  7. 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

  8. 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. PMID:26142564

  9. 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

  10. The catalytic decomposition of silver coated cinnamyl alcohol during water exposure and the formation of silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Dahle, S.; Höfft, O.; Viöl, W.; Maus-Friedrichs, W.

    2014-03-01

    Metastable Induced Electron Spectroscopy, Ultraviolet Photoelectron Spectroscopy (He I), X-ray Photoelectron Spectroscopy, and Quadrupole Mass Spectrometry are employed to study the interaction of water with Ag nanoparticles on cinnamyl alcohol films. The films have been prepared on Au(111) substrates by thermal evaporation. The water adsorption does not result in any chemical interaction with the silver nanoparticles at all, but the cinnamyl alcohol changes its chemical structure significantly. While water molecules induce a reduction of the organic groups, the film thickness seems to decrease. Thus, a decomposition of the cinnamyl alcohol films is proposed. Since no effects are observed during water interaction with pure cinnamyl alcohol films at all, a catalytic reaction appears to take place. No decomposition is found for cinnamyl alcohol adsorbed on a closed silver film, indicating that Ag nanoparticles are required for this catalytical decomposition. The MIES and UPS spectra indicate the existence of a closed metallic film directly after silver adsorption on cinnamyl alcohol, while they suggest the presence of silver nanoparticles after the exposure to water. The formation of silver nanoparticles therefore seems to happen concurrently to the catalytic decomposition of cinnamyl alcohol.

  11. 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…

  12. 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…

  13. A 3D alcoholic liver disease model on a chip.

    PubMed

    Lee, JaeSeo; Choi, BongHwan; No, Da Yoon; Lee, GeonHui; Lee, Seung-Ri; Oh, HyunJik; Lee, Sang-Hoon

    2016-03-14

    Alcohol is one of the main causes of liver diseases, and the development of alcoholic liver disease (ALD) treatment methods has been one of the hottest issues. For this purpose, development of in vitro models mimicking the in vivo physiology is one of the critical requirements, and they help to determine the disease mechanisms and to discover the treatment method. Herein, a three-dimensional (3D) ALD model was developed and its superior features in mimicking the in vivo condition were demonstrated. A spheroid-based microfluidic chip was employed for the development of the 3D in vitro model of ALD progression. We co-cultured rat primary hepatocytes and hepatic stellate cells (HSCs) in a fluidic chip to investigate the role of HSCs in the recovery of liver with ALD. An interstitial level of flow derived by an osmotic pump was applied to the chip to provide in vivo mimicking of fluid activity. Using this in vitro tool, we were able to observe structural changes and decreased hepatic functions with the increase in ethanol concentration. The recovery process of liver injured by alcohol was observed by providing fresh culture medium to the damaged 3D liver tissue for few days. A reversibly- and irreversibly-injured ALD model was established. The proposed model can not only be used for the research of alcoholic disease mechanism, but also has the potential for use in studies of hepatotoxicity and drug screening applications. PMID:26857817

  14. RECENT ENHANCEMENTS TO THE DIETARY EXPOSURE POTENTIAL MODEL

    EPA Science Inventory

    Presentation describes recent enhancements & new applications of the Dietary Exposure Potential Model (DEPM), a model developed to assist in design & interpretation of dietary exposure measurements. Model is an interactive system that provides dietary exposure estimates using dat...

  15. Neurocircuitry of alcohol addiction: synthesis from animal models.

    PubMed

    Koob, George F

    2014-01-01

    Alcoholism, more generically drug addiction, can be defined as a chronically relapsing disorder characterized by: (1) compulsion to seek and take the drug (alcohol); (2) loss of control in limiting (alcohol) intake; and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability), reflecting a motivational withdrawal syndrome, when access to the drug (alcohol) is prevented (defined here as dependence). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here, derived largely from animal models, is that a key component involves decreased brain reward function, increased brain stress function, and compromised executive function, all of which contribute to the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from decreases in reward neurotransmission in the ventral striatum, such as decreased dopamine and opioid peptide function in the nucleus accumbens (ventral striatum), but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Data from animal models that support this thesis show that acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. Alcoholism also involves substantial neuroadaptations that persist beyond acute withdrawal and trigger relapse and deficits in cognitive function that can also fuel compulsive drinking. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to

  16. Executive Function Predicts Adaptive Behavior in Children with Histories of Heavy Prenatal Alcohol Exposure and Attention Deficit/Hyperactivity Disorder

    PubMed Central

    Ware, Ashley L.; Crocker, Nicole; O’Brien, Jessica W.; Deweese, Benjamin N.; Roesch, Scott C.; Coles, Claire D.; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2011-01-01

    Purpose of Study Prenatal exposure to alcohol often results in disruption to discrete cognitive and behavioral domains, including executive function (EF) and adaptive functioning. In the current study, the relation between these two domains was examined in children with histories of heavy prenatal alcohol exposure, non-exposed children with a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and typically developing controls. Methods As part of a multisite study, three groups of children (8-18y, M = 12.10) were tested: children with histories of heavy prenatal alcohol exposure (ALC, N=142), non-exposed children with ADHD (ADHD, N=82), and typically developing controls (CON, N=133) who did not have ADHD or a history of prenatal alcohol exposure. Children completed subtests of the Delis-Kaplan Executive Function System (D-KEFS) and their primary caregivers completed the Vineland Adaptive Behavior Scales-II (VABS). Data were analyzed using regression analyses. Results Analyses showed that EF measures were predictive of adaptive abilities and significant interactions between D-KEFS measures and group were present. For the ADHD group, the relation between adaptive abilities and EF was more general, with three of the four EF measures showing a significant relation with adaptive score. In contrast, for the ALC group, this relation was specific to the nonverbal EF measures. In the CON group, performance on EF tasks did not predict adaptive scores over the influence of age. Conclusion These results support prior research in ADHD suggesting that EF deficits are predictive of poorer adaptive behavior and extend this finding to include children with heavy prenatal exposure to alcohol. However, the relation between EF and adaptive ability differed by group, suggesting unique patterns of abilities in these children. These results provide enhanced understanding of adaptive deficits in these populations, as well as demonstrate the ecological validity of laboratory

  17. Modeling and Predicting Pesticide Exposures

    EPA Science Inventory

    Models provide a means for representing a real system in an understandable way. They take many forms, beginning with conceptual models that explain the way a system works, such as delineation of all the factors and parameters of how a pesticide particle moves in the air after a s...

  18. HYDROCARBON SPILL EXPOSURE ASSESSMENT MODELING

    EPA Science Inventory

    Hydrocarbon spills impact drinking water supplies at down gradient locations. onventional finite difference and finite element models of multiphase, multicomponent flow have extreme requirements for both computer time and site data. ite data and the intent of the modeling often d...

  19. Radical Reeducation: Alcoholics Anonymous as a Model in Adult Education.

    ERIC Educational Resources Information Center

    Crossman, Lenard H.

    1980-01-01

    The peer self-help group approach used by Alcoholics Anonymous can be a model for other types of adult learning. The group's power, solidarity, experience sharing, and values clarification can provide positive social and educational experiences to others such as the chronically unemployed, illiterate adults, and high school dropouts. (SK)

  20. Relapse Prevention Model of Behavioral Maintenance: Implications for Alcohol Education.

    ERIC Educational Resources Information Center

    Rose-Colley, Mary; Cinelli, Bethann

    1992-01-01

    Describes Relapse Prevention as therapeutic modality, based on Social Learning Theory, used to prevent relapse for individuals who have completed treatment for substance abuse behaviors. Outlines relapse prevention theory and suggests various components of model be incorporated into alcohol education curricula. Outlines teaching strategies to…

  1. Alcohol-triggered signs of migraine: An animal model.

    PubMed

    Alabwah, Yaqoub; Ji, Yadong; Seminowicz, David A; Quiton, Raimi L; Masri, Radi

    2016-03-01

    We describe an animal model where characteristics of migraine can be triggered by alcohol administration. In rats chronically implanted with a cannula overlying the transverse sinus, we applied potassium chloride (KCl) (or saline) to the meninges to sensitize trigeminovascular afferents. We assessed effects of repeated KCl application on animal behavior using conditioned place avoidance paradigm. In KCl-treated rats we discovered that alcohol injections (0.2 mg/kg), but not saline, resulted in the development of extracephalic allodynia and signs of ongoing pain. PMID:27021138

  2. Modeling and cold start in alcohol-fueled engines

    SciTech Connect

    Markel, A.J.; Bailey, B.K.

    1998-05-01

    Neat alcohol fuels offer several benefits over conventional gasoline in automotive applications. However, their low vapor pressure and high heat of vaporization make it difficult to produce a flammable vapor composition from a neat alcohol fuel during a start under cold ambient conditions. Various methods have been introduced to compensate for this deficiency. In this study, the authors applied computer modeling and simulation to evaluate the potential of four cold-start technologies for engines fueled by near-neat alcohol. The four technologies were a rich combustor device, a partial oxidation reactor, a catalytic reformer, and an enhanced ignition system. The authors ranked the competing technologies by their ability to meet two primary criteria for cold starting an engine at {minus}25 deg C and also by several secondary parameters related to commercialization. Their analysis results suggest that of the four technologies evaluated, the enhanced ignition system is the best option for further development.

  3. EPA EXPOSURE MODELS LIBRARY AND INTEGRATED MODEL EVALUATION SYSTEM

    EPA Science Inventory

    The third edition of the U.S. Environmental Protection Agencys (EPA) EML/IMES (Exposure Models Library and Integrated Model Evaluation System) on CD-ROM is now available. The purpose of the disc is to provide a compact and efficient means to distribute exposure models, documentat...

  4. Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure.

    PubMed

    Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence

    2016-09-01

    Acute ethanol intoxication is associated with Rapid Alterations in Neuroimmune Gene Expression (RANGE), including increased Interleukin (IL)-6 and Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and suppressed IL-1β and Tumor necrosis factor (TNF) α, yet little is known about adaptations in cytokines across the first few ethanol exposures. Thus, the present studies examined central cytokines during intoxication (3h post-ethanol) following 2, 4 or 6 intragastric ethanol challenges (4g/kg) delivered either daily or every-other-day (EOD). Subsequent analyses of blood ethanol concentrations (BECs) and corticosterone were performed to determine whether the schedule of ethanol delivery would alter the pharmacokinetics of, or general sensitivity to, subacute ethanol exposure. As expected, ethanol led to robust increases in IL-6 and IκBα gene expression in hippocampus, amygdala and bed nucleus of the stria terminalis (BNST), whereas IL-1β and TNFα were suppressed, thereby replicating our prior work. Ethanol-dependent increases in IL-6 and IκBα remained significant in all structures - even after 6 days of ethanol. When these doses were administered EOD, modest IL-6 increases in BNST were observed, with TNFα and IL-1β suppressed exclusively in the hippocampus. Analysis of BECs revealed a small but significant reduction in ethanol after 4 EOD exposures - an effect which was not observed when ethanol was delivered after 6 daily intubations. These findings suggest that ethanol-induced RANGE effects are not simply a function of ethanol load per se, and underscore the critical role that ethanol dosing interval plays in determining the neuroimmune consequences of alcohol. PMID:27208497

  5. 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.

  6. Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

    PubMed Central

    Lachenmeier, Dirk W.; Rehm, Jürgen

    2015-01-01

    A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk). PMID:25634572

  7. Disease versus Social-Learning Models of Alcoholism in the Prediction of Alcohol Problem Recognition, Help-Seeking, and Stigma.

    ERIC Educational Resources Information Center

    Rather, Bruce C.

    1991-01-01

    Examined college students' (n=254) attitudes after they were presented with either a disease or social learning view of alcoholism. Presentation of a disease view strengthened endorsement of that model, but attitudes toward alcoholics, treatment effectiveness, problem recognition, and help-seeking were not significantly different between the…

  8. Psychoecological model of alcohol use in Mexican American adolescents.

    PubMed

    Chun, Heejung; Devall, Esther; Sandau-Beckler, Patricia

    2013-06-01

    In this study, we proposed and tested a structural model based on Bronfenbrenner's ecological systems theory in order to further understand alcohol use among Hispanic adolescents, who are at greater risk of alcohol use than adolescents of other racial/ethnic groups. Family cohesion, school connectedness, and peer influence were conceptualized as three primary process factors, while psychological distress was used as a mediating factor and Mexican culture orientation as a cultural factor. The sample comprised 444 Mexican American adolescents (aged 16-20) living along the U.S./Mexico border. The proposed model explained 33 % of the variance in alcohol use. Most of the hypothesized relationships in the proposed model were supported: (a) low family cohesion had significant indirect effects mediated through psychological distress, poor school connectedness, and negative peer influence; (b) poor school connectedness had significant indirect effects mediated through psychological distress and negative peer influence; (c) psychological distress had a significant direct effect as well as a significant indirect effect mediated through negative peer influence; and (d) negative peer influence had the strongest direct effect. However, contrary to the hypothesis, Mexican culture orientation was not a protective factor, but rather had a significant positive relationship with negative peer influence. Lastly, it was found that gender, school status, Anglo cultural orientation, and severity of alcohol use did not have any moderating effects. Based on the collective findings, suggestions for primary prevention programs designed to reduce underage drinking among Mexican American youth were given. PMID:23636580

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

    PubMed Central

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

    2015-01-01

    Fetal alcohol spectrum disorders (FASD) affect 2–5% of children. FASD have been shown to cause damage to multiple brain regions, but damage to the hippocampus specifically may explain deficits in learning and memory that are hallmark symptoms of FASD. The acetylcholine neurotransmitter system is a major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intragastric intubation to developing male rat pups (postnatal day [PD] 2–10; ethanol-treated [ET]), with controls receiving a sham intubation (IC) or no treatment (NC). In Experiment 1, in vivo microdialysis was used to measure acetylcholine efflux in adolescents (PD 32–35). During microdialysis, the effects of a high K+/Ca2+ aCSF solution (PD 32–33) and an acute galantamine (acetylcholinesterase [AChE] inhibitor) injection (2.0 mg/kg; PD 34–35) on acetylcholine efflux were measured. Alcohol-exposed animals did not differ in acetylcholine efflux at baseline. However, alcohol-exposed animals had a decrease in K+/Ca2+-induced acetylcholine efflux compared to non-treated controls, and an enhanced acetylcholine response to galantamine compared to both control groups. Experiment 2 tested whether chronic administration of galantamine (2.0 mg/kg; PD 11–30) could attenuate alcohol-induced learning deficits in the context pre-exposure facilitation effect (CPFE; PD 30–32). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Immunohistochemistry was used to measure expression of choline acetyltransferase (ChAT; medial septum), vesicular acetylcholine transporter (vAChT; ventral CA1), and the alpha7 nicotinic acetylcholine receptor (α7 nAChR; ventral CA1) following microdialysis (Exp. 1) or chronic galantamine and behavioral testing (Exp. 2). Neither alcohol exposure nor behavioral testing significantly altered the density of vAChT or α7 nAChRs in the ventral CA1 region of the

  10. 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. PMID:26180184

  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. 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

  13. 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

    2015-01-01

    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. PMID:26132299

  14. Ethylglucuronide in Maternal Hair as a Biomarker of Prenatal Alcohol Exposure

    PubMed Central

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

    2015-01-01

    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 might allow 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 (gamma glutamyltranspeptidase [GGT], carbohydrate-deficient transferrin [%dCDT], urine ethyl glucuronide [uEtG], urine ethyl sulfate [uEtS], and phosphatidylethanol [PEth]) in 85 pregnant women. Patients were recruited from a University of New Mexico prenatal clinic, which provides care to women with substance abuse and addiction disorders, and followed until early postpartum. 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 and other biomarkers. Proximal segments of hair were collected at enrollment (average 22.0 gestational weeks) and analyzed by liquid chromatography–tandem mass spectrometry (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 opioiddependent (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 in this cohort, 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

  15. DEVELOPING MEANINGFUL COHORTS FOR HUMAN EXPOSURE MODELS

    EPA Science Inventory

    This paper summarizes numerous statistical analyses focused on the U.S. Environmental Protection Agency's Consolidated Human Activity Database (CHAD), used by many exposure modelers as the basis for data on what people do and where they spend their time. In doing so, modelers ...

  16. 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

  17. 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

  18. In Vitro Modeling of Alcohol-Induced Liver Injury Using Human-Induced Pluripotent Stem Cells.

    PubMed

    Tian, Lipeng; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been associated with a majority of liver diseases and has been found to influence both fetal and adult liver functions. In spite of being one of the major causes of morbidity and mortality in the world, currently, there are no effective strategies that can prevent or treat alcoholic liver disease (ALD), due to a lack of human-relevant research models. Recent success in generation of functionally active mature hepatocyte-like cells from human-induced pluripotent cells (iPSCs) enables us to better understand the effects of alcohol on liver functions. Here, we describe the method and effect of alcohol exposure on multistage hepatic cell types derived from human iPSCs, in an attempt to recapitulate the early stages of liver tissue injury associated with ALD. We exposed different stages of iPSC-induced hepatic cells to ethanol at a pathophysiological concentration. In addition to stage-specific molecular markers, we measured several key cellular parameters of hepatocyte injury, including apoptosis, proliferation, and lipid accumulation. PMID:25520290

  19. POPULATION-BASED EXPOSURE MODELING FOR AIR POLLUTANTS AT EPA'S NATIONAL EXPOSURE RESEARCH LABORATORY

    EPA Science Inventory

    The US EPA's National Exposure Research Laboratory (NERL) has been developing, applying, and evaluating population-based exposure models to improve our understanding of the variability in personal exposure to air pollutants. Estimates of population variability are needed for E...

