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Sample records for repeated alcohol exposure

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

    Science.gov (United States)

    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

  2. Altered performance in a rat gambling task after acute and repeated alcohol exposure

    NARCIS (Netherlands)

    Spoelder, Marcia; Lesscher, Heidi M B; Hesseling, Peter; Baars, Annemarie M; Lozeman-van T Klooster, José G; Mijnsbergen, Rob; Vanderschuren, Louk J M J

    2015-01-01

    RATIONALE: A bidirectional relationship between alcohol use disorder (AUD) and deficits in impulse control and decision making has been suggested. However, the mechanisms by which neurocognitive impairments predispose to, or result from AUD remain incompletely understood. OBJECTIVES: The aim of this

  3. Fetal Alcohol Exposure

    Science.gov (United States)

    ... her child’s genetic make-up, and changes in gene activity caused by prenatal alcohol exposure. NIH . . . Turning Discovery Into Health ® National Institute on Alcohol Abuse and Alcoholism www. niaaa. nih. gov • 301.443.3860 Interventions ...

  4. Alcohol intake and colorectal cancer: a comparison of approaches for including repeated measures of alcohol consumption

    DEFF Research Database (Denmark)

    Thygesen, Lau Caspar; Wu, Kana; Grønbaek, Morten

    2008-01-01

    BACKGROUND: In numerous studies, alcohol intake has been found to be positively associated with colorectal cancer risk. However, the majority of studies included only one exposure measurement, which may bias the results if long-term intake is relevant.METHODS: We compared different approaches...... for including repeated measures of alcohol intake among 47,432 US men enrolled in the Health Professionals Follow-up Study. Questionnaires including questions on alcohol intake had been completed in 1986, 1990, 1994, and 1998. The outcome was incident colorectal cancer during follow-up from 1986 to 2002.RESULTS......: During follow-up, 868 members of the cohort experienced colorectal cancer. Baseline, updated, and cumulative average alcohol intakes were positively associated with colorectal cancer, with only minor differences among the approaches. These results support moderately increased risk for intake >30 g...

  5. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

    Science.gov (United States)

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

    2014-04-01

    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 h of exposure. EtOH levels gradually decreased to baseline 8 h 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 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 GABA(A) 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.

  6. Exposure to alcohol advertising and alcohol consumption among Australian adolescents.

    Science.gov (United States)

    Jones, Sandra C; Magee, Christopher A

    2011-01-01

    Underage drinking is a major problem in Australia and may be influenced by exposure to alcohol advertising. The objective of the present study was to collect data on 12-17 year old Australian adolescents' exposure to different types of alcohol advertising and examine the association between exposure to advertising and alcohol consumption. A cross-sectional survey of 1113 adolescents aged 12-17 years recruited with a variety of methods to gain a cross-section of participants across metropolitan, regional and rural New South Wales (including independent schools, mall intercepts and online). Participants answered a series of questions assessing adolescents' exposure to alcohol advertising across eight media (including television, Internet and point-of-sale). Alcohol consumption was assessed using three questions (initiation, recent consumption and frequency of consumption in the previous 12 months). The majority indicated that they had been exposed to alcohol advertisements on television, in newspapers and magazines, on the Internet, on billboards/posters and promotional materials and in bottleshops, bars and pubs; exposure to some of these types of alcohol advertisements was associated with increased alcohol consumption, with differences by age and gender. The results are consistent with studies from other countries and suggest that exposure to alcohol advertisements among Australian adolescents is strongly associated with drinking patterns. Given current high levels of drinking among Australian youth, these findings suggest the need to address the high levels of young people's exposure to alcohol advertising.

  7. Prenatal Alcohol Exposure and Cortical Angiogenesis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-02-01

    Full Text Available Researchers at Normandy University, and Rouen and Brest Universities, France studied the effects of prenatal alcohol exposure on the cortical microvascular and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF on activity, plasticity, and survival of microvessels in mice.

  8. Modeling repeated measurement data for occupational exposure assessment and epidemiology

    NARCIS (Netherlands)

    Peretz, Chava

    2004-01-01

    Repeated measurements designs, occur frequently in the assessment of exposure to toxic chemicals. This thesis deals with the possibilities of using mixed effects models for occupational exposure assessment and in the analysis of exposure response relationships. The model enables simultaneous estima

  9. Adolescent alcohol exposure: Burden of epigenetic reprogramming, synaptic remodeling, and adult psychopathology

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    Evan J Kyzar

    2016-05-01

    Full Text Available 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 delay 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.

  10. Socioeconomic determinants of exposure to alcohol outlets.

    Science.gov (United States)

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

    2015-05-01

    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. 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). 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. 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.

  11. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

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    Robins, Meridith T; Lu, Julie; van Rijn, Richard M

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  12. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Meridith T Robins

    Full Text Available The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61 exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

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

    Science.gov (United States)

    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

  14. Alcohol exposure during development: Impact on the epigenome

    OpenAIRE

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

    2013-01-01

    Fetal Alcohol Spectrum Disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes ...

  15. Physiological consequences of repeated exposures to conditioned fear.

    Science.gov (United States)

    Thompson, Robert S; Strong, Paul V; Fleshner, Monika

    2012-06-01

    Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days) to a context that they were conditioned to fear (conditioned fear test, CFT). Repeated exposure to CFT produced body weight loss, adrenal hypertrophy, thymic involution, and basal corticosterone elevation. In vivo biotelemetry measures revealed that CFT evokes sympathetic nervous system driven increases in heart rate (HR), mean arterial pressure (MAP), and core body temperature. Extinction of behavioral (freezing) and physiological responses to CFT was prevented using minimal reinstatement footshock. MAP responses to the CFT did not diminish across 20 days of exposure. In contrast, HR and cardiac contractility responses declined by day 15, suggesting a shift toward vascular-dominated MAP (a pre-clinical marker of CV dysfunction). Flattened diurnal rhythms, common to stress-related mood/anxiety disorders, were found for most physiological measures. Thus, repeated CFT produces adaptations indicative of the health damaging effects of psychological/emotional stress.

  16. Physiological Consequences of Repeated Exposures to Conditioned Fear

    Directory of Open Access Journals (Sweden)

    Robert S. Thompson

    2012-05-01

    Full Text Available Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days to a context that they were conditioned to fear (conditioned fear test, CFT. Repeated exposure to CFT produced body weight loss, adrenal hypertrophy, thymic involution, and basal corticosterone elevation. In vivo biotelemetry measures revealed that CFT evokes sympathetic nervous system driven increases in heart rate (HR, mean arterial pressure (MAP, and core body temperature. Extinction of behavioral (freezing and physiological responses to CFT was prevented using minimal reinstatement footshock. MAP responses to the CFT did not diminish across 20 days of exposure. In contrast, HR and cardiac contractility responses declined by day 15, suggesting a shift toward vascular-dominated MAP (a pre-clinical marker of CV dysfunction. Flattened diurnal rhythms, common to stress-related mood/anxiety disorders, were found for most physiological measures. Thus, repeated CFT produces adaptations indicative of the health damaging effects of psychological/emotional stress.

  17. Repeated trauma exposure does not impair distress reduction during imaginal exposure for posttraumatic stress disorder.

    Science.gov (United States)

    Jerud, Alissa B; Farach, Frank J; Bedard-Gilligan, Michele; Smith, Hillary; Zoellner, Lori A; Feeny, Norah C

    2017-08-01

    Based on experimental research on threat extinction, individuals exposed to repeated traumatic events may have impaired outcome in exposure therapy compared to those who have experienced a single trauma (Lang & McTeague, ). This study examined whether repeated trauma exposure predicts smaller changes in self-reported distress during imaginal exposure and worse outcomes for patients with posttraumatic stress disorder (PTSD). Adults (N = 116) with chronic PTSD received up to 10 sessions of prolonged exposure (PE) therapy. Trauma exposure was assessed via interview and number of traumatic events were summed for each participant. To examine reductions in distress during treatment, mean and peak values of distress during imaginal exposure were calculated for the first imaginal session (initial distress activation) and subsequent sessions (between-session change in distress). Change in PTSD symptoms from pre- to posttreatment and follow-up provided an additional index of outcome. In-session distress during imaginal exposure decreased over the course of treatment. PTSD symptoms also decreased over treatment, with gains being maintained through follow-up. Repeated trauma exposure was not significantly correlated with initial distress activation. Additionally, linear mixed-model analyses showed no significant association between repeated trauma exposure and between-session change in distress or PTSD symptoms. Contrary to recent speculation, repeated trauma exposure did not predict less change in self-reported distress during imaginal exposure or worse PTSD outcomes. The bench-to-bedside linkage of threat extinction to exposure therapy is discussed, noting strengths and weaknesses. Patients with repeated trauma exposure show reductions in distress with exposure treatment and benefit from PE as much as patients with single-exposure trauma histories. © 2016 Wiley Periodicals, Inc.

  18. Exposure to alcohol outlets in rural towns.

    Science.gov (United States)

    Morrison, Christopher

    2015-01-01

    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) with lower income, and (iii) which are adjacent to towns with higher income. Bayesian conditional autoregressive Poisson models examined counts of bars, restaurants, and off-premise outlets within 353 discrete towns of rural Victoria, Australia (mean population = 4,236.0, 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. 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. 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 nonresidents. In rural areas, these processes appear to operate between

  19. Cataract after repeated daily in vivo exposure to ultraviolet radiation.

    Science.gov (United States)

    Galichanin, Konstantin; Löfgren, Stefan; Söderberg, Per

    2014-12-01

    Epidemiological data indicate a correlation between lifelong exposure to ultraviolet radiation and cortical cataract. However, there is no quantitative experimental data on the effect of daily repeated in vivo exposures of the eye to UVR. Therefore, this experiment was designed to verify whether the dose additivity for UVR exposures holds through periods of time up to 30 d. Eighty rats were conditioned to a rat restrainer 5 d prior to exposure. All animals were divided into four exposure period groups of 1, 3, 10, and 30 d of exposure to UVR. Each exposure period group of 20 animals was randomly divided into five cumulated UVR dose subgroups. Eighteen-wk-old non-anesthetized albino Sprague-Dawley rats were exposed daily to UVR-300 nm for 15 min. One week after the last exposure, animals were sacrificed. The lenses were extracted for macroscopic imaging of dark-field anatomy, and degree of cataract was quantified by measurement of the intensity of forward lens light scattering. Maximum tolerable dose (MTD(2.3:16)), a statistically defined standard for sensitivity for the threshold for UVR cataract, was estimated for each exposure period. Exposed lenses developed cataract with varying appearance on the anterior surface. Single low doses of UVR accumulated to cause cataract during periods up to 30 d. MTD(2.3:16) for 1, 3, 10, and 30 d of repeated exposures was estimated to 4.70, 4.74, 4.80, and 6.00 kJ m(-2), respectively. In conclusion, the lens sensitivity to UVR-B for 18-wk-old Sprague-Dawley rats decreases with the increasing number of days being exposed.

  20. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

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    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits.

  1. Temporal alcohol availability predicts first-time drunk driving, but not repeat offending.

    Science.gov (United States)

    Schofield, Timothy P; Denson, Thomas F

    2013-01-01

    Alcohol availability has been linked to drunk driving, but research has not examined whether this relationship is the same for first-time and repeat offenses. We examined the relationship between the business hours of alcohol outlets licensed to serve alcohol for on-premises consumption and misdemeanor-level (first offense) and felony-level drunk driving (repeat offense) charges in New York State in 2009. Longer outlet business hours were associated with more misdemeanor drunk driving charges, but were not associated with felony drunk driving charges. The per capita density of on-premises alcohol outlets did not affect misdemeanor or felony drunk driving charges. The results suggest that temporal alcohol availability may be an impelling factor for first-time drunk driving, but other factors likely influence repeat drunk driving behaviors.

  2. Temporal alcohol availability predicts first-time drunk driving, but not repeat offending.

    Directory of Open Access Journals (Sweden)

    Timothy P Schofield

    Full Text Available Alcohol availability has been linked to drunk driving, but research has not examined whether this relationship is the same for first-time and repeat offenses. We examined the relationship between the business hours of alcohol outlets licensed to serve alcohol for on-premises consumption and misdemeanor-level (first offense and felony-level drunk driving (repeat offense charges in New York State in 2009. Longer outlet business hours were associated with more misdemeanor drunk driving charges, but were not associated with felony drunk driving charges. The per capita density of on-premises alcohol outlets did not affect misdemeanor or felony drunk driving charges. The results suggest that temporal alcohol availability may be an impelling factor for first-time drunk driving, but other factors likely influence repeat drunk driving behaviors.

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

    Science.gov (United States)

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

    2017-03-01

    Little is known about the extent and nature of youth exposure to online alcohol advertising, or factors that may be associated with exposure. The current study recruited middle school students who completed a paper survey and then logged each alcohol advertisement that they encountered over a 2-week period using cell phones as part of an ecological momentary assessment design. We examined the percentage of youth who reported exposure to online alcohol advertising in the past 2 weeks, average weekly rate of exposure, types of online alcohol advertisements youth reported seeing, and factors that increased youths' risk of exposure to online alcohol advertising. Analyses are based on 485 participants (47% female; 25% Hispanic, 25% White, 27% Black; 6% Asian, 16% other). Youth logged exposures to a total of 3,966 (16,018 weighted for underreporting) alcohol advertisements across the monitoring period; 154 (568 weighted) or 3.6% were online ads. Seventeen percent of youth reported seeing any online alcohol ad; the majority of online ads seen were video commercials (44.8%) and banner/side ads (26.6%). Factors associated with greater ad exposure were being older, rebellious, and Black race; greater parental monitoring and more hours spent on social media were associated with less exposure. Findings provide important information about adolescents' exposure to online alcohol advertising and what might contribute to a greater likelihood of exposure. Given that online ad exposure is linked to drinking behavior, prevention programming for younger adolescents should continue to address this issue to help youth make healthy choices regarding alcohol use. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use.

    Science.gov (United States)

    de Bruijn, Avalon; Tanghe, Jacqueline; de Leeuw, Rebecca; Engels, Rutger; Anderson, Peter; Beccaria, Franca; Bujalski, Michał; Celata, Corrado; Gosselt, Jordy; Schreckenberg, Dirk; Słodownik, Luiza; Wothge, Jördis; van Dalen, Wim

    2016-10-01

    This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for non-alcohol branded media exposure. Prospective observational study (11-12- and 14-17-month intervals), using a three-wave autoregressive cross-lagged model. School-based sample in 181 state-funded schools in Germany, Italy, Netherlands, Poland. A total of 9075 eligible respondents participated in the survey (mean age 14 years, 49.5% male. Adolescents reported their frequency of past-month drinking and binge drinking. Alcohol marketing exposure was measured by a latent variable with 13 items measuring exposure to online alcohol marketing, televised alcohol advertising, alcohol sport sponsorship, music event/festival sponsorship, ownership alcohol-branded promotional items, reception of free samples and exposure to price offers. Confounders were age, gender, education, country, internet use, exposure to non-alcohol sponsored football championships and television programmes without alcohol commercials. The analyses showed one-directional long-term effects of alcohol marketing exposure on drinking (exposure T1 on drinking T2: β = 0.420 (0.058), P exposure T2 on drinking T3: β = 0.200 (0.044), P exposure: P > 0.05). Similar results were found in the binge drinking model (exposure T1 on binge T2: β = 0.409 (0.054), P exposure T2 on binge T3: β = 0.168 (0.050), P = 0.001, 95% CI = 0.086-0.250; binge T1 and binge T2 on exposure: P > 0.05). There appears to be a one-way effect of alcohol marketing exposure on adolescents' alcohol use over time, which cannot be explained by either previous drinking or exposure to non-alcohol-branded marketing. © 2016 Society for the Study of Addiction.

  5. European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use

    NARCIS (Netherlands)

    Bruijn, A. de; Tanghe, J.; Leeuw, R.N.H. de; Engels, R.C.M.E.; Anderson, P.D.; Beccaria, F.; Bujalski, M.; Celata, C.; Gosselt, J.; Schreckenberg, D.; Slodownik, L.; Wothge, J.; Dalen, W. van

    2016-01-01

    Background and aims: This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for non-a

  6. European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use

    NARCIS (Netherlands)

    Bruijn, A. de; Tanghe, J.; Leeuw, R.N.H. de; Engels, R.C.M.E.; Anderson, P.D.; Beccaria, F.; Bujalski, M.; Celata, C.; Gosselt, J.; Schreckenberg, D.; Slodownik, L.; Wothge, J.; Dalen, W. van

    2016-01-01

    Background and aims: This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for

  7. European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use

    NARCIS (Netherlands)

    Bruijn, A. de; Tanghe, J.; Leeuw, R.N.H. de; Engels, R.C.M.E.; Anderson, P.D.; Beccaria, F.; Bujalski, M.; Celata, C.; Gosselt, J.; Schreckenberg, D.; Slodownik, L.; Wothge, J.; Dalen, W. van

    2016-01-01

    Background and aims: This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for non-a

  8. Prenatal Alcohol Exposure and the Developing Immune System.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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 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. PMID:24655090

  11. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats

    Directory of Open Access Journals (Sweden)

    Jessica Saalfield

    2015-12-01

    Full Text Available Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively would affect ethanol conditioned taste aversions 2 days (CTA1 and >3 weeks (CTA2 post-exposure using supersaccharin and saline as conditioning stimuli (CS, respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25% or water every 48 h from postnatal day (P 25–45 (early AIE or P45-65 (late AIE, or were left non-manipulated (NM. During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

  12. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

    Science.gov (United States)

    Saalfield, Jessica; Spear, Linda

    2015-12-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

  13. Acute versus repeated chocolate exposure: effects on intake and cravings in restrained and unrestrained eaters.

    Science.gov (United States)

    Coelho, Jennifer S; Nederkoorn, Chantal; Jansen, Anita

    2014-04-01

    The cue-reactivity model, which is based on conditioning processes, posits that repeated food exposure (in the absence of consumption) should decrease cue reactivity. To examine whether repeated chocolate exposure attenuates cravings and intake, relative to those exposed to an acute cue, a 2 (repeated vs acute cue) × 2 (restrained vs unrestrained eaters) design was employed. Fifty female participants were recruited. Repeated exposure reduced cravings in unrestrained eaters (relative to acute exposure), but increased cravings in restrained eaters. An interaction between restraint and exposure emerged on intake, such that restrained eaters ate less after acute exposure than did unrestrained eaters.

  14. Fetal alcohol exposure and development of the integument

    Directory of Open Access Journals (Sweden)

    Longhurst WD

    2016-05-01

    Full Text Available William D Longhurst,1 Jordan Ernst,2 Larry Burd3 1Center for Emergency Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA; 2University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA; 3Department of Pediatrics, North Dakota Fetal Alcohol Syndrome Center, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA Background: The physiology of fetal alcohol exposure changes across gestation. Early in pregnancy placental, fetal, and amniotic fluid concentrations of alcohol exposure are equivalent. Beginning in mid-pregnancy, the maturing fetal epidermis adds keratins which decrease permeability resulting in development of a barrier between fetal circulation and the amniotic fluid. Barrier function development is essential for viability in late pregnancy and in the extra-uterine environment. In this paper we provide a selected review of the effects of barrier function on fetal alcohol exposure. Methods: We utilized a search of PubMed and Google for all years in all languages for MeSH on Demand terms: alcohol drinking, amnion, amniotic fluid, epidermis, ethanol, female, fetal development, fetus, humans, keratins, permeability, and pregnancy. We also reviewed the reference lists of relevant papers and hand-searched reference lists of textbooks for additional references. Results: By 30 gestational weeks, development of barrier function alters the pathophysiology of ethanol dispersion between the fetus and amniotic fluid. Firstly, increases in the effectiveness of barrier function decreases the rate of diffusion of alcohol from fetal circulation across fetal skin into the amniotic fluid. This reduces the volume of alcohol entering the amniotic fluid. Secondly, barrier function increases the duration of fetal exposure by decreasing the rate of alcohol diffusion from amniotic fluid back into fetal circulation. Ethanol is then transported into

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

    Science.gov (United States)

    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. Biomarkers for the detection of prenatal alcohol exposure (PAE)

    DEFF Research Database (Denmark)

    Bjerregaard, Lene Berit Skov; Bager, Heidi; Husby, Steffen

    2017-01-01

    Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful...... method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing...... literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation...

  17. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

    Science.gov (United States)

    Adkins, B; O'Connor, R W; Dement, J M

    1987-06-01

    Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

  18. Conditioned learning in alcohol dependence: implications for cue exposure treatment.

    Science.gov (United States)

    Drummond, D C; Cooper, T; Glautier, S P

    1990-06-01

    A review of the literature pertinent to cue exposure treatment in alcohol dependence is presented. Psychological models of relapse, based on conditioning and social learning theories, are critically evaluated. In particular, attention is drawn to the potential implications for cue exposure research and treatment of an interaction between Pavlovian and operant conditioning, problems with the application of the concepts of arousal and craving and the importance of a systems model to understand physiological responses. It is concluded that no study has so far demonstrated a link between conditioned responses to alcohol-related cues and relapse, an assumption on which cue exposure treatment is based. Further, the evidence for the effectiveness of cue exposure as a treatment is lacking. Promising research directions are identified.

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

    Science.gov (United States)

    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.

  20. Embryonic alcohol exposure: Towards the development of a zebrafish model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Gerlai, Robert

    2015-11-01

    Fetal alcohol spectrum disorder (FASD) is a devastating disease of the brain caused by exposure to alcohol during prenatal development. Its prevalence exceeds 1%. The majority of FASD cases represent the milder forms of the disease which often remain undiagnosed, and even when diagnosed treatment options for the patient are limited due to lack of information about the mechanisms that underlie the disease. The zebrafish has been proposed as a model organism for exploring the mechanisms of FASD. Our laboratory has been studying the effects of low doses of alcohol during embryonic development in the zebrafish. This review discusses the methods of alcohol exposure, its effects on behavioral performance including social behavior and learning, and the potential underlying biological mechanisms in zebrafish. It is based upon a recent keynote address delivered by the author, and it focuses on findings obtained mainly in his own laboratory. It paints a promising future of this small vertebrate in FASD research.

  1. Effects of Prenatal Alcohol Exposure on the Developing Kidneys

    Directory of Open Access Journals (Sweden)

    Farahnak Assadi

    2008-04-01

    Full Text Available Objective: Clinical and experimental studies strongly suggest that prenatal alcohol exposure is associated with zinc deficiency and impaired renal tubular function. Whether maternal alcohol consumption during pregnancy causes renal tubular cell injury is unknown.Material & Methods: Renal function was studied in 8 infants with fetal alcohol syndrome (FAS and 8 healthy age-matched infants. Renal function and structure were also examined in 11 offspring of rats exposed to alcohol during gestation.Findings: Infants with FAS had limited ability to concentrate urine after water restriction (P<0.001 and impaired acidification after acute acid loading (P<0.001 compared to control group. Plasma zinc levels were lower (P<0.001 and urinary zinc excretion was higher (P<0.001 in infants with FAS compared to control infants. Scanning electron microscopic studies revealed cytoplasmic mitochondrial hypertrophy and vacuolar structures of the epithelial cells of the cortical collecting ducts in the rat kidney following fetal exposure to alcohol.Conclusion: These findings suggest that offspring of rats exposed to alcohol during fetal life have renal functional and structural abnormalities that may be responsible in the genesis of renal functional abnormalities as described in infants with FAS.

  2. Embryonic alcohol exposure impairs associative learning performance in adult zebrafish.

    Science.gov (United States)

    Fernandes, Yohaan; Tran, Steven; Abraham, Emil; Gerlai, Robert

    2014-05-15

    The zebrafish has been proposed for modeling fetal alcohol spectrum disorders (FASD). Previous FASD research with zebrafish employed high concentrations of alcohol and/or long exposure periods. Here, we exposed zebrafish eggs to low doses of alcohol (0, 0.25, 0.50, 0.75 and 1.0% (vol/vol); external bath application of which 1/20th may reach the inside of the egg) at 16-h post-fertilization (hpf) and only for a short duration (2h) in the hope to avoid gross morphological aberrations and to mimic the more frequent FASD exposure levels. Upon reaching adulthood the exposed and control zebrafish were tested for their associative learning performance in a plus-maze. Embryonic alcohol exposure led to no gross anatomical abnormalities and did not increase mortality. Unexposed (control) zebrafish showed excellent acquisition of association between a conditioned visual stimulus (CS) and food reward, demonstrated by their preference for the target zone of the maze that contained the CS during a probe trial in the absence of reward. However, alcohol-exposed fish showed no such preference and performed indistinguishable from random chance. Locomotor activity during training and the probe trial or the amount of food consumed during training did not differ between the embryonic alcohol exposed and unexposed (control) fish, suggesting that the impaired learning performance found was unlikely to be caused by altered motivation or motor function. Our results suggest that even very small amounts of alcohol reaching the embryo for only a short duration of time may have long lasting deleterious effects on cognitive function in vertebrates.

  3. The Effects of Repeated Exposure to Graphic Fear Appeals on Cigarette Packages: A Field Experiment

    NARCIS (Netherlands)

    Dijkstra, A.; Bos, C.

    2015-01-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on cigarett

  4. The Effects of Repeated Exposure to Graphic Fear Appeals on Cigarette Packages : A Field Experiment

    NARCIS (Netherlands)

    Dijkstra, Arie; Colin, Bos,

    2015-01-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on cigarett

  5. The Effects of Repeated Exposure to Graphic Fear Appeals on Cigarette Packages : A Field Experiment

    NARCIS (Netherlands)

    Dijkstra, Arie; Colin, Bos,

    2015-01-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on

  6. The Effects of Repeated Exposure to Graphic Fear Appeals on Cigarette Packages: A Field Experiment

    NARCIS (Netherlands)

    Dijkstra, A.; Bos, C.

    2015-01-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on

  7. Dealing with Consumer Differences in Liking during Repeated Exposure to Food; Typical Dynamics in Rating Behavior

    NARCIS (Netherlands)

    Dalenberg, Jelle R.; Nanetti, Luca; Renken, Remco J.; de Wijk, Rene A.; ter Horst, Gert J.

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in

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

    Science.gov (United States)

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

    2017-01-01

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

  9. Attenuated response to repeated daily ozone exposures in asthmatic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Gong, H. Jr.; Linn, W.S. [Rancho Low Amigos Medical Center, Downey, CA (United States); McManus, M.S. [Univ. of California, Los Angeles, CA (United States)

    1997-01-01

    The development of attenuated response ({open_quotes}tolerance{close_quotes}) to daily ozone (O{sub 3}) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures in unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O{sub 3} in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O{sub 3} exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 {degrees}C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O{sub 3} exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O{sub 3} day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O{sub 3} exposure and remained somewhat elevated after all subsequent O{sub 3} exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O{sub 3} predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O{sub 3} exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics. 27 refs., 3 figs., 4 tabs.

  10. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    Science.gov (United States)

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  11. Lens opacities after repeated exposure to ultraviolet radiation.

    Science.gov (United States)

    Michael, R; Löfgren, S; Söderberg, P G

    1999-12-01

    To investigate the effect of the interval between two, near-threshold exposures to ultraviolet radiation (UVR) on cataract development. One eye of Sprague-Dawley rats was exposed twice to 4 kJ/m2 narrow band UVR (lambdaMAX=300 nm) for 15 min each. The interval between exposures was 0, 6, 24 or 48 h. One week after the first exposure both lenses were removed for photography and measurement of the intensity of forward light scattering to quantify lens opacities. All exposed lenses developed cataract. Forward light scattering was the same after double exposure with no interval or a 6 h interval. Forward light scattering after a 24 or 48 h interval was nearly twofold greater than that following no interval or a 6 h interval. The exposed lenses in all groups had mild anterior surface opacities and intense equatorial opacities as judged with a stereomicroscope. Two, near-threshold UVR exposures at 0 or a 6 h interval produce the same degree of lens opacification. When the second exposure follows 24 or 48 h after the first, lenticular damage increases. Repair processes between 24 and 48 h after exposure appear to be sensitive to UVR, and an additional exposure during this time may aggravate cataract development.

  12. Positive affective interactions: The role of repeated exposure and copresence

    NARCIS (Netherlands)

    Shahid, S.; Krahmer, E.; Neerincx, M.; Swerts, M.