  20. Liver Proteome Analysis in a Rodent Model of Alcoholic Steatosis

    PubMed Central

    Newton, Billy W.; Russell, William K.; Russell, David H.; Ramaiah, Shashi; Jayaraman, Arul

    2009-01-01

    Alcoholic steatosis (AS) is the initial pathology associated with early stage alcoholic liver disease (ALD) and is characterized by the accumulation of fat in the liver. AS is considered clinically benign because it is reversible, and the progression of AS to alcoholic steatohepatitis (ASH) is a key step in the development of ALD. A two-dimensional gel electrophoresis (2DE) – mass spectrometry (MS) proteomic approach was used to investigate the protein expression pattern underlying AS, as the first step towards determining liver tissue biomarkers for early-stage ALD. Several proteins involved in fatty acid and amino acid metabolism were up-regulated in 3- and 6-week ethanol-fed rats relative to isocaloric controls, which suggest a higher energy demand upon chronic exposure to ethanol. In addition, the expression of two proteins associated with alcohol-induced oxidative stress, peroxiredoxin 6 (PRDX6) and aldehyde dehydrogenase 2 (ALDH2), was down-regulated in ethanol fed rats, and suggests an increase in reactive oxygen species and oxidative stress. In order to investigate if irreversible protein modification arising from oxidative stress during AS impact protein levels, the extent of carbonylated proteins in the ethanol and isocaloric groups was identified using mass spectrometry. The detection of modified proteins involved in anti-oxidant functions further supports the notion that oxidative modification of these proteins leads to protein turnover during AS. In addition, the carbonylation of betaine-homocysteine S-methyltransferase, a protein implicated in fatty liver development, in 3-week and 6-week ethanol exposed samples suggest that this protein could be a marker for early stage AS. PMID:19714808

  1. 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

  2. Effects of prenatal alcohol exposure on activity and learning in Sprague-Dawley rats.

    PubMed

    Westergren, S; Rydenhag, B; Bassen, M; Archer, T; Conradi, N G

    1996-12-01

    Nulliparous pregnant Sprague-Dawley rats were exposed to ethanol via a liquid diet technique (FAE, fetal alcohol exposure) or administered a fixed amount of control diet from gestational day 11 to day 21. The offspring, at 2-3 months of age, were studied in tests of mechanically monitored motor activity and learning acquisition in an automatized testing cage requiring an instrumental discriminative response, where the ability to learn and relearn correlations of a light signal to water presentation was monitored. A significantly reduced activity (i.e. ramp mounting behaviour) in a novel situation was obtained in the FAE group compared to controls. The initial disruption of ramp mounting behaviour could reflect alterations in either habituation to a novel test situation, altered neophobia, or some retardation in associating these responses with the outcome of water-availability. Adult FAE rats (six months of age) showed a tendency towards a lowered acquisition performance (p = 0.06) when tested in a circular Morris-type swim maze, but no detectable differences were shown in a motor activity test chamber situation. PMID:8981581

  3. Impaired arousal in rat pups with prenatal alcohol exposure is modulated by GABAergic mechanisms

    PubMed Central

    Sirieix, Chrystelle M; Tobia, Christine M; Schneider, Robert W; Darnall, Robert A

    2015-01-01

    Prenatal alcohol exposure (PAE) increases the risk for The Sudden Infant Death Syndrome (SIDS) in human infants. In rat pups, the arousal response to hypoxia is modulated by medullary raphe GABAergic mechanisms. We hypothesized that arousal to hypoxia is impaired by PAE, and is associated with an increase in medullary GABA and enhanced GABAergic activity. Pregnant dams received an ethanol liquid diet (ETOH), an iso-caloric pair fed diet (PF) or a standard chow diet (CHOW). We first measured the time to arousal (latency), during four episodes of hypoxia in P5, P15, and P21 CHOW, PF, and ETOH pups. We also measured brainstem GABA concentration in the same groups of pups. Finally, we injected artificial cerebrospinal fluid (aCSF), nipecotic acid (NIP) or gabazine into the medullary raphe of P15 and P21 pups receiving the three diets. For statistical analysis, the PF and CHOW groups were combined into a single CONTROL group. Our main finding was that compared to CONTROL, arousal latency to hypoxia is increased in ETOH pups at P15 and P21, and the concentration of brainstem GABA is elevated at P21. NIP administration in CONTROL pups led to arousal latencies similar in magnitude to those in ETOH pups after aCSF injection. NIP injected ETOH pups had no further increases in arousal latency. We conclude that PAE impairs arousal latency and this is mediated or modulated by medullary GABAergic mechanisms. PMID:26059034

  4. Establishment of the Tree Shrew as an Alcohol-Induced Fatty Liver Model for the Study of Alcoholic Liver Diseases

    PubMed Central

    Xing, Huijie; Jia, Kun; He, Jun; Shi, Changzheng; Fang, Meixia; Song, Linliang; Zhang, Pu; Zhao, Yue; Fu, Jiangnan; Li, Shoujun

    2015-01-01

    Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals’ suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs. PMID:26030870

  5. The association between exposure to violence, alcohol, and drugs and psychosocial and behavioral outcomes among Mexican-American adolescents of low socioeconomic status.

    PubMed

    Peinado, Jesus; Theresa Villanos, Maria; Singh, Namrata; Leiner, Marie

    2014-01-01

    The objective of this study was to investigate the association exposure to violence, drugs and alcohol has in shaping the psychosocial and behavioral profiles of Mexican American adolescents of low socioeconomic status. A cross-sectional study was conducted in which 881 Mexican-American adolescents described their exposure to violence, drugs, and alcohol, while their parents responded to a questionnaire about their children’'s behavioral, emotional, and social problems. Participant information was extracted from electronic record databases maintained in six university-based clinics in El Paso, Texas on the U.S. side of the border with Mexico. A total of 463 (52.6%) adolescents reported they had not been exposed to violence, alcohol, or drugs. The remaining 418 (47.4%) adolescents indicated only a single category of exposure: violence (25.1%), alcohol (24.9%), or drugs (8.6%). In addition, some adolescents reported combined exposure to violence and alcohol (13.4%), alcohol and drugs (14.6%), or violence, alcohol, and drugs (13.4%). The association between combined exposure to violence, drugs, and/or alcohol and the psychosocial and behavioral profiles of these Mexican-American adolescents showed an increased risk of emotional and behavioral problems. Little is known about the mental health of Mexican Americans who are exposed to alcohol, violence, and drugs, especially adolescents living in poverty in neighborhoods along the U.S.-Mexico border, who are at a high risk for these exposures. These findings highlight the risks associated with adolescent exposure to violence, drugs, and alcohol and the need for effective interventions within this subgroup of Mexican-American youth and their families. PMID:24652396

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

    PubMed Central

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

    2014-01-01

    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. PMID:25149913

  7. 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. PMID:22440689

  8. Alcohol-Dependent Liver Cell Necrosis in vitro: A New Model

    NASA Astrophysics Data System (ADS)

    Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel

    1981-04-01

    In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

  9. INHALATION EXPOSURE AND INTAKE DOSE MODEL IMPROVEMENTS

    EPA Science Inventory

    This presentation highlights recent human exposure model improvements and products developed by the EMRB in coordination with scientists in the OAQPS and provides insight into how these products are used by the OAQPS in its regulatory process. Besides providing a status report of...

  10. MEXAMS (METALS EXPOSURE ANALYSIS MODELING SYSTEM)

    EPA Science Inventory

    MEXAMS, the Metals Exposure Analysis Modeling System, provides an enhanced capability for assessing the impact of priority pollutant metals on aquatic systems. It allows the user to consider the complex chemistry affecting the behavior of metals in conjunction with the transport ...

  11. A Human Alcohol Self-Administration Paradigm to Model Individual Differences in Impaired Control over Alcohol Use

    PubMed Central

    Leeman, Robert F.; Corbin, William R.; Nogueira, Christine; Krishnan-Sarin, Suchitra; Potenza, Marc N.; O’Malley, Stephanie S.

    2014-01-01

    We developed an alcohol self-administration paradigm to model individual differences in impaired control. The paradigm includes moderate drinking guidelines meant to model limits on alcohol consumption, which are typically exceeded by people with impaired control. Possible payment reductions provided a disincentive for excessive drinking. Alcohol use above the guideline, despite possible pay reductions, was considered to be indicative of impaired control. Heavy-drinking 21–25 year-olds (N = 39) were randomized to an experimental condition including the elements of the impaired control paradigm or to a free-drinking condition without these elements. Alcohol self-administration was compared between these two conditions to establish the internal validity of the experimental paradigm. In both conditions, participants self-administered beer and non-alcoholic beverages for 3 hours in a bar setting with 1–3 other participants. Experimental condition participants self-administered significantly fewer beers and drank to lower blood-alcohol concentrations (BACs) on average than those in the free-drinking condition. Experimental condition participants were more likely than free-drinking condition participants to intersperse non-alcoholic beverages with beer and to drink at a slower pace. Although experimental condition participants drank more moderately than those in the free-drinking condition overall, their range of drinking was considerable (BAC range = .024–.097) with several participants drinking excessively. A lower initial subjective response to alcohol and earlier age of alcohol use onset were associated with greater alcohol self-administration in the experimental condition. Given the variability in response, the impaired control laboratory paradigm may have utility for preliminary tests of novel interventions in future studies and for identifying individual differences in problem-drinking risk. PMID:23937598

  12. An fMRI study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure

    PubMed Central

    Ware, Ashley L.; Infante, M. Alejandra; O’Brien, Jessica W.; Tapert, Susan F.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2014-01-01

    Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13–16 y) with histories of heavy prenatal alcohol exposure (AE, n = 21) and controls (CON, n = 21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AE < CON). The AE group demonstrated greater BOLD response in frontal, sensorimotor, striatal, and cingulate regions relative to controls, especially as task difficulty increased. When contrasting hard vs. easy inhibition trials, the AE group showed greater medial/superior frontal and cuneus BOLD response than controls. Results were unchanged after demographics and FAS diagnosis were statistically controlled. This was the first fMRI study to utilize a stop signal task, isolating fronto-striatal functioning, to assess response inhibition and the effects task difficulty in adolescents with prenatal alcohol exposure. Results suggest that heavy prenatal alcohol exposure disrupts neural function of this circuitry, resulting in immature cognitive processing and motor-association learning and neural compensation during response inhibition. PMID:25281280

  13. An fMRI study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure.

    PubMed

    Ware, Ashley L; Infante, M Alejandra; O'Brien, Jessica W; Tapert, Susan F; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

    2015-02-01

    Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13-16 y) with histories of heavy prenatal alcohol exposure (AE, n=21) and controls (CON, n=21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AEalcohol exposure. Results suggest that heavy prenatal alcohol exposure disrupts neural function of this circuitry, resulting in immature cognitive processing and motor-association learning and neural compensation during response inhibition. PMID:25281280

  14. 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. PMID:26260252

  15. 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

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

    PubMed Central

    Wagner, Jennifer L.; Zhou, Feng C.; Goodlett, Charles R.

    2014-01-01

    Binge-like alcohol exposure during the early postnatal period in rats and mice causes deficits in spatial learning and memory that persist into adulthood. Wozniak et al. (2004) reported that heavy binge alcohol exposure on postnatal day 7 (PD 7) in C57BL/6 (B6) mice produced profound spatial learning deficits in the Morris water maze when tested in adolescence (P30–39); when tested in adulthood, however, the deficits were greatly attenuated. Using a similar PD 7 binge alcohol exposure paradigm in B6 mice, we tested whether a single-day (PD 7 only) alcohol treatment produced place learning deficits in both adolescence and in adulthood, and further tested whether a more extended (3-day, PD 7–9) alcohol exposure would induce more severe and enduring deficits. B6 mice were given either 2 subcutaneous injections of alcohol (2.5 g/kg each) 2 h apart on PD 7 or on PD 7–9, and compared with controls that received saline vehicle injections and controls that received no injections. The alcohol injections on PD 7 produced average peak blood alcohol concentrations of 472 mg/dL and evoked typical patterns of activated caspase-3-positive neurons in the cortex, hippocampal formation, and striatum 6 h after the last injection. Mice were given standard place training or random location training in the Morris water maze either as adolescents (PD 30–39) or adults (PD 70–79). The adolescents acquired the place learning more slowly than adults, and the alcohol treatments produced only modest place acquisition deficits. In contrast, both the PD7 and the PD 7–9 alcohol treatments resulted in large and significant spatial learning impairments in adults. In contrast to the previous findings of Wozniak et al. (2004), these results indicate that binge alcohol exposure in the 3rd trimester equivalent produces significant and enduring deficits in spatial learning in B6 mice. PMID:24507877

  17. Modeling thermal protection outfits for fire exposures

    NASA Astrophysics Data System (ADS)

    Song, Guowen

    2002-01-01

    A numerical model has been developed that successfully predicts heat transfer through thermally protective clothing materials and garments exposed to intense heat. The model considers the effect of fire exposure to the thermophysical properties of materials as well as the air layers between the clothing material and skin surface. These experiments involved characterizing the flash fire surrounding the manikin by measuring the temperature of the flame above each thermal sensor in the manikin surface. An estimation method is used to calculate the heat transfer coefficient for each thermal sensor in a 4 second exposure to an average heat flux of 2.00cal/cm2sec. A parameter estimation method was used to estimate heat induced change in fabric thermophysical properties. The skin-clothe air gap distribution of different garments was determined using three-dimensional body scanning technology. Multi-layer skin model and a burn prediction method were used to predict second and third degree burns. The integrated generalized model developed was validated using the "Pyroman" Thermal Protective Clothing Analysis System with Kevlar/PBIRTM and NomexRTMIIIA coverall garments with different configuration and exposure time. A parametric study conducted using this numerical model indicated the influencing parameters on garment thermal protective performance in terms of skin burn damage subjected to 4 second flash fire exposure. The importance of these parameters is analyzed and distinguished. These parameters includes fabric thermophysical properties, PyromanRTM chamber flash fire characteristics, garment shrinkage and fit factors, as well as garment initial and test ambient temperature. Different skin models and their influence on burn prediction were also investigated using this model.

  18. Alcohol Abuse Enhances Neuroinflammation and Impairs Immune Responses in an Animal Model of Human Immunodeficiency Virus-1 Encephalitis

    PubMed Central

    Potula, Raghava; Haorah, James; Knipe, Bryan; Leibhart, Jessica; Chrastil, Jesse; Heilman, David; Dou, Huanyu; Reddy, Rindha; Ghorpade, Anuja; Persidsky, Yuri

    2006-01-01

    Neuroinflammatory disorders (including human immunodeficiency virus-1 encephalitis, HIVE) are associated with oxidative stress and inflammatory brain injury, and excessive alcohol use can exacerbate tissue damage. Using a murine model of HIVE, we investigated the effects of alcohol abuse on the clearance of virus-infected macrophages and neuroinflammation. Severe combined immunodeficient mice were reconstituted with human lymphocytes, and encephalitis was induced by intracranial injection of HIV-1-infected monocyte-derived macrophages (HIV-1+ MDM). Animals were fed an ethanol-containing diet beginning 2 weeks before lymphocyte engraftment and for the entire duration of the experiment. Lymphocyte engraftment was not altered by ethanol exposure. Alcohol-mediated immunosuppression in ethanol-fed mice was manifested by a significant decrease in CD8+/interferon-γ+ T lymphocytes, a fivefold increase in viremia, and diminished expression of immunoproteasomes in the spleen. Although both groups showed similar amounts of CD8+ T-lymphocyte infiltration in brain areas containing HIV-1+ MDMs, ethanol-fed mice featured double the amounts of HIV-1+ MDMs in the brain compared to controls. Ethanol-exposed mice demonstrated higher microglial reaction and enhanced oxidative stress. Alcohol exposure impaired immune responses (increased viremia, decreased immunoproteasome levels, and prevented efficient elimination of HIV-1+ MDMs) and enhanced neuroinflammation in HIVE mice. Thus, alcohol abuse could be a co-factor in progression of HIV-1 infection of the brain. PMID:16565506

  19. Modeling residential exposure to secondhand tobacco smoke

    NASA Astrophysics Data System (ADS)

    Klepeis, Neil E.; Nazaroff, William W.

    We apply a simulation model to explore the effect of a house's multicompartment character on a nonsmoker's inhalation exposure to secondhand tobacco smoke (SHS). The model tracks the minute-by-minute movement of people and pollutants among multiple zones of a residence and generates SHS pollutant profiles for each room in response to room-specific smoking patterns. In applying the model, we consider SHS emissions of airborne particles, nicotine, and carbon monoxide in two hypothetical houses, one with a typical four-room layout and one dominated by a single large space. We use scripted patterns of room-to-room occupant movement and a cohort of 5000 activity patterns sampled from a US nationwide survey. The results for scripted and cohort simulation trials indicate that the multicompartment nature of homes, manifested as inter-room differences in pollutant levels and the movement of people among zones, can cause substantial variation in nonsmoker SHS exposure.

  20. Exposure Modeling of Residential Air Exchange Rates for NEXUS Participants.

    EPA Science Inventory

    Due to cost and participant burden of personal measurements, air pollution health studies often estimate exposures using local ambient air monitors. Since outdoor levels do not necessarily reflect personal exposures, we developed the Exposure Model for Individuals (EMI) to improv...

  1. Exposure Modeling of Residential Air Exchange Rates for NEXUS Participants

    EPA Science Inventory

    Due to cost and participant burden of personal measurements, air pollution health studies often estimate exposures using local ambient air monitors. Since outdoor levels do not necessarily reflect personal exposures, we developed the Exposure Model for Individuals (EMI) to improv...

  2. Model for voluntary wine and alcohol consumption in rats.

    PubMed

    Arola, L; Roig, R; Cascón, E; Brunet, M J; Fornós, N; Sabaté, M; Raga, X; Batista, J; Salvadó, M J; Bladé, C

    1997-08-01

    It has been suggested that moderate consumption of ethanol and wine has a protective effect on human health. Animal models used to date for alcohol consumption can not mimic real situations in humans because the consumption is forced and/or excessive. The present study proposes to determine the effects of a voluntary and ad lib consumption model more similar to that of human behavior. Male Wistar rats had free access to either standard diet and water or the same diet plus red wine, sweet wine, or a solution equivalent to red wine (13.5% ethanol) or to sweet wine (20% ethanol + 130 g/L sucrose) for 30 days or 6 months. Daily wine consumption was 15.8 +/- 0.9 and 2.0 +/- 0.2 ml/day for sweet and red wines, respectively. The consumption of each of the alcoholic solutions was similar to that of the wine they were simulating. Drinking wine or ethanol did not affect food and water intakes or growth rate. Plasma metabolites were not substantially affected by consumption of wine or ethanol. Although moderate and high wine consumption did not change the activity of plasma marker enzymes of tissue damage, the consumption of the 2 alcoholic solutions caused a long-term increase in the activity of aspartate aminotransferase. It seems that wine consumption protects the organism from hepatic lesions induced by ethanol alone. PMID:9251979

  3. MAKING ANIMALS ALCOHOLIC: SHIFTING LABORATORY MODELS OF ADDICTION

    PubMed Central

    RAMSDEN, EDMUND

    2015-01-01

    The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field. PMID:25740698

  4. Reconstructing Exposures from Biomarkers using Exposure-Pharmacokinetic Modeling - A Case Study with Carbaryl

    EPA Science Inventory

    Sources of uncertainty involved in exposure reconstruction for a short half-life chemical, carbaryl, were characterized using the Cumulative and Aggregate Risk Evaluation System (CARES), an exposure model, and a human physiologically based pharmacokinetic (PBPK) model. CARES was...

  5. Exposure Space: Integrating Exposure Data and Modeling with Toxicity Information

    EPA Science Inventory

    Recent advances have been made in high-throughput (HTP) toxicity testing, e.g. from ToxCast, which will ultimately be combined with HTP predictions of exposure potential to support next-generation chemical safety assessment. Rapid exposure methods are essential in selecting chemi...

  6. Structure and thermodynamics of core-softened models for alcohols

    SciTech Connect

    Munaò, Gianmarco; Urbic, Tomaz

    2015-06-07

    The phase behavior and the fluid structure of coarse-grain models for alcohols are studied by means of reference interaction site model (RISM) theory and Monte Carlo simulations. Specifically, we model ethanol and 1-propanol as linear rigid chains constituted by three (trimers) and four (tetramers) partially fused spheres, respectively. Thermodynamic properties of these models are examined in the RISM context, by employing closed formulæ for the calculation of free energy and pressure. Gas-liquid coexistence curves for trimers and tetramers are reported and compared with already existing data for a dimer model of methanol. Critical temperatures slightly increase with the number of CH{sub 2} groups in the chain, while critical pressures and densities decrease. Such a behavior qualitatively reproduces the trend observed in experiments on methanol, ethanol, and 1-propanol and suggests that our coarse-grain models, despite their simplicity, can reproduce the essential features of the phase behavior of such alcohols. The fluid structure of these models is investigated by computing radial distribution function g{sub ij}(r) and static structure factor S{sub ij}(k); the latter shows the presence of a low−k peak at intermediate-high packing fractions and low temperatures, suggesting the presence of aggregates for both trimers and tetramers.

  7. IL-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury

    PubMed Central

    Rendon, Juan L.; Li, Xiaoling; Akhtar, Suhail; Choudhry, Mashkoor A.

    2012-01-01

    Interleukin (IL)–22 maintains gut epithelial integrity and expression of antimicrobial peptides (AMPs) Reg3β and Reg3γ. Our laboratory has shown that acute alcohol/ethanol (EtOH) exposure prior to burn injury results in increased gut permeability, intestinal T cell suppression and enhanced bacterial translocation. Herein, we determined the effect of combined EtOH intoxication and burn injury on intestinal levels of IL-22 as well as Reg3β and Reg3γ expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3β and Reg3γ levels, and bacterial load (e.g. gut bacterial growth) within the intestine following EtOH and burn injury. Male mice, ~25g, were gavaged with EtOH (2.9 mg/kg) prior to receiving a ~12.5% total body surface area full thickness burn. Mice were immediately treated with saline control or IL-22 (1 mg/kg) by i.p. injection. One day post injury, there was a significant decrease in intestinal IL-22, Reg3β and Reg3γ expression along with an increase in intestinal permeability and gut bacterial load following EtOH combined with burn injury, as compared to sham injury. Treatment with IL-22 normalized Reg3β and Reg3γ expression, and attenuated the increase in intestinal permeability following EtOH and burn injury. Qualitatively, IL-22 treatment reduced the bacterial load in nearly half of mice receiving EtOH combined with burn injury. Our data indicate that IL-22 maintains gut epithelial and immune barrier integrity following EtOH and burn injury; thus, the IL-22/AMP pathway may provide a therapeutic target for the treatment of patients who sustain burn injury under the influence of EtOH. PMID:23143063

  8. 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

  9. 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. PMID:25482413

  10. Prenatal alcohol exposure (PAE) and adolescent stress: Unmasking persistent attentional deficits in rats

    PubMed Central

    Comeau, Wendy L; Winstanley, Catharine A; Weinberg, Joanne

    2014-01-01

    Prenatal alcohol exposure (PAE) can produce a myriad of deficits. Unfortunately, affected individuals may also be exposed to the stress of an adverse home environment, contributing to deficits of attentional processes that are the hallmark of optimal executive function. Male offspring of ad libitum-fed Control (Con), Pairfed (PF), and PAE dams were randomly assigned to either a five day period of variable chronic mild stress (CMS) or no CMS (Non CMS) in adolescence. In adulthood, rats were trained in a non-match to sample task (T-maze), followed by extensive assessment in the five-choice serial reaction time task (5-CSRTT). Once rats acquired the 5-CSRTT (stable accuracy), rats were tested in three challenge conditions, 1) increased sustained attention, 2) selective attention and, 3) varying doses of d- amphetamine, an indirect dopamine and norepinephrine agonist. At birth and throughout the study, PAE offspring showed reduced body weight. Moreover, although PAE were comparable to Con animals in task acquisition, they were progressively less proficient with transitions to shorter stimulus durations (decreased accuracy and increased omissions). Five days of adolescent CMS increased basal corticosterone levels in adolescence and disrupted cognitive performance in adulthood. Further, CMS augmented PAE-related disturbances in acquisition and, to a lesser extent, disrupted attentional processes in Con and PF animals as well. Following task acquisition, challenges unmasked persistent attentional difficulties resulting from both PAE and adolescent CMS. In conclusion, PAE, adolescent CMS, and their interaction produced unique behavioural profiles that suggest vulnerability in select neurobiological processes at different stages of development. PMID:25059261

  11. 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. PMID:27322638

  12. POPULATION EXPOSURES TO PARTICULATE MATTER: A COMPARISON OF EXPOSURE MODEL PREDICTIONS AND MEASUREMENT DATA

    EPA Science Inventory

    The US EPA National Exposure Research Laboratory (NERL) is currently developing an integrated human exposure source-to-dose modeling system (HES2D). This modeling system will incorporate models that use a probabilistic approach to predict population exposures to environmental ...

  13. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABAA receptor δ subunit in cerebellar granule neurons and delays motor development in rats

    PubMed Central

    Diaz, Marvin R.; Vollmer, Cyndel C.; Zamudio-Bulcock, Paula A.; Vollmer, William; Blomquist, Samantha; Morton, Russell A.; Everett, Julie C.; Zurek, Agnieszka A.; Yu, Jieying; Orser, Beverley A.; Valenzuela, C. Fernando

    2014-01-01

    Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ~60 mM (~0.28 g/dl) during the 4 hours of exposure. EtOH levels gradually decreased to baseline 8 hrs after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased the expression of δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABAA receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats. PMID:24316160

  14. Animal Models of Fetal Alcohol Spectrum Disorders: Impact of the Social Environment

    ERIC Educational Resources Information Center

    Kelly, Sandra J.; Goodlett, Charles R.; Hannigan, John H.

    2009-01-01

    Animal models of fetal alcohol spectrum disorder (FASD) have been used to demonstrate the specificity of alcohol's teratogenic effects and some of the underlying changes in the central nervous system (CNS) and, more recently, to explore ways to ameliorate the effects of alcohol. The main point of this review is to highlight research findings from…

  15. EXPOSURE ASSESSMENT MODELING: A STATE-OF-THE-ART REVIEW

    EPA Science Inventory

    The state-of-the-art review of exposure assessment modeling describes currently available models that simulate the environmental fate of substances, the exposure to such substances, and the effects of such exposure. The focus is first on exposure and effects, where relatively lit...

  16. Impact of Exposure to Childhood Maltreatment on Transitions to Alcohol Dependence in Women and Men

    PubMed Central

    Oberleitner, Lindsay M.; Smith, Philip H.; Weinberger, Andrea H; Mazure, Carolyn M.; McKee, Sherry A.

    2016-01-01

    Background Childhood maltreatment decreases age of first use and speeds the transition from first use to dependence (i.e., telescoping) for alcohol use, however, it is currently unknown whether this influence is the same for men and women. Method Analyses were conducted with the National Epidemiologic Survey on Alcohol and Related Conditions (n=34,653). Outcome variables included: age of alcohol initiation and time to onset of DSM-IV alcohol dependence. Predictor variables included: gender and childhood maltreatment. Linear and Poisson regression analyses were conducted. Results Results demonstrated that in regards to age of drinking initiation, individuals who experienced childhood maltreatment initiated 1 year earlier than those without maltreatment, however, there was no interaction of this relationship with gender. Regarding the time to dependence, it was found that women who experienced childhood maltreatment demonstrated telescoping (shorter time between onset and dependence) compared to women without maltreatment and men (both with and without maltreatment). Conclusion Women with a history of childhood maltreatment are particularly vulnerable to an accelerated time from initiation of alcohol use until dependence, a pattern indicative of increased negative alcohol related outcomes. Findings highlight the need for development of gender-specific prevention efforts and behavioral treatments to aid in early intervention of problematic alcohol use in women. PMID:26130105

  17. Paternal Genetic Contribution Influences Fetal Vulnerability to Maternal Alcohol Consumption in a Rat Model of Fetal Alcohol Spectrum Disorder

    PubMed Central

    Sittig, Laura J.; Redei, Eva E.

    2010-01-01

    Background Fetal alcohol exposure causes in the offspring a collection of permanent physiological and neuropsychological deficits collectively termed Fetal Alcohol Spectrum Disorder (FASD). The timing and amount of exposure cannot fully explain the substantial variability among affected individuals, pointing to genetic influences that mediate fetal vulnerability. However, the aspects of vulnerability that depend on the mother, the father, or both, are not known. Methodology/Principal Findings Using the outbred Sprague-Dawley (SD) and inbred Brown Norway (BN) rat strains as well as their reciprocal crosses, we administered ethanol (E), pair-fed (PF), or control (C) diets to the pregnant dams. The dams' plasma levels of free thyroxine (fT4), triiodothyronine (T3), free T3 (fT3), and thyroid stimulating hormone (TSH) were measured to elucidate potential differences in maternal thyroid hormonal environment, which affects specific aspects of FASD. We then compared alcohol-exposed, pair fed, and control offspring of each fetal strain on gestational day 21 (G21) to identify maternal and paternal genetic effects on bodyweight and placental weight of male and female fetuses. Conclusions SD and BN dams exhibited different baseline hypothalamic-pituitary-thyroid function. Moreover, the thyroid function of SD dams was more severely affected by alcohol consumption while that of BN dams was relatively resistant. This novel finding suggests that genetic differences in maternal thyroid function are one source of maternal genetic effects on fetal vulnerability to FASD. The fetal vulnerability to decreased bodyweight after alcohol exposure depended on the genetic contribution of both parents, not only maternal contribution as previously thought. In contrast, the effect of maternal alcohol consumption on placental weight was consistent and not strain-dependent. Interestingly, placental weight in fetuses with different paternal genetic contributions exhibited opposite responses to

  18. Operation of the computer model for microenvironment atomic oxygen exposure

    NASA Technical Reports Server (NTRS)

    Bourassa, R. J.; Gillis, J. R.; Gruenbaum, P. E.

    1995-01-01

    A computer model for microenvironment atomic oxygen exposure has been developed to extend atomic oxygen modeling capability to include shadowing and reflections. The model uses average exposure conditions established by the direct exposure model and extends the application of these conditions to treat surfaces of arbitrary shape and orientation.

  19. Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats

    PubMed Central

    Boschen, K.E.; Criss, K.J.; Palamarchouk, V.; Roth, T.L.; Klintsova, A.Y.

    2015-01-01

    Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4–9, 5.25 g/kg/day) on expression of brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor in the hippocampal and frontal cortex of infant Long-Evans rats. Levels of BDNF protein were increased in the hippocampus, but not frontal cortex, of alcohol-exposed rats 24 hrs after the last dose, when compared with undisturbed (but not sham-intubated) control animals. BDNF protein levels showed a trend towards increase in hippocampus of sham-intubated animals as well, suggesting an effect of the intubation procedure. TrkB protein was increased in the hippocampus of alcohol-exposed animals compared to sham-intubated pups, indicating an alcohol-specific effect on receptor expression. In addition, expression of bdnf total mRNA in alcohol-exposed and sham-intubated pups was enhanced in the hippocampus; however, there was a differential effect of alcohol and intubation stress on exon I- and IV-specific mRNA transcripts. Further, plasma corticosterone was found to be increased in both alcohol-exposed and sham-intubated pups compared to undisturbed animals. Upregulation of BDNF could potentially represent a neuroprotective mechanism activated following alcohol exposure or stress. The results suggest that alcohol exposure and stress have both overlapping and unique effects on BDNF, and highlight the need for the stress of intubation to be taken into consideration in studies that implement this route of drug delivery. PMID:25805052

  20. Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats.

    PubMed

    Boschen, K E; Criss, K J; Palamarchouk, V; Roth, T L; Klintsova, A Y

    2015-06-01

    Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4-9, 5.25 g/kg/day) on expression of brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor in the hippocampal and frontal cortex of infant Long-Evans rats. Levels of BDNF protein were increased in the hippocampus, but not frontal cortex, of alcohol-exposed rats 24h after the last dose, when compared with undisturbed (but not sham-intubated) control animals. BDNF protein levels showed a trend toward increase in hippocampus of sham-intubated animals as well, suggesting an effect of the intubation procedure. TrkB protein was increased in the hippocampus of alcohol-exposed animals compared to sham-intubated pups, indicating an alcohol-specific effect on receptor expression. In addition, expression of bdnf total mRNA in alcohol-exposed and sham-intubated pups was enhanced in the hippocampus; however, there was a differential effect of alcohol and intubation stress on exon I- and IV-specific mRNA transcripts. Further, plasma corticosterone was found to be increased in both alcohol-exposed and sham-intubated pups compared to undisturbed animals. Upregulation of BDNF could potentially represent a neuroprotective mechanism activated following alcohol exposure or stress. The results suggest that alcohol exposure and stress have both overlapping and unique effects on BDNF, and highlight the need for the stress of intubation to be taken into consideration in studies that implement this route of drug delivery. PMID:25805052

  1. Alcohol lowers the vasoconstriction threshold in humans without affecting core cooling rate during mild cold exposure.

    PubMed

    Johnston, C E; Bristow, G K; Elias, D A; Giesbrecht, G G

    1996-01-01

    Elevated blood alcohol levels are often seen in hypothermia and hyperthermia related deaths, leading to the belief that alcohol renders humans poikilothermic. We examined the core temperature (Tco) thresholds for sweating, vasoconstriction and shivering as well as core cooling rates of seven subjects immersed in 28 degrees C water. On two separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects drank orange juice (7 ml.kg-1) prior to immersion during the control trial and 1 ml.kg-1 absolute ethanol, added to orange juice in a 1:6 ratio, during the alcohol trial. Mean blood alcohol concentration (breath analysis) was 0.097 +/- 0.010 g% at the start of cooling and 0.077 +/- 0.008 g% at the end of the cooling period. Alcohol lowered the vasoconstriction threshold by 0.32 +/- 0.2 degrees C and elevated finger tip blood flow, but had no effect on thresholds for sweating and shivering or core cooling rate. Considering these minor effects it is unlikely that moderate alcohol consumption predisposes individuals to hypothermia or hyperthermia via impaired thermoregulation, but rather likely due to behavioral factors. PMID:8897037

  2. DIETARY EXPOSURES OF YOUNG CHILDREN, PART 3: MODELLING

    EPA Science Inventory

    A deterministic model was used to model dietary exposure of young children. Parameters included pesticide residue on food before handling, surface pesticide loading, transfer efficiencies and children's activity patterns. Three components of dietary pesticide exposure were includ...

  3. Stochastic Human Exposure and Dose Simulation Model for Pesticides

    EPA Science Inventory

    SHEDS-Pesticides (Stochastic Human Exposure and Dose Simulation Model for Pesticides) is a physically-based stochastic model developed to quantify exposure and dose of humans to multimedia, multipathway pollutants. Probabilistic inputs are combined in physical/mechanistic algorit...

  4. EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS): USER MANUAL AND SYSTEM DOCUMENTATION

    EPA Science Inventory

    The Exposure Analysis Modeling System, first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals - pesticides, ...

  5. MULTIMEDIA CONTAMINANT FATE, TRANSPORT, AND EXPOSURE MODEL (MMSOILS)

    EPA Science Inventory

    The Multimedia Contaminant Fate, Transport, and Exposure Model (MMSOILS) estimates the human exposure and health risk associated with releases of contamination from hazardous waste sites. The methodology consists of a multimedia model that addresses the transport of a chemical in...

  6. Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure.