    2013-01-01

    We describe and evaluate a new interface to induce positive emotions in users: a digital, interactive adaptive mirror. We study whether the induced affect is repeatable after a fixed interval (Study 1) and how copresence influences the emotion induction (Study 2). Results show that participants syst

  13. Effects of hyperlipidemia on adaptive responses to repeated zinc exposure

    Science.gov (United States)

    In individuals with underlying atherosclerosis and coronary heart disease (CHD), exposure to near-road air pollution correlates epidemiologically with deleterious health outcome. Associated cardiotoxicity purportedly involves generation of reactive oxygen species (ROS) and activa...

  14. Repeated exposure to conditioned fear stress increases anxiety and delays sleep recovery following exposure to an acute traumatic stressor

    Directory of Open Access Journals (Sweden)

    Benjamin N Greenwood

    2014-10-01

    Full Text Available Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by humans, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to either no, mild (10, or severe (100 acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced REM and NREM sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep / wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep / wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders.

  15. Child and adolescent exposure to alcohol advertising in Australia's major televised sports.

    Science.gov (United States)

    Carr, Sherilene; O'Brien, Kerry S; Ferris, Jason; Room, Robin; Livingston, Michael; Vandenberg, Brian; Donovan, Robert J; Lynott, Dermot

    2016-07-01

    Exposure to alcohol advertising is associated with greater alcohol consumption in children and adolescents, and alcohol advertising is common in Australian sport. We examine child, adolescent and young adult exposure to alcohol advertising during three televised sports in Australia: Australian Football League (AFL), cricket and the National Rugby League (NRL). Alcohol advertising and audience viewing data were purchased for all AFL, cricket and NRL TV programs in Australia for 2012. We estimated children and adolescents (0-17 years) and young adults (18-29 years) exposure to alcohol advertising during AFL, cricket and NRL programs in the daytime (06:00-20:29 h), and night-time (20:30-23:59 h). There were 3544 alcohol advertisements in AFL (1942), cricket (941) and NRL programs (661), representing 60% of all alcohol advertising in sport TV, and 15% of all alcohol advertisements on Australian TV. These programs had a cumulative audience of 26.9 million children and adolescents, and 32 million young adults. Children and adolescents received 51 million exposures to alcohol advertising, with 47% of this exposure occurring during the daytime. Children and adolescents exposure to alcohol advertising was similar to young adults and peaked after 8.30pm. Child and adolescent and young adult's exposure to alcohol advertising is high when viewing sport TV in Australia in the daytime and night-time. Current alcohol advertising regulations are not protecting children and adolescents from exposure, particularly in prominent televised sports. The regulations should be changed to reduce children and adolescent excessive exposure to alcohol advertising when watching sport. [Carr S, O'Brien KS, Ferris J, Room R, Livingston M, Vandenberg B, Donovan RJ, Lynott D. Child and adolescent exposure to alcohol advertising in Australia's major televised sports. Drug Alcohol Rev 2016;35:406-411]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  16. Effects of repeated skin exposure to low nickel concentrations

    DEFF Research Database (Denmark)

    Nielsen, N H; Menné, T; Kristiansen, J

    1999-01-01

    and nickel allergy, either on normal or on SLS-treated forearm skin. The present study strongly suggests that the changes observed were specific to nickel exposure. Standardized methods to assess trace to moderate nickel exposure on the hands, and the associated effects in nickel-sensitized subjects...... with a group of patients who immersed a finger into water. The nickel concentrations used also provoked significant inflammatory skin changes on sodium lauryl sulphate (SLS)-treated forearm skin of the patients, whereas inflammatory skin changes were not observed in healthy volunteers without hand eczema...

  17. Stable acetaldehyde--protein adducts as biomarkers of alcohol exposure.

    Science.gov (United States)

    Conduah Birt, J E; Shuker, D E; Farmer, P B

    1998-02-01

    The consumption of alcoholic beverages has been associated with increased risks of a number of chronic disorders including cancers. It is still not clear whether ethyl alcohol or other components such as metabolites are directly involved in the carcinogenic process or whether the effects are due to the modulation of metabolism of other carcinogens. At present, there is no good biomarker of alcohol intake, particularly at low or moderate levels of consumption. A number of studies have shown the ability of the major metabolite acetaldehyde to react with proteins in vitro to give stable and unstable adducts. The interaction of acetaldehyde with model peptides, which correspond to N-terminal globin sequences, was studied. The major stable adduct was identified by mass spectrometry and NMR as a diastereoisomeric mixture of imidazolidinones. This is believed to be formed by reaction and cyclization of the initial Schiff base adduct with the N-terminal valine. Incubation of human globin with acetaldehyde (0-2 mM) yielded products which were identified as the N-terminal adducts by electrospray ionization mass spectrometry (ESI-MS) of proteolytic digests. The specificity and sensitivity of the analysis was improved by the use of on-line HPLC-ESI-MS. Tryptic digests of the modified globin which contained both the N-terminal acetaldehyde adducts of alpha-globin (heptapeptide) and beta-globin (octapeptide) were resolved. These results suggest that analysis of stable imidazolidinone adducts is a promising approach to estimation of alcohol exposure.

  18. Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder.

    Science.gov (United States)

    Åhs, Fredrik; Gingnell, Malin; Furmark, Tomas; Fredrikson, Mats

    2017-03-30

    Anxiety reduction following repeated exposure to stressful experiences is generally held to depend on neural processes involved in extinction of conditioned fear. We predicted that repeated exposure to stressful experiences would change activity throughout the circuitry serving extinction, including ventromedial prefrontal cortex (vmPFC), the hippocampus and the amygdala. To test this prediction, 36 participants diagnosed with SAD performed two successive speeches in front of an observing audience while regional cerebral blood flow (rCBF) was recorded using positron emission tomography. To control for non-anxiolytic effects of repeated exposure, rCBF was also measured during repeated presentations of neutral and angry facial expressions. Results showed that anxiety ratings and heart rate decreased from the first to the second speech, indicating an anxiolytic effect of repeated exposure. Exposure attenuated rCBF in the amygdala whereas no change in rCBF was observed in the vmPFC or hippocampus. The rCBF-reductions in the amygdala were greater following repetition of the speech task than repetition of face exposure indicating that they were specific to anxiety attenuation and not due to a reduced novelty. Our findings suggest that amygdala-related attenuation processes are key to understanding the working mechanisms of exposure therapy.

  19. Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo chlorpyrifos dosimetry and cholinesterase inhibition.

    Science.gov (United States)

    Lee, S; Poet, T S; Smith, J N; Hjerpe, A L; Gunawan, R; Timchalk, C

    2011-01-01

    Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos-oxon. Routine consumption of alcohol and tobacco modifies metabolic and physiological processes impacting the metabolism and pharmacokinetics of other xenobiotics, including pesticides. This study evaluated the influence of repeated ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE) response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po), and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro metabolism of CPF was evaluated. For in vivo studies, rats were treated with saline or ethanol (1 g/kg/d, po) + nicotine (1 mg/kg/d, sc) in addition to CPF (1 or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase (AChE) activities were measured in rats. There were differences in pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 ± 13 and 66 ± 7% of naive at 4 h post last CPF dosing, respectively). Although brain AChE activity was minimal inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment resulted in a similar trend (i.e., slightly less inhibition). No marked differences were observed in plasma ChE activities due to the alcohol + nicotine treatments. In vitro, CPF metabolism was not markedly affected by repeated ethanol or both ethanol + nicotine exposures. Compared with a previous study of nicotine and CPF exposure, there were no

  20. Striatal dopamine dynamics in mice following acute and repeated toluene exposure.

    Science.gov (United States)

    Apawu, Aaron K; Mathews, Tiffany A; Bowen, Scott E

    2015-01-01

    The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene's mechanism of action is unknown. The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry. Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene's locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25-50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice. These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.

  1. Repeated cue exposure effects on subjective and physiological indices of chocolate craving

    NARCIS (Netherlands)

    van Gucht, D.; Vansteenwegen, D.; Beckers, T.; Hermans, D.; Baeyens, F.; Van den Bergh, O.

    2008-01-01

    The aim of this study is to investigate the effects of repeated unreinforced exposure to chocolate cues in persons reporting chocolate craving. Participants in the experimental group (n ¼ 40) received 10 consecutive brief exposures to chocolate cues in each of two sessions, separated by 1-3 days.

  2. Repeated cue exposure effects on subjective and physiological indices of chocolate craving

    NARCIS (Netherlands)

    van Gucht, D.; Vansteenwegen, D.; Beckers, T.; Hermans, D.; Baeyens, F.; Van den Bergh, O.

    2008-01-01

    The aim of this study is to investigate the effects of repeated unreinforced exposure to chocolate cues in persons reporting chocolate craving. Participants in the experimental group (n ¼ 40) received 10 consecutive brief exposures to chocolate cues in each of two sessions, separated by 1-3 days. Co

  3. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    NARCIS (Netherlands)

    K.G. Akers (Katherine); S.A. Kushner (Steven); A.T. Leslie (Ana); L. Clarke (Laura); D. van der Kooy (Derek); J.P. Lerch (Jason); P.W. Frankland (Paul)

    2011-01-01

    textabstractBackground: Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific

  4. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    NARCIS (Netherlands)

    K.G. Akers (Katherine); S.A. Kushner (Steven); A.T. Leslie (Ana); L. Clarke (Laura); D. van der Kooy (Derek); J.P. Lerch (Jason); P.W. Frankland (Paul)

    2011-01-01

    textabstractBackground: Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavior

  5. Kerusakan Hati Akibat Keracunan Alkohol Berulang pada Tikus Wistar (LIVER DAMAGE DUE TO ALCOHOL INTOXICATION REPEAT IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Ni Made Suaniti

    2014-08-01

    Full Text Available The aims of this study was to determine the liver damage from alcohol intoxication in Wistar rats.The design used in this study was a randomized true experimental post test only control group design. Thestudy used 15 rats divided into 3 treatment groups each of which consists of 5 rats. The first group wasgiven distill water. The second group was given 5% alcohol, and the third group was given 20% alcohol. Ratswere treated with alcohol daily for six weeks. Biochemical markers were detected the levels of aldehydedehydrogenase (ALDH in serum and histological changes in liver tissue. ALDH is a biochemical markerof a sensitive and specific ethanol after chronic alcohol administration. Blood sample was collected at 6and 24 hours after the last peroral administration of repeated alcohol treatment, and serum levels ofALDH was tested by enzyme linked immunosorbent assay (ELISA. The results showed that the levels ofALDH in the blood of alcohol treated Wistar rats significantly higher as compared to those of control rats.ALDH levels increased by 83.11% after administration of 5% alcohol and 112.05% after administration of20% taken after 6 hours of alcohol for 6 weeks. On samples taken after 24 hours, ALDH levels by 95.11%after administration of 5% alcohol and 86.79% after administration of 20% alcohol. Oral treatment with20% alcohol chronically was led to changes in the microscopic structure (necrosis of liver tissue in Wistarrats. Liver tissue damage occured due to repeated use of alcohol is accompanied by increasing serum levelsof ALDH in Wistar rats.

  6. Mid-Childhood Bone Mass After Exposure to Repeat Doses of Antenatal Glucocorticoids: A Randomized Trial.

    Science.gov (United States)

    McKinlay, Christopher J D; Cutfield, Wayne S; Battin, Malcolm R; Dalziel, Stuart R; Crowther, Caroline A; Harding, Jane E

    2017-05-01

    Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity, but could have adverse effects on skeletal development. We assessed whether exposure to repeat antenatal betamethasone alters bone mass in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids. Women were randomized to a single dose of betamethasone or placebo, ≥7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at children underwent whole-body dual-energy radiograph absorptiometry at 6 to 8 years' corrected age. Of 212 eligible childhood survivors, 185 were studied (87%; 91 repeat betamethasone group; 94 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar whole-body bone mineral content (median repeat betamethasone: 553 g, interquartile range: 442-712 g; placebo: 567 g, interquartile range: 447-750 g; geometric mean ratio: 0.99; 95% confidence interval: 0.94-1.03, P = .55) and bone area (median repeat betamethasone 832 cm(2), interquartile range: 693-963 cm(2); placebo: 822 cm(2), interquartile range: 710-1020 cm(2); geometric mean ratio: 0.99, 95% confidence interval: 0.92-1.07, P = .75). Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not alter bone mass in mid-childhood. Copyright © 2017 by the American Academy of Pediatrics.

  7. Prenatal alcohol exposure and traumatic childhood experiences: A systematic review.

    Science.gov (United States)

    Price, Alan; Cook, Penny A; Norgate, Sarah; Mukherjee, Raja

    2017-05-25

    Prenatal alcohol exposure (PAE) and traumatic childhood experiences (trauma) such as abuse or neglect can each cause central nervous system neurobiological changes or structural damage which can manifest as cognitive and behavioural dysfunction. In cases where both exposures have occurred, the risk of neurodevelopmental impairment may be greater, but this interaction has not been well studied. Here we present a systematic review that identified five primary research studies which investigated either the impact of trauma in children with PAE, or of PAE in children with trauma. Due to the heterogeneity of studies, narrative analysis was applied. Children in these cohorts with both exposures were more likely to show deficits in language, attention, memory and intelligence, and exhibit more severe behavioural problems than children with one exposure in absence of the other. However, the current literature is scarce and methodologically flawed. Further studies are required that: assess dual exposure in other neurodevelopmental domains; feature developmentally impaired yet non-exposed controls; and account for the wide spectrum of effects and different diagnostic criteria associated with PAE. Copyright © 2017. Published by Elsevier Ltd.

  8. The Role of Repeated Exposure to Multimodal Input in Incidental Acquisition of Foreign Language Vocabulary.

    Science.gov (United States)

    Bisson, Marie-Josée; van Heuven, Walter J B; Conklin, Kathy; Tunney, Richard J

    2014-12-01

    Prior research has reported incidental vocabulary acquisition with complete beginners in a foreign language (FL), within 8 exposures to auditory and written FL word forms presented with a picture depicting their meaning. However, important questions remain about whether acquisition occurs with fewer exposures to FL words in a multimodal situation and whether there is a repeated exposure effect. Here we report a study where the number of exposures to FL words in an incidental learning phase varied between 2, 4, 6, and 8 exposures. Following the incidental learning phase, participants completed an explicit learning task where they learned to recognize written translation equivalents of auditory FL word forms, half of which had occurred in the incidental learning phase. The results showed that participants performed better on the words they had previously been exposed to, and that this incidental learning effect occurred from as little as 2 exposures to the multimodal stimuli. In addition, repeated exposure to the stimuli was found to have a larger impact on learning during the first few exposures and decrease thereafter, suggesting that the effects of repeated exposure on vocabulary acquisition are not necessarily constant.

  9. Repeated exposure to noise increases tolerance in a coral reef fish.

    Science.gov (United States)

    Nedelec, Sophie L; Mills, Suzanne C; Lecchini, David; Nedelec, Brendan; Simpson, Stephen D; Radford, Andrew N

    2016-09-01

    Some anthropogenic noise is now considered pollution, with evidence building that noise from human activities such as transportation, construction and exploration can impact behaviour and physiology in a broad range of taxa. However, relatively little research has considered the effects of repeated or chronic noise; extended exposures may result in habituation or sensitisation, and thus changes in response. We conducted a field-based experiment at Moorea Island to investigate how repeated exposure to playback of motorboat noise affected a coral reef fish (Dascyllus trimaculatus). We found that juvenile D. trimaculatus increased hiding behaviour during motorboat noise after two days of repeated exposure, but no longer did so after one and two weeks of exposure. We also found that naïve individuals responded to playback of motorboat noise with elevated ventilation rates, but that this response was diminished after one and two weeks of repeated exposure. We found no strong evidence that baseline blood cortisol levels, growth or body condition were affected by three weeks of repeated motorboat-noise playback. Our study reveals the importance of considering how tolerance levels may change over time, rather than simply extrapolating from results of short-term studies, if we are to make decisions about regulation and mitigation.

  10. Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine exposure in mice.

    Science.gov (United States)

    Tallarida, Christopher S; Corley, Gladys; Kovalevich, Jane; Yen, William; Langford, Dianne; Rawls, Scott M

    2013-11-27

    Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine exposure and attenuates development of behavioral sensitization produced by repeated cocaine exposure. An important question that has not yet been answered is whether or not CTX reduces behavioral sensitization to cocaine in cases in which the antibiotic is administered only during the period of cocaine absence that follows repeated cocaine exposure and precedes reintroduction to cocaine. We investigated this question using C57BL/6 mice. Mice pretreated with cocaine (15mg/kg×14 days) and then challenged with cocaine (15mg/kg) after 30 days of cocaine absence displayed sensitization of locomotor activity. For combination experiments, CTX injected during the 30 days of cocaine absence attenuated behavioral sensitization produced by cocaine challenge. In the case in which CTX was injected together with cocaine for 14 days, development of behavioral sensitization to cocaine challenge was also reduced. CTX attenuated the increase in locomotor activity produced by acute cocaine exposure; however, its efficacy was dependent on the dose of cocaine as inhibition was detected against 30mg/kg, but not 15mg/kg, of cocaine. These results from mice indicate that CTX attenuates locomotor activity produced by acute and repeated cocaine exposure and counters cocaine's locomotor activating properties in a paradigm in which the antibiotic is injected during the period of forced cocaine absence that follows repeated cocaine exposure.

  11. Production of ethyl alcohol by a repeated batch fermentation method. Kurikaeshi kaibun hakkoho ni yoru arukoru no seizoho

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, T. (Tokyo (Japan)); Takagi, Y. (Chiba (Japan)); Shiba, M. (Kagoshima (Japan))

    1994-01-11

    This invention relates to a production method of ethyl alcohol from sugar and starch raw materials by a repeated batch fermentation method and aims to provide a method to produce ethyl alcohol efficiently by accurate repetition. Conventional batch fermentation methods require the experiences and skill to confirm an end point of the fermentation and have a problem in a control of repeated batch fermentation. This invention uses a gas flow meter of a velocity head measurement type and judges an end point of fermentation at a time when the amount of the exhaust gas flow from the fermentation is 0.35 to 0.1 m[sup 3] per hour and per 1 kl fermentation liquid or below and the next batch fermentation is started. By this invention, ethyl alcohol is produced efficiently from the raw materials with less damage of the yeast and efficient repeated batch fermentation is realized. 6 figs., 1 tab.

  12. Children's exposure to alcohol marketing within supermarkets: An objective analysis using GPS technology and wearable cameras.

    Science.gov (United States)

    Chambers, T; Pearson, A L; Stanley, J; Smith, M; Barr, M; Ni Mhurchu, C; Signal, L

    2017-07-01

    Exposure to alcohol marketing within alcohol retailers has been associated with higher rates of childhood drinking, brand recognition, and marketing recall. This study aimed to objectively measure children's everyday exposure to alcohol marketing within supermarkets. Children aged 11-13 (n = 167) each wore a wearable camera and GPS device for four consecutive days. Micro-spatial analyses were used to examine exposures within supermarkets. In alcohol retailing supermarkets (n = 30), children encountered alcohol marketing on 85% of their visits (n = 78). Alcohol marketing was frequently near everyday goods (bread and milk) or entrance/exit. Alcohol sales in supermarkets should be banned in order to protect children from alcohol marketing. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Bessonneau, Vincent; Thomas, Olivier

    2012-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Olivier Thomas

    2012-03-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Repeated Exposure to Sublethal Doses of the Organophosphorus Compound VX Activates BDNF Expression in Mouse Brain

    Science.gov (United States)

    2012-01-01

    cresyl/-4 H-1: 3: 2-benzodioxa- phosphorin-2-oxide (CBDP) on organophosphate poisoning and its therapy. Arch. Toxicol. 42, 207–216. French, S. J... organophosphates or other environmental insults, have a greater FIG. 4. Mice that received repeated exposure to low levels of VX (0.2 LD50 and 0.4 LD50...to neuro- behavioral deficits and neuropathology. Although exposure to organophosphates such as pesticides has been shown to affect the expression of

  17. Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure.

    Science.gov (United States)

    Kalberg, Wendy O; Provost, Beth; Tollison, Sean J; Tabachnick, Barbara G; Robinson, Luther K; Eugene Hoyme, H; Trujillo, Phyllis M; Buckley, David; Aragon, Alfredo S; May, Philip A

    2006-12-01

    Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  20. The levels of kerosene components in biological samples after repeated dermal exposure to kerosene in rats.

    Science.gov (United States)

    Fujihara, Junko; Hieda, Yoko; Tsujino, Yoshio; Xue, Yuying; Takayama, Koji; Kimura, Kojiro; Dekio, Satoshi

    2004-04-01

    The current study was experimentally investigated using rats whether or not kerosene components are accumulated from daily repeated dermal exposure. Rats received daily 1h-exposure to kerosene for 5 days (5K), daily 1h-exposure for 4 days and left for 1 day (4KL), a single 1h-exposure (1K), a single 1h-exposure and left for 1 day (1KL), or a single 1h-exposure, sacrificed and left dead for 1 day (1KLD). Kerosene components, trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) in blood and tissues were determined by GC-MS. In blood, almost the same concentrations of TMBs were detected in the rats sacrificed immediately after exposure (5K, 1K and 1KLD), and only trace levels were detected in the rats sacrificed 1 day after exposure (4 and 1KL). Almost the same levels of AHCs in blood were detected among groups except for the rats sacrificed 1 day after a single exposure (1KL), in which AHCs were slightly lower. These results suggest that (1) AHCs tend to be accumulated from daily exposure, while TMBs do not, (2) the proportions of detected kerosene components in blood can be an indicator of whether the last exposure occurred just before death or not, (3) the kerosene levels last at least 1 day without blood circulation.

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

    Science.gov (United States)

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nicole M Mantella

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

  3. Sweet and sour preferences in young children and adults: role of repeated exposure

    NARCIS (Netherlands)

    Liem, D.G.; Graaf, de C.

    2004-01-01

    The authors investigated the influence of repeated exposure to orangeades with added sucrose and different concentrations of citric acid, on the taste preferences of 6- to-11-year-old children and young adults. During an intervention study of 8 days, 59 children (9.2±0.9 years) and 46 young adults (

  4. Repeated toluene exposure increases c-Fos in catecholaminergic cells of the nucleus accumbens shell.

    Science.gov (United States)

    Tomaszycki, Michelle L; Aulerich, Kelsey E; Bowen, Scott E

    2013-01-01

    Toluene is a frequently abused solvent. Previous studies have suggested that toluene acts like other drugs of abuse, specifically on the dopaminergic system in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the mesolimbic pathway. Although changes in dopamine (DA) levels and c-Fos have been observed in both acute and repeated exposure paradigms, the extent to which c-Fos is localized to catecholaminergic cells is unknown. The present study tested the effects of repeated toluene exposure (1000-4000ppm) on locomotor activity and cells containing c-Fos, tyrosine hydroxylase (TH), or both in the core and shell of the NAc, as well as the anterior and posterior VTA. We focused our study on adolescents, since adolescence is a time of great neural change and a time when individuals tend to be more susceptible to drug abuse. In early tests, toluene dose-dependently increased locomotor activity. Repeated exposure to the highest concentration of toluene resulted in sensitization to toluene's effects on locomotor activity. Although the number of cells immunopositive for c-Fos or TH did not significantly differ across groups, cells immunopositive for TH+c-Fos were higher in the NAc shell of animals exposed to 4000ppm than in animals exposed to air (control) or 1000ppm. Taken together, these findings demonstrate that repeated high dose toluene exposure increases locomotor activity as well as activation of catecholaminergic cells in the shell of the NAc. © 2013 Elsevier Inc. All rights reserved.

  5. Effect of Repeated Exposures on Word Learning in Quiet and Noise

    Science.gov (United States)

    Blaiser, Kristina M.; Nelson, Peggy B.; Kohnert, Kathryn

    2015-01-01

    This study examines the impact of repeated exposures on word learning of preschool children with and without hearing loss (HL) in quiet and noise conditions. Participants were 19 children with HL and 17 peers with normal hearing (NH). Children were introduced to 16 words: 8 in quiet and 8 in noise conditions. Production and identification scores…

  6. Sweet and sour preferences in young children and adults: role of repeated exposure

    NARCIS (Netherlands)

    Liem, D.G.; Graaf, de C.

    2004-01-01

    The authors investigated the influence of repeated exposure to orangeades with added sucrose and different concentrations of citric acid, on the taste preferences of 6- to-11-year-old children and young adults. During an intervention study of 8 days, 59 children (9.2±0.9 years) and 46 young adults

  7. Timing of moderate level prenatal alcohol exposure influences gene expression of sensory processing behavior in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Mary L Schneider

    2009-11-01

    Full Text Available Sensory processing disorder (SPD, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR, and striatal dopamine (DA function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections.

  8. Effects of Repeated Ethanol Exposures on NMDA Receptor Expression and Locomotor Sensitization in Mice Expressing Ethanol Resistant NMDA Receptors

    Science.gov (United States)

    den Hartog, Carolina R.; Gilstrap, Meghin; Eaton, Bethany; Lench, Daniel H.; Mulholland, Patrick J.; Homanics, Gregg. E.; Woodward, John J.

    2017-01-01

    Evidence from a large number of preclinical studies suggests that chronic exposure to drugs of abuse, such as psychostimulants or ethanol induces changes in glutamatergic transmission in key brain areas associated with reward and control of behavior. These changes include alterations in the expression of ionotropic glutamate receptors including N-methyl-D-aspartate receptors (NMDAR) that are important for regulating neuronal activity and synaptic plasticity. NMDA receptors are inhibited by ethanol and reductions in NMDA-mediated signaling are thought to trigger homestatic responses that limit ethanol's effects on glutamatergic transmission. Following repeated exposures to ethanol, these homeostatic responses may become unstable leading to an altered glutamatergic state that contributes to the escalations in drinking and cognitive deficits observed in alcohol-dependent subjects. An important unanswered question is whether ethanol-induced changes in NMDAR expression are modulated by the intrinsic sensitivity of the receptor to ethanol. In this study, we examined the effects of ethanol on NMDAR subunit expression in cortical (orbitofrontal, medial prefrontal), striatal (dorsal and ventral striatum) and limbic (dorsal hippocampus, basolateral amygdala) areas in mice genetically modified to express ethanol-resistant receptors (F639A mice). These mice have been previously shown to drink more ethanol than their wild-type counterparts and have altered behavioral responses to certain actions of ethanol. Following long-term voluntary drinking, F639A mice showed elevations in GluN2A but not GluN1 or GluN2B expression as compared to wild-type mice. Mice treated with repeated injections with ethanol (2–3.5 g/kg; i.p.) showed changes in NMDAR expression that varied in a complex manner with genotype, brain region, subunit type and exposure protocol all contributing to the observed response. F639A mice, but not wild-type mice, showed enhanced motor activity following repeated

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

    Science.gov (United States)

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

    2000-01-01

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

  10. Prolonged Increase in the Sensitivity of the Posterior Ventral Tegmental Area to the Reinforcing Effects of Ethanol following Repeated Exposure to Cycles of Ethanol Access and Deprivation

    OpenAIRE

    Rodd, Zachary A.; Bell, Richard L.; McQueen, Victoria K.; Davids, Michelle R.; Hsu, Cathleen C.; Murphy, James M.; Li, Ting-Kai; Lumeng, Lawrence; McBride, William J.

    2005-01-01

    The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of ...