    PubMed

    Migliorini, Robyn; Moore, Eileen M; Glass, Leila; Infante, M Alejandra; Tapert, Susan F; Jones, Kenneth Lyons; Mattson, Sarah N; Riley, Edward P

    2015-10-01

    Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n = 32) and non-exposed controls (CON, n = 21). Adolescents (12-17 years) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on inhibition accuracy. Regression analyses with the rcACC revealed a significant group × ACC interaction. A smaller rcACC surface area was associated with slower inhibition completion time for AE but was not significantly associated with inhibition in CON. After accounting for processing speed, smaller rcACC surface area was associated with worse (i.e., slower) inhibition regardless of group. Examining processing speed independently, a decrease in rcACC surface area was associated with faster processing speed for CON but not significantly associated with processing speed in AE. Results support the theory that caudal ACC may monitor reaction time in addition to inhibition and highlight the possibility of delayed ACC neurodevelopment in prenatal alcohol exposure. PMID:26025509

  7. Modeling Impaired Hippocampal Neurogenesis after Radiation Exposure.

    PubMed

    Cacao, Eliedonna; Cucinotta, Francis A

    2016-03-01

    Radiation impairment of neurogenesis in the hippocampal dentate gyrus is one of several factors associated with cognitive detriments after treatment of brain cancers in children and adults with radiation therapy. Mouse models have been used to study radiation-induced changes in neurogenesis, however the models are limited in the number of doses, dose fractions, age and time after exposure conditions that have been studied. The purpose of this study is to develop a novel predictive mathematical model of radiation-induced changes to neurogenesis using a system of nonlinear ordinary differential equations (ODEs) to represent the time, age and dose-dependent changes to several cell populations participating in neurogenesis as reported in mouse experiments exposed to low-LET radiation. We considered four compartments to model hippocampal neurogenesis and, consequently, the effects of radiation treatment in altering neurogenesis: (1) neural stem cells (NSCs), (2) neuronal progenitor cells or neuroblasts (NB), (3) immature neurons (ImN) and (4) glioblasts (GB). Because neurogenesis is decreasing with increasing mouse age, a description of the age-related dynamics of hippocampal neurogenesis is considered in the model, which is shown to be an important factor in comparisons to experimental data. A key feature of the model is the description of negative feedback regulation on early and late neuronal proliferation after radiation exposure. The model is augmented with parametric descriptions of the dose and time after irradiation dependences of activation of microglial cells and a possible shift of NSC proliferation from neurogenesis to gliogenesis reported at higher doses (∼10 Gy). Predictions for dose-fractionation regimes and for different mouse ages, and prospects for future work are then discussed. PMID:26943452

  8. Behavioral deficits induced by third-trimester equivalent alcohol exposure in male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis but are still rescued with voluntary exercise.

    PubMed

    Hamilton, G F; Bucko, P J; Miller, D S; DeAngelis, R S; Krebs, C P; Rhodes, J S

    2016-11-01

    Prenatal alcohol exposure can produce permanent alterations in brain structure and profound behavioral deficits. Mouse models can help discover mechanisms and identify potentially useful interventions. This study examined long-term influences of either a single or repeated alcohol exposure during the third-trimester equivalent on survival of new neurons in the hippocampus, behavioral performance on the Passive avoidance and Rotarod tasks, and the potential role of exercise as a therapeutic intervention. C57BL/6J male mice received either saline or 5g/kg ethanol split into two s.c. injections, two hours apart, on postnatal day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned on PD21 and received either a running wheel or remained sedentary from PD35-PD80/81. From PD36-45, mice received i.p. injections of 50mg/kg bromodeoxyuridine (BrdU) to label dividing cells. Behavioral testing occurred between PD72-79. Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) was measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in either experiment. Running significantly increased number of BrdU+ and DCX+ cells in both treatment groups. Alcohol-induced deficits on Rotarod performance and acquisition of the Passive avoidance task (Day 1) were evident only in Experiment 2 and running rescued these deficits. These data suggest neonatal alcohol exposure does not result in long-term impairments in adult hippocampal neurogenesis in the mouse model. Three doses of ethanol were necessary to induce behavioral deficits. Finally, the mechanisms by which exercise ameliorated the neonatal alcohol induced behavioral deficits remain unknown. PMID:27491590

  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". PMID:24275070

  10. Different Antiulcer Activities of Pantoprazole in Stress, Alcohol and Pylorus Ligation-Induced Ulcer Models

    PubMed Central

    Bae, Dae-Kwon; Park, Dongsun; Lee, Sun Hee; Yang, Goeun; Yang, Yun-Hui; Kim, Tae Kyun; Choi, Young Jin; Kim, Jwa Jin; Jeon, Jeong Hee; Jang, Min-Jung; Choi, Ehn-Kyoung; Hwang, Seock-Yeon

    2011-01-01

    Antiulcer effects of pantoprazole, a proton-pump inhibitor, on water-immersion restraint stress (WIRS)-, alcohol (ethanol)- and pylorus ligation-induced gastric ulcers were investigated in male rats. Rats were orally administered with pantoprazole 30 min prior to exposure to various types of ulcer inducers. In stress-induced ulcer model, rats were subjected to WIRS at 22℃ for 4 hours, and the degree of ulcer (in mm) was evaluated. In alcohol-induced ulcer model, rats were orally administered with pure (100%) ethanol (1 mL/kg), and the ulcer lesions were measured 1 hour after ethanol challenge. In pylorus ligation-induced ulcer model, rats were subjected to pylorus ligation, and the degree of erosions and ulcers was scored 17 hours after the operation. Pantoprazole attenuated the ulcer lesions induced by WIRS in a dose-dependent manner, exhibiting a median effective dose (ED50) value of 0.78 mg/kg. By comparison, pantoprazole was effective at relatively-high doses for the improvement of ethanol-induced ulcers, showing an ED50 value of 20.5 mg/kg. Notably, pantoprazole was practically ineffective (ED50>50.0) in pylorus ligation model. Taken together, it was confirmed that pantoprazole showed inhibitory activity on gastric ulcers induced by stress and alcohol, but was ineffective on pylorus ligation-induced ulcer. Therefore, the results indicate that proton-pump inhibitors including pantoprazole might reveal highly-different effects according to the type of ulcer inducers, and that the prescription of antiulcer agents should be carefully selected. PMID:21826160

  11. Trends in binge and heavy drinking, alcohol-related problems, and combat exposure in the U.S. military.

    PubMed

    Bray, Robert M; Brown, Janice M; Williams, Jason

    2013-07-01

    Population-based Department of Defense health behavior surveys were examined for binge and heavy drinking among U.S. active duty personnel. From 1998-2008, personnel showed significant increases in heavy drinking (15% to 20%) and binge drinking (35% to 47%). The rate of alcohol-related serious consequences was 4% for nonbinge drinkers, 9% for binge drinkers, and 19% for heavy drinkers. Personnel with high combat exposure had significantly higher rates of heavy (26.8%) and binge (54.8%) drinking than their counterparts (17% and 45%, respectively). Heavy and binge drinking put service members at high risk for problems that diminish force readiness and psychological fitness. PMID:23869454

  12. Magnetic Resonance-based imaging in animal models of Fetal Alcohol Spectrum Disorder

    PubMed Central

    O'Leary-Moore, Shonagh K.; Parnell, Scott E.; Lipinski, Robert J.; Sulik, Kathleen K.

    2012-01-01

    Magnetic resonance imaging (MRI) techniques, such as magnetic resonance microscopy (MRM), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), have recently been applied to the study of both normal and abnormal structure and neurochemistry in small animals. Herein, findings from studies in which these methods have been used for the examination of animal models of Fetal Alcohol Spectrum Disorder (FASD) are discussed. Emphasis is placed on results of imaging studies in fetal and postnatal mice that have highlighted the developmental stage dependency of prenatal ethanol exposure-induced CNS defects. Consideration is also given to the promise of methodological advances to allow in vivo studies of aberrant brain and behavior relationships in model animals and to the translational nature of this work. PMID:21445552

  13. Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment.

    PubMed

    Vetreno, Ryan P; Hall, Joseph M; Savage, Lisa M

    2011-11-01

    Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone. PMID:21256970

  14. 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. PMID:25554482

  15. The Social Predictors of Adolescent Alcohol Misuse: A Test of the Social Development Model*

    PubMed Central

    LONCZAK, HEATHER S.; HUANG, BU; CATALANO, RICHARD F.; HAWKINS, J. DAVID; HILL, KARL G.; ABBOTT, ROBERT D.; RYAN, JEANNE A. M.; KOSTERMAN, RICK

    2007-01-01

    Objective This study was conducted to investigate the ability of the social development model (SDM) to predict alcohol misuse at age 16 and to investigate the ability of the SDM to mediate the effects of alcohol use at age 14 on alcohol misuse at age 16. Method The sample of 807 (411 males) is from the longitudinal panel of the Seattle Social Development Project which, in 1985, surveyed all consenting fifth-grade students from 18 elementary schools serving high-crime neighborhoods in Seattle, Washington. Alcohol use was measured at age 14, predictors of alcohol misuse were measured at age 15 and alcohol misuse was measured at age 16. Structural equation modeling was used to examine the fit of the model to the data. Results All factor loadings were highly significant and the measurement model achieved a good fit with the data (Comparative Fit Index [CFI] = 0.93). A second-order structural model fit the data well (CFI = 0.91) and also explained 45% of the variance in alcohol misuse at age 16. The SDM partially and significantly mediated the direct effect of age-14 alcohol use on age-16 alcohol misuse. Conclusions The risk and protective processes specified by the SDM serve as potential targets for the prevention or reduction of adolescent alcohol misuse. PMID:11327184

  16. A Dual-Process Model of the Alcohol-Behavior Link for Social Drinking

    ERIC Educational Resources Information Center

    Moss, Antony C.; Albery, Ian P.

    2009-01-01

    A dual-process model of the alcohol-behavior link is presented, synthesizing 2 of the major social-cognitive approaches: expectancy and myopia theories. Substantial evidence has accrued to support both of these models, and recent neurocognitive models of the effects of alcohol on thought and behavior have provided evidence to support both as well.…

  17. DOES ALCOHOL CONTRIBUTE TO THE CONFLUENCE MODEL OF SEXUAL ASSAULT PERPETRATION?

    PubMed Central

    PARKHILL, MICHELE R.; ABBEY, ANTONIA

    2015-01-01

    The confluence model of sexual assault provides a useful theoretical integration of factors that influence men’s likelihood of committing sexual assault (Malamuth, Sockloskie, Koss, & Tanaka, 1991). This study replicates and extends the confluence model by including alcohol at multiple levels. Participants’ usual alcohol consumption and alcohol consumption in sexual situations were included as predictor variables. The number of sexually aggressive acts that participants committed after consuming alcohol and the number of sexually aggressive acts participants committed when sober were separately calculated so that the predictors of each could be distinguished. Participants were 356 men who completed a survey that included measures that assessed the key components of the confluence model. Results of path analyses indicated that the expanded model fit the data well, with both general and situational measures of alcohol use predicting frequency of sexual assault when drinking alcohol. These findings highlight the importance of developing universal and targeted prevention programs for young men. PMID:26405374

  18. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    PubMed

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application. PMID:26617183

  19. Alcohol-related amnesia and dementia: Animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment

    PubMed Central

    Vetreno, Ryan P.; Hall, Joseph M.; Savage, Lisa M.

    2011-01-01

    Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models—from repeated and chronic ethanol exposure to thiamine deficiency—is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone. PMID:21256970

  20. Effect of prenatal exposure of alcohol in the morphology of developing rat embryo.

    PubMed

    Ghimire, S R; Dhungel, S; Rai, D; Jha, C B; Saxena, A K; Maskey, D

    2008-03-01

    The objective this study was to observe the morphological changes in developing rat embryo exposed to alcohol in utero. Virgin female Wistar rats in experimental group (n=15) were given 20% (v/v) alcohol two weeks before mating and throughout the gestational period through oral route. The controls (n=15) were also maintained and were given the tap water. On gestational day 15 (GD15) and 19 (GD19), five rats from each group were sacrificed by cervical dislocation and the abdomen was incised to expose the uterine horn. The number of implantation sites and resorptions were counted and recorded. The body weight and length of the fetuses were also recorded. The litter size and body weight of the newborn were also recorded at the time of birth from the remaining dam. The incidence of resorption was higher in alcohol treated group than in control which was found to be 25% and 8.7% at days 15 and 19 respectively. The body weight and length of fetuses were found to be decreased and was significant at GD15 (p<0.001 for weight and p<0.05 for length). Similarly, the litter size and body weight of newborn were also found to be decreased significantly (p<0.05 for litter size and p<0.01 for body weight). The present study shows that the maternal consumption of alcohol during pregnancy has adverse effect on fetal viability and development of growing embryo. PMID:18700630

  1. Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence

    PubMed Central

    Richardson, Heather N.; Chan, Stephanie H.; Crawford, Elena F.; Lee, Youn Kyung; Funk, Cindy K.; Koob, George F.; Mandyam, Chitra D.

    2009-01-01

    Experimenter-delivered alcohol decreases adult hippocampal neurogenesis, and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis was observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggests a loss in neuronal turnover and indicates that the hippocampal neurogenic niche is highly vulnerable to alcohol. PMID:19501165

  2. A POPULATION EXPOSURE MODEL FOR PARTICULATE MATTER: SHEDS-PM

    EPA Science Inventory

    The US EPA National Exposure Research Laboratory (NERL) has developed a population exposure and dose model for particulate matter (PM) that will be publicly available in Fall 2002. The Stochastic Human Exposure and Dose Simulation (SHEDS-PM) model uses a probabilistic approach ...

  3. 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

  4. The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model.

    PubMed

    Washburn, Shannon E; Tress, Ursula; Lunde, Emilie R; Chen, Wei-Jung A; Cudd, Timothy A

    2013-02-01

    Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment. In this study, we hypothesized that repeated elevations in cortisol from chronic binge alcohol are responsible at least in part for fetal neuronal deficits. Animals were divided into four treatment groups: normal control, pair-fed saline control, alcohol and cortisol. The magnitude of elevation in cortisol in response to alcohol was mimicked in the cortisol group by infusing pregnant ewes with hydrocortisone for 6 h on each day of the experiment, and administering saline during the first hour in lieu of alcohol. The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109 until GD 132. Peak maternal blood alcohol concentration in the alcohol group was 239 ± 7 mg/dl. The fetal brains were collected and processed for stereological cell counting on GD 133. The estimated total number of fetal cerebellar Purkinje cells, the reference volume and the Purkinje cell density were not altered in response to glucocorticoid infusion in the absence of alcohol. These results suggest that glucocorticoids independently during the third trimester equivalent may not produce fetal cerebellar Purkinje cell loss. However, the elevations in cortisol along with other changes induced by alcohol could together lead to brain injury seen in the fetal alcohol spectrum disorders. PMID:23218665

  5. A NEW METHOD OF LONGITUDINAL DIARY ASSEMBLY FOR EXPOSURE MODELING

    EPA Science Inventory

    Many stochastic human exposure models require the construction of longitudinal time-activity diaries to evaluate the time sequence of concentrations encountered, and hence, the pollutant exposure for the simulated individuals. However, most of the available data on human activiti...

  6. A PROBABILISTIC MODELING FRAMEWORK FOR PREDICTING POPULATION EXPOSURES TO BENZENE

    EPA Science Inventory

    The US Environmental Protection Agency (EPA) is modifying their probabilistic Stochastic Human Exposure Dose Simulation (SHEDS) model to assess aggregate exposures to air toxics. Air toxics include urban Hazardous Air Pollutants (HAPS) such as benzene from mobile sources, part...

  7. Evaluating Rapid Models for High-Throughput Exposure Forecasting (SOT)

    EPA Science Inventory

    High throughput exposure screening models can provide quantitative predictions for thousands of chemicals; however these predictions must be systematically evaluated for predictive ability. Without the capability to make quantitative, albeit uncertain, forecasts of exposure, the ...

  8. Explaining Alcohol Use and Suicide Risk: A Moderated Mediation Model Involving Insomnia Symptoms and Gender

    PubMed Central

    Nadorff, Michael R.; Salem, Taban; Winer, E. Samuel; Lamis, Dorian A.; Nazem, Sarra; Berman, Mitchell E.

    2014-01-01

    Study Objectives: The purpose of the study was to examine whether insomnia symptoms and nightmares mediated the relation between alcohol use and suicide risk. Further, we examined whether this mediation was moderated by gender. Design: The study consisted of questionnaires administered online examining insomnia symptoms, nightmares, alcohol use, and suicide risk. Setting: University. Patients or Participants: 375 undergraduate students at a large, public university in the southeastern United States. Interventions: N/A. Measurements and Results: Results indicated that insomnia symptoms significantly mediated the relation between alcohol use and suicide risk; however, this mediation was moderated by gender. For women, there was both a direct effect of alcohol use on suicide risk as well as an indirect effect of alcohol use through insomnia symptoms increasing suicide risk. For men, there was no direct effect of alcohol use on suicide risk, but there was a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms. Nightmares were not related to alcohol use, and the association between nightmares and suicide risk was found to be independent of alcohol use Conclusions: Insomnia symptoms are an important factor in explaining the mechanism by which alcohol use increases suicide risk. Citation: Nadorff MR, Salem T, Winer ES, Lamis DA, Nazem S, Berman ME. Explaining alcohol use and suicide risk: a moderated mediation model involving insomnia symptoms and gender. J Clin Sleep Med 2014;10(12):1317-1323. PMID:25325605

  9. HUMAN EXPOSURE MODELING: CONCEPTS, METHODS, AND TOOLS

    EPA Science Inventory

    Understanding human exposure is critical when estimating the occurrence of deleterious effects that could follow contact with environmental contaminants. For many pollutants, the intensity, duration, frequency, route, and timing of exposure is highly variable, particularly whe...

  10. Animal Models for Medication Development and Application to Treat Fetal Alcohol Effects.

    PubMed

    Barron, S; Hawkey, A; Fields, L; Littleton, J M

    2016-01-01

    Ethanol consumption during pregnancy can have lifelong consequences for the offspring, their family and society. Fetal alcohol spectrum disorders (FASD) include a range of physical and behavioral effects with the most significant impact occurring as a result of the effects of ethanol on the developing central nervous system (CNS). To date, there are no FDA approved drugs that have been tested that prevent/reduce or specifically treat the symptoms of FASD. There are several promising lines of research from rodent models aimed at reducing the neurotoxic effects of ethanol on the developing CNS or in treating the resulting behavioral impairments but these have not yet moved to clinical testing. The current review discusses some of the most promising targets for intervention and provides a review of the past and ongoing efforts to develop and screen pharmacological treatments for reducing the effects of prenatal ethanol exposure. PMID:27055621

  11. Beyond the Disease Model: Reframing the Etiology of Alcoholism from a Spiritual Perspective

    ERIC Educational Resources Information Center

    Bliss, Donna Leigh

    2009-01-01

    The disease model of alcoholism, which has gained prominence since the mid-20th century as the major etiological model of alcoholism, suffers from several limitations including its overemphasis on biological factors at the expense of other psychosocial factors, in addition to its lack of consistency with a holistic, social work…

  12. Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Gyongyosi, Benedek; Lowe, Patrick; Szabo, Gyongyi

    2016-01-01

    AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD). METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA). RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice. CONCLUSION: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC. PMID:27122661

  13. DEVELOPMENT OF A DIETARY EXPOSURE POTENTIAL MODEL FOR EVALUATING DIETARY EXPOSURE TO CHEMICAL RESIDUES IN FOOD

    EPA Science Inventory

    The Dietary Exposure Potential Model (DEPM) is a computer-based model developed for estimating dietary exposure to chemical residues in food. The DEPM is based on food consumption data from the 1987-1988 Nationwide Food Consumption Survey (NFCS) administered by the United States ...