  11. Effects of prenatal alcohol exposure and attention-deficit/hyperactivity disorder on adaptive functioning.

    Science.gov (United States)

    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 L; Riley, Edward P; Mattson, Sarah N

    2014-05-01

    Heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) are associated with adaptive behavior deficits. This study examined the interaction between these 2 factors on parent ratings of adaptive behavior. As part of a multisite study, primary caregivers of 317 children (8 to 16 years, M = 12.38) completed the Vineland Adaptive Behavior Scales-Second Edition (VABS-II). Four groups of subjects were included: children with prenatal alcohol exposure with ADHD (AE+, n = 82), children with prenatal alcohol exposure 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 analyses of covariance. There were significant main effects of AE (p 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 = 0.007, partial η(2) = 0.024, but not Daily Living Skills or Socialization domains (ps > 0.27). 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. As found previously, both prenatal alcohol exposure and ADHD increase adaptive behavior deficits in all domains. However, these 2 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 broaden our understanding of how ADHD exacerbates behavioral outcomes in this population. Copyright © 2014

  12. Effect of repeated exposures and sociality on novel food acceptance and consumption by orangutans.

    Science.gov (United States)

    Hardus, Madeleine E; Lameira, Adriano R; Wich, Serge A; de Vries, Han; Wahyudi, Rachmad; Shumaker, Robert W; Menken, Steph B J

    2015-01-01

    Hundreds of rehabilitant great apes have been released into the wild, and thousands await release. However, survival rates after release can be as low as 20%. Several factors influence individuals' survival rates, one of which is the capacity to obtain an adequate diet once released. Released individuals are faced with a mixture of familiar and novel foods in an unfamiliar forest; therefore, it is important to understand how they increase acceptance and consumption of novel foods. This is especially vital for omnivorous species, such as wild great apes, which consume several hundred species of different foods. We assessed the effects of repeated exposures and sociality (i.e. co-feeding in the presence of one or more other individuals) on the acceptance and consumption of novel foods by captive orangutans (Pongo sp). Repeated exposures of food (novel, at first) did not cause an increase of acceptance of food; in other words, the orangutans did not start to eat a food item after being exposed to that food more often, but repeated exposures of food increased consumption (i.e. quantity). After repeated exposures, the orangutans also became gradually more familiar with the food, decreasing their explorative behaviour. The presence of co-feeding conspecifics resulted in an increased acceptance of the novel food by orangutans, and they ate a larger amount of said foods than when alone. Repeated exposure and sociality may benefit rehabilitant great apes in augmenting and diversifying diet and, once practiced before release, may accelerate an individuals' adaptation to their new habitat, improving survival chances. Great ape rescue, rehabilitation and reintroduction require large financial and logistic investments; however, their effectiveness may be improved at low cost and low effort through the suggested measures.

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

    Science.gov (United States)

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

    2015-06-01

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

  14. Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice.

    Science.gov (United States)

    Wang, Lai; Wu, Lin; Wang, Xiaoqing; Deng, Jiexin; Ma, Zhanyou; Fan, Wenjuan; He, Weiya; Deng, Jinbo

    2015-11-01

    In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose-dependent manner (palcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (palcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (palcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis.

  15. Can the Palatability of Healthy, Satiety-Promoting Foods Increase with Repeated Exposure during Weight Loss?

    Science.gov (United States)

    Anguah, Katherene O.-B.; Lovejoy, Jennifer C.; Craig, Bruce A.; Gehrke, Malinda M.; Palmer, Philip A.; Eichelsdoerfer, Petra E.; McCrory, Megan A.

    2017-01-01

    Repeated exposure to sugary, fatty, and salty foods often enhances their appeal. However, it is unknown if exposure influences learned palatability of foods typically promoted as part of a healthy diet. We tested whether the palatability of pulse containing foods provided during a weight loss intervention which were particularly high in fiber and low in energy density would increase with repeated exposure. At weeks 0, 3, and 6, participants (n = 42; body mass index (BMI) 31.2 ± 4.3 kg/m2) were given a test battery of 28 foods, approximately half which had been provided as part of the intervention, while the remaining half were not foods provided as part of the intervention. In addition, about half of each of the foods (provided as part or not provided as part of the intervention) contained pulses. Participants rated the taste, appearance, odor, and texture pleasantness of each food, and an overall flavor pleasantness score was calculated as the mean of these four scores. Linear mixed model analyses showed an exposure type by week interaction effect for taste, texture and overall flavor pleasantness indicating statistically significant increases in ratings of provided foods in taste and texture from weeks 0 to 3 and 0 to 6, and overall flavor from weeks 0 to 6. Repeated exposure to these foods, whether they contained pulses or not, resulted in a ~4% increase in pleasantness ratings. The long-term clinical relevance of this small increase requires further study. PMID:28231094

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

    OpenAIRE

    Tyler, Christina R; Allan, Andrea M.

    2014-01-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute h...

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

    Science.gov (United States)

    Fernandes, Yohaan; Rampersad, Mindy; Gerlai, And Robert

    2015-10-01

    Zebrafish naturally form social groups called shoals. Previously, we have shown that submerging zebrafish eggs into low concentrations of alcohol (0.00, 0.25, 0.50, 0.75 and 1.00 vol/vol% external bath concentration) during development (24h post-fertilization) for two hours resulted in impaired shoaling response in seven month old young adult zebrafish. Here we investigate whether this embryonic alcohol exposure induced behavioural deficit persists to older age. Zebrafish embryos were exposed either to fresh system water (control) or to 1% alcohol for two hours, 24h after fertilization, and were raised in a high-density tank system. Social behaviour was tested by presenting the experimental fish with a computer animated group of zebrafish images, while automated tracking software measured their behaviour. Control fish were found to respond strongly to animated conspecific images by reducing their distanceand remaining close to the images during image presentation, embryonic alcohol treated fish did not. Our results suggest that the impaired shoaling response of the alcohol exposed fish was not due to altered motor function or visual perception, but likely to a central nervous system alteration affecting social behaviour itself. We found the effects of embryonic alcohol exposure on social behaviour not to diminish with age, a result that demonstrates the deleterious and potentially life-long consequences of exposure to even small amount of alcohol during embryonic development in vertebrates. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Repeated Ketamine Exposure Induces an Enduring Resilient Phenotype in Adolescent and Adult Rats

    Science.gov (United States)

    Parise, Eric M.; Alcantara, Lyonna F.; Warren, Brandon L.; Wright, Katherine N.; Hadad, Roey; Sial, Omar K.; Kroeck, Kyle G.; Iñiguez, Sergio D.; Bolaños-Guzmán, Carlos A.

    2013-01-01

    Background Major Depressive Disorder (MDD) afflicts up to 10% of adolescents. However, nearly 50% of those afflicted are considered non-responsive to available treatments. Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist has shown potential as a rapid-acting and long-lasting treatment for MDD in adults. Thus, the effectiveness and functional consequences of ketamine exposure during adolescence were explored. Methods Adolescent male rats (postnatal day [PD] 35) received two ketamine (0, 5, 10 or 20 mg/kg) injections, 4 hours apart, after exposure to day 1 of the forced swim test (FST). The next day, rats were re-exposed to the FST to assess ketamine-induced antidepressant-like responses. Separate groups were exposed to chronic unpredictable stress (CUS) to confirm findings from the FST. After these initial experiments, adolescent naïve rats were exposed to either 1 or 15 consecutive days (PD35–49) of ketamine (20 mg/kg) twice/daily. Ketamine's influence on behavioral reactivity to rewarding (i.e., sucrose preference) and aversive (i.e., elevated plus-maze, FST) circumstances was then assessed 2 months after treatment. To control for age-dependent effects, adult rats (PD75–89) were exposed to identical experimental conditions. Results Ketamine (20 mg/kg) reversed the CUS-induced depression-like behaviors in the FST. Repeated ketamine exposure resulted in anxiolytic- and antidepressant-like responses 2 months after drug exposure. None of the ketamine doses used were capable of inducing drug-seeking behaviors as measured by place preference conditioning. Conclusions Repeated ketamine exposure induces enduring resilient-like responses regardless of age of exposure. These findings point to ketamine, and its repeated exposure, as a potentially useful antidepressant during adolescence. PMID:23790225

  19. The effects of repeated exposure to graphic fear appeals on cigarette packages: A field experiment.

    Science.gov (United States)

    Dijkstra, Arie; Bos, Colin

    2015-03-01

    Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on cigarette packages. In this field-experiment, 118 smokers were assigned to 1 of 2 conditions with either graphic fear appeals or textual warnings on their cigarette packages. During 3 weeks, fear and disgust were assessed 6 times. The intention to quit smoking after 3 weeks and quitting activity during the 3 weeks were the dependent measures. The effects of 3 pretest individual difference moderators were tested: disengagement beliefs, number of cigarettes smoked a day, and readiness to quit. Three weeks of exposure to the graphic fear appeals led to a stronger intention to quit, but only when smokers scored low on disengagement beliefs, or were heavier smokers. In addition, smokers low in disengagement more often reported to have cut down on smoking in the graphic condition. There were no indications of habituation of fear and disgust over the 3 weeks. The effects of graphic fear appeals depended on smokers' characteristics: The moderators may explain the mixed findings in the literature. The lack of habituation may be caused by the renewal of the graphics every few days. The used field-experimental design with natural repeated exposure to graphics is promising.

  20. Acquired (dis)liking of natural cheese in different repeated exposure environment.

    Science.gov (United States)

    Go, Jung-Eun; Kim, Mi-Ran; Chung, Seo-Jin

    2017-09-01

    This study investigated the development of (dis)liking of various types of natural cheese with repeated exposures among Korean young females in two environment settings. Six types of natural cheese with varying flavor and texture characteristics were selected: Brie, Emmental, Gorgonzola, Gouda, Parmigiano-Reggiano and sharp Cheddar. The subjects were randomly divided into two groups (individual evaluation vs. social interaction) and exposed to all six types of cheeses eight times for 4 weeks. The acceptance scores for these cheeses were monitored at the beginning (first taste test) and end (second taste test) of the exposure test as well as 1 month after the completion of exposure test (third taste test). The results showed that the acceptance of cheese was affected by the cheese type and the number of test trials but not by tasting environment. The acceptance levels were higher for Brie, Gouda and sharp Cheddar than for Emmental, Gorgonzola and Parmigiano-Reggiano. When the subjects were exposed to Brie, Emmental, Gouda, and sharp Cheddar repeatedly, their acceptance level increased significantly. This study demonstrated that the liking of natural cheese can occur through repeated exposure to the cheese, but with the outcome varying with the type of cheese. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Analyzing repeated measures semi-continuous data, with application to an alcohol dependence study.

    Science.gov (United States)

    Liu, Lei; Strawderman, Robert L; Johnson, Bankole A; O'Quigley, John M

    2016-02-01

    Two-part random effects models (Olsen and Schafer,(1) Tooze et al.(2)) have been applied to repeated measures of semi-continuous data, characterized by a mixture of a substantial proportion of zero values and a skewed distribution of positive values. In the original formulation of this model, the natural logarithm of the positive values is assumed to follow a normal distribution with a constant variance parameter. In this article, we review and consider three extensions of this model, allowing the positive values to follow (a) a generalized gamma distribution, (b) a log-skew-normal distribution, and (c) a normal distribution after the Box-Cox transformation. We allow for the possibility of heteroscedasticity. Maximum likelihood estimation is shown to be conveniently implemented in SAS Proc NLMIXED. The performance of the methods is compared through applications to daily drinking records in a secondary data analysis from a randomized controlled trial of topiramate for alcohol dependence treatment. We find that all three models provide a significantly better fit than the log-normal model, and there exists strong evidence for heteroscedasticity. We also compare the three models by the likelihood ratio tests for non-nested hypotheses (Vuong(3)). The results suggest that the generalized gamma distribution provides the best fit, though no statistically significant differences are found in pairwise model comparisons.

  2. Initial subjective reward: Single-exposure conditioned place preference to alcohol in mice

    Directory of Open Access Journals (Sweden)

    Judith E. Grisel

    2014-11-01

    Full Text Available 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 1.5g/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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Sara Peñasco

    2015-01-01

    Full Text Available 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.

  5. Early maternal deprivation enhances voluntary alcohol intake induced by exposure to stressful events later in life.

    Science.gov (United States)

    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.

  6. The association of media exposure and media literacy with adolescent alcohol and tobacco use.

    Science.gov (United States)

    Chang, Fong-ching; Miao, Nae-fang; Lee, Ching-mei; Chen, Ping-hung; Chiu, Chiung-hui; Lee, Shu-ching

    2016-04-01

    This study examined the relationship of media exposure and media literacy to alcohol and tobacco use among adolescents in Taiwan. A total of 2992 10th-grade students recruited from 26 high schools in Taipei, Taiwan, completed a questionnaire in 2010. The multivariable analysis results indicated that the students with higher alcohol and tobacco media exposure were more likely to use alcohol and tobacco and have intentions to drink and smoke, while students with higher media literacy were less likely to use alcohol and have intentions to drink and smoke.

  7. In vitro and in vivo models of acute alcohol exposure

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc; Gyongyi Szabo

    2009-01-01

    Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse,and identifies their suitability for biomedical research.

  8. A model of human nasal epithelial cells adapted for direct and repeated exposure to airborne pollutants.

    Science.gov (United States)

    Bardet, Gaëlle; Achard, Sophie; Loret, Thomas; Desauziers, Valérie; Momas, Isabelle; Seta, Nathalie

    2014-08-17

    Airway epithelium lining the nasal cavity plays a pivotal role in respiratory tract defense and protection mechanisms. Air pollution induces alterations linked to airway diseases such as asthma. Only very few in vitro studies to date have succeeded in reproducing physiological conditions relevant to cellular type and chronic atmospheric pollution exposure. We therefore, set up an in vitro model of human Airway Epithelial Cells of Nasal origin (hAECN) close to real human cell functionality, specifically adapted to study the biological effects of exposure to indoor gaseous pollution at the environmental level. hAECN were exposed under air-liquid interface, one, two, or three-times at 24 h intervals for 1 h, to air or formaldehyde (200 μg/m(3)), an indoor air gaseous pollutant. All experiments were ended at day 4, when both cellular viability and cytokine production were assessed. Optimal adherence and confluence of cells were obtained 96 h after cell seeding onto collagen IV-precoated insert. Direct and repeated exposure to formaldehyde did not produce any cellular damage or IL-6 production change, although weak lower IL-8 production was observed only after the third exposure. Our model is significantly better than previous ones due to cell type and the repeated exposure protocol.

  9. Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

    Science.gov (United States)

    Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

    2012-04-01

    The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

  10. HEARING LOSS IN THE RHESUS MONKEY AFTER REPEATED EXPOSURES TO IDENTICAL NOISES,

    Science.gov (United States)

    hearing loss in monkeys. Five animals were exposed to repeated single-pulse noises alternately at 72- and 96-hour intervals, to observe intersubject and intra-subject variations in hearing behavior under similar physical-noise conditions. Audiograms were taken periodically, from two minutes after exposure to 72 hours later, for 2 and 4 kc test tones. There were distinctive differences in individual-animal patterns of hearing loss and recovery. Two animals clearly showed smaller hearing losses during the later exposure sessions, and that loss

  11. Enhanced resistance to UV-B radiation in Anabaena sp. PCC 7120 (Cyanophyceae) by repeated exposure.

    Science.gov (United States)

    Qin, Hongjie; Li, Dunhai

    2014-07-01

    In natural habitats, organisms especially phytoplankton are not always continuously subjected to ultraviolet-B radiation (UVBR). By simulation of the natural situation, the N2-fixing cyanobacterium Anabaena sp. PCC 7120 was subjected to UV-B exposure and recovery cycles. A series of morphological and physiological changes were observed in Anabaena sp. PCC 7120 under repeated UVBR when compared with controls. Such as the breakage of filaments, intervals between heterocysts, heterocyst frequency, total carbohydrate, and carotenoids were increased, while the nitrogenase activity and photosynthetic activity were inhibited by repeated UVBR; however, these activities could recover when UV-B stress was removed. Unexpectedly, the over-compensatory growth was observed at the end of the second round of exposure and recovery cycle. Our results showed that discontinuous UVBR could increase the growth rate and the tolerance as well as repair capacity of Anabaena sp. PCC 7120. These results indicate that moderate UVBR may increase the growth of cyanobacteria in natural habitats.

  12. Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients.

    Science.gov (United States)

    Crunelle, Cleo L; Yegles, Michel; De Doncker, Mireille; Dom, Geert; Cappelle, Delphine; Maudens, Kristof E; van Nuijs, Alexander L N; Covaci, Adrian; Neels, Hugo

    2015-02-01

    Ethyl glucuronide (EtG), a minor metabolite of alcohol, is used as a sensitive marker in hair to detect the retrospective consumption of alcohol. The proximal 0-3 cm hair segment is often used for analysis, providing information on alcohol consumption over the past 3 months. Using more distal segments would allow the detection of alcohol consumption over longer time periods, thereby addressing the chronicity of the consumption. In view of this, permanent coloring and bleaching were shown in vitro to alter EtG concentrations in hair, but no in vivo studies are available to prove or disprove this. To investigate the influence of repeated bleaching and permanent coloring on EtG concentrations in vivo and to assess the stability of EtG concentrations in distal compared to proximal hair segments. Hair samples from alcohol-dependent patients with uncolored/unbleached (N=4), permanent coloration (N=5) and bleached hair (N=5) were analyzed in two to six 3 cm long segments for EtG concentrations, and alcohol consumption and hair cosmetic treatments were assessed. We observed that hair bleaching and permanent coloring reduces EtG concentrations by 82±11% and 65±24%, respectively, with correlations between the number of cosmetic treatments and the decrease in EtG concentrations. EtG remained stable in untreated hair samples up to 18 cm. EtG is a sensitive marker to assess chronic alcohol consumption up to 18 months in alcohol-dependent patients with no cosmetic hair treatments. However, in alcohol-dependent patients who color or bleach their hair, care should be taken when interpreting EtG measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Industry self-regulation of alcohol marketing: a systematic review of content and exposure research.

    Science.gov (United States)

    Noel, Jonathan K; Babor, Thomas F; Robaina, Katherine

    2017-01-01

    With governments relying increasingly upon the alcohol industry's self-regulated marketing codes to restrict alcohol marketing activity, there is a need to summarize the findings of research relevant to alcohol marketing controls. This paper provides a systematic review of studies investigating the content of, and exposure to, alcohol marketing in relation to self-regulated guidelines. Peer-reviewed papers were identified through four literature search engines: SCOPUS, Web of Science, PubMed and PsychINFO. Non-peer-reviewed reports produced by public health agencies, alcohol research centers, non-governmental organizations and government research centers were also identified. Ninety-six publications met the inclusion criteria. Of the 19 studies evaluating a specific marketing code and 25 content analysis studies reviewed, all detected content that could be considered potentially harmful to children and adolescents, including themes that appeal strongly to young men. Of the 57 studies of alcohol advertising exposure, high levels of youth exposure and high awareness of alcohol advertising were found for television, radio, print, digital and outdoor advertisements. Youth exposure to alcohol advertising has increased over time, even as greater compliance with exposure thresholds has been documented. Violations of the content guidelines within self-regulated alcohol marketing codes are highly prevalent in certain media. Exposure to alcohol marketing, particularly among youth, is also prevalent. Taken together, the findings suggest that the current self-regulatory systems that govern alcohol marketing practices are not meeting their intended goal of protecting vulnerable populations. © 2016 Society for the Study of Addiction.

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

    Science.gov (United States)

    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

  15. Eye lens radiation exposure and repeated head CT scans: A problem to keep in mind

    Energy Technology Data Exchange (ETDEWEB)

    Michel, Morgane; Jacob, Sophie [Institute for Radiological Protection and Nuclear Safety, IRSN/DRPH/SRBE/Laboratoire d' Epidemiologie, BP 17, 92 262 Fontenay-aux-Roses (France); Roger, Gilles [Otolaryngology Department, Trousseau Hospital, Paris (France); Pelosse, Beatrice [Ophthalmology Department, Trousseau Hospital, Paris (France); Laurier, Dominique [Institute for Radiological Protection and Nuclear Safety, IRSN/DRPH/SRBE/Laboratoire d' Epidemiologie, BP 17, 92 262 Fontenay-aux-Roses (France); Le Pointe, Hubert Ducou [Radiology Department, Trousseau Hospital, Paris (France); Bernier, Marie-Odile, E-mail: marie-odile.bernier@irsn.fr [Institute for Radiological Protection and Nuclear Safety, IRSN/DRPH/SRBE/Laboratoire d' Epidemiologie, BP 17, 92 262 Fontenay-aux-Roses (France)

    2012-08-15

    Objectives: The deterministic character of radiation-induced cataract is being called into question, raising the possibility of a risk in patients, especially children, exposed to ionizing radiation in case of repeated head CT-scans. This study aims to estimate the eye lens doses of a pediatric population exposed to repeated head CTs and to assess the feasibility of an epidemiological study. Methods: Children treated for a cholesteatoma, who had had at least one CT-scan of the middle ear before their tenth birthday, were included. Radiation exposure has been assessed from medical records and telephone interviews. Results: Out of the 39 subjects contacted, 32 accepted to participate. A total of 76 CT-scans were retrieved from medical records. At the time of the interview (mean age: 16 years), the mean number of CT per child was 3. Cumulative mean effective and eye lens doses were 1.7 mSv and 168 mGy, respectively. Conclusion: A relatively high lens radiation dose was observed in children exposed to repeated CT-scans. Due to that exposure and despite the difficulties met when trying to reach patients' families, a large scale epidemiological study should be performed in order to assess the risk of radiation-induced cataracts associated with repeated head CT.

  16. Influence of repeated daily menthol exposure on human temperature regulation and perception.

    Science.gov (United States)

    Gillis, D Jason; Weston, Neil; House, James R; Tipton, Michael J

    2015-02-01

    A single exposure to menthol can, depending on concentration, enhance both cool sensations and encourage body heat storage. This study tested whether there is an habituation in either response after repeated-daily exposures. Twenty-two participants were assigned to one of three spray groups: Control (CON; n=6), 0.05% L-menthol (M(0.05%); n=8), and 0.2% L-menthol (M(0.2%); n=8). On Monday (20°C, 50% rh) participants were sprayed with 100 mL of solution and undertook 40 min of cycling at 45% of their peak power (Ex1), from Tuesday to Thursday (30°C, 50% rh) they were sprayed twice daily whilst resting (R1 to R6), Friday was a repeat of Monday (Ex2). Thermal sensation (TS), thermal comfort, perceived exertion, irritation, rectal and skin temperature (Tsk), skin blood flow (SkBF) and sweat rate were monitored. A two-way ANOVA (alpha=0.05) compared responses from the beginning (Ex1, R1) and end (Ex2, R5) of the testing week. M(0.2%) induced significantly (PMenthol caused a heat storage response, mediated by vasoconstriction, at the beginning and end of the week, suggesting the habituation of TS occurred in a pathway specific to sensation. In summary, the cooling influence of 0.2% menthol habituates after repeated-daily exposures, but with no habituation in heat storage.

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

    Science.gov (United States)

    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.

  18. Enhancing consumer liking of low salt tomato soup over repeated exposure by herb and spice seasonings.

    Science.gov (United States)

    Ghawi, Sameer Khalil; Rowland, Ian; Methven, Lisa

    2014-10-01

    There is strong evidence for the link between high dietary sodium and increased risk of cardiovascular disease which drives the need to reduce salt content in foods. In this study, herb and spice blends were used to enhance consumer acceptability of a low salt tomato soup (0.26% w/w). Subjects (n = 148) scored their liking of tomato soup samples over 5 consecutive days. The first and last days were pre-and post-exposure visits where all participants rated three tomato soup samples; standard, low salt and low salt with added herbs and spices. The middle 3 days were the repeated exposure phase where participants were divided into three balanced groups; consuming the standard soup, the low salt soup, or the low salt soup with added herbs and spices. Reducing salt in the tomato soup led to a significant decline in consumer acceptability, and incorporating herbs and spices did not lead to an immediate enhancement in liking. However, inclusion of herbs and spices enhanced the perception of the salty taste of the low salt soup to the same level as the standard. Repeated exposure to the herbs and spice-modified soup led to a significant increase in the overall liking and liking of flavour, texture and aftertaste of the soup, whereas no changes in liking were observed for the standard and low salt tomato soups over repeated exposure. Moreover, a positive trend in increasing the post-exposure liking of the herbs and spices soup was observed. The findings suggest that the use of herbs and spices is a useful approach to reduce salt content in foods; however, herbs and spices should be chosen carefully to complement the food as large contrasts in flavour can polarise consumer liking. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    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.

  20. Fine structures and states of water in poly(vinyl alcohol) hydrogels prepared by repeated freezing and thawing

    OpenAIRE

    1997-01-01

    Investigations have been made into the relationship between structure and states of water in unfrozen poly (vinyl alcohol) (PVA) hydrogels prepared by repeated freezing and thawing of aqueous solution with various PVA concentrations. The states of water were investigated by using a pulsed nuclear magnetic resonance spectroscopy. Every unfrozen PVA hydrogel gave only one spin-lattice relaxation time (T-1) value. T-1 of all unfrozen hydrogels were smaller than that of free water and decreased w...

  1. Seroepidemiological studies indicate frequent and repeated exposure to Campylobacter spp. during childhood.

    Science.gov (United States)

    Ang, C W; Teunis, P F M; Herbrink, P; Keijser, J; Van Duynhoven, Y H T P; Visser, C E; Van Pelt, W

    2011-09-01

    The annual number of episodes of clinical gastroenteritis caused by Campylobacter spp. in The Netherlands is estimated to be 75 000, i.e. once per 200 person life-years. This number is based on extrapolation of culture results from population-based studies. The number of culture-confirmed cases of Campylobacter infection peaks in the first 3 years of life and again between the ages of 20 and 25 years. The seroepidemiology of Campylobacter describes the relationship between age and exposure to Campylobacter and reflects both symptomatic and asymptomatic infections. Using a validated ELISA system, antibodies to Campylobacter were measured in an age-stratified sample (n=456) of the PIENTER serum collection of the Dutch general population. The seroprevalence of Campylobacter IgG antibodies increased with age, reaching almost 100% at age 20 years. Antibody levels steadily increased with age until young adulthood, suggesting repeated exposure to Campylobacter. In conclusion, seroepidemiological data demonstrated repeated exposures to Campylobacter throughout life, most of which do not lead to clinical symptoms. From young adulthood, >95% of the population in The Netherlands had serological evidence for exposure to Campylobacter.

  2. 5-Day repeated inhalation and 28-day post-exposure study of graphene.

    Science.gov (United States)

    Shin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il Je

    2015-01-01

    Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concentration (0.68 ± 0.14 mg/m(3) graphene) and (3) high concentration (3.86 ± 0.94 mg/m(3) graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body weights or organ weights of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was observed in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was observed in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concentrations and time points used in this study.

  3. Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei.

    Science.gov (United States)

    Sabourin, P J; Sun, J D; MacGregor, J T; Wehr, C M; Birnbaum, L S; Lucier, G; Henderson, R F

    1990-05-01

    Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased. Exposure to the same level of benzene for an additional 2 weeks did not further increase the frequency of micronuclei in PCEs. These results indicate

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

    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.

  6. Neurotoxicity of prenatal alcohol exposure on medullary pre-Bötzinger complex neurons in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Ming-li Ji; Yun-hong Wu; Zhi-bin Qian

    2015-01-01

    Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is un-known whether the 5-hydroxytryptamine 2A receptor (5-HT2AR) is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10% (v/v) throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2AR protein and mRNA levels in the pre-Bötzing-er complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduc-tion was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10%alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These ifndings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2AR protein and mRNA levels.

  7. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    Science.gov (United States)

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period.

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

    Science.gov (United States)

    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 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.

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

    Directory of Open Access Journals (Sweden)

    Jill A. Poole

    2012-07-01

    Full Text Available 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

  10. Dealing with consumer differences in liking during repeated exposure to food; typical dynamics in rating behavior.

    Science.gov (United States)

    Dalenberg, Jelle R; Nanetti, Luca; Renken, Remco J; de Wijk, René A; Ter Horst, Gert J

    2014-01-01

    Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in consumers; averaging will mix and hide possible subgroups of consumer behaviors, leading to a misinterpretation of the results. To deal with the variability in consumer liking, we propose to use clustering on data from consumer-product combinations to investigate the nature of the behavioral differences within the complete dataset. The resulting behavioral clusters can then be used to describe product acceptance. To test this approach we used two independent data sets in which young adults were repeatedly exposed to drinks and snacks, respectively. We found that five typical consumer behaviors existed in both datasets. These behaviors differed both in the average level of liking as well as its temporal dynamics. By investigating the distribution of a single product across typical consumer behaviors, we provide more precise insight in how consumers divide in subgroups based on their product liking (i.e. product modality). This work shows that taking into account and using interindividual differences can unveil information about product acceptance that would otherwise be ignored.

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

    Directory of Open Access Journals (Sweden)

    Sarah Treit

    Full Text Available 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

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

    Science.gov (United States)

    Peltzer, Karl; Pengpid, Supa; Tepirou, Chher

    2016-01-01

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

  13. Solitary Versus Social Drinking: An Experimental Study on Effects of Social Exposures on In Situ Alcohol Consumption

    NARCIS (Netherlands)

    Kündig, H.; Kuntsche, E.N.

    2012-01-01

    BACKGROUND: Whereas the effects of modeling and of drinking contexts on alcohol use are documented, studies are lacking regarding the effect of given social exposures on actual alcohol consumption during drinking episodes (i.e., in situ alcohol consumption, the quantity of alcohol actually ingested

  14. A decrease in the size of the basal ganglia following prenatal alcohol exposure: a preliminary report.

    Science.gov (United States)

    Mattson, S N; Riley, E P; Jernigan, T L; Garcia, A; Kaneko, W M; Ehlers, C L; Jones, K L

    1994-01-01

    Prenatal alcohol exposure is known to cause damage to the central nervous system. This study sought to further elucidate the structural brain damage that occurs following prenatal alcohol exposure in both children and rats. Two children with histories of maternal alcohol abuse but who did not qualify for a diagnosis of Fetal Alcohol Syndrome (FAS), based on established criteria, underwent magnetic resonance imaging. Reduced volumes were found for the cerebrum and cerebellum. In addition, the proportional volume of the basal ganglia was reduced, although the proportional volumes of cortical and subcortical fluid, cortical gray matter, limbic and nonlimbic cortex, and diencephalic structures were unaffected. These findings are compared with our recent MRI findings in two cases of FAS. In addition, the caudate-putamen and ventricular areas were assessed in rats exposed to alcohol prenatally. Whereas the overall brain section area was not reduced in size, the area of the caudate-putamen was reduced and that of the ventricles was enlarged.

  15. Impaired Odor Identification in Children with Histories of Heavy Prenatal Alcohol Exposure

    Science.gov (United States)

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

    2013-01-01

    Prenatal alcohol exposure can lead to behavioral and cognitive impairments across multiple domains. Many of the brain regions impacted by prenatal alcohol exposure are also linked with olfactory processing, and odor identification deficits have been documented in certain neurological disorders associated with these brain regions. As odor identification following prenatal alcohol exposure is not well studied, we compared odor identification in children with prenatal exposure to alcohol (AE) to typically developing controls (CON) (N = 16/group). It was hypothesized that children in the AE group would perform more poorly than children in the CON group on the San Diego Odor Identification Test, an identification test of 8 common household odorants. Children exposed to alcohol during prenatal development were significantly impaired in olfactory identification (M = 5.95, SE = 0.37) compared to typically developing controls (M = 7.24, SE = 0.37). These findings confirmed the hypothesis that prenatal exposure to alcohol is associated with odor identification deficits, and suggest that further research is warranted to identify the mechanisms underlying these deficits, the integrity of brain areas that are involved, and to determine whether olfactory performance might contribute to better identification of children at risk for behavioral and cognitive deficits. PMID:23683527

  16. Early adolescent, multi-ethnic, urban youth's exposure to patterns of alcohol-related neighborhood characteristics.

    Science.gov (United States)

    Tobler, Amy L; Komro, Kelli A; Maldonado-Molina, Mildred M

    2009-10-01

    This study identified heterogeneous classes of alcohol-related neighborhood characteristics to which multi-ethnic, early adolescents in urban communities are exposed. The sample comprised 4,215 youth from 42 community areas in Chicago, Illinois who completed surveys at the beginning of 6th grade (2002). Neighborhood measures included: (1) mean number of alcohol outlets per 1,000 population per community area; (2) alcohol purchase attempt rate by pseudo-underage youth; (3) average number of alcohol advertisements within 1,500 feet of each school per community; and (4) a Census 2000-based deprivation index. Parents and community leaders provided data on perceived neighborhood problems and parental prevention actions, and neighborhood strength and preventive action by communities, law enforcement, and community organizations, respectively. Multilevel latent class analysis identified the number and characteristics of heterogeneous latent neighborhood classes in which these youth are exposed. Five classes best described the heterogeneity among the sample: (1) Low social capital/low exposure/high access to alcohol (19.8%), (2) Low social capital/low exposure/low access to alcohol (24.5%), (3) Moderate social capital/low exposure/high access to alcohol (30.0%), (4) Moderate social capital/moderate exposure/low access to alcohol (20.1%), and (5) High social capital/moderate exposure/high access to alcohol (5.6%). The racial/ethnic distribution among the classes varied considerably. Results suggest there is substantive heterogeneity among this seemingly homogeneous urban population. Further, they highlight the socioeconomic disadvantage of these inner-city communities and the resource disparity across the racial/ethnic groups. Understanding the nuances among communities may lend to development of more efficacious preventive interventions and policy initiatives, inform theory, and help prioritize limited resources.

  17. Repeated exposure to media violence is associated with diminished response in an inhibitory frontolimbic network.

    Science.gov (United States)

    Kelly, Christopher R; Grinband, Jack; Hirsch, Joy

    2007-12-05

    Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. Using functional magnetic resonance imaging (fMRI), we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression.

  18. The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure.

    Science.gov (United States)

    Talikka, Marja; Kostadinova, Radina; Xiang, Yang; Mathis, Carole; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Merg, Celine; Geertz, Marcel; Martin, Florian; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2014-01-01

    Exposure to cigarette smoke (CS) is linked to the development of respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the respiratory system and promising alternative to animal experimentation.

  19. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

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

    Science.gov (United States)

    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. A Systematic Review of the Impact of Exposure to Internet-Based Alcohol-Related Content on Young People's Alcohol Use Behaviours.

    Science.gov (United States)

    Gupta, Himanshu; Pettigrew, Simone; Lam, Tina; Tait, Robert J

    2016-11-01

    To conduct a systematic review of studies exploring the relationship between exposure to Internet-based alcohol-related content and alcohol use among young people. Searches of electronic databases and reference lists of relevant articles were conducted to retrieve studies of relevance up until December 2015. Full texts of the studies that met the inclusion criteria were read, appraised for quality using the Kmet forms and guidelines, and included in this review. Fifteen relevant studies were identified. The included studies were a mix of cross-sectional, longitudinal, experimental and qualitative studies conducted in the USA, the UK, Australia and New Zealand. The age range of the participants involved in these studies was 12-25 years. Included studies employed a variety of study designs and a range of different exposure variables and outcome measures. Studies demonstrated significant associations between exposure to Internet-based alcohol-related content and intentions to drink and positive attitudes towards alcohol drinking among young people. Exposure to alcohol-related content on the Internet might predispose young people to patterns of alcohol use by promoting alcohol as a natural and vital part of life. However, the research exploring the influence of this novel form of advertising on young people's alcohol use is emergent, and comprised primarily of cross-sectional studies. To evaluate the direction of the association between exposure to online alcohol-related content and alcohol use, we call for further research based on longitudinal designs. From 15 relevant studies identified, this review reports significant associations between exposure to Internet-based alcohol-related content and intentions to drink and positive attitudes towards alcohol drinking among young people, with different influences found at different stages of alcohol use. ©The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  2. Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

    Science.gov (United States)

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

    2016-01-01

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

  3. The effects of repeated low-level blast exposure on hearing in marines

    Directory of Open Access Journals (Sweden)

    Lina R Kubli

    2017-01-01

    Full Text Available Background: The study evaluates a group of Military Service Members specialized in blast explosive training called “Breachers” who are routinely exposed to multiple low-level blasts while teaching breaching at the U.S. Marine Corps in Quantico Virginia. The objective of this study was to determine if there are any acute or long-term auditory changes due to repeated low-level blast exposures used in training. The performance of the instructor group “Breachers” was compared to a control group, “Engineers”. Methods: A total of 11 Breachers and four engineers were evaluated in the study. The participants received comprehensive auditory tests, including pure-tone testing, speech-in-noise (SIN measures, and central auditory behavioral and objective tests using early and late (P300 auditory evoked potentials over a period of 17 months. They also received shorter assessments immediately following the blast-exposure onsite at Quantico. Results: No acute or longitudinal effects were identified. However, there were some interesting baseline effects found in both groups. Contrary to the expected, the onsite hearing thresholds and distortion product otoacoustic emissions were slightly better at a few frequencies immediately after blast-exposure than measurements obtained with the same equipment weeks to months after each blast-exposure. Conclusions: To date, the current study is the most comprehensive study that evaluates the long-term effects of blast-exposure on hearing. Despite extensive testing to assess changes, the findings of this study suggest that the levels of current exposures used in this military training environment do not seem to have an obvious deleterious effect on hearing.

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

    Science.gov (United States)

    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.

  5. The role of exposure history on HIV acquisition: insights from repeated low-dose challenge studies.

    Directory of Open Access Journals (Sweden)

    Roland R Regoes

    Full Text Available To assess the efficacy of HIV vaccine candidates or preventive treatment, many research groups have started to challenge monkeys repeatedly with low doses of the virus. Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection. I developed stochastic models to analyze previously published challenge data. In the mathematical models, I allowed for variation of the animals' susceptibility to infection across challenge repeats, or across animals. In none of the studies I analyzed, I found evidence for an immunizing effect of non-infecting challenges, and in most studies, there is no evidence for variation in the susceptibilities to the challenges across animals. A notable exception was a challenge experiment by Letvin et al. Sci Translat Med (2011 conducted with the strain SIVsmE660. The challenge data of this experiment showed significant susceptibility variation from animal-to-animal, which is consistent with previously established genetic differences between the involved animals. For the studies which did not show significant immunizing effects and susceptibility differences, I conducted a power analysis and could thus exclude a very strong immunization effect for some of the studies. These findings validate the assumption that non-infecting challenges do not immunize an animal - an assumption that is central in the argument that repeated low-dose challenge experiments increase the statistical power of preclinical HIV vaccine trials. They are also relevant for our understanding of the role of exposure history for HIV acquisition and forecasting the epidemiological spread of HIV.

  6. Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

    Science.gov (United States)

    Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

    2015-01-01

    Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

  7. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  8. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

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

    Science.gov (United States)

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

    2011-03-01

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

  10. Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

    Directory of Open Access Journals (Sweden)

    Sammeta V. Raju

    2013-07-01

    Full Text Available Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 h did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.

  11. Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex.

    Science.gov (United States)

    Campanac, Emilie; Hoffman, Dax A

    2013-06-01

    The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D(2) activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D(2)-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.

  12. Attentional bias for food and alcohol cues after exposure to commercial advertising : a consumer neuroscience approach

    OpenAIRE

    Keitiline Ramos Viacava

    2015-01-01

    Understanding how commercial stimuli may affect individuals’ behavior and health is one of the main questions in Consumer Neuroscience. Thus, the main aim of this thesis was to investigate the role of exposure to commercial advertising on attentional bias for food and alcohol cues in a set of studies. There were similarities in the use of visuoperceptual content in advertisements for tobacco, alcohol and food in Brazil (study 1); and high proportion (75%) of unhealthy food commercials in the ...

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

    Science.gov (United States)

    2007-08-03

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

  14. A new treatment for cognitive disorders related to in utero exposure to alcohol

    Institute of Scientific and Technical Information of China (English)

    Shuang Li; Yan Zhang; Feng Zhu; Bin Zhang; Jianying Lin; Chunyang Xu; Wancai Yang; Wei Hao; Ruiling Zhang

    2013-01-01

    Maternal alcohol consumption during pregnancy has detrimental effects on fetal central nervous system development. Maternal alcohol consumption prior to and during pregnancy significantly affects cognitive functions in offspring, which may be related to changes in cyclin-dependent kinase 5 because it is associated with modulation of synaptic plasticity and impaired learning and memory. In this study, we examined adult offspring in a maternal alcohol consumption model in rats. Y-maze test results showed that in utero exposure to alcohol impairs learning and memory capacities. Cyclin-dependent kinase 5 mRNA and protein expressions in the hippocampus of the offspring were significantly elevated, as assayed by quantitative real-time PCR and reverse transcription-PCR, immunofluorescence, and immuno-precipitation. Our experimental findings strongly suggest that altered cyclin-dependent kinase 5 may mediate impaired learning and memory in adult rats that were exposed to alcohol by maternal consumption while in utero.

  15. Assessing variability and comparing short-term biomarkers of styrene exposure using a repeated measurements approach.

    Science.gov (United States)

    Fustinoni, S; Manini, P; Campo, L; De Palma, G; Andreoli, R; Mutti, A; Bertazzi, P A; Rappaport, S M

    2010-01-15

    The aim of this work is to compare several short-term biomarkers of styrene exposure, namely urinary styrene (StyU), mercapturic acids (M1+M2), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), and 4-vinylphenol conjugates (VP), for use as biomarkers of exposure in epidemiologic studies. A repeated measurements protocol (typically 4 measurements per worker over 6 weeks) was applied to measure airborne styrene (StyA) and urinary biomarkers in 10 varnish and 8 fiberglass reinforced plastic workers. Estimated geometric mean personal exposures to StyA were 2.96mg/m(3) in varnish workers and 15.7mg/m(3) in plastic workers. The corresponding levels of StyU, M1+M2, MA, PGA, MA+PGA, PHG and VP were 5.13microg/L, 0.111, 38.2, 22.7, 62.6, 0.978, and 3.97mg/g creatinine in varnish workers and 8.38microg/L, 0.303, 146, 83.4, 232, 2.85 and 3.97mg/g creatinine in plastic workers. Within-worker (sigma(wY)(2)) and between-worker (sigma(bY)(2)) variance components were estimated from the log-transformed data as were the corresponding fold ranges containing 95% of the respective lognormal distributions of daily levels ((w)R(0.95)) and subject-specific mean levels ((b)R(0.95)). Estimates of (w)R(0.95) (range: 4-26) were generally smaller than those of (b)R(0.95) (range: 5-790) for both environmental and biological markers; this indicates that exposures varied much more between workers than within workers in these groups. Since attenuation bias in an estimated exposure-response relationship increases with the variance ratio lambda=sigma(wY)(2)/sigma(bY)(2), we estimated values of lambda for all exposure measures in our study. Values of lambda were typically much less than one (median=0.220) and ranged from 0.089 for M1+M2 in plastic workers to 1.38 for PHG in varnish workers. Since values of lambda were 0.147 and 0.271 for StyA in varnish workers and plastic workers, respectively, compared to 0.178 and 0.210 for MA in the same groups, our results suggest that either

  16. Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

    Science.gov (United States)

    Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

    2017-02-01

    The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe2 O3 -NPs) could be toxic to mice testis. Fe2 O3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe2 O3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe2 O3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe2 O3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe2 O3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe2 O3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe2 O3 -NPs exposure may be associated with Fe2 O3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe2 O3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe2 O3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017.

  17. The hidden price of repeated traumatic exposure: Different cognitive deficits in different first-responders

    Directory of Open Access Journals (Sweden)

    Einat eLevy-Gigi

    2014-08-01

    Full Text Available Studies on first responders who are repeatedly exposed to traumatic events report low levels of PTSD symptoms and diagnosis. However, neuroimaging and behavioral studies show that traumatic exposure is associated with brain and cognitive dysfunctions. Taking together it may suggest that traumatic exposure have a price, which is not sufficiently defined by the standard PTSD measures. In a recent study we revealed that similar to individuals with PTSD, non-PTSD highly exposed firefighters display a selective impairment in hippocampal related functions. In the current study we aimed to test whether different first responders display a similar impairment. We concentrated on unique populations of active duty firefighters and criminal scene-investigators (CSI police, who are frequently exposed to similar levels and types of traumatic events, and compared them to civilian matched-controls with no history of trauma-exposure. We used a hippocampal dependent cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context related information. We predicted and found that all participants were equally able to acquire and retain stimulus-outcome associations. However, there were significant differences in reversal learning between the groups. Performance among firefighters replicated our prior findings; they struggled to learn that a previously negative context is later associated with a positive outcome. CSI police on the other hand showed a selective impairment in reversing the outcome of a negative cue. Hence after learning that a specific cue is associated with a negative outcome, they could not learn that later it is associated with a positive outcome. Performance in both groups did not correlate with levels of PTSD, anxiety, depression or behavioral inhibition symptoms. The results provide further evidence of the hidden price of traumatic exposure, suggesting that this price may differ as a

  18. Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

    OpenAIRE

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

    2016-01-01

    Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increa...

  19. [Exposure to alcohol among adolescent students and associated factors].

    Science.gov (United States)

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

    2014-02-01

    To describe the prevalence of alcohol consumption among adolescent school students and identify its individual and contextual associated factors. 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 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). The results reinforce the importance of viewing alcohol consumption among adolescents as a complex, multifactorial and socially determined phenomenon.

  20. Polymorphisms of the dopamine D4 receptor gene (DRD4 VNTR) and cannabinoid CB1 receptor gene (CNR1) are not strongly related to cue-reactivity after alcohol exposure.

    Science.gov (United States)

    van den Wildenberg, Esther; Janssen, Rob G J H; Hutchison, Kent E; van Breukelen, Gerard J P; Wiers, Reinout W

    2007-06-01

    Polymorphisms in the D4 dopamine receptor gene (DRD4) and the CB1 cannabinoid receptor gene (CNR1) have been associated with a differential response to alcohol after consumption. The goal of the present study was to investigate whether heavy drinkers with these polymorphisms would respond with enhanced cue-reactivity after alcohol exposure. Eighty-eight male heavy drinkers were genotyped for the DRD4 variable number of tandem repeats (VNTR) [either DRD4 long (L) or short (S)] and the CNR1 rs2023239 polymorphism (either CT/CC or TT). Participants were exposed to water and beer in 3-minute trials. Dependent variables of main interest were subjective craving for alcohol, subjective arousal and salivary reactivity. Overall, no strong evidence was found for stronger cue-reactivity (= outcome difference between beer and water trial) in the DRD4 L and CNR1 C allele groups. The DRD4 VNTR polymorphism tended to moderate salivary reactivity such that DRD4 L participants showed a larger beverage effect than the DRD4 S participants. Unexpectedly, the DRD4 L participants reported, on average, less craving for alcohol and more subjective arousal during cue exposure, compared with the DRD4 S participants. As weekly alcohol consumption increased, the CNR1 C allele group tended to report more craving for alcohol during the alcohol exposure than the T allele group. The DRD4 and CNR1 polymorphisms do not appear to strongly moderate cue-reactivity after alcohol cue exposure, in male heavy drinkers.

  1. Perfectionism Affects Blood Pressure in Response to Repeated Exposure to Stress.

    Science.gov (United States)

    Albert, Phebe; Rice, Kenneth G; Caffee, Lauren

    2016-04-01

    This pilot study examined the effects of perfectionism on blood pressure (BP) in response to repeated exposure to mental arithmetic stressors. College students (N = 30) in a laboratory setting were administered a series of challenging mathematical tasks. BP was measured at baseline and after each task. Multilevel modelling analyses revealed that BP tended to decline over the course of the mathematical tasks. However, higher levels of performance standards predicted relatively stable levels of systolic BP, whereas moderate and lower levels of standards predicted declines in systolic BP. Higher levels of self-critical perfectionism predicted generally sustained levels of diastolic BP, with moderate and low self-criticism predicting declines in diastolic BP during the repeated stressors. These preliminary results suggest that students with higher levels of perfectionism may be at risk for physiological problems associated with stress reactivity, perhaps especially so in situations in which they experience persistent stress. Although results were qualified by a relatively small sample size, effects were statistically significant and supported the importance of examining the short-term and long-term implications of the effects of perfectionism on cardiovascular function and the different implications of elevations in systolic and diastolic BP.

  2. Women's risk of repeat abortions is strongly associated with alcohol consumption: a longitudinal analysis of a Russian national panel study, 1994-2009.

    Directory of Open Access Journals (Sweden)

    Katherine Keenan

    Full Text Available Abortion rates in Russia, particularly repeat abortions, are among the highest in the world, and abortion complications make a substantial contribution to the country's high maternal mortality rate. Russia also has a very high rate of hazardous alcohol use. However, the association between alcohol use and abortion in Russia remains unexplored. We investigated the longitudinal predictors of first and repeat abortion, focussing on women's alcohol use as a risk factor. Follow-up data from 2,623 women of reproductive age (16-44 years was extracted from 14 waves of the Russian Longitudinal Monitoring Survey (RLMS, a nationally representative panel study covering the period 1994-2009. We used discrete time hazard models to estimate the probability of having a first and repeat abortion by social, demographic and health characteristics at the preceding study wave. Having a first abortion was associated with demographic factors such as age and parity, whereas repeat abortions were associated with low education and alcohol use. After adjustment for demographic and socioeconomic factors, the risk of having a repeat abortion increased significantly as women's drinking frequency increased (P<0.001, and binge drinking women were significantly more likely to have a repeat abortion than non-drinkers (OR 2.28, 95% CI 1.62-3.20. This association was not accounted for by contraceptive use or a higher risk of pregnancy. Therefore the determinants of first and repeat abortion in Russia between 1994-2009 were different. Women who had repeat abortions were distinguished by their heavier and more frequent alcohol use. The mechanism for the association is not well understood but could be explained by unmeasured personality factors, such as risk taking, or social non-conformity increasing the risk of unplanned pregnancy. Heavy or frequent drinkers constitute a particularly high risk group for repeat abortion, who could be targeted in prevention efforts.

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

    Science.gov (United States)

    2013-11-08

    Excessive alcohol consumption accounted for an estimated 4,700 deaths and 280,000 years of potential life lost among youths aged 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 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.

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

    OpenAIRE

    Olivier Thomas; Vincent Bessonneau

    2012-01-01

    International audience; 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 ...

  5. Increases in fruit intakes in older low consumers of fruit following two community-based repeated exposure interventions.

    Science.gov (United States)

    Appleton, K M

    2013-03-14

    The present study investigated the value of two repeated exposure interventions for increasing intakes of fruit in older people. A total of ninety-five participants (aged 65 years and over) were randomised to receive either one (E1), five (E5) or five plus (E5+) exposures to fruit over a 5-week period. Fruit exposures occurred in community-based church and social groups, through fruit-tasting sessions involving familiar fruits and novel fruit products and dishes (E1, E5, E5+), and through fruit provision (E5+). Daily intakes of fruit and vegetables were assessed before and after all interventions. Liking for all fruits was also measured during repeated exposure (E5, E5+). In low consumers of fruit (one portion/d or less), fruit intakes increased significantly in the repeated exposure groups (E5, E5+) (t(30) = 5·79, Polder low consumers of fruit, although no benefits of additional fruit provision were found. Repeated exposure was also easy to implement, of low cost and enjoyable.

  6. Repeated Exposure to Dissection Does Not Influence Students’ Attitudes towards Human Body Donation for Anatomy Teaching

    Directory of Open Access Journals (Sweden)

    Philip Maseghe Mwachaka

    2016-01-01

    Full Text Available The use of unclaimed bodies for anatomical dissection has been the main method of instruction at our institution. There is however a shortage of cadavers for dissection given the increase in the number of medical schools as well as in the number of students enrolling in these schools. This shortage could be mitigated by having voluntary human body donation programs. This study aimed at assessing the attitudes of medical students and surgical residents towards body donation for anatomy learning. We conducted an online survey involving 72 first-year medical students and 41 surgical residents at University of Nairobi who had completed one year of anatomy dissection. For the medical students, this was their first dissection experience while it was the second exposure for the surgery trainees. Most of the surgical trainees (70.7% and medical students (68.1% were opposed to self-body donation. This was mainly due to cultural (37% and religious (20% barriers. Surprisingly, of those not willing to donate themselves, 67.9% (82.8% surgical trainees, 59.2% medical students would recommend the practice to other people. Exposure to repeated dissection does not change the perceptions towards body donation. It is noteworthy that culture and religion rank high as clear barriers amongst this “highly informed” group of potential donors.

  7. Occupational hazards of traditional healers: repeated unprotected blood exposures risk infectious disease transmission.

    Science.gov (United States)

    Audet, Carolyn M; Salato, José; Blevins, Meridith; Silva, Wilson; González-Calvo, Lázaro; Vermund, Sten H; Gaspar, Felisbela

    2016-11-01

    Healers provide support for acute and chronic illnesses in rural Mozambique, such as socially acceptable traditional 'vaccinations' (subcutaneous cuts in the skin to rub herbs directly into the bloody lesion). We aimed to document the frequency of blood exposure by traditional practitioners in Mozambique. We conducted surveys with a simple random sample of 236 traditional healers in Zambézia province. Chi-square and Wilcoxon rank-sum tests were used to compare 'injection' behaviours across districts. Healers treated a median of eight patients in the past month (IQR: 4-15). About 75% conducted 'injections'. These healers 'injected' a median of four patients (IQR: 1-8), used a new razor a median of three times (IQR: 1-8), and almost never used gloves. Lifetime blood exposures among those who provided 'injections' during treatments were estimated to be 1758 over a healer's career. The majority of healers are exposed repeatedly to patient blood. Given the high prevalence of HIV, hepatitis B and C virus, and other blood-borne agents, specific healer practices are an occupational hazard and reuse of razors is risky for their clients. © 2016 John Wiley & Sons Ltd.

  8. Repeated exposure of acidic beverages on esthetic restorative materials: An in-vitro surface microhardness study.

    Science.gov (United States)

    Xavier, Arun M; Sunny, Steffy M; Rai, Kavita; Hegde, Amitha M

    2016-07-01

    A manifold increase in the consumption of aerated beverages has witnessed a twin increase in tooth wear and raised demand for esthetic restorative materials. This study aimed to evaluate the surface microhardness changes of esthetic restorative materials following treatment with aerated beverages in an in-vitro situation. The initial surface microhardness of the restorative materials GC Fuji II LC, GC Fuji IX, Nano Glass ionomer, Resin and Nano composite was recorded. These materials were studied under 3 groups that included those exposed to the acidic beverages daily, weekly once in a month and those that had no exposures at all. The final surface microhardness of the materials was recorded following experimentation and was subjected to statistical comparisons. The restorative materials were compared for their surface microhardness changes following respective treatments using the T-test and One-way ANOVA analysis. Inter-comparisons between the groups showed statistical significance (pmaterials revealed surface microhardness loss; the maximum reduction noticed with the Nano glass ionomer cement tested (pmaterials markedly reduced upon repeated exposures with acidic beverages; the product with phosphoric acid producing the maximum surface microhardness loss. Restorative materials, acidic beverages, surface microhardness, resin composites, glass ionomers.

  9. Repeated Exposure to Dissection Does Not Influence Students' Attitudes towards Human Body Donation for Anatomy Teaching.

    Science.gov (United States)

    Mwachaka, Philip Maseghe; Mandela, Pamela; Saidi, Hassan

    2016-01-01

    The use of unclaimed bodies for anatomical dissection has been the main method of instruction at our institution. There is however a shortage of cadavers for dissection given the increase in the number of medical schools as well as in the number of students enrolling in these schools. This shortage could be mitigated by having voluntary human body donation programs. This study aimed at assessing the attitudes of medical students and surgical residents towards body donation for anatomy learning. We conducted an online survey involving 72 first-year medical students and 41 surgical residents at University of Nairobi who had completed one year of anatomy dissection. For the medical students, this was their first dissection experience while it was the second exposure for the surgery trainees. Most of the surgical trainees (70.7%) and medical students (68.1%) were opposed to self-body donation. This was mainly due to cultural (37%) and religious (20%) barriers. Surprisingly, of those not willing to donate themselves, 67.9% (82.8% surgical trainees, 59.2% medical students) would recommend the practice to other people. Exposure to repeated dissection does not change the perceptions towards body donation. It is noteworthy that culture and religion rank high as clear barriers amongst this "highly informed" group of potential donors.

  10. Repeated exposure to media violence is associated with diminished response in an inhibitory frontolimbic network.

    Directory of Open Access Journals (Sweden)

    Christopher R Kelly

    Full Text Available BACKGROUND: Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging (fMRI, we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. CONCLUSIONS: These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression.

  11. Respiratory toxicity of repeated exposure to particles produced by traffic and sugar cane burning.

    Science.gov (United States)

    Mazzoli-Rocha, Flavia; Carvalho, Giovanna M C; Lanzetti, Manuella; Valença, Samuel S; Silva, Luiz F F; Saldiva, Paulo H N; Zin, Walter A; Faffe, Débora S

    2014-01-15

    We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15μg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures.