  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. Model of the cooperative rearranging region for polyhydric alcohols

    NASA Astrophysics Data System (ADS)

    Nakanishi, Masahiro; Nozaki, Ryusuke

    2011-07-01

    A simplified model of a hydrogen-bonding network is proposed in order to clarify the microscopic structure of the cooperative rearranging region (CRR) in Adam-Gibbs theory [G. Adam and J. H. Gibbs, J. Chem. Phys.JCPSA60021-960610.1063/1.1696442 43, 139 (1965)]. Our model can be solved analytically, and it successfully explains the reported systematic features of the glass transition of polyhydric alcohols. In this model, hydrogen bonding is formulated based on binding free energy. Assuming a cluster of molecules connected by double hydrogen bonds is a CRR and approximating the hydrogen-bonding network as a Bethe lattice in percolation theory, the temperature dependence of the structural relaxation time can be obtained analytically. Reported data on relaxation times are well described by the obtained equation. By taking the lower limit of the binding free energy with this equation, the Vogel-Fulcher-Tammann equation can be derived. Consequently, the fragility index and glass transition temperature can be expressed as functions of the number of OH groups in a molecule, and this relation agrees well with the reported experimental data.

  16. Extraction of exposure modeling parameters of thick resist

    NASA Astrophysics Data System (ADS)

    Liu, Chi; Du, Jinglei; Liu, Shijie; Duan, Xi; Luo, Boliang; Zhu, Jianhua; Guo, Yongkang; Du, Chunlei

    2004-12-01

    Experimental and theoretical analysis indicates that many nonlinear factors existing in the exposure process of thick resist can remarkably affect the PAC concentration distribution in the resist. So the effects should be fully considered in the exposure model of thick resist, and exposure parameters should not be treated as constants because there exists certain relationship between the parameters and resist thickness. In this paper, an enhanced Dill model for the exposure process of thick resist is presented, and the experimental setup for measuring exposure parameters of thick resist is developed. We measure the intensity transmittance curve of thick resist AZ4562 under different processing conditions, and extract the corresponding exposure parameters based on the experiment results and the calculations from the beam propagation matrix of the resist films. With these modified modeling parameters and enhanced Dill model, simulation of thick-resist exposure process can be effectively developed in the future.

  17. Effect of Naltrexone During Extinction of Alcohol-Reinforced Responding and During Repeated Cue-Conditioned Reinstatement Sessions in a Cue Exposure Style Treatment

    PubMed Central

    Williams, Keith L.; Schimmel, Jasmine S.

    2008-01-01

    The ability of alcohol-related cues to promote craving can be attenuated independently by giving the opioid antagonist naltrexone (NTX) or by subjecting alcohol-dependent patients to a cue exposure treatment. The effects of cue exposure treatment may be enhanced if conducted in the presence of NTX. The purpose of these experiments was to determine if NTX given during extinction of responding for alcohol in rats would alter cue-conditioned reinstatement of responding and to determine if NTX, paired with repeated cue-conditioned reinstatement, would reduce subsequent cue-conditioned reinstatement or reacquisition of self-administration in the absence of NTX. Rats lever-pressed for alcohol in the presence of an olfactory cue. Visual and auditory stimuli were presented during alcohol delivery. In the first experiment, rats were injected with saline or 3 mg/kg NTX prior to extinction sessions followed by cue-conditioned reinstatement tests. In the second experiment, extinction was followed by cue-conditioned reinstatement sessions presented twice per week. The rats received saline or NTX (3 and 10 mg/kg) prior to several sessions. All rats received reinstatement tests with and without a pretreatment of NTX followed by reacquisition of alcohol self-administration. NTX had no effect on responding during extinction or on subsequent cue-conditioned reinstatement. Only 10 mg/kg NTX reduced responding during the twice weekly reinstatement sessions. The twice weekly NTX treatment had no effect on subsequent cue-conditioned reinstatement in the absence of NTX. Reacquisition of responding for alcohol was reduced in the group receiving saline during repeated reinstatement sessions while this effect was blocked in the NTX group. These findings support the notion that NTX given during a brief abstinence period (i.e., extinction) has minimal effects on future sensitivity to alcohol cues and alcohol consumption. NTX given during repeated alcohol cue exposure does not alter the

  18. Implications of genomic signatures in the differential vulnerability to fetal alcohol exposure in C57BL/6 and DBA/2 mice

    PubMed Central

    Lossie, Amy C.; Muir, William M.; Lo, Chiao-Ling; Timm, Floyd; Liu, Yunlong; Gray, Whitney; Zhou, Feng C.

    2014-01-01

    Maternal alcohol consumption inflicts a multitude of phenotypic consequences that range from undetectable changes to severe dysmorphology. Using tightly controlled murine studies that deliver precise amounts of alcohol at discrete developmental stages, our group and other labs demonstrated in prior studies that the C57BL/6 and DBA/2 inbred mouse strains display differential susceptibility to the teratogenic effects of alcohol. Since the phenotypic diversity extends beyond the amount, dosage and timing of alcohol exposure, it is likely that an individual's genetic background contributes to the phenotypic spectrum. To identify the genomic signatures associated with these observed differences in alcohol-induced dysmorphology, we conducted a microarray-based transcriptome study that also interrogated the genomic signatures between these two lines based on genetic background and alcohol exposure. This approach is called a gene x environment (GxE) analysis; one example of a GxE interaction would be a gene whose expression level increases in C57BL/6, but decreases in DBA/2 embryos, following alcohol exposure. We identified 35 candidate genes exhibiting GxE interactions. To identify cis-acting factors that mediated these interactions, we interrogated the proximal promoters of these 35 candidates and found 241 single nucleotide variants (SNVs) in 16 promoters. Further investigation indicated that 186 SNVs (15 promoters) are predicted to alter transcription factor binding. In addition, 62 SNVs created, removed or altered the placement of a CpG dinucleotide in 13 of the proximal promoters, 53 of which overlapped putative transcription factor binding sites. These 53 SNVs are also our top candidates for future studies aimed at examining the effects of alcohol on epigenetic gene regulation. PMID:24966868

  19. Implications of genomic signatures in the differential vulnerability to fetal alcohol exposure in C57BL/6 and DBA/2 mice.

    PubMed

    Lossie, Amy C; Muir, William M; Lo, Chiao-Ling; Timm, Floyd; Liu, Yunlong; Gray, Whitney; Zhou, Feng C

    2014-01-01

    Maternal alcohol consumption inflicts a multitude of phenotypic consequences that range from undetectable changes to severe dysmorphology. Using tightly controlled murine studies that deliver precise amounts of alcohol at discrete developmental stages, our group and other labs demonstrated in prior studies that the C57BL/6 and DBA/2 inbred mouse strains display differential susceptibility to the teratogenic effects of alcohol. Since the phenotypic diversity extends beyond the amount, dosage and timing of alcohol exposure, it is likely that an individual's genetic background contributes to the phenotypic spectrum. To identify the genomic signatures associated with these observed differences in alcohol-induced dysmorphology, we conducted a microarray-based transcriptome study that also interrogated the genomic signatures between these two lines based on genetic background and alcohol exposure. This approach is called a gene x environment (GxE) analysis; one example of a GxE interaction would be a gene whose expression level increases in C57BL/6, but decreases in DBA/2 embryos, following alcohol exposure. We identified 35 candidate genes exhibiting GxE interactions. To identify cis-acting factors that mediated these interactions, we interrogated the proximal promoters of these 35 candidates and found 241 single nucleotide variants (SNVs) in 16 promoters. Further investigation indicated that 186 SNVs (15 promoters) are predicted to alter transcription factor binding. In addition, 62 SNVs created, removed or altered the placement of a CpG dinucleotide in 13 of the proximal promoters, 53 of which overlapped putative transcription factor binding sites. These 53 SNVs are also our top candidates for future studies aimed at examining the effects of alcohol on epigenetic gene regulation. PMID:24966868

  20. Alcohol and Other Drug Prevention on College Campuses: Model Programs

    ERIC Educational Resources Information Center

    US Department of Education, 2008

    2008-01-01

    In response to recent alcohol-related tragedies and to ongoing concern about unacceptable levels of alcohol and other drug use on college campuses, Congress authorized the U.S. Department of Education to identify and promote effective campus-based prevention programs. Since 1999, the U.S. Department of Education has awarded approximately $3.5…

  1. Alcohol and Other Drug Prevention on College Campuses: Model Programs.

    ERIC Educational Resources Information Center

    Office of Elementary and Secondary Education (ED), Washington, DC. Safe and Drug Free Schools Program.

    In response to growing awareness of and concern about alcohol and other drug problems, institutions of higher education are implementing policies and programs in an attempt to curb alcohol and other drug use and its associated negative consequences. Momentum is building for comprehensive prevention approaches that combine traditional education…

  2. A Structural Model of Alcohol Use Pathways among Latino Youth

    ERIC Educational Resources Information Center

    Yan, Fang Alice; Beck, Kenneth H.; Howard, Donna; Shattuck, Teresa Downs; Kerr, Melissa Hallmark

    2008-01-01

    Objectives: To determine the pathways to alcohol use among adolescents. Methods: A cross-sectional study of risk and protective factors among a sample of Latino youth (aged 11-13) was conducted. Results: Peer norms and school connectedness had direct pathways to alcohol use. Self-concept was related to peer norms. Youth who were less acculturated…

  3. Alcoholic cardiomyopathy

    PubMed Central

    Guzzo-Merello, Gonzalo; Cobo-Marcos, Marta; Gallego-Delgado, Maria; Garcia-Pavia, Pablo

    2014-01-01

    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy (ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM. PMID:25228956

  4. A Rasch Model Analysis of Alcohol Consumption and Problems Across Adolescence and Young Adulthood

    PubMed Central

    Kahler, Christopher W.; Hoeppner, Bettina B.; Jackson, Kristina M.

    2010-01-01

    Background Recent investigations using item response modeling have begun to conceptualize alcohol consumption, problems, and dependence as representing points along a single continuum of alcohol involvement. Such a conceptualization may be of particular benefit to measurement of alcohol involvement in adolescents, but investigations to date have been limited to adult samples and may not generalize to adolescents due to age-related developmental differences. Methods This study used Rasch model analyses to examine the properties of indices of alcohol consumption and problems among 6,353 adolescents, aged 12 to 18 years, in Wave 1 of the Add Health survey. A particular focus was on whether the functioning of items changed when these adolescents were re-interviewed in Wave 3 when they were 18 to 24 years of age. Results Rasch model analyses supported the unidimensionality and additive properties of the items in the Wave 1 data. Comparisons of Wave 1 and Wave 3 data indicated differential item functioning in most of the items such that items related to alcohol consumption were more severe during adolescence, whereas items related to alcohol problems were more severe in young adulthood. Conclusions A valid index of alcohol involvement in adolescents can be constructed combining indices of alcohol consumption and alcohol problems. Such an index covers a range of severity and functions similarly across sex and race/ethnicity. A similar index can be constructed in young adulthood. However, the interpretation of scores must be attentive to developmental differences. In particular, for adolescents, indices of alcohol consumption are relatively closer in severity to indices of alcohol problems than they are among young adults. Thus, alcohol problems are more likely among adolescents than young adults given a similar level of drinking. PMID:19183135

  5. 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.

  6. 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

  7. Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding.

    PubMed

    Tian, Fengwei; Chi, Feifei; Wang, Gang; Liu, Xiaoming; Zhang, Qiuxiang; Chen, Yongquan; Zhang, Hao; Chen, Wei

    2015-12-01

    Lactobacillus rhamnosus CCFM1107 was screened for high antioxidative activity from 55 lactobacilli. The present study attempted to explore the protective properties of L. rhamnosus CCFM1107 in alcoholic liver injury. A mouse model was induced by orally feeding alcohol when simultaneously treated with L. rhamnosus CCFM1107, the drug Hu-Gan- Pian (HGP), L. rhamnosus GG (LGG), and L. plantarum CCFM1112 for 3 months. Biochemical analysis was performed for both serum and liver homogenate. Detailed intestinal flora and histological analyses were also carried out. Our results indicated that the administration of L. rhamnosus CCFM1107 significantly inhibited the increase in the levels of serum aminotransferase and endotoxin, as well as the levels of triglyceride (TG) and cholesterol (CHO) in the serum and in the liver. Glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were elevated while the levels of malondialdehyde (MDA) were decreased. The enteric dysbiosis caused by alcohol was restored by increasing the numbers of both lactobacilli and bifidobacteria and decreasing the numbers of both enterococci and enterobacter. Histological analysis confirmed the protective effect of L. rhamnosus CCFM1107. Compared with the other lactobacilli and to the drug Hu-Gan-Pian, there is a high chance that L. rhamnosus CCFM1107 provides protective effects on alcoholic liver injury by reducing oxidative stress and restoring the intestinal flora. PMID:26626356

  8. A Mediational Model of Racial Discrimination and Alcohol-Related Problems Among African American College Students

    PubMed Central

    Boynton, Marcella H; O’Hara, Ross E; Covault, Jonathan; Scott, Denise; Tennen, Howard

    2014-01-01

    Objective: Racial discrimination has been identified as an important predictor of alcohol-related outcomes for African Americans. The goal of the current study was to extend previously found links between lifetime discrimination, alcohol use, and alcohol problems as well as to elucidate the affective mechanisms underlying these associations, as moderated by gender. Method: A multiple-groups structural equation model was computed using survey data collected from 619 students from a historically Black college/university. Results: The final model provided excellent fit to the data, explaining 6% of the variance in alcohol consumption and 37% of the variance in alcohol problems. Discrimination was a significant predictor of alcohol-related problems but not, by and large, level of use. For men, anger—but not discrimination-specific anger—was a significant partial mediator of the link between discrimination and both alcohol use and alcohol problems. Depression partially mediated the link between discrimination and alcohol problems for both men and women. Conclusions: The results suggest that, for African Americans whose drinking leads to drinking-related problems, discrimination and poor affective self-regulation are highly relevant and predictive factors, especially for men. PMID:24650816

  9. Alcohol disrupts sleep homeostasis

    PubMed Central

    Thakkar, Mahesh M.; Sharma, Rishi; Sahota, Pradeep

    2014-01-01

    Alcohol is a potent somnogen and one of the most commonly used “over the counter” sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to understand how and where alcohol acts to affect sleep. We have conducted a series of experiments using two different species, rats and mice, as animal models, and a combination of multi-disciplinary experimental methodologies to examine and understand anatomical and cellular substrates mediating the effects of acute and chronic alcohol exposure on sleep-wakefulness. The results of our studies suggest that the sleep-promoting effects of alcohol may be mediated via alcohol’s action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Lesions of the BF cholinergic neurons or blockade of AD A1 receptors results in attenuation of alcohol-induced sleep promotion, suggesting that AD and BF cholinergic neurons are critical for sleep-promoting effects of alcohol. Since binge alcohol consumption is a highly prevalent pattern

  10. Correspondence of parent report and laboratory measures of inattention and hyperactivity in children with heavy prenatal alcohol exposure.

    PubMed

    Glass, Leila; Graham, Diana M; Deweese, Benjamin N; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

    2014-01-01

    Clinical research and practice support a multi-method approach to validating behavioral problems in children. We examined whether parent-reported symptoms of hyperactivity and inattention (using the Disruptive Behavior Disorder Rating Scale) were substantiated by objective laboratory measures [hyperactivity measured by wrist-worn actigraphy (ACT) and inattention assessed using a 20-minute continuous performance task (CPT)] in three age- and demographically-matched groups of school-age children: children with prenatal alcohol exposure (AE), non-exposed children with idiopathic ADHD (ADHD), and controls (CON). Results indicated that the clinical groups (AE, ADHD) had significantly higher parent-reported levels for both domains compared to the CON group, and did not differ from each other. On the laboratory measures, the clinical groups were more inattentive than controls on the CPT, but did not differ from each other. In contrast, the ADHD group had higher objective activity on the ACT than AE and CON, which did not differ from each other. Thus, laboratory measures differentially validated parent reports in a group-dependent manner. Actigraphy substantiated parent-reported hyperactivity for children in the ADHD group but not for children in the AE group, while the CPT validated parent-reported inattention for both clinical groups. Although the majority of children in the AE group met the criteria for ADHD, objective activity levels were not different from controls, indicating that hyperactivity may be a less prominent feature in the AE group. Thus, while there is considerable overlap between the effects of prenatal alcohol exposure and ADHD, differences in behavioral profiles may be clinically useful in differential diagnosis. Further, these data indicate that objective measures should be used to validate parent reports. PMID:24512965

  11. Prenatal Alcohol Exposure, Adaptive Function, and Entry into Adult Roles in a Prospective Study of Young Adults

    PubMed Central

    Lynch, Mary Ellen; Kable, Julie A.; Coles, Claire D.