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

    Science.gov (United States)

    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

  13. Exposure to Online Alcohol Marketing and Adolescents' Drinking: A Cross-sectional Study in Four European Countries.

    Science.gov (United States)

    de Bruijn, Avalon; Engels, Rutger; Anderson, Peter; Bujalski, Michal; Gosselt, Jordy; Schreckenberg, Dirk; Wohtge, Jördis; de Leeuw, Rebecca

    2016-09-01

    The Internet is the leading medium among European adolescents in contemporary times; even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in four European countries. A total of 9038 students with a mean age of 14.05 (SD 0.82) participated in a school-based survey in Germany, Italy, the Netherlands and Poland. Logistic regression analyses of cross-sectional cross-country survey data were undertaken. Exposure to online alcohol marketing, televised alcohol advertising and ownership of alcohol-branded items was estimated to be controlled for relevant confounders. Onset of drinking and binge drinking in the past 30 days were included in the study as outcome variables. Adjusted for relevant confounders, higher exposure to (online) alcohol marketing exposure was found to be related to the odds of starting to drink (p online alcohol marketing was found to interact more strongly with drinking outcomes than passive exposure to online alcohol marketing. Youngsters in the four European countries report frequent exposure to online alcohol marketing. The association between this exposure and adolescents' drinking was robust and seems consistent across national contexts. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  14. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Science.gov (United States)

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  15. Accumbal FosB/DeltaFosB immunoreactivity and conditioned place preference in alcohol-preferring AA rats and alcohol-avoiding ANA rats treated repeatedly with cocaine.

    Science.gov (United States)

    Marttila, Kristiina; Petteri Piepponen, T; Kiianmaa, Kalervo; Ahtee, Liisa

    2007-07-30

    Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.

  16. Probabilistic dietary exposure to ethyl carbamate from fermented foods and alcoholic beverages in the Korean population.

    Science.gov (United States)

    Choi, B; Ryu, D; Kim, C-I; Lee, J-Y; Choi, A; Koh, E

    2017-09-04

    The occurrence of ethyl carbamate was investigated in fermented foods and alcoholic beverages of the Korean total diet study. The concentrations of ethyl carbamate ranged from not detected to 166.5 μg kg(-1). Dietary exposure to ethyl carbamate was estimated by the probabilistic method. Estimated intakes of ethyl carbamate from foods and alcoholic beverages were 4.12 ng kg(-1) body weight (bw) per day for average consumers and 12.37 ng kg(-1) bw/day for 95th percentile high consumers. The major foods contributing to ethyl carbamate exposure were soy sauce (63%), followed by maesilju (plum liqueur, 30%), whisky (5%), and bokbunjaju (black raspberry wine, 2%). On the basis of the benchmark dose lower confidence limit 10% (BMDL10) of 0.3 mg kg(-1) bw/day, margins of exposure were 128,000 for mean exposure and 40,000 for 95th percentile exposure. This indicates that the exposure of the Korean general population for ethyl carbamate is of low concern. However, careful vigilance should be continued for high consumers of fermented foods and alcoholic beverages.

  17. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures

    DEFF Research Database (Denmark)

    Vestergaard, M; Wisborg, K; Henriksen, TB

    2005-01-01

    of extensive brain growth and differentiation in this period. We evaluated the association between prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures in 2 population-based birth cohorts. METHODS: The Aarhus Birth Cohort consisted of 25,196 children of mothers who were...... Birth Cohort, but the corresponding association was weak in the Aalborg-Odense cohort. We found no association between maternal alcohol and coffee consumption and the risk for febrile seizures. The results were similar for simple and complex febrile seizures. CONCLUSIONS: Our data suggest that prenatal...... exposure to low to moderate levels of alcohol and coffee has no impact on the risk for febrile seizures, whereas a modest smoking effect cannot be ruled out....

  18. A randomized controlled study of exposure therapy as aftercare for alcohol use disorder

    DEFF Research Database (Denmark)

    Mellentin, Angelina Isabella; Nielsen, Bent; Nielsen, Anette Søgaard

    2016-01-01

    Background It is well documented that individuals with Alcohol Use Disorder (AUD) respond well during evidence-based psychological treatment, but also that a large proportion relapses when discharged from treatment and confronted with alcohol in real life. Cue Exposure Treatment (CET) focuses...... on exposing individuals to alcohol cues in order to reduce cravings as well as the likelihood of relapse. The aims of the study are: 1) to investigate whether CET aftercare delivered via a smartphone or in group sessions increases the effect of Cognitive Behavioural Treatment in groups of alcohol dependent...... individuals; 2) to investigate whether CET as a smartphone application is as or more effective than CET group therapy, and 3) to investigate whether CET as a smartphone application is more cost-effective than CET group aftercare and Aftercare as Usual. Design and methods The study will be implemented...

  19. Associations of repeated high alcohol use with unsafe driving behaviors, traffic offenses, and traffic crashes among young drivers: Findings from the New Zealand Drivers Study.

    Science.gov (United States)

    Begg, Dorothy; Brookland, Rebecca; Connor, Jennie

    2017-02-17

    The objective of this study was to describe self-reported high alcohol use at each of the 3 licensing stages of graduated driver licensing and its relationship to drink-driving behaviors, intentional risky driving, aggressive driving, alcohol traffic offenses, non-alcohol traffic offenses, and traffic crashes. The New Zealand Drivers Study (NZDS) is a multistage, prospective cohort study of newly licensed drivers interviewed at all 3 stages of the graduated driver licensing system: learner (baseline), restricted (intermediate), and full license. At each stage, alcohol use was self-reported using the Alcohol Use Disorders Identification Test (AUDIT-C), with high alcohol use defined as a score of ≥4 for males and ≥3 for females. Sociodemographic and personality data were obtained at the baseline interview. Alcohol-related, intentional risky, and aggressive driving behaviors were self-reported following each license stage. Traffic crashes and offenses were identified from police records. Crashes were also self-reported. Twenty-six percent (n = 397) reported no high alcohol use, 22% at one license stage, 30% at 2 stages, and 22% at 3 stages. Poisson regression results (unadjusted and adjusted) showed that the number of stages where high alcohol use was reported was significantly associated with each of the outcomes. For most outcomes, and especially the alcohol-involved outcomes, the relative risk increased with the number of stages of high alcohol use. We found that high alcohol use was common among young newly licensed drivers and those who repeatedly reported high alcohol use were at a significantly higher risk of unsafe driving behaviors. Recently introduced zero blood alcohol concentration (BAC) should help to address this problem, but other strategies are required to target persistent offenders.

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

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    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...... late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume....

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

    Science.gov (United States)

    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…

  2. Youth alcohol brand consumption and exposure to brand advertising in magazines.

    Science.gov (United States)

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

    2014-07-01

    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. 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. 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. 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.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

  6. Statistical modeling of volume of alcohol exposure for epidemiological studies of population health: the US example

    Directory of Open Access Journals (Sweden)

    Gmel Gerrit

    2010-03-01

    Full Text Available Abstract Background Alcohol consumption is a major risk factor in the global burden of disease, with overall volume of exposure as the principal underlying dimension. Two main sources of data on volume of alcohol exposure are available: surveys and per capita consumption derived from routine statistics such as taxation. As both sources have significant problems, this paper presents an approach that triangulates information from both sources into disaggregated estimates in line with the overall level of per capita consumption. Methods A modeling approach was applied to the US using data from a large and representative survey, the National Epidemiologic Survey on Alcohol and Related Conditions. Different distributions (log-normal, gamma, Weibull were used to model consumption among drinkers in subgroups defined by sex, age, and ethnicity. The gamma distribution was used to shift the fitted distributions in line with the overall volume as derived from per capita estimates. Implications for alcohol-attributable fractions were presented, using liver cirrhosis as an example. Results The triangulation of survey data with aggregated per capita consumption data proved feasible and allowed for modeling of alcohol exposure disaggregated by sex, age, and ethnicity. These models can be used in combination with risk relations for burden of disease calculations. Sensitivity analyses showed that the gamma distribution chosen yielded very similar results in terms of fit and alcohol-attributable mortality as the other tested distributions. Conclusions Modeling alcohol consumption via the gamma distribution was feasible. To further refine this approach, research should focus on the main assumptions underlying the approach to explore differences between volume estimates derived from surveys and per capita consumption figures.

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

    Directory of Open Access Journals (Sweden)

    Stephen Mason

    2012-01-01

    Full Text Available 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.

  8. Cognitive factors contributing to spelling performance in children with prenatal alcohol exposure.

    Science.gov (United States)

    Glass, Leila; Graham, Diana M; Akshoomoff, Natacha; Mattson, Sarah N

    2015-11-01

    Heavy prenatal alcohol exposure is associated with impaired school functioning. Spelling performance has not been comprehensively evaluated. We examined whether children with heavy prenatal alcohol exposure demonstrate deficits in spelling and related abilities, including reading, and tested whether there are unique underlying mechanisms for observed deficits in this population. Ninety-six school-age children made up 2 groups: children with heavy prenatal alcohol exposure (AE, n = 49) and control children (CON, n = 47). Children completed select subtests from the Wechsler Individual Achievement Test-Second Edition and the NEPSY-II. Group differences and relations between spelling and theoretically related cognitive variables were evaluated using multivariate analysis of variance and Pearson correlations. Hierarchical regression analyses were used to assess contributions of group membership and cognitive variables to spelling performance. The specificity of these deficits and underlying mechanisms was tested by examining the relations between reading ability, group membership, and cognitive variables. Groups differed significantly on all variables. Group membership and phonological processing significantly contributed to spelling performance, whereas for reading, group membership and all cognitive variables contributed significantly. For both reading and spelling, group × working memory interactions revealed that working memory contributed independently only for alcohol-exposed children. Alcohol-exposed children demonstrated a unique pattern of spelling deficits. The relation of working memory to spelling and reading was specific to the AE group, suggesting that if prenatal alcohol exposure is known or suspected, working memory ability should be considered in the development and implementation of explicit instruction. (c) 2015 APA, all rights reserved).

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

    Science.gov (United States)

    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

  10. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Sven Kroener

    Full Text Available In the present study, we used a mouse model of chronic intermittent ethanol (CIE exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC. In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP showed that CIE exposure was associated with altered expression of long-term potentiation (LTP. Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC.

  11. Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Saba Moghimi

    Full Text Available Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

  12. Self-Reported Youth and Adult Exposure to Alcohol Marketing in Traditional and Digital Media: Results of a Pilot Survey.

    Science.gov (United States)

    Jernigan, David H; Padon, Alisa; Ross, Craig; Borzekowski, Dina

    2017-03-01

    Alcohol marketing is known to be a significant risk factor for underage drinking. However, little is known about youth and adult exposure to alcohol advertising in digital and social media. This study piloted a comparative assessment of youth and adult recall of exposure to online marketing of alcohol. From September to October 2013, a pilot survey of past 30-day exposure to alcohol advertising and promotional content in traditional and digital media was administered to a national sample of 1,192 youth (ages 13 to 20) and 1,124 adults (ages ≥21) using a prerecruited Internet panel maintained by GfK Custom Research. The weighted proportions of youth and adults who reported this exposure were compared by media type and by advertising and promotional content. Youth were more likely than adults to recall exposure to alcohol advertising on television (69.2% vs. 61.9%), radio (24.8% vs. 16.7%), billboards (54.8% vs. 35.4%), and the Internet (29.7% vs. 16.8%), but less likely to recall seeing advertising in magazines (35.7% vs. 36.4%). Youth were also more likely to recall seeing advertisements and pictures on the Internet of celebrities using alcohol (36.1% vs. 20.8%) or wearing clothing promoting alcohol (27.7% vs. 15.9%), and actively respond (i.e., like, share, or post) to alcohol-related content online. Youth report greater exposure to alcohol advertising and promotional content than adults in most media, including on the Internet. These findings emphasize the need to assure compliance with voluntary industry standards on the placement of alcohol advertising and the importance of developing better tools for monitoring youth exposure to alcohol marketing, particularly on the Internet. Copyright © 2017 by the Research Society on Alcoholism.

  13. Repeated exposure to odors induces affective habituation of perception and sniffing

    Directory of Open Access Journals (Sweden)

    Camille eFerdenzi

    2014-04-01

    Full Text Available Olfactory perception, and especially hedonic evaluation of odors, is highly flexible, but some mechanisms involved in this flexibility remain to be elucidated. In the present study we aimed at better understanding how repeated exposure to odors can affect their pleasantness. We tested the hypothesis of an affective habituation to the stimuli, namely a decrease of emotional intensity over repetitions. More specifically, we tested whether this effect is subject to inter-individual variability and whether it can also be observed at the olfactomotor level. Twenty-six participants took part in the experiment during which they had to smell two odorants, anise and chocolate, presented twenty times each. On each trial, sniff duration and volume were recorded and paired with ratings of odor pleasantness and intensity. For each smell, we distinguished between likers and dislikers, namely individuals giving positive and negative initial hedonic evaluations. Results showed a significant decrease in pleasantness with time when the odor was initially pleasant (likers, while unpleasantness remained stable or slightly decreased when the odor was initially unpleasant (dislikers. This deviation towards neutrality was interpreted as affective habituation. This effect was all the more robust as it was observed for both odors and corroborated by sniffing, an objective measurement of odor pleasantness. Affective habituation to odors can be interpreted as an adaptive response to stimuli that prove over time to be devoid of positive or negative outcome on the organism. This study contributes to a better understanding of how olfactory preferences are shaped through exposure, depending on the individual’s own initial perception of the odor.

  14. Impact of product information and repeated exposure on consumer liking, sensory perception and concept associations of local apple juice

    DEFF Research Database (Denmark)

    Stolzenbach, Sandra; Bredie, Wender Laurentius Petrus; Christensen, Rune Haubo Bojesen

    2013-01-01

    The impact of product information and repeated exposure of local apple juice on consumer liking, sensory perception and concept associations was studied. Findings showed that consumers had high expectations towards the studied local apples juices. Consequently, the liking for the local apple juic...

  15. Repeated exposures to cobalt or chromate on the hands of patients with hand eczema and contact allergy to that metal

    DEFF Research Database (Denmark)

    Nielsen, N H; Kristiansen, J; Borg, L

    2000-01-01

    The present study aimed at evaluating the effects of daily repeated exposures to low cobalt or chromate concentrations on the hands of patients with hand eczema and cobalt or chromate allergy. For 2 weeks, the patients immersed a finger for 10 min daily into the appropriate metal salt solution in...

  16. Effect of repeated and prolonged exposure to low concentrations of Low Molecular Weight chemicals on local lymph node responses

    NARCIS (Netherlands)

    Jong WH de; Beek M ter; Veenman C; Klerk A de; Loveren H van; TOX

    2006-01-01

    The results of the local lymph node assay are not for all compounds useful as starting point for a quantitative risk assessment. This study describes the effects after repeated exposure of the skin to a concentration of a sensitizer below the threshold used in the local lymph node assay. Positive re

  17. Chronic Ethanol Exposure Effects on Vitamin D Levels Among Subjects with Alcohol Use Disorder

    Science.gov (United States)

    Ogunsakin, Olalekan; Hottor, Tete; Mehta, Ashish; Lichtveld, Maureen; McCaskill, Michael

    2016-01-01

    Vitamin D has been previously recognized to play important roles in human immune system and function. In the pulmonary system, vitamin D regulates the function of antimicrobial peptides, especially cathelicidin/LL-37. Human cathelicidin/LL-37 is a bactericidal, bacteriostatic, and antiviral endogenous peptide with protective immune functions. Chronic exposure to excessive alcohol has the potential to reduce levels of vitamin D (inactive vitamin D [25(OH)D3] and active vitamin D [1, 25(OH)2D3]) and leads to downregulation of cathelicidin/LL-37. Alcohol-mediated reduction of LL-37 may be partly responsible for increased incidence of more frequent and severe respiratory infections among subjects with alcohol use disorder (AUD). The objective of this study was to investigate the mechanisms by which alcohol exerts its influence on vitamin D metabolism. In addition, the aim was to establish associations between chronic alcohol exposures, levels of pulmonary vitamin D, and cathelicidin/LL-37 using broncho-alveolar lavage fluid samples of subjects with AUD and healthy controls. Findings from the experiment showed that levels of inactive vitamin D (25(OH)D3), active vitamin D (1, 25(OH)2D3), cathelicidin/LL-37, and CYP27B1 proteins were significantly reduced (P < 0.05) when compared with the matched healthy control group. However, CYP2E1 was elevated in all the samples examined. Chronic exposure to alcohol has the potential to reduce the levels of pulmonary vitamin D and results in subsequent downregulation of the antimicrobial peptide, LL-37, in the human pulmonary system. PMID:27795667

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

    Science.gov (United States)

    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.

  19. Alcohol

    Science.gov (United States)

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

  20. Alcohol

    Science.gov (United States)

    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 ...

  1. Moderate alcohol exposure compromises neural tube midline development in prenatal brain.

    Science.gov (United States)

    Zhou, Feng C; Sari, Youssef; Powrozek, Teresa; Goodlett, Charles R; Li, Ting-Kai

    2003-08-12

    We previously reported that fetal alcohol treatment compromised the development of the midline raphe and the serotonin neurons contained in it. In this study, we report that the timely development of midline neural tissue during neural tube formation is sensitive to alcohol exposure. Pregnant dams were treated from embryonic day 7 (E7, prior to neurulation) or E8.5 (at neurulation) with the following diets: (a) alcohol (ALC), given as either a 20% or 25% ethanol-derived calorie (EDC) liquid diet, or (b) isocaloric liquid diet pair-fed (PF), or (c) standard rat chow (Chow). Fetal brains from each group were examined on E13, E15, or E18. Neural tube development was compromised as a result of alcohol exposure in the following ways: (1) approximately 60% of embryos at E13 and 20% at E15 showed perforation of the floor plate in the diencephalic vesicle, (2) although completely closed at E13, 70-80% of embryos failed to complete the formation of neural tissue at the roof as the alcohol exposure continued to E15, and (3) 60-80% of embryos show delayed 'occlusion' of the ventral canal by newly formed nestin-positive neuroepithelial cells and S100beta-positive glia in the brainstem of E15. The compromised (incomplete) neural tube midline (cNTM) occurred near the ventricles at E13 and E15, but was later completed at E18. In all cases, the cNTM was accompanied by an enlarged ventricle, and dose-dependent brain weight reduction. The midline of the neural tube at the roof and floor plates is known to mediate timely trophic induction for neural differentiation. Prenatal midline deficits also have the potential to affect the development of midline neurons such as raphe, septal nuclei, and the timely crossing of commissural fibers. The results of the liquid diet alcohol exposure paradigm suggest it is more a model for Alcohol-Related Neurodevelopmental Disorder (ARND) featuring neuropsychiatric disorders than for full-blown fetal alcohol syndrome (FAS) with noticeable facial

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

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.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

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

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.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

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

    NARCIS (Netherlands)

    Koordeman, R.; Anschutz, D.J.; Engels, R.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)

  5. Effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections

    Institute of Scientific and Technical Information of China (English)

    Mustafa; Atas; Burhan; Baskan; Ayse; zkse; Fatma; Mutlu; Sarιgüzel; Süleyman; Demircan; Emine; Pangal

    2014-01-01

    AIM:To evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections.METHODS:Seventy-two eyes of 36 patients [36 eyes in control group, 36 eyes in intravitreal injection(IVI) group]were enrolled in the study. All the eyes had at least one IVI and had diabetic macular edema(DME) or age-related macular degeneration(ARMD). Moxifloxacin was prescribed to all the patients four times a day for five days following injection. Conjunctival cultures were obtained from the lower fornix via standardized technique with every possible effort made to minimize contamination from the lids, lashes, or skin. Before the application of any ophthalmic medication, conjunctival cultures were obtained from both eyes using sterile cotton culture. An automated microbiology system was used to identify the growing bacteria and determine antibiotic sensitivity.RESULTS:The bacterial cultures were isolated from 72 eyes of 36 patients, sixteen of whom patients(44.4%)were male and twenty(55.6%) were female. Average age was 68.4 ±9.0(range 50-86). The average number of injections before taking cultures was 3.1+1.0. Forty-eight(66.7%) of 72 eyes had at least one significant organism.There was no bacterial growth in 8(20.5%) of IVI eyes and in 16(44.4%) of control eyes(P =0.03). Of the bacteria isolated from culture, 53.8% of coagulase negative staphylococci(CoNS) in IVI eyes and 47.2%CoNS in control eyes. This difference between IVI eyes and control eyes about bacteria isolated from culture was not statistically significant(P =0.2). Eleven of 25 bacteria(44.0%) isolated from IVI eyes and 11(57.9%) of 19 bacteria isolated from control eyes were resistant to oxacillin. The difference in frequency of moxifloxacine resistance between two groups was not statistically significant(12.0% in IVI eyes and 21.1% in control eyes)(P =0.44). There were no cases of resistance to vancomycin, teicoplanin and linezolid

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

    Directory of Open Access Journals (Sweden)

    Gillian F. Hamilton

    2012-12-01

    Full Text Available 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.

  7. Persistent dose-dependent changes in brain structure in young adults with low-to-moderate alcohol exposure in utero.

    Science.gov (United States)

    Eckstrand, Kristen L; Ding, Zhaohua; Dodge, Neil C; Cowan, Ronald L; Jacobson, Joseph L; Jacobson, Sandra W; Avison, Malcolm J

    2012-11-01

    Many children with heavy exposure to alcohol in utero display characteristic alterations in brain size and structure. However, the long-term effects of low-to-moderate alcohol exposure on these outcomes are unknown. Using voxel-based morphometry and region-of-interest analyses, we examined the influence of lower doses of alcohol on gray and white matter composition in a prospectively recruited, homogeneous, well-characterized cohort of alcohol-exposed (n = 11, age 19.5 ± 0.3 years) and control (n = 9, age 19.6 ± 0.5 years) young adults. A large proportion of the exposed individuals were born to mothers whose alcohol consumption during pregnancy was in the low-to-moderate range. There were no differences in total brain volume or total gray or white matter volume between the exposed and control groups. However, gray matter volume was reduced in alcohol-exposed individuals in several areas previously reported to be affected by high levels of exposure, including the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus. Notably, this gray matter loss was dose dependent, with higher exposure producing more substantial losses. These results indicate that even at low doses, alcohol exposure during pregnancy impacts brain development and that these effects persist into young adulthood. Copyright © 2012 by the Research Society on Alcoholism.

  8. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    Directory of Open Access Journals (Sweden)

    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

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

    Science.gov (United States)

    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

  10. Change in tensile properties of neoprene and nitrile gloves after repeated exposures to acetone and thermal decontamination.

    Science.gov (United States)

    Gao, Pengfei; Tomasovic, Beth

    2005-11-01

    This study investigated the change in tensile properties of neoprene and nitrile gloves after repeated cycles of exposure to acetone, followed by thermal decontamination. The glove was exposed to acetone (outer surface in contact with chemical), subjected to thermal decontamination, and tested for the tensile strength and the ultimate elongation. Thermal decontamination was carried out inside an oven for 16 hours at 100 degrees C. The exposure/decontamination procedure was repeated for a maximum of 10 cycles. For neoprene versus acetone, the mean tensile strength consistently decreased after each exposure/decontamination cycle. Multiple comparisons indicated that the mean tensile strengths between the new swatches and each exposure/decontamination group were significantly different (p 0.05). The mean tensile strength for the new swatches was 37.1 MPa and the mean tensile strength after nine exposure/decontamination cycles was 36.0 MPa, with a loss less than 3%. The largest single cycle loss for ultimate elongation occurred during the first exposure/decontamination cycle for both glove materials. In our previous study, decisions regarding the effectiveness of the decontamination process were based on having no discernible change in the breakthrough time and steady-state permeation rate. The results of this study indicate that the effectiveness of the decontamination process cannot be based on permeation parameters alone but must also take into account the change in physical properties.

  11. Androgen receptor gene CAG repeat length as modifier of the association between Persistent Organohalogen Pollutant exposure markers and semen characteristics

    DEFF Research Database (Denmark)

    Giwercman, Aleksander; Rylander, Lars; Rignell-Hydbom, Anna;

    2007-01-01

    OBJECTIVES: Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed...... and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA. RESULTS: A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count...

  12. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture

    Directory of Open Access Journals (Sweden)

    Oluyomi Stephen Adeyemi

    2014-01-01

    Full Text Available This study determined the effect of the oral and repeated administration of Fijk herbal mixture on rat biochemical and morphological parameters. Twenty-four Wistar rats were distributed into four groups of 6. Group A served as control and received oral administration of distilled water daily. The experimental groups B, C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45 mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood and liver samples were collected and used for the biochemical and morphological analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST, triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose-dependent elevation in the plasma atherogenic index. The histopathology examinations of rat liver sections revealed inimical cellular alterations caused by repeated exposure to Fijk. Study provides evidence that oral and repeated exposure to Fijk in rats raised the atherogenic index and potentiated oxidative stress as well as hepatic injury.

  13. Understanding Specific Effects of Prenatal Alcohol Exposure on Brain Structure in Young Adults

    OpenAIRE

    Chen, Xiangchuan; Coles, Claire D.; Lynch, Mary E; Hu, Xiaoping

    2011-01-01

    Prenatal alcohol exposure (PAE) is associated with various adverse effects on human brain and behavior. Recently, neuroimaging studies have begun to identify PAE effects on specific brain structures. Investigation of such specific PAE effects is important for understanding the teratogenic mechanism of PAE on human brain, which is critical for differentiating PAE from other disorders. In this structural MRI study with young adults, PAE effects on the volumes of automatically segmented cortical...

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

    Science.gov (United States)

    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.

  15. Changes on expected taste perception of probiotic and conventional yogurts made from goat milk after rapidly repeated exposure.

    Science.gov (United States)

    Costa, M P; Balthazar, C F; Franco, R M; Mársico, E T; Cruz, A G; Conte, C A

    2014-05-01

    Goat milk yogurt is an excellent source of fatty acids, protein, and minerals; however, it is not well accepted by many consumers, due to its typical flavor derived from caprylic, capric, and caproic acids present in this milk and dairy products. Recently, the repeated-exposure test has been used to increase the consumption of particular foods. This methodology has been used to increase children's willingness to eat food in some settings and has also been used to reduce sodium in soup. Based on these considerations, the aim of this study was to investigate whether repeated exposures may increase acceptance of both goat milk yogurt and probiotic goat milk yogurt. In a pre-exposure session, a total of 45 panelists (28 females and 17 males) from southeastern Brazil, who were not used to consuming dairy goat milk, evaluated the expected taste perception and the perceived liking after tasting 3 yogurt preparations. Then, consumers were randomly divided into 3 groups and participated in rapidly repeated exposure sessions performed within 6 d. Each panelist consumed only the yogurt that he or she would be exposed to. The day after the exposure sessions, all panelists returned to participate in the postexposure session and were asked to evaluate acceptance, familiarity, and the "goaty taste" characteristic of each yogurt. Regarding the expected liking before tasting, results showed higher expectations for cow milk yogurt compared with goat milk yogurt, which proved that consumers were not familiar with the goat milk yogurt. Likewise, only cow milk yogurt presented high acceptance and familiarity rates, confirming that these panelists were used to consuming cow milk products. With respect to the rapidly repeated exposure, 6 d were enough to significantly increase the consumers' familiarity with goat milk yogurt and probiotic goat milk yogurt. However, this method was not suitable to significantly increase the acceptance of such products. Nonetheless, a correlation existed

  16. Mediation of the Relationship between Maternal Phthalate Exposure and Preterm Birth by Oxidative Stress with Repeated Measurements across Pregnancy.

    Science.gov (United States)

    Ferguson, Kelly K; Chen, Yin-Hsiu; VanderWeele, Tyler J; McElrath, Thomas F; Meeker, John D; Mukherjee, Bhramar

    2017-03-01

    Mediation analysis is useful for understanding mechanisms and has been used minimally in the study of the environment and disease. We examined mediation of the association between phthalate exposure during pregnancy and preterm birth by oxidative stress. This nested case-control study of preterm birth (n = 130 cases, 352 controls) included women who delivered in Boston, Massachusestts, from 2006 through 2008. Phthalate metabolites and 8-isoprostane, an oxidative stress biomarker, were measured in urine from three visits in pregnancy. We applied four counterfactual mediation methods: method 1, utilizing exposure and mediator averages; method 2, using averages but allowing for an exposure-mediator interaction; method 3, incorporating longitudinal measurements of the exposure and mediator; and method 4, using longitudinal measurements and allowing for an exposure-mediator interaction. We observed mediation of the associations between phthalate metabolites and all preterm birth by 8-isoprostane, with the greatest estimated proportion mediated observed for spontaneous preterm births specifically. Fully utilizing repeated measures of the exposure and mediator improved precision of indirect (i.e., mediated) effect estimates, and including an exposure-mediator interaction increased the estimated proportion mediated. For example, for mono(2-ethyl-carboxy-propyl) phthalate (MECPP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), the percent of the total effect mediated by 8-isoprostane increased from 47% to 60% with inclusion of an exposure-mediator interaction term, in reference to a total adjusted odds ratio of 1.67 or 1.48, respectively. This demonstrates mediation of the phthalate-preterm birth relationship by oxidative stress, and the utility of complex regression models in capturing mediated associations when repeated measures of exposure and mediator are available and an exposure-mediator interaction may exist. Citation: Ferguson KK, Chen YH, VanderWeele TJ, Mc

  17. Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol

    OpenAIRE

    De Giorgio Andrea; Comparini Sara E; Intra Francesca; Granato Alberto

    2012-01-01

    Abstract Background Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder. Methods Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin stri...

  18. Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol

    OpenAIRE

    De Giorgio, Andrea; Comparini, Sara E; Intra, Francesca Sangiuliano; Granato, Alberto

    2012-01-01

    Background Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder. Methods Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neur...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

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

    Directory of Open Access Journals (Sweden)

    Xu Li

    2016-08-01

    Full Text Available 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.

  3. Maternal And Neonatal Plasma MicroRNA Biomarkers For Fetal Alcohol Exposure In An Ovine Model

    Science.gov (United States)

    Balaraman, Sridevi; Lunde, E. Raine; Sawant, Onkar; Cudd, Timothy A.; Washburn, Shannon E.; Miranda, Rajesh C.

    2014-01-01

    Background Plasma or circulating miRNAs (cirmiRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate. Methods Pregnant sheep were exposed to a binge model of ethanol consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a three-trimester equivalent period from gestational day (GD) 4 to GD 132. MiRNA profiles were assessed by quantitative PCR analysis in plasma, erythrocyte and leukocytes obtained from non-pregnant ewes, and plasma from pregnant ewes 24 hours following the last binge ethanol episode, and from newborn lambs, at birth on ~GD 147. Results Pregnant ewe and newborn lamb cirmiRNA profiles were similar to each other and different from non-pregnant female plasma, erythrocyte or leukocyte miRNAs. Significant changes in cirmiRNA profiles were observed in the ethanol-exposed ewe, and at birth, in the in utero, ethanol-exposed lamb. CirmiRNAs including miR-9, -15b, -19b and -20a were sensitive and specific measures of ethanol exposure in both pregnant ewe and newborn lamb. Additionally, ethanol exposure altered guide to passenger strand cirmiRNA ratios in the pregnant ewe, but not in the lamb. Conclusion Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. CirmiRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and neonate, and may constitute an important shared endocrine biomarker that is vulnerable to the maternal environment. PMID:24588274

  4. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    OpenAIRE

    Ana ePalomino; Francisco Javier ePavon; Eduardo eBlanco Calvo; Antonia eSerrano; Sergio eArrabal; Patricia eRivera; Antonio eVargas; Ainhoa eBilbao; Leticia eRubio; Fernando eRodriguez de Fonseca; Juan eSuarez

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid recept...

  5. Inhibition of Voltage-Gated Calcium Channels After Subchronic and Repeated Exposure of PC12 Cells to Different Classes of Insecticides.

    Science.gov (United States)

    Meijer, Marieke; Brandsema, Joske A R; Nieuwenhuis, Desirée; Wijnolts, Fiona M J; Dingemans, Milou M L; Westerink, Remco H S

    2015-10-01

    We previously demonstrated that acute inhibition of voltage-gated calcium channels (VGCCs) is a common mode of action for (sub)micromolar concentrations of chemicals, including insecticides. However, because human exposure to chemicals is usually chronic and repeated, we investigated if selected insecticides from different chemical classes (organochlorines, organophosphates, pyrethroids, carbamates, and neonicotinoids) also disturb calcium homeostasis after subchronic (24 h) exposure and after a subsequent (repeated) acute exposure. Effects on calcium homeostasis were investigated with single-cell fluorescence (Fura-2) imaging of PC12 cells. Cells were depolarized with high-K(+) saline to study effects of subchronic or repeated exposure on VGCC-mediated Ca(2+) influx. The results demonstrate that except for carbaryl and imidacloprid, all selected insecticides inhibited depolarization (K(+))-evoked Ca(2+) influx after subchronic exposure (IC50's: approximately 1-10 µM) in PC12 cells. These inhibitory effects were not or only slowly reversible. Moreover, repeated exposure augmented the inhibition of the K(+)-evoked increase in intracellular calcium concentration induced by subchronic exposure to cypermethrin, chlorpyrifos, chlorpyrifos-oxon, and endosulfan (IC50's: approximately 0.1-4 µM). In rat primary cortical cultures, acute and repeated chlorpyrifos exposure also augmented inhibition of VGCCs compared with subchronic exposure. In conclusion, compared with subchronic exposure, repeated exposure increases the potency of insecticides to inhibit VGCCs. However, the potency of insecticides to inhibit VGCCs upon repeated exposure was comparable with the inhibition previously observed following acute exposure, with the exception of chlorpyrifos. The data suggest that an acute exposure paradigm is sufficient for screening chemicals for effects on VGCCs and that PC12 cells are a sensitive model for detection of effects on VGCCs. © The Author 2015. Published by Oxford

  6. Mitochondrial tolerance to single and repeat exposure to simulated sunlight in human epidermal and dermal skin cells.

    Science.gov (United States)

    Kelly, J; Murphy, J E J

    2016-12-01

    Sunlight represents the primary threat to mitochondrial integrity in skin given the unique nature of the mitochondrial genome and its proximity to the electron transport chain. The accumulation of mitochondrial DNA (mtDNA) mutations is a key factor in many human pathologies and this is linked to key roles of mitochondrial function in terms of energy production and cell regulation. The main objective of this study was to evaluate solar radiation induced changes in mitochondrial integrity, function and dynamics in human skin cells using a Q-Sun solar simulator to deliver a close match to the intensity of summer sunlight. Spontaneously immortalised human skin epidermal keratinocytes (HaCaT) and Human Dermal Fibroblasts (HDFn) were divided into two groups. Group A were irradiated once and Group B twice 7days apart and evaluated using cell survival, viability and mitochondrial membrane potential (MMP) and mass at 1, 4 and 7days post one exposure for Group A and 1, 4, 7 and 14days post second exposure for Group B. Viability and survival of HaCaT and HDFn cells decreased after repeat exposure to Simulated Sunlight Irradiation (SSI) with no recovery. HDFn cells showed no loss in MMP after one or two exposures to SSI compared to HaCaT cells which showed a periodic loss of MMP after one exposure with a repeat exposure causing a dramatic decrease from which cells did not recover. Mitochondrial Mass in exposed HDFn cells was consistent with control after one or two exposures to SSI; however mitochondrial mass was significantly decreased in HaCaT cells. Data presented here suggests that mitochondria in epidermal cells are more sensitive to sunlight damage compared to mitochondria in dermal cells, despite their origin, confirming a skin layer specific sensitivity to sunlight, but not as expected. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Exposure to ambient air particulate matter and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tarantino, Giovanni; Capone, Domenico; Finelli, Carmine

    2013-07-07

    The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters liver disease (NAFLD), the most common chronic liver disease in Western countries. For far too long literature data have been fixated on pulmonary diseases and/or cardiovascular disease, as consequence of particulate exposure, ignoring the link between the explosion of obesity with related syndromes such as NAFLD and air pollution, the worst characteristics of nowadays civilization. In order to delineate a clear picture of this major health problem, further studies should investigate whether and at what extent cigarette smoking and exposure to ambient air PM2.5 impact the natural history of patients with obesity-related NAFLD, i.e., development of non alcoholic steatohepatitis, disease characterized by a worse prognosis due its progression towards fibrosis and hepatocarcinoma.

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

    Directory of Open Access Journals (Sweden)

    E.M. Meintjes

    2014-01-01

    Full Text Available 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.

  9. Embryonic Alcohol Exposure Leading to Social Avoidance and Altered Anxiety Responses in Adult Zebrafish.

    Science.gov (United States)

    Baggio, Suelen; Mussulini, Ben Hur; de Oliveira, Diogo Losch; Gerlai, Robert; Rico, Eduardo Pacheco

    2017-09-04

    Fetal Alcohol Spectrum Disorders (FASD) is a syndrome characterized by neurological and behavioral impairments. A recently discovered hallmark of FASD is impaired social behavior. Avoidance of social interaction typical of FASD may be the result of increased anxiety. Previously, the zebrafish was successfully used to model embryonic alcohol induced social abnormalities. Here, we analyzed both anxiety and social responses using a zebrafish FASD model, in adult fish. We exposed zebrafish embryos to low concentrations of ethanol (0.1%; 0.25%; 0.5% and 1% v/v) for 2h at, 24hours post-fertilization, to mimic the most prevalent milder FASD cases, and investigated the ensuing alterations in adult, 4-month-old, zebrafish. We studied social interaction in the social preference task and anxiety in the novel tank task. We observed an ethanol dose dependent reduction of time spend in the conspecific zone compared to control, corroborating prior findings. We also found significant changes in the novel tank (e.g. increased bottom dwell time, increased distance to top) suggesting elevated anxiety to control, but we also found, using an anxiolytic drug buspirone, that reduction of anxiety is associated with reduced shoaling. Our results confirm that embryonic alcohol exposure disrupts social behavior, and also show that its effects on anxiety related phenotypes may be genotype, alcohol administration method, experimental procedure and test-context dependent. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of repeated exposure to malathion on growth, food consumption, and locomotor performance of the western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    Holem, Ryan R. [University of Georgia, Savannah River Ecology Laboratory, Aiken, SC 29801 (United States); ENTRIX, Inc., Okemos, MI 48864 (United States); Hopkins, William A. [University of Georgia, Savannah River Ecology Laboratory, Aiken, SC 29801 (United States); Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States)], E-mail: hopkinsw@vt.edu; Talent, Larry G. [Natural Resource Ecology and Management, Oklahoma State University, Stillwater, OK 74078 (United States)

    2008-03-15

    Effects of repeated pollutant exposure on growth, locomotor performance, and behavior have rarely been evaluated in reptiles. We administered three doses of malathion (2.0, 20, or 100 mg/kg body weight) to western fence lizards (Sceloporus occidentalis) over an 81 day period. Eight and 23% mortality occurred at 20 and 100 mg/kg (p = 0.079) and 85% of lizards in the 100 mg/kg group exhibited clinical symptoms of poisoning. Growth, food consumption, body condition index, and terrestrial locomotor performance were not significantly influenced by malathion. However, arboreal sprint velocity was significantly reduced in lizards receiving 100 mg/kg. Fifty percent of lizards in the 100 mg/kg group also refused to sprint in the arboreal setting (p = 0.085). Based on these results, arboreal locomotor performance was the most sensitive metric of exposure we evaluated. Further study of compounds such as malathion is warranted due to highly variable application rates and exposure scenarios. - Repeated exposure of western fence lizards to malathion caused reduced arboreal performance and some mortality but growth, food consumption, and terrestrial performance were not affected.

  11. Novel oxytocin gene expression in the hindbrain is induced by alcohol exposure: transgenic zebrafish enable visualization of sensitive neurons.

    Directory of Open Access Journals (Sweden)

    Caitrín M Coffey

    Full Text Available BACKGROUND: Fetal Alcohol Spectrum Disorders (FASD are a collection of disorders resulting from fetal ethanol exposure, which causes a wide range of physical, neurological and behavioral deficits including heightened susceptibility for alcoholism and addictive disorders. While a number of mechanisms have been proposed for how ethanol exposure disrupts brain development, with selective groups of neurons undergoing reduced proliferation, dysfunction and death, the induction of a new neurotransmitter phenotype by ethanol exposure has not yet been reported. PRINCIPAL FINDINGS: The effects of embryonic and larval ethanol exposure on brain development were visually monitored using transgenic zebrafish expressing cell-specific green fluorescent protein (GFP marker genes. Specific subsets of GFP-expressing neurons were highly sensitive to ethanol exposure, but only during defined developmental windows. In the med12 mutant, which affects the Mediator co-activator complex component Med12, exposure to lower concentrations of ethanol was sufficient to reduce GFP expression in transgenic embryos. In transgenic embryos and larva containing GFP driven by an oxytocin-like (oxtl promoter, ethanol exposure dramatically up-regulated GFP expression in a small group of hindbrain neurons, while having no effect on expression in the neuroendocrine preoptic area. CONCLUSIONS: Alcohol exposure during limited embryonic periods impedes the development of specific, identifiable groups of neurons, and the med12 mutation sensitizes these neurons to the deleterious effects of ethanol. In contrast, ethanol exposure induces oxtl expression in the hindbrain, a finding with profound implications for understanding alcoholism and other addictive disorders.

  12. Cholecalciferol attenuates perseverative behavior associated with developmental alcohol exposure in rats in a dose-dependent manner.

    Science.gov (United States)

    Idrus, N M; Happer, J P; Thomas, J D

    2013-07-01

    Alcohol is a known teratogen that is estimated to affect 2-5% of the births in the U.S. Prenatal alcohol exposure can produce physical features such as facial dysmorphology, physiological alterations such as cell loss in the central nervous system (CNS), and behavioral changes that include hyperactivity, cognitive deficits, and motor dysfunction. The range of effects associated with prenatal alcohol exposure is referred to as fetal alcohol spectrum disorders (FASD). Despite preventative measures, some women continue to drink while pregnant. Therefore, identifying interventions that reduce the severity of FASD is critical. This study investigated one such potential intervention, vitamin D3, a nutrient that exerts neuroprotective properties. The present study determined whether cholecalciferol, a common vitamin D3 nutritional supplement, could serve as a means of mitigating alcohol-related learning deficits. Using a rat model of FASD, cholecalciferol was given before, during, and after 3rd trimester equivalent alcohol exposure. Three weeks after cholecalciferol treatment, subjects were tested on a serial spatial discrimination reversal learning task. Animals exposed to ethanol committed significantly more errors compared to controls. Cholecalciferol treatment reduced perseverative behavior that is associated with developmental alcohol exposure in a dose-dependent manner. These data have important implications for the treatment of FASD and suggest that cholecalciferol may reduce some aspects of FASD. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

  13. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Ana ePalomino

    2014-03-01

    Full Text Available Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression (CB1 receptors and enzymes that produce (DAGLα/β and NAPE-PLD and degrade (MAGL and FAAH eCB were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system (glutamate synthesizing enzymes LGA and KGA, mGluR3/5 metabotropic receptors, and NR1/2A/2B/2C-NMDA and GluR1/2/3/4-AMPA ionotropic receptor subunits and the gene expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-AG production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that

  14. In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry

    2010-01-01

    In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through...... national registers as possibly having strabismus. Relative risk estimates were adjusted for year of birth, social class, maternal smoking, maternal age at birth, and maternal coffee and tea consumption. The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996.......92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light...

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

    Science.gov (United States)

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

    2016-01-01

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

  16. In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry;

    2010-01-01

    In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through.......92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light...... national registers as possibly having strabismus. Relative risk estimates were adjusted for year of birth, social class, maternal smoking, maternal age at birth, and maternal coffee and tea consumption. The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996...

  17. Intervention strategies for children vulnerable for school failure due to exposure to drugs and alcohol.

    Science.gov (United States)

    Smith, G H

    1993-11-01

    Children and youth exposed in utero to drugs and alcohol and/or who are growing up in a family in which these substances are misused are vulnerable for failure at all age levels, prenatally through adulthood. This article reviews developmental issues presented by children and youth vulnerable for school failure either due to the biological effects of prenatal exposure to drugs and/or environmental issues resulting from growing up in a family in which misuse of drugs and alcohol occurs. Characteristics and needs of these students with recommendations for educational and community-based system of services to them and their families are discussed. Model programs serving children and youth prenatally through school age are identified.

  18. Neuronal reduction in frontal cortex of primates after prenatal alcohol exposure.

    Science.gov (United States)

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

    2009-01-07

    Children with fetal alcohol spectrum disorders (FASD) show behavioral and intellectual impairments that indicate frontal lobe dysfunction, but the extent of damage to this region has not been clarified by brain imaging studies. This study uses the St Kitts vervet monkey, a species that voluntarily consumes beverage alcohol, to examine the effects of prenatal ethanol exposure. Pregnant vervets were allowed to drink the equivalent of 3-5 standard drinks four times a week during the third trimester. Using unbiased stereology, we estimated neuronal reduction and found significantly fewer cells in the frontal lobes of FASD offspring as well as an increased density of interstitial white matter neurons. These cytoarchitectonic effects are consistent with the behavioral and cognitive changes observed in FASD.

  19. Repeated exposures to blue light-activated eosin Y enhance inactivation of E. faecalis biofilms, in vitro.

    Science.gov (United States)

    Marinic, Karlo; Manoil, Daniel; Filieri, Anna; Wataha, John C; Schrenzel, Jacques; Lange, Norbert; Bouillaguet, Serge

    2015-09-01

    In dentistry, antibacterial photodynamic therapy (a-PDT) has shown promising results for inactivating bacterial biofilms causing carious, endodontic and periodontal diseases. In the current study, we assessed the ability of eosin Y exposed to 3 irradiation protocols at inactivating Enterococcus faecalis biofilms, in vitro. E. faecalis biofilms formed on hydroxyapatite disks were incubated with eosin Y (10-80μM), then activated with blue light using different irradiation protocols. Biofilms exposed to continuous exposure were incubated for 40min before being light-activated for 960 s. For the intermittent exposure, biofilms were exposed 4 times to the light/photosensitizer combination (960 s total) without renewing the photosensitizer. For repeated a-PDT, the same light dose was delivered in a series of 4 irradiation periods separated by dark periods; fresh photosensitizer was added between each light irradiation. After treatment, bacteria were immediately labeled with LIVE/DEAD BacLight Bacterial Viability kit and viability was assessed by flow cytometry (FCM). Results were statistically analyzed using one-way ANOVA and Tukey multiple comparison intervals (α=0.05). The viability of E. faecalis biofilms exposed to 10μM eosin Y, was significantly reduced compared to controls (light only-eosin Y only). After a second exposure to blue light-activated eosin Y, viability significantly decreased from 58% to 12% whereas 6.5% of the bacterial biofilm remained live after a third exposure (p<0.05). Only 3.5% of the bacterial population survived after the fourth exposure. The results of this study indicate that blue light-activated eosin Y can photoinactivate E. faecalis biofilms grown on hydroxyapatite disks. Also, repeated exposures to blue light-activated eosin Y were shown to significantly improve efficacy. Further studies seem warranted to optimize the antibacterial activity of blue light-activated eosin Y on major oral pathogens. Copyright © 2015 Elsevier B.V. All

  20. Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

    NARCIS (Netherlands)

    Rennen, M.A.J.; Nordheim, K.; Houben, G.F.; Heer, C. de

    2002-01-01

    Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in

  1. Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

    NARCIS (Netherlands)

    Rennen, M.A.J.; Nordheim, K.; Houben, G.F.; Heer, C. de

    2002-01-01

    Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in

  2. NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

    Science.gov (United States)

    This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult rats were maintained on a chlorpyrifos-containing diet to p...

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

    Energy Technology Data Exchange (ETDEWEB)

    Nekvasil, N.; Baggio, C. (St. Mary' s Coll., Notre Dame, IN (United States))

    1992-02-26

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

  4. Effect of alcohol exposure on hepatic superoxide generation and hepcidin expression

    Institute of Scientific and Technical Information of China (English)

    Duygu; Dee; Harrison-Findik; Sizhao; Lu; Emily; M; Zmijewski; Jocelyn; Jones; Matthew; C; Zimmerman

    2013-01-01

    AIM: To understand the role of mitochondrial-produced superoxide(O 2 ?) in the regulation of iron-regulatory hormone, hepcidin by alcohol in the liver. METHODS: For alcohol experiments, manganese superoxide dismutase knockout mice heterozygous for Sod2 gene expression(Sod2 +/) and age-matched littermate control mice(LMC), expressing Sod2 gene on both alleles, were exposed to either 10%(w/v) ethanol in the drinking water or plain water(control) for 7 d. Total cellular O 2 ? levels in hepatocytes isolated from the livers of mice were measured by electron paramagnetic resonance spectroscopy. The mitochondrial-targeted, O 2 ?-sensitive fluorogenic probe, MitoSOX Red and flow cytometry were utilized to measure O 2 ? in mitochondria. Gene and protein expression were determined by Taqman Real-time quantitative PCR and Western blotting, respectively. RESULTS: Sod2 +/- mice expressed 40% less MnSOD protein(SOD2) in hepatocytes compared to LMC mice. The deletion of Sod2 allele did not alter the basal expression level of hepcidin in the liver. 10% ethanol exposure for 1 wk inhibited hepatic hepcidin mRNA expression three-fold both in Sod2 +/ and LMC mice. O 2 ? levels in hepatocytes of untreated Sod2 +/ mice were three-fold higher than in untreated LMC mice, as observed by electron paramagnetic resonance spectroscopy. O 2 ? levels in mitochondria of Sod2 +/ mice were four-fold higher than in mitochondria of untreated LMC mice, as measured by MitoSOX Red fluorescence and flow cytometry. Alcohol induced a two-fold higher increase in O 2 ? levels in hepatocytes of LMC mice than in Sod2 +/ mice compared to respective untreated counterparts. In contrast, 1 wk alcohol exposure did not alter mitochondrial O 2 ? levels in both Sod2 +/- and control mice. CONCLUSION: Mitochondrial O2 ? is not involved in the inhibition of liver hepcidin transcription and thereby regulation of iron metabolism by alcohol. These findings also suggest that short-term alcohol consumption significantly

  5. Changes of lead speciation and microbial toxicity in soil treated with repeated Pb exposure in the presence of BDE209.

    Science.gov (United States)

    Zhang, Rong; Zhang, Wei; Liu, Gao; Lin, Kuangfei; Fu, Rongbing

    2016-03-01

    Lead (Pb) and decabromodiphenyl ether (BDE209) are main pollutants at electric waste (e-waste) recycling sites (EWRSs), and their joint toxicological effects have received extensive attention. Frequently, soil pollution at EWRSs usually results from the occurrence of repeated single or multiple pollution events, with continuous impacts on soil microorganisms. Therefore, a laboratory incubation study was conducted to determine Pb bioavailability and microbial toxicity in repeated Pb-polluted soil in the presence of BDE209 for the first time. We evaluated the impacts of repetitive exposure trials on chemical fractions of Pb, and the results showed that repeated single Pb pollution event resulted in an increase of carbonates fraction of Pb, which was different from one-off single Pb exposure. Moreover, one-off Pb-treated groups exhibited higher I R (reduced partition index) values on day 30 and all treatments remained the same I R level at the end of incubation period. The parameters of microbial toxicity were well reflected by soil enzymes. During the entire incubation, the dehydrogenase and urease activities were significantly inhibited by Pb (P soil enzymes were clearly observed (P < 0.05 or 0.01). Such observations would provide useful information for ecological effects of Pb and BDE209 at EWRSs.

  6. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

    Science.gov (United States)

    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

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

    Science.gov (United States)

    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.

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

    OpenAIRE

    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],...

  9. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures

    DEFF Research Database (Denmark)

    Vestergaard, M; Wisborg, K; Henriksen, TB

    2005-01-01

    of extensive brain growth and differentiation in this period. We evaluated the association between prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures in 2 population-based birth cohorts. METHODS: The Aarhus Birth Cohort consisted of 25,196 children of mothers who were...... follow-up. We extracted from medical records additional information on febrile seizures in children in the Aarhus Birth Cohort who were born between 1989 and 1992. RESULTS: We found a slightly increased risk for febrile seizures in children who were exposed to 10 or more cigarettes per day in the Aarhus...

  10. Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice.

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    Full Text Available Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15 µg/animal every 2(nd day for 6 days (a total of 4 exposures, and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α in the bronchoalveolar lavage (BAL fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP and TNF α concentrations, systolic blood pressure (SBP as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1. Pretreatment with curcumin by oral gavage (45 mg/kg 1 h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.

  11. Social disparities in children’s exposure to second hand smoke at home: a repeated cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Pisinger Charlotta

    2012-09-01

    Full Text Available Abstract Background Exposure to second hand smoke (SHS is an important preventable cause of morbidity and mortality in children. We hypothesised that there has been a growth in social inequality in children’s exposure to SHS at home over time. The purpose of this study was to investigate temporal change in smoking in homes including children, focusing on the socioeconomic differences. Methods Data is from a repeated cross-sectional survey, ‘Health Profiles of the Capital Region of Denmark’ conducted in 2007 and 2010, in 29 municipalities. The response rate was 52.3%, in both surveys. Our study included persons aged 25 to 64, living with children ≤15 years of age; N=9,289 in 2007 and 12,696 in 2010. Analyses were weighted for size of municipality and for non-response, which was higher among men and among persons who were younger, had a lower income, were living alone, were unemployed, and/or were of an ethnicity other than Danish. Regression analyses were used to investigate smoking in homes including children across parent/adult education levels, focusing on temporal changes. Results There were significant large socioeconomic differences in both 2007 and 2010. In 2010 it was more than 11 times more likely for a child to be exposed to SHS at home if the parent had very low education than if they were highly educated (p Conclusions Marked social inequalities in children’s exposure to SHS and a significant temporal decrease in exposure, independent of the education level of the parent/adult, were found in repeated large cross-sectional population-based studies. Social disparities have persisted over time, but not increased. Both clinical and population policy interventions will be needed in order to control child SHS exposure. We call for legislative protection of children from tobacco smoke inside their home as a supplement to parental education and support for smoking cessation.

  12. Prenatal alcohol exposure and language delay in 2-year-old children: the importance of dose and timing on risk.

    Science.gov (United States)

    O'Leary, Colleen; Zubrick, Stephen R; Taylor, Catherine L; Dixon, Glenys; Bower, Carol

    2009-02-01

    The aim of this study was to investigate the association of dose and timing of prenatal alcohol exposure with early language acquisition. We examined language delay in a randomly selected, population-based sample of Western Australian children born in 1995-1996 whose mothers had agreed to participate in a longitudinal study on health-related behaviors and who had completed the 2-year questionnaire (N = 1739). Information on alcohol consumption was collected at 3 months after birth for four periods; the three months pre-pregnancy and for each trimester separately. Prenatal alcohol exposure was grouped into none, low, moderate-heavy and binge (>5) based on the total quantity consumed per week, quantity consumed per occasion, and frequency of consumption. The communication scale from the Ages & Stages Questionnaire was used to evaluate language delay. Logistic regression analysis was used to generate odds ratios and 95% confidence intervals, adjusted for confounding factors. There was no association between low levels of alcohol consumption and language delay at any time period, although there was a nonsignificant 30% increase in risk when moderate-to-heavy levels of alcohol were consumed in the third trimester. Children exposed to a binge pattern of maternal alcohol consumption in the second trimester had nonsignificant, three-fold increased odds of language delay, with a similar estimate following third trimester alcohol exposure after controlling for covariates. This study did not detect an association between low levels of prenatal alcohol exposure and language delay when compared with women who abstained from alcohol during pregnancy. A nonsignificant threefold increase in the likelihood of language delay was seen in children whose mothers binged during late pregnancy. However, the small numbers of women with a binge-drinking pattern in late pregnancy limited the power of this study; studies analyzing larger numbers of children exposed to binge drinking in late

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

    Directory of Open Access Journals (Sweden)

    Omkaram Gangisetty

    Full Text Available 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.

  14. Repeated exposure to amphetamine during adolescence alters inhibitory tone in the medial prefrontal cortex following drug re-exposure in adulthood

    Science.gov (United States)

    Cox, Charles L.; Gulley, Joshua M.