    2015-01-01

    Introduction Although many studies have demonstrated effects of prenatal alcohol exposure (PAE) on physical, cognitive, and behavioral development in children, few have focused on the long term effects on adults. In this study, data are presented on adaptive function and entry into adult roles in a community sample of young adults with PAE. The expectation was that prenatally exposed adults would show lower adaptive functioning and more difficulty with entry into adult roles than the non-exposed control group and that these effects would be related to the severity of PAE effects. Method The predominantly African-American, low income sample included adults with a wide range of prenatal exposure (n = 123) as well as control groups for socioeconomic (SES) (n = 59) and disability (n = 54) status. The mothers of the alcohol-exposed and SES-control group participants were recruited before birth and offspring have been followed up periodically. The disability control group was recruited in adolescence. The adults were interviewed about adaptive function in day-to-day life and adult role entry. Collateral adults who were well-acquainted with each participant were interviewed concerning adaptive function. Results Results showed that adults who were dysmorphic and/or cognitively affected by PAE had difficulty with adaptive function and entry into adult roles. Males showing cognitive effects with no physical effects were the most severely affected. Results for exposed adults not showing physical or cognitive effects were similar to or more positive than those of the control group for most outcomes. Conclusion PAE has long-term effects on adaptive outcomes in early adulthood. Additional research should focus on possible interventions at this transition and on factors contributing to the adjustment of the exposed, but unaffected participants. PMID:26247662

  12. Exposure-Based Cat Modeling, Available data, Advantages, & Limitations

    NASA Astrophysics Data System (ADS)

    Michel, Gero; Hosoe, Taro; Schrah, Mike; Saito, Keiko

    2010-05-01

    This paper discusses the advantages and disadvantages of exposure data for cat-modeling and considers concepts of scale as well as the completeness of data and data scoring using field/model examples. Catastrophe modeling based on exposure data has been considered the panacea for insurance-related cat modeling since the late 1980's. Reasons for this include: • The ability to extend risk modeling to consider data beyond historical losses, • Usability across many relevant scales, • Flexibility in addressing complex structures and policy conditions, and • Ability to assess dependence of risk results on exposure-attributes and exposure-modifiers, such as lines of business, occupancy types, and mitigation features, at any given scale. In order to calculate related risk, monetary exposure is correlated to vulnerabilities that have been calibrated with historical results, plausibility concepts, and/or physical modeling. While exposure based modeling is widely adopted, we also need to be aware of its limitations which include: • Boundaries in our understanding of the distribution of exposure, • Spatial interdependence of exposure patterns and the time-dependence of exposure, • Incomplete availability of loss information to calibrate relevant exposure attributes/structure with related vulnerabilities and losses, • The scale-dependence of vulnerability, • Potential for missing or incomplete communication of assumptions made during model calibration, • Inefficiencies in the aggregation or disaggregation of vulnerabilities, and • Factors which can influence losses other than exposure, vulnerability, and hazard. Although we might assume that the higher the resolution the better, regional model calibration is often limited to lower than street level resolution with higher resolution being achieved by disaggregating results using topographic/roughness features with often loosely constrained and/or varying effects on losses. This suggests that higher accuracy

  13. Predictive Models of Alcohol Use Based on Attitudes and Individual Values

    ERIC Educational Resources Information Center

    Del Castillo Rodríguez, José A. García; López-Sánchez, Carmen; Soler, M. Carmen Quiles; Del Castillo-López, Álvaro García; Pertusa, Mónica Gázquez; Campos, Juan Carlos Marzo; Inglés, Cándido J.

    2013-01-01

    Two predictive models are developed in this article: the first is designed to predict people' attitudes to alcoholic drinks, while the second sets out to predict the use of alcohol in relation to selected individual values. University students (N = 1,500) were recruited through stratified sampling based on sex and academic discipline. The…

  14. Biomass alcohols as potential petroleum alternatives in the fuel and petrochemical industries: A generalized network model

    NASA Astrophysics Data System (ADS)

    Farina, R. F.

    A generalized network model called PETNET is developed to address this problem. The focus of the analysis presented is the role of biomass alcohols as potential alternatives to fossil hydrocarbons as raw materials in the petrochemical and oil industries. Illustrative scenarios for biomass-based alcohol replacements are investigated with PETNET by solving for alternative assumptions of price, capacity, resource availability and process technology.

  15. A Small Group Model for Working with Elementary School Children of Alcoholics.

    ERIC Educational Resources Information Center

    McNair, Robert; Arman, John F.

    2000-01-01

    Outlines a small group model that provides elementary school counselors with a creative way to help children of alcoholics build resiliency and develop protective strategies. Emphasizes the importance of the school counselor in taking a proactive approach and reaching out to help children develop the skills needed to survive an alcoholic home.…

  16. Alcohol exposure during late gestation adversely affects myocardial development with implications for postnatal cardiac function.

    PubMed

    Goh, Joanna M; Bensley, Jonathan G; Kenna, Kelly; Sozo, Foula; Bocking, Alan D; Brien, James; Walker, David; Harding, Richard; Black, M Jane

    2011-02-01

    Prenatal exposure to high levels of ethanol is associated with cardiac malformations, but the effects of lower levels of exposure on the heart are unclear. Our aim was to investigate the effects of daily exposure to ethanol during late gestation, when cardiomyocytes are undergoing maturation, on the developing myocardium. Pregnant ewes were infused with either ethanol (0.75 g/kg) or saline for 1 h each day from gestational days 95 to 133 (term ∼145 days); tissues were collected at 134 days. In sheep, cardiomyocytes mature during late gestation as in humans. Within the left ventricle (LV), cardiomyocyte number was determined using unbiased stereology and cardiomyocyte size and nuclearity determined using confocal microscopy. Collagen deposition was quantified using image analysis. Genes relating to cardiomyocyte proliferation and apoptosis were examined using quantitative real-time PCR. Fetal plasma ethanol concentration reached 0.11 g/dL after EtOH infusions. Ethanol exposure induced significant increases in relative heart weight, relative LV wall volume, and cardiomyocyte cross-sectional area. Ethanol exposure advanced LV maturation in that the proportion of binucleated cardiomyocytes increased by 12%, and the number of mononucleated cardiomyocytes was decreased by a similar amount. Apoptotic gene expression increased in the ethanol-exposed hearts, although there were no significant differences between groups in total cardiomyocyte number or interstitial collagen. Daily exposure to a moderate dose of ethanol in late gestation accelerates the maturation of cardiomyocytes and increases cardiomyocyte and LV tissue volume in the fetal heart. These effects on cardiomyocyte growth may program for long-term cardiac vulnerability. PMID:21076018

  17. Modelling anxiety disorders following chemical exposures.

    PubMed

    Adamec, R

    1994-01-01

    The effects of kindling and inverse benzodiazepine receptor agonist beta-carbolines on animal models of anxiety are briefly reviewed in relation to affective disorder associated with chemical exposure. Recent experimental results are described. In the present study, cats were given the inverse benzodiazepine receptor agonist, FG-7142, a powerful anxiogenic compound in humans and animals. Neural transmission in pathways involved in defensive behavior in the cat was monitored using evoked potential techniques. Change in these pathways was related to behavioral changes induced by the drug. It was found that a single dose of FG-7142 lastingly increased defensive response to rodents for at least 40 days after drug administration. Behavioral change was specific to defensive response, since approach-attack behavior remained unchanged, replicating previous studies. The benzodiazepine receptor antagonist, Flumazenil, reversed the increase in defensiveness in a drug-dependent manner, replicating previous findings. Increased defensiveness was paralleled by a delayed onset potentiation of neural transmission between the amygdala and the medial hypothalamus of the left hemisphere. Potentiation in the left hemisphere was transient, decaying between 6 and 12 days after the drug. There was a longer lasting potentiation (LTP) of activity evoked in the left and right amygdalo-periacqueductal gray pathways and in the right amygdalo-medial hypothalamic pathway. Potentiation in these pathways appeared at the time of behavioral change. Potentiation of the right amygdalo-periacqueductal gray and right amygdalo-medial hypothalamic pathways persisted until the end of the experiment. In contrast, potentiation of the left amygdalo-periacqueductal gray pathway faded by 40 days after the drug. Flumazenil decreased potentiation ony in the right amygdalo-periacqueductal gray pathway. These data strongly suggest that lasting affective change is mediated by lasting changes in particular efferents

  18. Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders.

    PubMed

    Glass, Leila; Ware, Ashley L; Mattson, Sarah N

    2014-01-01

    Alcohol consumption during pregnancy can have deleterious consequences for the fetus, including changes in central nervous system development leading to permanent neurologic alterations and cognitive and behavioral deficits. Individuals affected by prenatal alcohol exposure, including those with and without fetal alcohol syndrome, are identified under the umbrella of fetal alcohol spectrum disorders (FASD). While studies of humans and animal models confirm that even low to moderate levels of exposure can have detrimental effects, critical doses of such exposure have yet to be specified and the most clinically significant and consistent consequences occur following heavy exposure. These consequences are pervasive, devastating, and can result in long-term dysfunction. This chapter summarizes the neurobehavioral, neurologic, and neuroimaging characteristics of FASD, focusing primarily on clinical research of individuals with histories of heavy prenatal alcohol exposure, although studies of lower levels of exposure, particularly prospective, longitudinal studies, will be discussed where relevant. PMID:25307589

  19. A Comparison of the Different Animal Models of Fetal Alcohol Spectrum Disorders and Their Use in Studying Complex Behaviors

    PubMed Central

    Patten, Anna R.; Fontaine, Christine J.; Christie, Brian R.

    2014-01-01

    Prenatal ethanol exposure (PNEE) has been linked to widespread impairments in brain structure and function. There are a number of animal models that are used to study the structural and functional deficits caused by PNEE, including, but not limited to invertebrates, fish, rodents, and non-human primates. Animal models enable a researcher to control important variables such as the route of ethanol administration, as well as the timing, frequency and amount of ethanol exposure. Each animal model and system of exposure has its place, depending on the research question being undertaken. In this review, we will examine the different routes of ethanol administration and the various animal models of fetal alcohol spectrum disorders (FASD) that are commonly used in research, emphasizing their strengths and limitations. We will also present an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on behavior across the lifespan, focusing on learning and memory, olfaction, social, executive, and motor functions. Special emphasis will be placed where the various animal models best represent deficits observed in the human condition and offer a viable test bed to examine potential therapeutics for human beings with FASD. PMID:25232537

  20. 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)

  1. Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters.

    PubMed

    Yang, J Y; Kwak, H S; Han, J Y; 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

  2. An overview of human exposure modeling activities at the USEPA's National Exposure Research Laboratory.

    PubMed

    Furtaw, E J

    2001-06-01

    The computational modeling of human exposure to environmental pollutants is one of the primary activities of the US Environmental Protection Agency (USEPA)s National Exposure Research Laboratory (NERL). Assessment of human exposures is a critical part of the overall risk assessment paradigm. In exposure assessment, we analyze the source-to-dose sequence of processes, in which pollutants are released from sources into the environment, where they may move through multiple environmental media, and to human receptors via multiple pathways. Exposure occurs at the environment-human interface, where pollutants are contacted in the course of human activities. Exposure may result in a dose, by which chemicals enter the body through multiple portals of entry, primarily inhalation, ingestion, and dermal absorption. Within the body, absorbed pollutants are distributed to, metabolized within, and eliminated from various organs and tissues, where they may cause toxicologic responses or adverse health effects. The NERL's modeling efforts are directed at improving our understanding of this sequence of processes, by characterizing the various factors influencing exposures and dose, and their associated variabilities and uncertainties. Modeling at the NERL is one of three essential programmatic elements, along with measurements and methods development. These are pursued interactively to advance our understanding of exposure-related processes. Exposure models are developed and run using the best currently available measurement data to simulate and predict population exposure and dose distributions, and to identify the most important factors and their variabilities and uncertainties. This knowledge is then used to guide the development of improved methods and measurements needed to obtain better data to improve the assessment and reduce critical uncertainties. These models and measurement results are tools that can be used in risk assessments and in risk management decisions in order

  3. Olfactory Impact of Higher Alcohols on Red Wine Fruity Ester Aroma Expression in Model Solution.

    PubMed

    Cameleyre, Margaux; Lytra, Georgia; Tempere, Sophie; Barbe, Jean-Christophe

    2015-11-11

    This study focused on the impact of five higher alcohols on the perception of fruity aroma in red wines. Various aromatic reconstitutions were prepared, consisting of 13 ethyl esters and acetates and 5 higher alcohols, all at the average concentrations found in red wine. These aromatic reconstitutions were prepared in several matrices. Sensory analysis revealed the interesting behavior of certain compounds among the five higher alcohols following their individual addition or omission. The "olfactory threshold" of the fruity pool was evaluated in several matrices: dilute alcohol solution, dilute alcohol solution containing 3-methylbutan-1-ol or butan-1-ol individually, and dilute alcohol solution containing the mixture of five higher alcohols, blended together at various concentrations. The presence of 3-methylbutan-1-ol or butan-1-ol alone led to a significant decrease in the "olfactory threshold" of the fruity reconstitution, whereas the mixture of alcohols raised the olfactory threshold. Sensory profiles highlighted changes in the perception of fruity nuances in the presence of the mixture of higher alcohols, with specific perceptive interactions, including a relevant masking effect on fresh- and jammy-fruit notes of the fruity mixture in both dilute alcohol solution and dearomatized red wine matrices. When either 3-methylbutan-1-ol or butan-1-ol was added to the fruity reconstitution in dilute alcohol solution, an enhancement of butyric notes was reported with 3-methylbutan-1-ol and fresh- and jammy-fruit with butan-1-ol. This study, the first to focus on the impact of higher alcohols on fruity aromatic expression, revealed that these compounds participate, both quantitatively and qualitatively, in masking fruity aroma perception in a model fruity wine mixture. PMID:26529563

  4. MODELING CARBON MONOXIDE (CO) EXPOSURES WITHIN MICROENVIRONMENTS GIVEN PERSONAL EXPOSURE MONITORING DATA

    EPA Science Inventory

    Data collected at ambient fixed sites may not adequately reflect personal CO exposures, as they most often miss exposures resulting from CO emissions from sources in the immediate physical surroundings of individuals, such as within automobiles. he SHAPE model was proposed to acc...

  5. EVALUATION OF OZONE EXPOSURE INDICES IN EXPOSURE-RESPONSE MODELING (JOURNAL VERSION)

    EPA Science Inventory

    In exposure-response modeling, a major concern is the numerical definition of exposure in relating crop loss to O3, yet few indices have been considered. The paper addresses research in which plant growth was regressed for soybean, wheat, cotton, corn, and sorghum against 613 num...

  6. Effects of stress on alcohol drinking: a review of animal studies

    PubMed Central

    Lopez, Marcelo F.; Doremus-Fitzwater, Tamara L.

    2011-01-01

    Rationale While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results. Objectives This paper reviews results from animal studies in which alcohol consumption is evaluated under conditions of acute/sub-chronic stress exposure or models of chronic stress exposure. Evidence also is presented indicating that chronic intermittent alcohol exposure serves as a stressor that consequently influences drinking. Results The effects of various acute/sub-chronic stress procedures on alcohol consumption have generally been mixed, but most study outcomes suggest either no effect or decreased alcohol consumption. In contrast, most studies indicate that chronic stress, especially when administered early in development, results in elevated drinking later in adulthood. Chronic alcohol exposure constitutes a potent stressor itself, and models of chronic intermittent alcohol exposure reliably produce escalation of voluntary alcohol consumption. Conclusions A complex and dynamic interplay among a wide array of genetic, biological, and environmental factors govern stress responses, regulation of alcohol drinking, and the circumstances in which stress modulates alcohol consumption. Suggestions for future directions and new approaches are presented that may aid in developing more sensitive and valid animal models that not only better mimic the clinical situation, but also provide greater understanding of mechanisms that underlie the complexity of stress effects on alcohol drinking. PMID:21850445

  7. Data Sources Available for Modeling Environmental Exposures in Older Adults

    EPA Science Inventory

    This report, “Data Sources Available for Modeling Environmental Exposures in Older Adults,” focuses on information sources and data available for modeling environmental exposures in the older U.S. population, defined here to be people 60 years and older, with an emphasis on those...

  8. Stochastic Human Exposure and Dose Simulation Model for Wood Preservatives

    EPA Science Inventory

    SHEDS-Wood (Stochastic Human Exposure and Dose Simulation Model for Wood Preservatives) is a physically-based stochastic model that was developed to quantify exposure and dose of children to wood preservatives on treated playsets and residential decks. Probabilistic inputs are co...

  9. USEPA SHEDS MODEL: METHODOLOGY FOR EXPOSURE ASSESSMENT FOR WOOD PRESERVATIVES

    EPA Science Inventory

    A physically-based, Monte Carlo probabilistic model (SHEDS-Wood: Stochastic Human Exposure and Dose Simulation model for wood preservatives) has been applied to assess the exposure and dose of children to arsenic (As) and chromium (Cr) from contact with chromated copper arsenat...

  10. MODELING ENVIRONMENTAL EXPOSURES TO PARTICULATE MATTER AND PESTICIDES

    EPA Science Inventory

    This presentation describes initial results from on-going research at EPA on modeling human exposures to particulate matter and residential pesticides. A first generation probabilistic population exposure model for Particulate Matter (PM), specifically for predicting PM1o and P...

  11. Operation of the computer model for microenvironment solar exposure

    NASA Technical Reports Server (NTRS)

    Gillis, J. R.; Bourassa, R. J.; Gruenbaum, P. E.

    1995-01-01

    A computer model for microenvironmental solar exposure was developed to predict solar exposure to satellite surfaces which may shadow or reflect on one another. This document describes the technical features of the model as well as instructions for the installation and use of the program.

  12. MODELING MULTIPATHWAY EXPOSURES OF CHILDREN AND ADULTS TO PESTICIDES

    EPA Science Inventory

    A probabilistic model of individual exposure to chlorpyrifos has been developed in support of the United States Environmental Protection Agency (US EPA) National Human Exposure Assessment Survey (NHEXAS) and the Food Quality Protection Act (FQPA) program. The model examines a v...