    2016-01-01

    Behavioral sensitization following repeated amphetamine (AMPH) exposure is associated with changes in GABA function in the medial prefrontal cortex (mPFC). In rats exposed to AMPH during adolescence compared to adulthood, there are unique patterns of sensitization that may reflect age-dependent differences in drug effects on prefrontal GABAergic function. In the current study, we used a sensitizing regimen of repeated AMPH exposure in adolescent and adult rats to determine if a post-withdrawal AMPH challenge would alter inhibitory transmission in the mPFC in a manner that depends on age of exposure. Male Sprague-Dawley rats were treated with saline or 3 mg/kg AMPH (i.p.) during adolescence [postnatal day (P) 27 to P45] or adulthood (P85 to P103) and were sacrificed either at similar ages in adulthood (~P133; Experiment 1) or after similar withdrawal times (3-4 weeks; Experiment 2). Spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in vitro from deep layer pyramidal cells in the mPFC using the whole-cell configuration. We found no effect of AMPH pre-exposure on baseline sIPSC frequency. Subsequent application of AMPH (25 μM) produced a stable increase in sIPSC frequency in controls, suggesting that AMPH increases inhibitory tone in the mPFC. However, AMPH failed to increase sIPSCs in adolescent- or adult-exposed rats. In Experiment 2, where withdrawal period was kept similar for both exposure groups, AMPH induced a suppression of sIPSC activity in adolescent-exposed rats. These results suggest that sensitizing treatment with AMPH during adolescence or adulthood dampens inhibitory influences on mPFC pyramidal cells, but potentially through different mechanisms. PMID:27085589

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

    Science.gov (United States)

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

    2011-07-01

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

  16. Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in experiments involving computer-assisted self-infusion of ethanol (CASE).

    Science.gov (United States)

    Zimmermann, Ulrich S; Mick, Inge; Laucht, Manfred; Vitvitskiy, Victor; Plawecki, Martin H; Mann, Karl F; O'Connor, Sean

    2009-03-01

    Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration.

  17. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  18. Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse

    Energy Technology Data Exchange (ETDEWEB)

    Vanyukov, M.M.; Moss, H.B.; Tarter, R.E. [Univ. of Pittsburg, PA (United States)] [and others

    1995-04-24

    An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with {open_quotes}long{close_quotes} alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. 22 refs., 1 fig., 3 tabs.

  19. Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

    DEFF Research Database (Denmark)

    Lof, A.; Lam, Henrik Rye; Gullstrand, E.

    1999-01-01

    spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure....... Two hours after the end of exposure the n-decane concentration decreased to about 25% in blood and 50% in brain. A similar pattern of elimination was also observed for n-nonane, n-undecane and total white spirit in blood and brain. In fat tissue the concentrations of n-nonane, n-decane, n......-undecane, and total white spirit increased during the 3 weeks of exposure. The time to reach steady-state concentrations is longer than 3 weeks. After the 3 weeks' exposure the fat tissue concentration of n-nonane, n-decane, n-undecane, and total white spirit decreased very slowly compared with the rate of decrease...

  20. Effects of Repeated Cocaine Exposure on Habit Learning and Reversal by N-Acetylcysteine

    Science.gov (United States)

    Corbit, Laura H; Chieng, Billy C; Balleine, Bernard W

    2014-01-01

    Exposure to drugs of abuse can result in a loss of control over both drug- and nondrug-related actions by accelerating the transition from goal-directed to habitual control, an effect argued to reflect changes in glutamate homeostasis. Here we examined whether exposure to cocaine accelerates habit learning and used in vitro electrophysiology to investigate its effects on measures of synaptic plasticity in the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas critical for actions and habits, respectively. We then administered N-acetylcysteine (NAC) in an attempt to normalize glutamate homeostasis and hence reverse the cellular and behavioral effects of cocaine exposure. Rats received daily injections of cocaine (30 mg/kg) for 6 days and were then trained to lever press for a food reward. We used outcome devaluation and whole-cell patch-clamp electrophysiology to assess the behavioral and cellular effects of cocaine exposure. We then examined the ability of NAC to reverse the effects of cocaine exposure on these measures. Cocaine treatment produced a deficit in goal-directed action, as assessed by outcome devaluation, and increased the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in the DMS but not in the DLS. Importantly, NAC treatment both normalized EPSC frequency and promoted goal-directed control in cocaine-treated rats. The promotion of goal-directed control has the potential to improve treatment outcomes in human cocaine addicts. PMID:24531561

  1. Comparison of Adaptive Behavior in Children With Heavy Prenatal Alcohol Exposure or Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Crocker, Nicole; Vaurio, Linnea; Riley, Edward P.; Mattson, Sarah N.

    2012-01-01

    Background Adaptive behavior, the ability to respond successfully to everyday demands, may be especially sensitive to the effects of heavy prenatal alcohol exposure. Similar adaptive dysfunction is common in other developmental disorders including attention-deficit/hyperactivity disorder (ADHD). ADHD is frequently present in alcohol-exposed children and this overlap in clinical presentation makes identification of alcohol-exposed children difficult. Direct comparison of children with prenatal alcohol exposure and ADHD may yield distinct patterns of cognitive and behavioral performance and add to growing knowledge of the neuropsychological and behavioral profile of prenatal alcohol exposure. Therefore, the aim of the current study was to compare adaptive behavior in children with histories of heavy prenatal alcohol exposure (ALC), nonexposed children with ADHD (ADHD), and typically developing controls (CON). Methods Sixty-five children (ALC = 22, ADHD = 23, CON = 20) were selected from a larger ongoing study of the behavioral teratogenicity of alcohol. Alcohol-exposed and control participants were selected to match the ADHD subjects on age, sex, socioeconomic status, and race/ethnicity. Caregivers were administered the Vineland Adaptive Behavior Scales, a semi-structured interview, and were asked to rate their child’s behavior on 3 domains of adaptive function. Data were analyzed using regression techniques. Results Relative to controls, children in both the ALC and ADHD groups showed adaptive behavior deficits on all 3 domains and children in the ALC group were significantly more impaired than the ADHD group on the daily living skills domain. Within the ALC group, socialization standard scores were lower at older ages. This negative relationship between age and standard scores in the ALC group was also observed on the communication domain, a finding not previously reported. Conclusions This study suggests that both children with prenatal alcohol exposure and

  2. Alcohol

    NARCIS (Netherlands)

    Hendriks, H.F.; Tol, A. van

    2005-01-01

    Alcohol consumption affects overall mortality. Light to moderate alcohol consumption reduces the risk of coronary heart disease; epidemiological, physiological and genetic data show a causal relationship. Light to moderate drinking is also associated with a reduced risk of other vascular diseases an

  3. Visual-spatial abilities relate to mathematics achievement in children with heavy prenatal alcohol exposure.

    Science.gov (United States)

    Crocker, Nicole; Riley, Edward P; Mattson, Sarah N

    2015-01-01

    The current study examined the relationship between mathematics and attention, working memory, and visual memory in children with heavy prenatal alcohol exposure and controls. Subjects were 56 children (29 AE, 27 CON) who were administered measures of global mathematics achievement (WRAT-3 Arithmetic & WISC-III Written Arithmetic), attention, (WISC-III Digit Span forward and Spatial Span forward), working memory (WISC-III Digit Span backward and Spatial Span backward), and visual memory (CANTAB Spatial Recognition Memory and Pattern Recognition Memory). The contribution of cognitive domains to mathematics achievement was analyzed using linear regression techniques. Attention, working memory, and visual memory data were entered together on Step 1 followed by group on Step 2, and the interaction terms on Step 3. Model 1 accounted for a significant amount of variance in both mathematics achievement measures; however, model fit improved with the addition of group on Step 2. Significant predictors of mathematics achievement were Spatial Span forward and backward and Spatial Recognition Memory. These findings suggest that deficits in spatial processing may be related to math impairments seen in FASD. In addition, prenatal alcohol exposure was associated with deficits in mathematics achievement, above and beyond the contribution of general cognitive abilities. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  4. Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine

    Directory of Open Access Journals (Sweden)

    Catherine E. Creeley

    2013-07-01

    Full Text Available Anesthetic and anti-epileptic drugs used in pediatric and obstetric medicine and several drugs, including alcohol, that are abused by pregnant women, trigger widespread neuroapoptosis in the developing brain of several animal species, including non-human primates. Caffeine (CAF is often administered to premature infants to stimulate respiration, and these infants are also exposed simultaneously to anesthetic drugs for procedural sedation and/or surgical procedures. Pregnant women who abuse alcohol or other apoptogenic drugs also may heavily consume CAF. We administered CAF to infant mice alone or in combination with alcohol, phencyclidine, diazepam, midazolam, ketamine, or isoflurane, which are drugs of abuse and/or drugs frequently used in pediatric medicine, and found that CAF weakly triggers neuroapoptosis by itself and markedly potentiates the neuroapoptogenic action of each of these other drugs. Exposure of infant mice to CAF + phencyclidine resulted in long-term impairment in behavioral domains relevant to attention deficit/hyperactivity disorder, whereas exposure to CAF + diazepam resulted in long-term learning/memory impairment. At doses used in these experiments, these behavioral impairments either did not occur or were substantially less pronounced in mice exposed to CAF alone or to phencyclidine or diazepam alone. CAF currently enjoys the reputation of being highly beneficial and safe for use in neonatal medicine. Our data suggest the need to consider whether CAF may have harmful as well as beneficial effects on the developing brain, and the need for research aimed at understanding the full advantage of its beneficial effects while avoiding its potentially harmful effects.

  5. Exposure of children and adolescents to alcohol marketing on social media websites.

    Science.gov (United States)

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

    2014-01-01

    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. 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. 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. 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.

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

    Science.gov (United States)

    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

  7. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    Science.gov (United States)

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome.

  8. Effect of brief, repeated hyperbaric exposures on susceptibility to nitrogen narcosis.

    Science.gov (United States)

    Rogers, W H; Moeller, G

    1989-05-01

    We investigated the effect of brief, repetitive exposures to 5.5 ATA (148 fsw) in a hyperbaric chamber on adaptation to nitrogen narcosis. A standing-steadiness task, which measures body sway, was administered to 2 groups of 3 chamber-qualified men at 5.5 ATA and 1.3 ATA [10 fsw (control)] on each of 12 successive days to determine if an initial performance decrement at 5.5 ATA would be ameliorated with time. Standing steadiness was significantly worse at 5.5 ATA than at 1.3 ATA across all 12 exposures. There were also changes in standing steadiness from day to day, but these changes occurred in both the test and control depths. There was no day-x-depth interaction that would have indicated that the initial performance decrement at 5.5 ATA was reduced with repetitive exposures. These results are taken as evidence that there is little or no behavioral adaptation to nitrogen narcosis in response to brief, repetitive exposures to narcosis-inducing hyperbaric air.

  9. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

    OpenAIRE

    Gershkovich, Pavel; Wasan, Kishor M.; Ribeyre, Charles; Ibrahim, Fady; McNeill, John H

    2015-01-01

    Purpose: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrh...

  10. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Gloria A. Santa-Gonzalez

    2016-10-01

    Full Text Available Many environmental and physiological stresses are chronic. Thus, cells are constantly exposed to diverse types of genotoxic insults that challenge genome stability, including those that induce oxidative DNA damage. However, most in vitro studies that model cellular response to oxidative stressors employ short exposures and/or acute stress models. In this study, we tested the hypothesis that chronic and repeated exposure to a micromolar concentration of hydrogen peroxide (H2O2 could activate DNA damage responses, resulting in cellular adaptations. For this purpose, we developed an in vitro model in which we incubated mouse myoblast cells with a steady concentration of ~50 μM H2O2 for one hour daily for seven days, followed by a final challenge of a 10 or 20X higher dose of H2O2 (0.5 or 1 mM. We report that intermittent long-term exposure to this oxidative stimulus nearly eliminated cell toxicity and significantly decreased genotoxicity (in particular, a >5-fold decreased in double-strand breaks resulting from subsequent acute exposure to oxidative stress. This protection was associated with cell cycle arrest in G2/M and induction of expression of nine DNA repair genes. Together, this evidence supports an adaptive response to chronic, low-level oxidative stress that results in genomic protection and up-regulated maintenance of cellular homeostasis.

  11. The development of behavioral and endocrine abnormalities in rats after repeated exposure to direct and indirect stress.

    Science.gov (United States)

    Daniels, Willie Mark Uren; de Klerk Uys, Joachim; van Vuuren, Petra; Stein, Daniel Joseph

    2008-04-01

    The present study compared the effects of direct and indirect stress on the behavior and hypothalamic-pituitary-adrenal axis of rats. Animals were placed in a two compartment box. In one compartment the direct stressed rat was subjected to electric foot shocks randomly applied for 10 minutes (0.5 mA of 1 s duration). In the adjacent compartment, the indirect stressed rats witnessed the application of these electric foot shocks. Our data showed substantial behavioral changes in the open field test, but limited effects in the elevated plus maze. The findings suggested that single and repeated stress exposure may have different consequences, that the effects of stress exposure may develop over time and persist for an extended period, and that both direct and indirect stressed rats displayed a hyposensitive HPA axis following acute restraint stress. Overall our observations moderately indicate direct exposure to elicit behavioral changes, and both direct and indirect exposure to stress to result in aberrations within the neuroendocrine system. With additional development our stress models may be considered for studying the complex interrelationship between an external stressor, and the experience of the organism.

  12. 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.

    Science.gov (United States)

    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.

  13. Single and repeated sevoflurane or desflurane exposure does not impair spatial memory performance of young adult mice.

    Science.gov (United States)

    Kilicaslan, Alper; Belviranli, Muaz; Okudan, Nilsel; Nurullahoglu Atalik, Esra

    2013-12-01

    Volatile anesthetics are known to disturb the spatial memory in aged rodents, but there is insufficient information on their effects on young adult rodents. The aim of this study was to compare the effects of single and repeated exposure to desflurane and sevoflurane on spatial learning and memory functions in young adult mice. Balb/c mice (2 months old) were randomly divided into six equal groups (n = 8). The groups with single inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or vehicle gas for 4 h, respectively. The groups with repeated inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or vehicle gas for 2 h a day during 5 consecutive days. Spatial learning and memory were tested in the Morris water maze 24 h after exposure. In the learning phase, the parameters associated with finding the hidden platform and swimming speed, and in the memory phase, time spent in the target quadrant and the adjacent quadrants, were assessed and compared between the groups. In the 4-day learning process, there was no significant difference between the groups in terms of mean latency to platform, mean distance traveled and average speed (P > 0.05). During the memory-test phase, all mice exhibited spatial memory, but there was no significant difference between the groups in terms of time spent in the target quadrant (P > 0.05). Sevoflurane and desflurane anesthesia did not impair acquisition learning and retention memory in young adult mice.

  14. Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age.

    Science.gov (United States)

    Liu, Jianhui; Zhao, Yanhong; Yang, Junjun; Zhang, Xiaoqing; Zhang, Wei; Wang, Peijun

    2017-02-01

    Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.

  15. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Science.gov (United States)

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and

  16. Prenatal exposure to alcohol and 3,4-methylenedioxymethamphetamine (ecstasy) alters adult hippocampal neurogenesis and causes enduring memory deficits.

    Science.gov (United States)

    Canales, Juan J; Ferrer-Donato, Agueda

    2014-01-01

    Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.

  17. Social behavior of offspring following prenatal cocaine exposure in rodents: a comparison with prenatal alcohol

    Directory of Open Access Journals (Sweden)

    Sonya Krishna Sobrian

    2011-11-01

    Full Text Available Clinical and experimental reports suggest that prenatal cocaine exposure(PCEalters 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 conmplex. 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.

  18. Effects of repeated exposure of diazinon on cholinesterase activity and growth in snakehead fish (Channa striata).

    Science.gov (United States)

    Cong, Nguyen Van; Phuong, Nguyen Thanh; Bayley, Mark

    2009-03-01

    The organophosphate insecticide diazinon is widely used in the Mekong river delta and often applied several times per rice crop. In the present study, juvenile snakehead fish Channa striata, which is a commercially important inhabitant of rice fields, were exposed twice to 4-day pulses of 0.016, 0.079 or 0.35mg/L of diazinon, separated by a 2 week interval to imitate the exposure conditions in the field. After the 4-day exposures to these environmentally realistic concentrations, the fish were moved to clean water for recovery. During this experiment, which lasted a total of 2 months, the individual growth rates and brain cholinesterase levels were measured. We show not only that diazinon caused long term inhibition of brain ChE activity, which was still significantly depressed at the termination of the experiment, but also that the highest of these realistic concentrations caused a significant 30% growth inhibition.

  19. Writing content predicts benefit from written expressive disclosure: Evidence for repeated exposure and self-affirmation.

    Science.gov (United States)

    Niles, Andrea N; Byrne Haltom, Kate E; Lieberman, Matthew D; Hur, Christopher; Stanton, Annette L

    2016-01-01

    Expressive disclosure regarding a stressful event improves psychological and physical health, yet predictors of these effects are not well established. The current study assessed exposure, narrative structure, affect word use, self-affirmation and discovery of meaning as predictors of anxiety, depressive and physical symptoms following expressive writing. Participants (N = 50) wrote on four occasions about a stressful event and completed self-report measures before writing and three months later. Essays were coded for stressor exposure (level of detail and whether participants remained on topic), narrative structure, self-affirmation and discovery of meaning. Linguistic Inquiry and Word Count software was used to quantify positive and negative affect word use. Controlling for baseline anxiety, more self-affirmation and detail about the event predicted lower anxiety symptoms, and more negative affect words (very high use) and more discovery of meaning predicted higher anxiety symptoms three months after writing. Findings highlight the importance of self-affirmation and exposure as predictors of benefit from expressive writing.

  20. Effects of chronic dietary selenomethionine exposure on repeat swimming performance, aerobic metabolism and methionine catabolism in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Thomas, Jith K; Wiseman, Steve; Giesy, John P; Janz, David M

    2013-04-15

    In a previous study we reported impaired swimming performance and greater stored energy in adult zebrafish (Danio rerio) after chronic dietary exposure to selenomethionine (SeMet). The goal of the present study was to further investigate effects of chronic exposure to dietary SeMet on repeat swimming performance, oxygen consumption (MO2), metabolic capacities (standard metabolic rate [SMR], active metabolic rate [AMR], factorial aerobic scope [F-AS] and cost of transport [COT]) and gene expression of energy metabolism and methionine catabolism enzymes in adult zebrafish. Fish were fed SeMet at measured concentrations of 1.3, 3.4, 9.8 or 27.5 μg Se/g dry mass (d.m.) for 90 d. At the end of the exposure period, fish from each treatment group were divided into three subgroups: (a) no swim, (b) swim, and (c) repeat swim. Fish from the no swim group were euthanized immediately at 90 d and whole body triglycerides, glycogen and lactate, and gene expression of energy metabolism and methionine catabolism enzymes were determined. Individual fish from the swim group were placed in a swim tunnel respirometer and swimming performance was assessed by determining the critical swimming speed (U(crit)). After both Ucrit and MO2 analyses, fish were euthanized and whole body energy stores and lactate were determined. Similarly, individual fish from the repeat swim group were subjected to two U(crit) tests (U(crit-1) and U(crit-2)) performed with a 60 min recovery period between tests, followed by determination of energy stores and lactate. Impaired swim performance was observed in fish fed SeMet at concentrations greater than 3 μg Se/g in the diet. However, within each dietary Se treatment group, no significant differences between single and repeat U(crits) were observed. Oxygen consumption, SMR and COT were significantly greater, and F-AS was significantly lesser, in fish fed SeMet. Whole body triglycerides were proportional to the concentration of SeMet in the diet. While

  1. Alcohol

    Science.gov (United States)

    ... changes that come from drinking alcohol can make people do stupid or embarrassing things, like throwing up or peeing on themselves. Drinking also gives people bad breath, and no one enjoys a hangover. ...

  2. Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides.

    Science.gov (United States)

    Lee, Young S; Lewis, John A; Ippolito, Danielle L; Hussainzada, Naissan; Lein, Pamela J; Jackson, David A; Stallings, Jonathan D

    2016-01-18

    Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits), but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of subchronic CPF neurotoxicity, adult male Long Evans (LE) rats were administered CPF at 3 or 10mg/kg/d (s.c.) for 21 days. We quantified mRNA and non-coding RNA (ncRNA) expression profiles by RNA-seq, microarray analysis and small ncRNA sequencing technology in the CA1 region of the hippocampus. Hippocampal slice immunohistochemistry was used to determine CPF-induced changes in protein expression and localization patterns. Neither dose of CPF caused overt clinical signs of cholinergic toxicity, although after 21 days of exposure, cholinesterase activity was decreased to 58% or 13% of control levels in the hippocampus of rats in the 3 or 10mg/kg/d groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10mg/kg/d dose group relative to controls. Of the 1382 differentially expressed genes identified by RNA-seq and microarray analysis, 67 were common to both approaches. Differential expression of six of these genes (Bdnf, Cort, Crhbp, Nptx2, Npy and Pnoc) was verified in an independent CPF exposure study; immunohistochemistry demonstrated that CRHBP and NPY were elevated in the CA1 region of the hippocampus at 10mg/kg/d CPF. Gene ontology enrichment analysis suggested association of these genes with receptor-mediated cell survival signaling pathways. miR132/212 was also elevated in the CA1 hippocampal region, which may play a role in the disruption of neurotrophin-mediated cognitive processes after CPF administration. These findings identify potential mediators of CPF-induced neurobehavioral deficits following subchronic exposure to CPF at

  3. Hyperalgesic priming (type II) induced by repeated opioid exposure: maintenance mechanisms.

    Science.gov (United States)

    Araldi, Dioneia; Ferrari, Luiz F; Levine, Jon D

    2017-07-01

    We previously developed a model of opioid-induced neuroplasticity in the peripheral terminal of the nociceptor that could contribute to opioid-induced hyperalgesia, type II hyperalgesic priming. Repeated administration of mu-opioid receptor (MOR) agonists, such as DAMGO, at the peripheral terminal of the nociceptor, induces long-lasting plasticity expressed, prototypically as opioid-induced hyperalgesia and prolongation of prostaglandin E2-induced hyperalgesia. In this study, we evaluated the mechanisms involved in the maintenance of type II priming. Opioid receptor antagonist, naloxone, induced hyperalgesia in DAMGO-primed paws. When repeatedly injected, naloxone-induced hyperalgesia, and hyperalgesic priming, supporting the suggestion that maintenance of priming involves changes in MOR signaling. However, the knockdown of MOR with oligodeoxynucleotide antisense did not reverse priming. Mitogen-activated protein kinase and focal adhesion kinase, which are involved in the Src signaling pathway, previously implicated in type II priming, also inhibited the expression, but not maintenance of priming. However, when Src and mitogen-activated protein kinase inhibitors were coadministered, type II priming was reversed, in male rats. A second model of priming, latent sensitization, induced by complete Freund's adjuvant was also reversed, in males. In females, the inhibitor combination was only able to inhibit the expression and maintenance of DAMGO-induced priming when knockdown of G-protein-coupled estrogen receptor 30 (GPR30) in the nociceptor was performed. These findings demonstrate that the maintenance of DAMGO-induced type II priming, and latent sensitization is mediated by an interaction between, Src and MAP kinases, which in females is GPR30 dependent.

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

    Science.gov (United States)

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

    2015-05-01

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

  5. Neurobehavioral toxicity of a repeated exposure (14 days to the airborne polycyclic aromatic hydrocarbon fluorene in adult Wistar male rats.

    Directory of Open Access Journals (Sweden)

    Julie Peiffer

    Full Text Available Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene were detected at both concentrations (1.5 and 150 ppb, demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene.

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

    Science.gov (United States)

    Tyler, Christina R; Allan, Andrea M

    2014-08-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  8. Effects of heat exposure and 3% dehydration achieved via hot water immersion on repeated cycle sprint performance.

    Science.gov (United States)

    Kraft, Justin A; Green, James M; Bishop, Phillip A; Richardson, Mark T; Neggers, Yasmin H; Leeper, James D

    2011-03-01

    This study examined effects of heat exposure with and without dehydration on repeated anaerobic cycling. Males (n = 10) completed 3 trials: control (CT), water-bath heat exposure (∼39°C) to 3% dehydration (with fluid replacement) (HE), and similar heat exposure to 3% dehydration (DEHY). Hematocrit increased significantly from pre to postheat immersion in both HE and DEHY. Participants performed 6 × 15s cycle sprints (30s active recovery). Mean Power (MP) was significantly lower vs. CT (596 ± 66 W) for DEHY (569 ± 72 W), and the difference approached significance for HE (582 ± 76 W, p = 0.07). Peak Power (PP) was significantly lower vs. CT (900 ± 117 W) for HE (870 ± 128 W) and approached significance for DEHY (857 ± 145 W, p = 0.07). Postsprint ratings of perceived exertion was higher during DEHY (6.4 ± 2.0) and HE (6.3 ± 1.6) than CT (5.7 ± 2.1). Combined heat and dehydration impaired MP and PP (decrements greatest in later bouts) with HE performance intermediate to CT and DEHY.

  9. Chronic alcohol exposure disrupts CB1 regulation of GABAergic transmission in the rat basolateral amygdala.

    Science.gov (United States)

    Varodayan, Florence P; Bajo, Michal; Soni, Neeraj; Luu, George; Madamba, Samuel G; Schweitzer, Paul; Roberto, Marisa

    2017-05-01

    The basolateral nucleus of the amygdala (BLA) is critical to the pathophysiology of anxiety-driven alcohol drinking and relapse. The endogenous cannabinoid/type 1 cannabinoid receptor (eCB/CB1 ) system curbs BLA-driven anxiety and stress responses via a retrograde negative feedback system that inhibits neurotransmitter release, and BLA CB1 activation reduces GABA release and drives anxiogenesis. Additionally, decreased amygdala CB1 is observed in abstinent alcoholic patients and ethanol withdrawn rats. Here, we investigated the potential disruption of eCB/CB1 signaling on GABAergic transmission in BLA pyramidal neurons of rats exposed to 2-3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent activity. This retrograde tonic eCB/CB1 signaling was diminished in chronic ethanol exposed rats, suggesting a functional impairment of the eCB/CB1 system. In contrast, acute ethanol increased GABAergic transmission similarly in naïve and chronic ethanol exposed rats, via both presynaptic and postsynaptic mechanisms. Notably, CB1 activation impaired ethanol's facilitation of GABAergic transmission across both groups, but the AM251-induced and ethanol-induced facilitation of GABA release was additive, suggesting independent presynaptic sites of action. Collectively, the present findings highlight a critical CB1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state. © 2016 Society for the Study of Addiction.

  10. Motion sickness severity and physiological correlates during repeated exposures to a rotating optokinetic drum

    Science.gov (United States)

    Hu, Senqi; Grant, Wanda F.; Stern, Robert M.; Koch, Kenneth L.

    1991-01-01

    Fifty-two subjects were exposed to a rotating optokinetic drum. Ten of these subjects who became motion sick during the first session completed two additional sessions. Subjects' symptoms of motion sickness, perception of self-motion, electrogastrograms (EGGs), heart rate, mean successive differences of R-R intervals (RRI), and skin conductance were recorded for each session. The results from the first session indicated that the development of motion sickness was accompanied by increased EGG 4-9 cpm activity (gastric tachyarrhythmia), decreased mean succesive differences of RRI, increased skin conductance levels, and increased self-motion perception. The results from the subjects who had three repeated sessions showed that 4-9 cpm EGG activity, skin conductance levels, perception of self-motion, and symptoms of motion sickness all increased significantly during the drum rotation period of the first session, but increased significantly less during the following sessions. Mean successive differences of RRI decreased significantly during the drum rotation period for the first session, but decreased significantly less during the following sessions. Results show that the development of motion sickness is accompanied by an increase in gastric tachyarrhythmia, and an increase in sympathetic activity and a decrease in parasympathetic activity, and that adaptation to motion sickness is accompanied by the recovery of autonomic nervous system balance.

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

    Science.gov (United States)

    Jain, Ram B

    2015-03-01

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

  12. [Prenatal alcohol exposure as an etiological factor in neuropsychiatric diseases of childhood, adolescence and adulthood].