  13. Advanced REACH Tool: a Bayesian model for occupational exposure assessment.

    PubMed

    McNally, Kevin; Warren, Nicholas; Fransman, Wouter; Entink, Rinke Klein; Schinkel, Jody; van Tongeren, Martie; Cherrie, John W; Kromhout, Hans; Schneider, Thomas; Tielemans, Erik

    2014-06-01

    This paper describes a Bayesian model for the assessment of inhalation exposures in an occupational setting; the methodology underpins a freely available web-based application for exposure assessment, the Advanced REACH Tool (ART). The ART is a higher tier exposure tool that combines disparate sources of information within a Bayesian statistical framework. The information is obtained from expert knowledge expressed in a calibrated mechanistic model of exposure assessment, data on inter- and intra-individual variability in exposures from the literature, and context-specific exposure measurements. The ART provides central estimates and credible intervals for different percentiles of the exposure distribution, for full-shift and long-term average exposures. The ART can produce exposure estimates in the absence of measurements, but the precision of the estimates improves as more data become available. The methodology presented in this paper is able to utilize partially analogous data, a novel approach designed to make efficient use of a sparsely populated measurement database although some additional research is still required before practical implementation. The methodology is demonstrated using two worked examples: an exposure to copper pyrithione in the spraying of antifouling paints and an exposure to ethyl acetate in shoe repair. PMID:24665110

  14. Advanced REACH Tool: A Bayesian Model for Occupational Exposure Assessment

    PubMed Central

    McNally, Kevin; Warren, Nicholas; Fransman, Wouter; Entink, Rinke Klein; Schinkel, Jody; van Tongeren, Martie; Cherrie, John W.; Kromhout, Hans; Schneider, Thomas; Tielemans, Erik

    2014-01-01

    This paper describes a Bayesian model for the assessment of inhalation exposures in an occupational setting; the methodology underpins a freely available web-based application for exposure assessment, the Advanced REACH Tool (ART). The ART is a higher tier exposure tool that combines disparate sources of information within a Bayesian statistical framework. The information is obtained from expert knowledge expressed in a calibrated mechanistic model of exposure assessment, data on inter- and intra-individual variability in exposures from the literature, and context-specific exposure measurements. The ART provides central estimates and credible intervals for different percentiles of the exposure distribution, for full-shift and long-term average exposures. The ART can produce exposure estimates in the absence of measurements, but the precision of the estimates improves as more data become available. The methodology presented in this paper is able to utilize partially analogous data, a novel approach designed to make efficient use of a sparsely populated measurement database although some additional research is still required before practical implementation. The methodology is demonstrated using two worked examples: an exposure to copper pyrithione in the spraying of antifouling paints and an exposure to ethyl acetate in shoe repair. PMID:24665110

  15. A statistical framework for the validation of a population exposure model based on personal exposure data

    NASA Astrophysics Data System (ADS)

    Rodriguez, Delphy; Valari, Myrto; Markakis, Konstantinos; Payan, Sébastien

    2016-04-01

    Currently, ambient pollutant concentrations at monitoring sites are routinely measured by local networks, such as AIRPARIF in Paris, France. Pollutant concentration fields are also simulated with regional-scale chemistry transport models such as CHIMERE (http://www.lmd.polytechnique.fr/chimere) under air-quality forecasting platforms (e.g. Prev'Air http://www.prevair.org) or research projects. These data may be combined with more or less sophisticated techniques to provide a fairly good representation of pollutant concentration spatial gradients over urban areas. Here we focus on human exposure to atmospheric contaminants. Based on census data on population dynamics and demographics, modeled outdoor concentrations and infiltration of outdoor air-pollution indoors we have developed a population exposure model for ozone and PM2.5. A critical challenge in the field of population exposure modeling is model validation since personal exposure data are expensive and therefore, rare. However, recent research has made low cost mobile sensors fairly common and therefore personal exposure data should become more and more accessible. In view of planned cohort field-campaigns where such data will be available over the Paris region, we propose in the present study a statistical framework that makes the comparison between modeled and measured exposures meaningful. Our ultimate goal is to evaluate the exposure model by comparing modeled exposures to monitor data. The scientific question we address here is how to downscale modeled data that are estimated on the county population scale at the individual scale which is appropriate to the available measurements. To assess this question we developed a Bayesian hierarchical framework that assimilates actual individual data into population statistics and updates the probability estimate.

  16. Comparing prediction models for radiographic exposures

    NASA Astrophysics Data System (ADS)

    Ching, W.; Robinson, J.; McEntee, M. F.

    2015-03-01

    During radiographic exposures the milliampere-seconds (mAs), kilovoltage peak (kVp) and source-to-image distance can be adjusted for variations in patient thicknesses. Several exposure adjustment systems have been developed to assist with this selection. This study compares the accuracy of four systems to predict the required mAs for pelvic radiographs taken on a direct digital radiography system (DDR). Sixty radiographs were obtained by adjusting mAs to compensate for varying combinations of source-to-image distance (SID), kVp and patient thicknesses. The 25% rule, the DuPont Bit System and the DigiBit system were compared to determine which of these three most accurately predicted the mAs required for an increase in patient thickness. Similarly, the 15% rule, the DuPont Bit System and the DigiBit system were compared for an increase in kVp. The exposure index (EI) was used as an indication of exposure to the DDR. For each exposure combination the mAs was adjusted until an EI of 1500+/-2% was achieved. The 25% rule was the most accurate at predicting the mAs required for an increase in patient thickness, with 53% of the mAs predictions correct. The DigiBit system was the most accurate at predicting mAs needed for changes in kVp, with 33% of predictions correct. This study demonstrated that the 25% rule and DigiBit system were the most accurate predictors of mAs required for an increase in patient thickness and kVp respectively. The DigiBit system worked well in both scenarios as it is a single exposure adjustment system that considers a variety of exposure factors.

  17. EFFECTS OF CORRELATED PROBABILISTIC EXPOSURE MODEL INPUTS ON SIMULATED RESULTS

    EPA Science Inventory

    In recent years, more probabilistic models have been developed to quantify aggregate human exposures to environmental pollutants. The impact of correlation among inputs in these models is an important issue, which has not been resolved. Obtaining correlated data and implementi...

  18. ASSESSING RESIDENTIAL EXPOSURE USING THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION (SHEDS) MODEL

    EPA Science Inventory

    As part of a workshop sponsored by the Environmental Protection Agency's Office of Research and Development and Office of Pesticide Programs, the Aggregate Stochastic Human Exposure and Dose Simulation (SHEDS) Model was used to assess potential aggregate residential pesticide e...

  19. Exposures from indoor powder releases: models and experiments

    SciTech Connect

    Cooper, D.W.; Horowitz, M.

    1986-04-01

    Two models of the dispersion of a solid contaminant in a room were compared. The first model was the perfect mixing model. widely used in room air modeling to predict concentration, thus exposure (the integral of concentration over time). The second model was the turbulent puff diffusion model, sometimes used in atmospheric dispersion modeling. The models predicted different consequences from a solid contaminant release in a room, such as from a bulk-loading operation or a spill. The predicted exposures from a release were evaluated for both models. The models also were compared against data from an illustrative set of experimental measurements with the use of powder spill as a source. In the room, the exposures decreased almost inversely with distance, behavior more in accord with the turbulent puff model than with the perfect mixing model.

  20. A dermatotoxicokinetic model of human exposures to jet fuel.

    PubMed

    Kim, David; Andersen, Melvin E; Nylander-French, Leena A

    2006-09-01

    Workers, both in the military and the commercial airline industry, are exposed to jet fuel by inhalation and dermal contact. We present a dermatotoxicokinetic (DTK) model that quantifies the absorption, distribution, and elimination of aromatic and aliphatic components of jet fuel following dermal exposures in humans. Kinetic data were obtained from 10 healthy volunteers following a single dose of JP-8 to the forearm over a surface area of 20 cm2. Blood samples were taken before exposure (t = 0 h), after exposure (t = 0.5 h), and every 0.5 h for up to 3.5 h postexposure. The DTK model that best fit the data included five compartments: (1) surface, (2) stratum corneum (SC), (3) viable epidermis, (4) blood, and (5) storage. The DTK model was used to predict blood concentrations of the components of JP-8 based on dermal-exposure measurements made in occupational-exposure settings in order to better understand the toxicokinetic behavior of these compounds. Monte Carlo simulations of dermal exposure and cumulative internal dose demonstrated no overlap among the low-, medium-, and high-exposure groups. The DTK model provides a quantitative understanding of the relationship between the mass of JP-8 components in the SC and the concentrations of each component in the systemic circulation. The model may be used for the development of a toxicokinetic modeling strategy for multiroute exposure to jet fuel. PMID:16801332

  1. Radiation exposure modeling and project schedule visualization

    SciTech Connect

    Jaquish, W.R.; Enderlin, V.R.

    1995-10-01

    This paper discusses two applications using IGRIP (Interactive Graphical Robot Instruction Program) to assist environmental remediation efforts at the Department of Energy (DOE) Hanford Site. In the first application, IGRIP is used to calculate the estimated radiation exposure to workers conducting tasks in radiation environments. In the second, IGRIP is used as a configuration management tool to detect interferences between equipment and personnel work areas for multiple projects occurring simultaneously in one area. Both of these applications have the capability to reduce environmental remediation costs by reducing personnel radiation exposure and by providing a method to effectively manage multiple projects in a single facility.

  2. Best-practices approach to determination of blood alcohol concentration (BAC) at specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling and post-mortem alcohol generation and transport considerations.

    PubMed

    Cowan, Dallas M; Maskrey, Joshua R; Fung, Ernest S; Woods, Tyler A; Stabryla, Lisa M; Scott, Paul K; Finley, Brent L

    2016-07-01

    Alcohol concentrations in biological matrices offer information regarding an individual's intoxication level at a given time. In forensic cases, the alcohol concentration in the blood (BAC) at the time of death is sometimes used interchangeably with the BAC measured post-mortem, without consideration for alcohol concentration changes in the body after death. However, post-mortem factors must be taken into account for accurate forensic determination of BAC prior to death to avoid incorrect conclusions. The main objective of this work was to describe best practices for relating ante-mortem and post-mortem alcohol concentrations, using a combination of modeling, empirical data and other qualitative considerations. The Widmark modeling approach is a best practices method for superimposing multiple alcohol doses ingested at various times with alcohol elimination rate adjustments based on individual body factors. We combined the selected ante-mortem model with a suggestion for an approach used to roughly estimate changes in BAC post-mortem, and then analyzed the available data on post-mortem alcohol production in human bodies and potential markers for alcohol production through decomposition and putrefaction. Hypothetical cases provide best practice approaches as an example for determining alcohol concentration in biological matrices ante-mortem, as well as potential issues encountered with quantitative post-mortem approaches. This study provides information for standardizing BAC determination in forensic toxicology, while minimizing real world case uncertainties. PMID:27041394

  3. 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

  4. The feasibility and cost of neonatal screening for prenatal alcohol exposure by measuring phosphatidylethanol in dried blood spots

    PubMed Central

    Bakhireva, Ludmila N.; Savich, Renate D.; Raisch, Dennis W.; Cano, Sandra; Annett, Robert D.; Leeman, Lawrence; Garg, Mahek; Goff, Chelsea; Savage, Daniel D.

    2012-01-01

    Background Accurate confirmation of prenatal alcohol exposure (PAE) is required as a diagnostic criterion for the majority of children adversely affected by PAE who do not manifest the physical features associated with Fetal Alcohol Syndrome. A number of ethanol biomarkers have been used to assess PAE, often with suboptimal results. The purpose of this study was to evaluate the feasibility and cost of PAE screening in newborns by measuring phosphatidylethanol (PEth) in dried blood spot (DBS) cards. Methods The feasibility of collecting an additional DBS card during routine newborn screening and the background prevalence of PAE were evaluated in a de-identified sample of newborn children delivered at the University of New Mexico Hospital. Electronic orders to collect DBS cards from newborns who continue to bleed after the routine newborn screen, glucose or hematocrit testing were initiated for all infants delivered during a 4-week timeframe. Specimens were sent to a contract laboratory for PEth analysis by liquid chromatography-tandem mass spectrometry. A cost analysis was conducted to compare the cost of PAE screening by PEth in DBS vs. PEth in conventional blood specimens and by meconium fatty acid ethyl esters (FAEE). Results From 230 collected cards, 201 (87.4%) had at least one full blood spot (amount sufficient for PEth analysis), and 6.5% had PEth >20ng/mL indicative of potential PAE in late pregnancy. PAE screening by PEth in DBS is logistically simpler and less expensive compared to two other screening approaches. Conclusions These results indicate that screening for PAE in DBS cards is a feasible procedure and that a majority of infants have enough blood after the routine heel prick to fill an additional card. Moreover, screening by PEth analysis from DBS cards is cost-efficient. The acceptability of such screening by parents and corresponding ethical issues remain to be investigated. PMID:23421919

  5. Universal screening for prenatal alcohol exposure: a progress report of a pilot study in the region of Grey Bruce, Ontario.

    PubMed

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

    2010-06-01

    The main objective of this study is to evaluate the clinical utility of meconium analysis for fatty acid ethyl esters as a universal screening tool intended for the detection of newborns at risk for fetal alcohol spectrum disorder. This will be accomplished by assessing the rate of voluntary participation in a nonanonymous neonatal screening program and by determining the logistics of implementing the necessary follow-up and interventions as part of routine care. Additionally, this study will determine the predictive value of fatty acid ethyl ester-positive meconium with regard to neurodevelopmental delays. This is an ongoing prospective cohort study. Written informed consent is sought from all Grey Bruce women delivering at participating birthing sites. Collected meconium samples are tested for fatty acid ethyl esters by headspace-solid-phase microextraction followed by gas chromatography-mass spectrometry. Children with positive results are followed up through an existing public health program involving regular home visits and assessments of developmental milestones by a public health nurse. These children and matched control subjects also undergo neurodevelopmental testing at 3 and 18 months of age by a clinical psychologist using Bayley Scales of Infant and Toddler Development. If delays are detected, the child is referred to diagnostic services and appropriate intervention programs. This study has been granted ethics approval and enrollment began in November 2008 at St. Joseph's Health Care in London, Ontario. The first positive case has been identified and the follow-up is currently being conducted by the public health unit. The successful completing of this study will reveal the population's willingness to participate in a neonatal screening program for prenatal alcohol exposure and determine the costs, feasibility, and utility of implementing such programs in clinical practice. PMID:20445484

  6. IMPACT OF EMISSION REDUCTIONS ON EXPOSURES AND EXPOSURE DISTRIBUTIONS: APPLICATION OF A GEOGRAPHIC EXPOSURE MODEL

    EPA Science Inventory

    Anticipated results include the following. (1) We will estimate intake fraction (i.e., the fraction of emissions that are inhaled) for major source categories, over time, and by spatial location. Higher intake fraction indicates a greater exposure reduction per emission reduct...

  7. Hepatic microtubule acetylation and stability induced by chronic alcohol exposure impair nuclear translocation of STAT3 and STAT5B, but not Smad2/3.

    PubMed

    Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

    2012-12-15

    Although alcoholic liver disease is clinically well described, the molecular basis for alcohol-induced hepatotoxicity is not well understood. Previously, we found that alcohol exposure led to increased microtubule acetylation and stability in polarized, hepatic WIF-B cells and in livers from ethanol-fed rats. Because microtubules are known to regulate transcription factor nuclear translocation and dynamic microtubules are required for translocation of at least a subset of these factors, we examined whether alcohol-induced microtubule acetylation and stability impair nuclear translocation. We examined nuclear delivery of factors representing the two mechanisms by which microtubules regulate translocation. To represent factors that undergo directed delivery, we examined growth hormone-induced STAT5B translocation and IL-6-induced STAT3 translocation. To represent factors that are sequestered in the cytoplasm by microtubule attachment until ligand activation, we examined transforming growth factor-β-induced Smad2/3 translocation. We found that ethanol exposure selectively impaired translocation of the STATs, but not Smad2/3. STAT5B delivery was decreased to a similar extent by addition of taxol (a microtubule-stabilizing drug) or trichostatin A (a deacetylase inhibitor), agents that promote microtubule acetylation in the absence of alcohol. Thus the alcohol-induced impairment of STAT nuclear translocation can be explained by increased microtubule acetylation and stability. Only ethanol treatment impaired STAT5B activation, indicating that microtubules are not important for its activation by Jak2. Furthermore, nuclear exit was not changed in treated cells, indicating that this process is also independent of microtubule acetylation and stability. Together, these results raise the exciting possibility that deacetylase agonists may be effective therapeutics for the treatment of alcoholic liver disease. PMID:23064763

  8. Regression mixture models of alcohol use and risky sexual behavior among criminally-involved adolescents.

    PubMed

    Schmiege, Sarah J; Levin, Michael E; Bryan, Angela D

    2009-12-01

    Adolescents involved with the criminal justice system engage in high levels of both risky sexual behavior and alcohol use. Yet a strong relationship between the two constructs has not been consistently observed, possibly due to heterogeneity in the data. Regression mixture models were estimated in the current study to address such potential heterogeneity. Criminally-involved adolescents (n = 409) were clustered into latent classes based on patterns of the regression of two measures of risky sexual behavior, condom use and frequency of intercourse, on alcohol use. A three-class solution emerged where alcohol use did not significantly predict either risky sex outcome for approximately 25% of the sample; alcohol use negatively predicted condom use and positively predicted frequency of intercourse for approximately 38% of participants; and alcohol use negatively predicted condom use but not frequency of intercourse for the remaining participants. These classes were then distinguished on the basis of five covariates previously found to influence either alcohol use, risky sexual behavior, or the relationship between the two: self-esteem, gender, participant age, relationship status, and impulsivity/sensation-seeking. High self-esteem, being female, being older, and being in a relationship predicted membership in the class with no observed relationship of alcohol use to risky sex, relative to the other classes. Implications of the present findings are discussed in terms of exploring different risky sex and alcohol use patterns within criminally involved adolescents, as well as understanding the effectiveness of interventions for subgroups of individuals. PMID:19459047

  9. Predicting problematic alcohol use with the DSM-5 alternative model of personality pathology.

    PubMed

    Creswell, Kasey G; Bachrach, Rachel L; Wright, Aidan G C; Pinto, Anthony; Ansell, Emily

    2016-01-01

    High comorbidity between personality disorders and alcohol use disorders appears related to individual differences in underlying personality dimensions of behavioral undercontrol and affective dysregulation. However, very little is known about how the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5) Section III trait model of personality pathology relates to alcohol problems or how the strength of the relationship between personality pathology and alcohol problems changes with age and across gender. The current study examined these questions in a sample of 877 participants using the General Assessment of Personality Disorder to assess general personality dysfunction, the Personality Inventory for DSM-5 to measure specific traits, and the Alcohol Use Disorder Identification Test (AUDIT) to assess problematic alcohol use. Results demonstrated that general personality pathology (Criterion A) was significantly related to problematic alcohol use after controlling for age and gender effects. Furthermore, 2 of the 5 higher-order personality trait domains (Criterion B), Antagonism and Disinhibition, remained significant predictors of problematic alcohol use after accounting for the influence of general personality pathology; however, general personality pathology no longer predicted hazardous alcohol use once Antagonism and Disinhibition were added into the model. Finally, these 2 specific traits interacted with age, such that Antagonism was a stronger predictor of AUDIT scores among older individuals and Disinhibition was a stronger predictor of alcohol problems among younger individuals. Findings support the general validity of this new personality disorder diagnostic system and suggest important age effects in the relationship between traits and problematic alcohol use. (PsycINFO Database Record PMID:26389625

  10. MULTIMEDIA HUMAN EXPOSURE AND RISK ASSESSMENT MODELING

    EPA Science Inventory

    Exposures and health risk comparisons from different sites may be used for allocating limited resources available for remedial action. It is important that comparisons between different sites use similar levels of site-specific data and/or screening level data. Risk assessment c...

  11. Using optical coherence tomography to rapidly phenotype and quantify congenital heart defects associated with prenatal alcohol exposure

    PubMed Central

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Noonan, Amanda I.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Background The most commonly used method to analyze congenital heart defects involves serial sectioning and histology. However, this is often a time-consuming process where the quantification of cardiac defects can be difficult due to problems with accurate section registration. Here we demonstrate the advantages of using optical coherence tomography, a comparatively new and rising technology, to phenotype avian embryo hearts in a model of Fetal Alcohol Syndrome where a binge-like quantity of alcohol/ethanol was introduced at gastrulation. Results The rapid, consistent imaging protocols allowed for the immediate identification of cardiac anomalies, including ventricular septal defects and misaligned/missing vessels. Interventricular septum thicknesses and vessel diameters for three of the five outflow arteries were also significantly reduced. Outflow and atrio-ventricular valves were segmented using image processing software and had significantly reduced volumes compared to controls. This is the first study to our knowledge that has 3-D reconstructed the late-stage cardiac valves in precise detail in order to examine their morphology and dimensions. Conclusion We believe therefore that OCT, with its ability to rapidly image and quantify tiny embryonic structures in high resolution, will serve as an excellent and cost-effective preliminary screening tool for developmental biologists working with a variety of experimental/disease models. PMID:25546089

  12. 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

  13. A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

    PubMed Central

    Bell, Richard L.; Hauser, Sheketha; Rodd, Zachary A.; Liang, Tiebing; Sari, Youssef; McClintick, Jeanette; Rahman, Shafiqur; Engleman, Eric A.

    2016-01-01

    The purpose of this review is to present up-to-date pharmacological, genetic and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein we sought to place the P rat’s behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this paper discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general. PMID:27055615

  14. A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction.

    PubMed

    Bell, R L; Hauser, S; Rodd, Z A; Liang, T; Sari, Y; McClintick, J; Rahman, S; Engleman, E A

    2016-01-01

    The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general. PMID:27055615

  15. Effects of short-term prenatal alcohol exposure on neuronal membrane order in rats.

    PubMed

    Vorhees, C V; Rauch, S; Hitzemann, R

    1988-02-01

    Long-Evans rat dams were treated with ethanol (4 g/kg, twice daily) by gavage on gestational days 10-14. This dosage schedule has been shown to produce significant behavioral and ponderal teratogenicity. Pair-fed dams were gavaged with isocaloric amounts of sucrose. All offspring were reared by untreated, surrogate dams. Pups were sacrificed on days 3 and 28, and whole brain neuronal plasma membranes were prepared for analysis by a fluorescence polarization technique using 1,6-diphenyl-1,3,5-hexatriene as the membrane probe. On day 3, steady-state anisotropy was significantly decreased in the ethanol-treated pups. Arrhenius plots revealed that this difference was associated with a change on both membrane entropy and enthalpy. By day 28, the differences between groups disappeared. These data would be consistent with the view that the brief gestational ethanol exposure delays neuronal maturation. PMID:3359307

  16. 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. PMID:26529506

  17. Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers

    PubMed Central

    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. PMID:26529506

  18. Process Model of Grief Therapy in an Alcohol Treatment Program.

    ERIC Educational Resources Information Center

    Martin, Sherri; Privette, Gayle

    1989-01-01

    Discusses a psychoeducational, experiential group for members of an alcohol treatment program which addressed loss, personal reaction to loss, and grief as a healing process. Explores the relationship between grieving and addiction, and presents the protocol for the group experience. (Author)

  19. Drinking, Driving, and Crashing: A Traffic-Flow Model of Alcohol-Related Motor Vehicle Accidents*

    PubMed Central

    Gruenewald, Paul J.; Johnson, Fred W.

    2010-01-01

    Objective: This study examined the influence of on-premise alcohol-outlet densities and of drinking-driver densities on rates of alcohol-related motor vehicle crashes. A traffic-flow model is developed to represent geographic relationships between residential locations of drinking drivers, alcohol outlets, and alcohol-related motor vehicle crashes. Method: Cross-sectional and time-series cross-sectional spatial analyses were performed using data collected from 144 geographic units over 4 years. Data were obtained from archival and survey sources in six communities. Archival data were obtained within community areas and measured activities of either the resident population or persons visiting these communities. These data included local and highway traffic flow, locations of alcohol outlets, population density, network density of the local roadway system, and single-vehicle nighttime (SVN) crashes. Telephone-survey data obtained from residents of the communities were used to estimate the size of the resident drinking and driving population. Results: Cross-sectional analyses showed that effects relating on-premise densities to alcohol-related crashes were moderated by highway traffic flow. Depending on levels of highway traffic flow, 10% greater densities were related to 0% to 150% greater rates of SVN crashes. Time-series cross-sectional analyses showed that changes in the population pool of drinking drivers and on-premise densities interacted to increase SVN crash rates. Conclusions: A simple traffic-flow model can assess the effects of on-premise alcohol-outlet densities and of drinking-driver densities as they vary across communities to produce alcohol-related crashes. Analyses based on these models can usefully guide policy decisions on the siting of on-premise alcohol outlets. PMID:20230721

  20. MODELING AGGREGATE CHLORPYRIFOS EXPOSURE AND DOSE TO CHILDREN

    EPA Science Inventory

    To help address the aggregate exposure assessment needs of the Food Quality Protection Act, a physically-based probabilistic model (SHEDS-Pesticides, version 3) has been applied to estimate aggregate chlorpyrifos exposure and dose to children. Two age groups (0-4, 5-9 years) a...

  1. A comparison of the prevalence of prenatal alcohol exposure obtained via maternal self-reports versus meconium testing: a systematic literature review and meta-analysis

    PubMed Central

    2014-01-01

    Background Maternal self-reports, used for the detection of prenatal alcohol exposure (PAE), may lack validity, necessitating the use of an objective biomarker. The detection of fatty acid ethyl esters (products of non-oxidative ethanol metabolism) in meconium has been established as a novel biomarker of PAE. The purpose of the current study was to compare the prevalence of PAE as reported via maternal self-reports with the results of meconium testing, and to quantify the disparity between these two methods. Methods A systematic literature search for studies reporting on the prevalence of PAE, using maternal self-reports in combination with meconium testing, was conducted using multiple electronic bibliographic databases. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated based on eight studies, using the Mantel-Haenszel method, assuming a random effects model. A random effects meta-regression was performed to test for a difference. Results The pooled prevalence of PAE as measured by meconium testing was 4.26 (95% CI: 1.34-13.57) times the pooled prevalence of PAE as measured by maternal self-reports. Large variations across the studies in regard to the difference between estimates obtained from maternal self-reports and those obtained from meconium testing were observed. Conclusions If maternal self-reports are the sole information source upon which health care professionals rely, a number of infants who were prenatally exposed to alcohol are not being recognized as such. However, further research is needed in order to validate existing biomarkers, as well as discover new biomarkers, for the detection of PAE. PMID:24708684

  2. Interaction of occupational manganese exposure and alcohol drinking aggravates the increase of liver enzyme concentrations from a cross-sectional study in China

    PubMed Central

    2013-01-01

    Background Over exposure to manganese (Mn) can damage the human central nervous system and potentially cause liver toxicity. Alcohol drinking is also one of the well-known harmful factors to hepatic organism. The interaction between Mn exposure and alcohol consumption to liver function was investigated in this study. Methods A total of 1112 on-the-spot workers were included in the cross-sectional survey from a large scale of manganese exposed workers healthy cohort (MEWHC) in a ferro-manganese refinery company. A questionnaire was used to collect the demographic information, occupational history, and alcohol drinking habits. Occupational health examination was carried out for each worker. The five key serum indices, including total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT), and aspartate transaminase (AST), were determined to evaluate the liver function of each subject. Results Workers exposed to high levels of Mn had significantly elevated serum concentrations of liver enzymes (DBILI: 3.84±1.20 μmol/L, ALT: 27.04±19.12 IU/L, and AST: 29.96±16.68 IU/L), when compared to those in the low-exposure group (DBIL: 3.54±0.85 μmol/L, ALT: 20.38±10.97 IU/L, and AST: 26.39±8.07 IU/L), all P<0.01. These serum indices had a significantly increasing trend with the elevation of Mn exposure level (Ptrend <0.01). In addition, the workers with alcohol drinking also showed higher concentrations of liver enzymes than those non-drinkers, especially, and there was significant interaction between Mn exposure and alcohol consumption in terms of these three indices (P<0.001). Conclusions Occupational exposure to Mn can lead to a dose-dependent increase of liver enzyme concentrations, and interact with alcohol drinking to potentially aggravate the liver damage. It will be important for Mn exposed workers to control drinking and also assess liver function in the occupational health examination. PMID:23587294

  3. 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. PMID:25940002

  4. Development of a standard documentation protocol for communicating exposure models.

    PubMed

    Ciffroy, P; Altenpohl, A; Fait, G; Fransman, W; Paini, A; Radovnikovic, A; Simon-Cornu, M; Suciu, N; Verdonck, F

    2016-10-15

    An important step in building a computational model is its documentation; a comprehensive and structured documentation can improve the model applicability and transparency in science/research and for regulatory purposes. This is particularly crucial and challenging for environmental and/or human exposure models that aim to establish quantitative relationships between personal exposure levels and their determinants. Exposure models simulate the transport and fate of a contaminant from the source to the receptor and may involve a large set of entities (e.g. all the media the contaminants may pass though). Such complex models are difficult to be described in a comprehensive, unambiguous and accessible way. Bad communication of assumptions, theory, structure and/or parameterization can lead to lack of confidence by the user and it may be source of errors. The goal of this paper is to propose a standard documentation protocol (SDP) for exposure models, i.e. a generic format and a standard structure by which all exposure models could be documented. For this purpose, a CEN (European Committee for Standardisation) workshop was set up with objective to agree on minimum requirements for the amount and type of information to be provided on exposure models documentation along with guidelines for the structure and presentation of the information. The resulting CEN workshop agreement (CWA) was expected to facilitate a more rigorous formulation of exposure models description and the understanding by users. This paper intends to describe the process followed for defining the SDP, the standardisation approach, as well as the main components of the SDP resulting from a wide consultation of interested stakeholders. The main outcome is a CEN CWA which establishes terms and definitions for exposure models and their elements, specifies minimum requirements for the amount and type of information to be documented, and proposes a structure for communicating the documentation to different

  5. Role of the satiety factor oleoylethanolamide in alcoholism.

    PubMed

    Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; Gómez de Heras, Raquel; Orio, Laura; Alén, Francisco; Ciccocioppo, Roberto; Cravatt, Benjamin F; Parsons, Loren H; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2016-07-01

    Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism. PMID:26037332

  6. Is 'disease model' an appropriate term to describe the alcohol dependence syndrome?

    PubMed

    Gorman, D M

    1989-01-01

    Caetano (Concepts of alcohol dependence: the two worlds of research and treatment. Alcohol and Alcoholism 23, 225-227, 1988) has suggested that in the U.S.A. opposition from the disease model has been the main reason for the limited application of the alcohol dependence syndrome. In Britain, the charge that the syndrome is a poorly disguised version of the disease model has had a similar effect. This paper describes the main features of the crude biomedical disease model, which critics equate with the alcohol dependence syndrome. It is concluded that the alcohol dependence syndrome does not conform to this, in that it is not presented by its proponents as a discrete entity identified by a core psycho-biological pathology and carries no built-in assumptions about causal processes. It is argued that instead of setting-up and championing competing all-embracing conceptual models, both clinicians and researchers should be flexible and imaginative in their use of concepts. PMID:2697203

  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

    2016-03-01

    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. PMID:26824193

  8. 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.

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

    PubMed

    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. PMID:23386196

  10. Reconstructing exposures from biomarkers using exposure-pharmacokinetic modeling--A case study with carbaryl.

    PubMed

    Brown, Kathleen; Phillips, Martin; Grulke, Christopher; Yoon, Miyoung; Young, Bruce; McDougall, Robin; Leonard, Jeremy; Lu, Jingtao; Lefew, William; Tan, Yu-Mei

    2015-12-01

    Sources of uncertainty involved in exposure reconstruction for short half-life chemicals were characterized using computational models that link external exposures to biomarkers. Using carbaryl as an example, an exposure model, the Cumulative and Aggregate Risk Evaluation System (CARES), was used to generate time-concentration profiles for 500 virtual individuals exposed to carbaryl. These exposure profiles were used as inputs into a physiologically based pharmacokinetic (PBPK) model to predict urinary biomarker concentrations. These matching dietary intake levels and biomarker concentrations were used to (1) compare three reverse dosimetry approaches based on their ability to predict the central tendency of the intake dose distribution; and (2) identify parameters necessary for a more accurate exposure reconstruction. This study illustrates the trade-offs between using non-iterative reverse dosimetry methods that are fast, less precise and iterative methods that are slow, more precise. This study also intimates the necessity of including urine flow rate and elapsed time between last dose and urine sampling as part of the biomarker sampling collection for better interpretation of urinary biomarker data of short biological half-life chemicals. Resolution of these critical data gaps can allow exposure reconstruction methods to better predict population-level intake doses from large biomonitoring studies. PMID:26545325

  11. The Varied Uses of Conditioned Place Preference in Behavioral Neuroscience Research: An Investigation of Alcohol Administration in Model Organisms

    PubMed Central

    Lucke-Wold, Brandon

    2016-01-01

    Place conditioning procedures have been used to study human addiction to alcohol for the past several years. This experimental resource has been utilized successfully due to the fact that investigators can carefully manipulate the experimental design in order to explore specific hypotheses. Only three choices exist regarding animal response to place conditioning: aversion, preference, or no change. This review provides an in-depth analysis of five variables commonly adjusted or changed in place conditioning experiments with ethanol. These include: apparatus design, administration methods, choice of model organism, age of model organism, and model paradigms. It is suggested that the two-chamber design, the intragastric administration, the mouse model, the adolescent age group, and the pre-exposure to stress paradigm are the best current options available in place conditioning experiments with ethanol. The basis for evaluation used throughout this review is that investigators should adjust the variables employed in place conditioning experiments in a manner that most accurately represents and models complex human addiction to alcohol.

  12. Modeling of In-vehicle PM2.5 Exposure Using the Stochastic Human Exposure and Dose Simulation Model

    PubMed Central

    Liu, Xiaozhen; Frey, H. Christopher; Cao, Ye; Deshpande, Bela

    2010-01-01

    Factors that influence in-vehicle PM2.5 exposure are indentified and assessed. The methodology used in the current version of Stochastic Exposure and Dose Simulation model for Particulate Matter (SHEDS-PM) for in-vehicle PM2.5 concentration is reviewed, and alternative modeling approaches are identified and evaluated. SHEDS-PM uses a linear regression model to estimate in-vehicle PM2.5 concentration based on ambient PM2.5 concentration, such as from a fixed site monitor (FSM) or a grid cell average concentration estimate from an air quality model. The ratio of in-vehicle to FSM concentration varies substantially with respect to location, vehicle type and other factors. SHEDS-PM was used to estimate PM2.5 exposure for 1% of people living in Wake County, NC in order to assess the importance of in-vehicle exposures. In-vehicle PM2.5 exposure can be as much as half of the total exposure for some individuals, depending on employment status and the time spent in-vehicle during commuting. An alternative modeling approach is explored based on the use of a dispersion model to estimate near-road PM2.5 concentration based on FSM data and a mass balance model for estimating in-vehicle concentration. Recommendations for updating the input data to the existing model, and implementation of the alternative modeling approach are made. PMID:21209848

  13. Experimental rat model for alcohol-induced osteonecrosis of the femoral head

    PubMed Central

    Okazaki, Shunichiro; Nagoya, Satoshi; Tateda, Kenji; Katada, Ryuichi; Mizuo, Keisuke; Watanabe, Satoshi; Yamashita, Toshihiko; Matsumoto, Hiroshi

    2013-01-01

    Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber–DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1–24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model. PMID:24020403

  14. EXPOSURE ANALYSIS MODELING SYSTEM: REFERENCE MANUAL FOR EXAMS 2

    EPA Science Inventory

    The Exposure Analysis Modeling System (EXAMS), published in 1982 (EPA-600/3-82-023), provides rapid evaluations of the behavior of synthetic organic chemicals in aquatic ecosystems. EXAMS combines laboratory data describing reactivity and thermodynamic properties of chemicals wit...

  15. Making Organisms Model Human Behavior: Situated Models in North-American Alcohol Research, 1950-onwards

    PubMed Central

    Leonelli, Sabina; Ankeny, Rachel A.; Nelson, Nicole C.; Ramsden, Edmund

    2014-01-01

    Argument We examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, as often the case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied. PMID:25233743