    Science.gov (United States)

    Evrard, Sergio Gustavo

    2010-01-01

    In Argentina, prenatal alcohol exposure (PAE) is an almost neglected condition as an important etiological factor for the induction of a wide spectrum of neuropsychiatric diseases that may appear during childhood, adolescence or adulthood. Children born to alcoholic mothers may show a spectrum of diseases ranging from an apparent normality to a profound mental retardation, passing through epilepsy, attention deficit disorders with or without hyperactivity, autism and pervasive developmental disorders, and different types of learning disorders. When adolescents, they may develop different kinds of personality disorders and substance abuse disorders. Finally, in adulthood, they may suffer from different types of affective and psychotic disorders, among others. A great number of those children may not develop their full mental and social potentiality as free individuals. They usually have diverse types of cognitive, attentional, mnemonic and affective impairments. Not infrequently, they engage in antisocial behaviors, have school or work troubles. In this work, I review the present clinical classifications of the disorders emerging from a PAE and the several neuropsychiatric diseases that can be induced by them, in order to call attention to the Argentinian neuropsychiatric community about the increasingly, although underdiagnosed, frequency of these disorders in our country.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures

    DEFF Research Database (Denmark)

    Vestergaard, M; Wisborg, K; Henriksen, TB

    2005-01-01

    OBJECTIVE: Febrile seizure is a common type of seizure in childhood, probably caused by both genetic and early environmental factors. Little is known about the effect of environmental factors that operate in prenatal life, although the fetal brain may be particular vulnerable as a result...... of extensive brain growth and differentiation in this period. We evaluated the association between prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures in 2 population-based birth cohorts. METHODS: The Aarhus Birth Cohort consisted of 25,196 children of mothers who were...... follow-up. We extracted from medical records additional information on febrile seizures in children in the Aarhus Birth Cohort who were born between 1989 and 1992. RESULTS: We found a slightly increased risk for febrile seizures in children who were exposed to 10 or more cigarettes per day in the Aarhus...

  16. An evaluation of social skills in children with and without prenatal alcohol exposure.

    Science.gov (United States)

    Rasmussen, C; Becker, M; McLennan, J; Urichuk, L; Andrew, G

    2011-09-01

    The goal of this study was to examine social skills deficits among children with and without prenatal alcohol exposure (PAE) who were both referred to a respite programme. Thirty-seven children with PAE and 23 non-exposed children (aged 3 to 8 years) were evaluated on the Social Skills Rating System (SSRS) by their caregivers and respite workers. As compared with the non-exposed children, those with PAE showed more deficits on caregiver ratings of responsibility, hyperactivity, internalizing problems and overall social skills, as well as respite worker ratings of hyperactivity. The social skills among the PAE group were not related to home placement variables. Among both groups, caregivers rated social skills lower than respite workers, and among the PAE group, girls tended to display more social skills deficits than boys. The SSRS is useful in identifying unique social skills deficits among children with PAE. © 2010 Blackwell Publishing Ltd.

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

    Science.gov (United States)

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

    2011-08-01

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

  18. Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

    Science.gov (United States)

    Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

    2017-02-01

    Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

  19. Effect of prenatal alcohol exposure on childhood academic outcomes: contrasting maternal and paternal associations in the ALSPAC study.

    Directory of Open Access Journals (Sweden)

    Rosa Alati

    Full Text Available 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.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.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.

  20. Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats.

    Science.gov (United States)

    Bowen, Michael T; Carson, Dean S; Spiro, Adena; Arnold, Jonathon C; McGregor, Iain S

    2011-01-01

    Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33-42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A "booster" shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

  1. Using eyeblink classical conditioning as a test of the functional consequences of exposure of the developing cerebellum to alcohol.

    Science.gov (United States)

    Green, John T

    2003-01-01

    Exposure of the developing brain to alcohol produces profound Purkinje cell loss in the cerebellum, and deficits in tests of motor coordination. However, the precise relationship between these two sets of findings has been difficult to determine. Eyeblink classical conditioning is known to engage a discrete brainstem-cerebellar circuit, making it an ideal test of cerebellar functional integrity after developmental alcohol exposure. In eyeblink conditioning, one of the deep cerebellar nuclei, the interpositus nucleus, as well as specific Purkinje cell populations, are sites of convergence for CS and US information. A series of studies have shown that eyeblink conditioning is impaired in both weanling and adult rats given binge-like exposure to alcohol as neonates, and that these deficits can be traced, at least in part, to impaired activation of cerebellar interpositus nucleus neurons and to an overall reduction in the deep cerebellar nuclear cell population. Because particular cerebellar cell populations are utilized in well-defined ways during eyeblink conditioning, conclusions regarding specific changes in the mediation of behavior by these cell populations are greatly strengthened. Further studies will be directed towards the impact of early exposure to alcohol on the functionality of specific Purkinje cell populations, as well as towards brainstem areas that process the tone CS and the somatosensory US.

  2. Exposure to online alcohol marketing and adolescents' drinking: A cross-sectional study in four European countries

    NARCIS (Netherlands)

    Bruijn, A. de; Engels, R.C.M.E.; Anderson, P.D.; Bujalski, M.; Gosselt, J.; Schreckenberg, D.; Wohtge, J.; Leeuw, R.N.H. de

    2016-01-01

    Aims: The Internet is the leading medium among European adolescents in contemporary times; even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in

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

    Science.gov (United States)

    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…

  4. Biomarkers for detection of prenatal alcohol exposure: a critical review of fatty acid ethyl esters in meconium.

    Science.gov (United States)

    Burd, Larry; Hofer, Ryan

    2008-07-01

    The objective of this study was a review of published studies utilizing measurement of fatty acid ethyl esters (FAEE) in meconium as biomarkers for prenatal alcohol exposure. We completed a literature search of PubMed using the terms meconium, fatty acid ethyl esters, biomarkers, and prenatal alcohol exposure. We included only peer reviewed studies utilizing analysis of meconium for the presence of FAEE in humans through the year 2007. We found 10 articles reporting on original research examining the relationship of FAEE from meconium and prenatal alcohol exposure (PAE). The 10 articles used six different PAE assessment strategies and four different analytical techniques for determining FAEE endpoints. The articles included 2,221 subjects (range 4 to 725) with 455 (20.5%) subjects identified as exposed using the methods stated in the articles. FAEE levels above the studies' respective cutoffs were reported for 502 (22.6%) subjects. The accurate identification of alcohol-exposed pregnancies represents a significant challenge in the development of FAEE detection cutoffs to maximize the sensitivity and specificity of the test. We present several options for the improvement of exposure assessment in future studies of FAEE as biomarkers for PAE. (c) 2008 Wiley-Liss, Inc.

  5. Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

    Science.gov (United States)

    Sulaiman, Siti Amrah

    2017-01-01

    Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung. PMID:28127418

  6. Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

    Directory of Open Access Journals (Sweden)

    Suk Peng Tang

    2017-01-01

    Full Text Available Paraquat (PQ is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day, Tualang honey (1.0 g/kg/day, or ubiquinol (0.2 g/kg/day throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week or PQ (10 mg/kg/week once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p<0.05. The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

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

    Science.gov (United States)

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

    2013-03-01

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

  8. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone

    Energy Technology Data Exchange (ETDEWEB)

    López-Arnau, Raúl; Martínez-Clemente, José [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Rodrigo, Teresa [Animal Experimentation Unit of Psychology and Pharmacy, University of Barcelona (Spain); Pubill, David [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Camarasa, Jorge, E-mail: jcamarasa@ub.edu [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Escubedo, Elena [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain)

    2015-07-01

    Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3 × 25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26 ± 2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D{sub 2} dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone. - Highlights: • We studied the dopaminergic and serotonergic neurotoxicity of mephedrone in rats. • Mephedrone induced a transient hypothermia following sustained hyperthermia. • In a weekend consumption pattern, mephedrone induced selective neurotoxicity. • Mephedrone generated oxidative stress. • Mephedrone induced an impairment in memory function.

  9. Effects of repeated exposure to 4-nonylphenol on the zooplankton community in littoral enclosures

    Energy Technology Data Exchange (ETDEWEB)

    O`Halloran, S.L.; Liber, K.; Gangl, J.A. [Univ. of Wisconsin, Superior, WI (United States). Lake Superior Research Inst.; Knuth, M.L. [Environmental Protection Agency, Duluth, MN (United States). Mid-Continent Ecology Div.

    1999-03-01

    The effects of 4-nonylphenol (NP) on freshwater zooplankton were evaluated in 18 littoral enclosure mesocosms in northeastern Minnesota. The 18 enclosures were allocated to three blocks of six units with each block including two untreated control enclosures and one enclosure for each of four NP treatments. Treated enclosures received 11 applications of NP over a 20-d period between July 8 and 28, 1993. Maximum NP concentrations measured in the water column 2 h after each application averaged ({+-} SD) 5 {+-} 4, 23 {+-} 11, 76 {+-} 21, and 243 {+-} 41 {micro}g/L over the 11 applications. Nonylphenol dissipated rapidly from the water column but was more persistent in sediments and in/on macrophytes. All cladoceran and copepod taxa were significantly reduced in abundance at 243 {+-} 41 {micro}g/L; some sensitive taxa were also affected by 76 {+-} 21 and 23 {+-} 11 {micro}g/L. While many rotifer taxa were unaffected at any of the test concentrations, several were affected at {ge} 76 {+-} 21 {micro}g/L. Ostracods were only affected at 2,243 {+-} 41 {micro}g/L. No zooplankton taxon was affected at 5 {+-} 4 {micro}g/L. The period of maximum impact usually occurred within 1 to 7 d of the last NP application, and recovery to control abundance levels generally occurred within 7 to 28 d of the last NP application. Two sensitive taxa, Acroperus and Calanoida, did not recover at {ge} 76 {+-} 21 {micro}g/L by the end of the study. The maximum acceptable toxicant concentration for protection of all zooplankton taxa was estimated at {approximately} 10 {micro}g/L, although overall community diversity was unaffected at 23 {+-} 11. The water was the most probable route of NP exposure, but the greater persistence of NP residues in/on macrophytes may have contributed to the lack of recovery of some macrophyte-associated taxa.

  10. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone.

    Science.gov (United States)

    López-Arnau, Raúl; Martínez-Clemente, José; Rodrigo, Teresa; Pubill, David; Camarasa, Jorge; Escubedo, Elena

    2015-07-01

    Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3×25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26±2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D2 dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. The Potential Impact of a "No-Buy" List on Youth Exposure to Alcohol Advertising on Cable Television.

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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

  14. Responses of soil ammonia-oxidizing microorganisms to repeated exposure of single-walled and multi-walled carbon nanotubes.

    Science.gov (United States)

    Chen, Qinglin; Wang, Hui; Yang, Baoshan; He, Fei; Han, Xuemei; Song, Ziheng

    2015-02-01

    The impacts of carbon nanotubes (CNTs) including single-walled carbon nanotubes (SWNTs) and multi-walled carbon nanotubes (MWNTs) on soil microbial biomass and microbial community composition (especially on ammonium oxidizing microorganisms) have been evaluated. The first exposure of CNTs lowered the microbial biomass immediately, but the values recovered to the level of the control at the end of the experiment despite the repeated addition of CNTs. The abundance and diversity of ammonium-oxidizing archaea (AOA) were higher than that of ammonium-oxidizing bacteria (AOB) under the exposure of CNTs. The addition of CNTs decreased Shannon-Wiener diversity index of AOB and AOA. Two-way ANOVA analysis showed that CNTs had significant effects on the abundance and diversity of AOB and AOA. Dominant terminal restriction fragments (TRFs) of AOB exhibited a positive relationship with NH4(+), while AOA was on the contrary. It implied that AOB prefer for high-NH4(+) soils whereas AOA is favored in low NH4(+) soils in the CNT-contaminated soil. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The sensory response to capsaicin during repeated topical exposures: differential effects on sensations of itching and pungency.

    Science.gov (United States)

    Green, B G; Shaffer, G S

    1993-06-01

    Changes in sensory irritation were measured during repeated topical exposures to capsaicin over 2 days. The perceived intensities of itching and pungent sensations, predominantly burning and stinging/pricking, were assessed every 60 sec during 5 applications of capsaicin at inter-stimulus intervals (ISI) of 90 min (Exp. 1) or 15 min (Exp. 2) and in follow-up tests 24 h later. Psychophysical measurements were obtained with a hand-held dynamometer in conjunction with the method of magnitude production. When the ISI was 90 min, itching and pungency were both significantly reduced (i.e., desensitization occurred) by the fifth exposure; however, the reduction occurred more rapidly and dramatically for itching. After 24 h, desensitization remained significant only for itching. When the ISI was 15 min, the sensations on day 1 first intensified in a manner consistent with sensitization, then declined in a manner consistent with desensitization; compared to pungency, itch exhibited less sensitization and more desensitization. On day 2, overall intensity was less for both categories of sensation, primarily because of a reduction in sensitization. Marked individual differences were observed in the overall sensitivity to capsaicin, the time course of sensation, the susceptibility to capsaicin-induced itch, and the rate and duration of sensitization and desensitization. The results are discussed in terms of current hypotheses about the sensory mechanisms that underlie chemically induced itch and the use of capsaicin as a topical analgesic and antipruritic.

  16. A Study for the Characteristic Changes Under the Repeated Thermal Exposure in the Process of Repairing Aircraft Sandwich Structures

    Science.gov (United States)

    Kim, Yun Hae; Han, Joong Won; Kim, Don Won; Choi, Byung Keun; Murakami, R.

    Delamination can be observed in the sound areas during and/or after a couple times exposure to the elevated curing temperature due to the repeated repair condition. This study was conducted for checking the degree of degradation of properties of the cured parts and delamination between skin prepreg and honeycomb core. Specimens with glass honeycomb sandwich construction and glass/epoxy prepreg were prepared. The specimens were cured 1 to 5 times at 260°F in an autoclave and each additionally exposed 50, 100 and 150 hours in the 260°F oven. Each specimen was tested for tensile strength, compressive strength, flatwise tensile strength and interlaminar shear strength. To monitor the characteristics of the resin itself, the cured resin was tested using DMA and DSC. As a results, the decrease of Tg value were observed in the specific specimen which is exposed over 50 hrs at 260°F. This means the change or degradative of resin properties is also related to the decrease of flatwise tensile properties. Accordingly, minimal exposure on the curing temperature is recommended for parts in order to prevent the delation and maintain the better condition.

  17. Repeated Cycles of Chronic Intermittent Ethanol Exposure Increases Basal Glutamate in the Nucleus Accumbens of Mice without affecting glutamate transport

    Directory of Open Access Journals (Sweden)

    William C. Griffin

    2015-02-01

    Full Text Available Repeated cycles of chronic intermittent ethanol (CIE exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc is significantly elevated in ethanol dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na+ dependent and Na+ independent conditions to determine whether the function of excitatory amino acid transporters (EAATs; also known as system XAG or of system Xc- (Glial cysteine-glutamate exchanger was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (~2 –fold in the NAc of CIE exposed mice (i.e. ethanol-dependent compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na+ dependent nor Na+ independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical-striatal pathways underlies the increases in extracellular glutamate found in the nucleus accumbens of ethanol-dependent mice.

  18. Effect of repeated nicotine exposure on high-affinity nicotinic acetylcholine receptor density in spontaneously hypertensive rats.

    Science.gov (United States)

    Hohnadel, Elizabeth J; Hernandez, Caterina M; Gearhart, Debra A; Terry, Alvin V

    Spontaneously hypertensive rats (SHRs) are often used as a model of attention deficit hyperactivity disorder (ADHD) and to investigate the effects of hypertension on cognitive function. Further, they appear to have reduced numbers of central nicotinic acetylcholine receptors (nAChRs) and, therefore, may be useful to model certain aspects of Alzheimer's disease (AD) and other forms of dementia given that a decrease in nAChRs is thought to contribute to cognitive decline in these disorders. In the present study, based on reports that chronic nicotine exposure increases nAChRs in several mammalian models, we tested the hypothesis that repeated exposures to a relatively low dose of the alkaloid would ameliorate the receptor deficits in SHR. Thus, young-adult SHRs and age-matched Wistar-Kyoto (WKY) control rats were treated with either saline or nicotine twice a day for 14 days (total daily dose = 0.7 mg/kg nicotine base) and then sacrificed. Quantitative receptor autoradiography with [125I]-IPH, an epibatidine analog, revealed: (1) that high-affinity nAChRs were higher in saline-treated WKY (control) rats compared to saline-treated SHRs in 18 of the 19 brain region measured, although statistically different only in the mediodorsal thalamic nuclei, (2) that nicotine significantly increased nAChR binding in WKY rats in six brain areas including cortical regions and the anterior thalamic nucleus, (3) that there were no cases where nicotine significantly increased nAChR binding in SHRs. These results indicate that subjects deficient in nAChRs may be less sensitive to nAChR upregulation with nicotine than normal subjects and require higher doses or longer periods of exposure.

  19. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    Science.gov (United States)

    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-06-17

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

  3. Quantification of print, radio and television exposure among previous blood donors in Kenya: an opportunity for encouraging repeat donation in a resource-limited setting?

    Science.gov (United States)

    Basavaraju, S V; Mwangi, J; Kellogg, T A; Odawo, L; Marum, L H

    2010-10-01

    Blood services in sub-Saharan Africa experience blood shortages and low retention of voluntary, non-remunerated donors. To boost collections by encouraging repeat donations, the Kenya National Blood Transfusion Service is exploring the likelihood of reaching previous donors through targeted print, radio and television advertising. We analysed data from a national AIDS Indicator Survey to determine whether previous donors have significant exposure to media. Respondents reporting history of blood donation had significantly higher exposure to print, radio and television media than those without history of blood donation. Targeted media campaigns encouraging repeat donation are likely to reach previous donors even in resource-limited settings.

  4. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart.

    Directory of Open Access Journals (Sweden)

    Maren Weischer

    2014-03-01

    Full Text Available Cross-sectional studies have associated short telomere length with smoking, body weight, physical activity, and possibly alcohol intake; however, whether these associations are due to confounding is unknown. We tested these hypotheses in 4,576 individuals from the general population cross-sectionally, and with repeat measurement of relative telomere length 10 years apart. We also tested whether change in telomere length is associated with mortality and morbidity in the general population. Relative telomere length was measured with quantitative polymerase chain reaction. Cross-sectionally at the first examination, short telomere length was associated with increased age (P for trend across quartiles = 3 × 10(-77, current smoking (P = 8 × 10(-3, increased body mass index (P = 7 × 10(-14, physical inactivity (P = 4 × 10(-17, but not with increased alcohol intake (P = 0.10. At the second examination 10 years later, 56% of participants had lost and 44% gained telomere length with a mean loss of 193 basepairs. Change in leukocyte telomere length during 10 years was associated inversely with baseline telomere length (P<1 × 10(-300 and age at baseline (P = 1 × 10(-27, but not with baseline or 10-year inter-observational tobacco consumption, body weight, physical activity, or alcohol intake. Prospectively during a further 10 years follow-up after the second examination, quartiles of telomere length change did not associate with risk of all-cause mortality, cancer, chronic obstructive pulmonary disease, diabetes mellitus, ischemic cerebrovascular disease, or ischemic heart disease. In conclusion, smoking, increased body weight, and physical inactivity were associated with short telomere length cross-sectionally, but not with telomere length change during 10 years observation, and alcohol intake was associated with neither. Also, change in telomere length did not associate prospectively with mortality or morbidity in the general population.

  5. Effect of replacing sugar with non-caloric sweeteners in beverages on the reward value after repeated exposure.

    Directory of Open Access Journals (Sweden)

    Sanne Griffioen-Roose

    Full Text Available BACKGROUND: The reward value of food is partly dependent on learned associations. It is not yet known whether replacing sugar with non-caloric sweeteners in food is affecting long-term acceptance. OBJECTIVE: To determine the effect of replacing sugar with non-caloric sweeteners in a nutrient-empty drink (soft drink versus nutrient-rich drink (yoghurt drink on reward value after repeated exposure. DESIGN: We used a randomized crossover design whereby forty subjects (15 men, 25 women with a mean ± SD age of 21 ± 2 y and BMI of 21.5 ± 1.7 kg/m(2 consumed a fixed portion of a non-caloric sweetened (NS and sugar sweetened (SS versions of either a soft drink or a yoghurt drink (counterbalanced for breakfast which were distinguishable by means of colored labels. Each version of a drink was offered 10 times in semi-random order. Before and after conditioning the reward value of the drinks was assessed using behavioral tasks on wanting, liking, and expected satiety. In a subgroup (n=18 fMRI was performed to assess brain reward responses to the drinks. RESULTS: Outcomes of both the behavioral tasks and fMRI showed that conditioning did not affect the reward value of the NS and SS versions of the drinks significantly. Overall, subjects preferred the yoghurt drinks to the soft drinks and the ss drinks to the NS drinks. In addition, they expected the yoghurt drinks to be more satiating, they reduced hunger more, and delayed the first eating episode more. Conditioning did not influence these effects. CONCLUSION: Our study showed that repeated consumption of a non-caloric sweetened beverage, instead of a sugar sweetened version, appears not to result in changes in the reward value. It cannot be ruled out that learned associations between sensory attributes and food satiating capacity which developed preceding the conditioning period, during lifetime, affected the reward value of the drinks.

  6. Endangered North Atlantic right whales (Eubalaena glacialis) experience repeated, concurrent exposure to multiple environmental neurotoxins produced by marine algae.

    Science.gov (United States)

    Doucette, Gregory J; Mikulski, Christina M; King, Kristen L; Roth, Patricia B; Wang, Zhihong; Leandro, Luis F; DeGrasse, Stacey L; White, Kevin D; De Biase, Daniela; Gillett, Roxanne M; Rolland, Rosalind M

    2012-01-01

    The western North Atlantic population of right whales (Eubalaena glacialis) is one of the most critically endangered of any whale population in the world. Among the factors considered to have potentially adverse effects on the health and reproduction of E. glacialis are biotoxins produced by certain microalgae responsible for causing harmful algal blooms. The worldwide incidence of these events has continued to increase dramatically over the past several decades and is expected to remain problematic under predicted climate change scenarios. Previous investigations have demonstrated that N. Atlantic right whales are being exposed to at least two classes of algal-produced environmental neurotoxins-paralytic shellfish toxins (PSTs) and domoic acid (DA). Our primary aims during this six-year study (2001-2006) were to assess whether the whales' exposure to these algal biotoxins occurred annually over multiple years, and to what extent individual whales were exposed repeatedly and/or concurrently to one or both toxin classes. Approximately 140 right whale fecal samples obtained across multiple habitats in the western N. Atlantic were analyzed for PSTs and DA. About 40% of these samples were attributed to individual whales in the North Atlantic Right Whale Catalog, permitting analysis of biotoxin exposure according to sex, age class, and reproductive status/history. Our findings demonstrate clearly that right whales are being exposed to both of these algal biotoxins on virtually an annual basis in multiple habitats for periods of up to six months (April through September), with similar exposure rates for females and males (PSTs: ∼70-80%; DA: ∼25-30%). Notably, only one of 14 lactating females sampled did not contain either PSTs or DA, suggesting the potential for maternal toxin transfer and possible effects on neonatal animals. Moreover, 22% of the fecal samples tested for PSTs and DA showed concurrent exposure to both neurotoxins, leading to questions of interactive

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  9. Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

    OpenAIRE

    Lubin, Jay H.; Purdue, Mark; Kelsey, Karl; Zhang, Zuo-Feng; Winn, Debbie; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neonilia; Sturgis, Erich M.; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M.; Rudnai, Peter; Neto, Jose Eluf; Muscat, Joshua

    2009-01-01

    Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, an...

  10. Prevention of diabetes in NOD mice by repeated exposures to a contact allergen inducing a sub-clinical dermatitis.

    Directory of Open Access Journals (Sweden)

    Kaare Engkilde

    Full Text Available BACKGROUND: Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT cells, since involvement of NKT cells could suggest an innate connection between the two diseases. METHOD: NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. RESULTS: It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004. Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. CONCLUSION: The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the

  11. Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

    Science.gov (United States)

    Engkilde, Kaare; Buschard, Karsten; Hansen, Axel Kornerup; Menné, Torkil; Johansen, Jeanne Duus

    2010-01-01

    Background Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutanous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases. Method NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. Results It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. Conclusion The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site. The

  12. Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats.

    Directory of Open Access Journals (Sweden)

    Michael T Bowen

    Full Text Available Previous studies have suggested that administration of oxytocin (OT can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48 during a key developmental epoch (early adolescence altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33-42. OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood, consumption of beer but not water was significantly less in the OT pre-treated rats. A "booster" shot of OT (1 mg/kg given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

  13. The effects of low to moderate alcohol exposure in early pregnancy on IQ in 5-year-old children

    DEFF Research Database (Denmark)

    Eriksen, Hanne-Lise Falgreen; Mortensen, Erik Lykke; Kilburn, Tina R.

    2012-01-01

    the effects of low to moderate maternal alcohol consumption during early pregnancy on children's intelligence (IQ) at age 5 years. Design Prospective follow-up study. Setting Neuropsychological testing in four Danish cities 2003-2008. Population A cohort of 1628 women and their children sampled from...... the Danish National Birth Cohort. Methods Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R). Parental education, maternal IQ, maternal smoking in pregnancy......Please cite this paper as: Falgreen Eriksen H, Mortensen E, Kilburn T, Underbjerg M, Bertrand J, Støvring H, Wimberley T, Grove J, Kesmodel U. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-old children. BJOG 2012;119:1191-1200. Objective To examine...

  14. Response of the Hypothalamic-Pituitary-Adrenal System to Repeated Moderate Psychoemotional Stress Exposure Is Associated with Behavioral Parameters.

    Science.gov (United States)

    Goncharova, N D; Chigarova, O A; Oganyan, T E

    2017-05-01

    Individual features of the response of the hypothalamic-pituitary-adrenal axis (HPAA) to repeated moderate stress exposure (daily 2-h restraint stress for 10 days) was studied in young female rhesus monkeys with healthy normal behavior and combined group of female rhesus monkeys with abnormal depression-like and anxious behavior. No between-group differences in the response of ACTH and cortisol were found on day 1. On day 10, a rapid and less pronounced increase in ACTH secretion was observed in all animals in comparison with day 1. Analysis of between-group differences in HPAA response showed higher increase in ACTH level and lower increase in cortisol concentration in animals with depression-like and anxious behavior. These changes were similar to the previously described differences in the response of the adenohypophysis and adrenal cortex to acute restraint stress in old monkeys with similar behavior. Thus, individuals with depression-like and anxious behavior demonstrate impaired stress-induced reactivity of HPAA as early as in young age.

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

    Directory of Open Access Journals (Sweden)

    Yunji Hwang

    Full Text Available 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.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.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.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.

  16. Does industry self-regulation protect young people from exposure to alcohol marketing? A review of compliance and complaint studies.

    Science.gov (United States)

    Noel, Jonathan K; Babor, Thomas F

    2017-01-01

    Exposure to alcohol marketing is considered to be potentially harmful to adolescents. In addition to statutory regulation, industry self-regulation is a common way to protect adolescents from alcohol marketing exposures. This paper critically reviews research designed to evaluate the effectiveness of the alcohol industry's compliance procedures to manage complaints when alcohol marketing is considered to have violated a self-regulatory code. Peer-reviewed papers were identified through four literature search engines: PubMed, SCOPUS, PsychINFO and CINAHL. Non-peer-reviewed reports produced by public health agencies, alcohol research centers, non-governmental organizations, government research centers and national industry advertising associations were also included. The search process yielded three peer-reviewed papers, seven non-peer reviewed reports published by academic institutes and non-profit organizations and 20 industry reports. The evidence indicates that the complaint process lacks standardization across countries, industry adjudicators may be trained inadequately or biased and few complaints are upheld against advertisements pre-determined to contain violations of a self-regulatory code. The current alcohol industry marketing complaint process used in a wide variety of countries may be ineffective at removing potentially harmful content from the market-place. The process of determining the validity of complaints employed by most industry groups appears to suffer from serious conflict of interest and procedural weaknesses that could compromise objective adjudication of even well-documented complaints. In our opinion the current system of self-regulation needs major modifications if it is to serve public health objectives, and more systematic evaluations of the complaint process are needed. © 2016 Society for the Study of Addiction.

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

    Science.gov (United States)

    Mellentin, Angelina Isabella; Stenager, Elsebeth; Nielsen, Bent; Nielsen, Anette Søgaard; Yu, Fei

    2017-01-30

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

  18. Inhibition of voltage-gated calcium channels after subchronic and repeated exposure of PC12 cells to different classes of insecticides

    NARCIS (Netherlands)

    Meijer, Marieke; Brandsema, Joske A R; Nieuwenhuis, Desirée; Wijnolts, Fiona M J; Dingemans, Milou M L; Westerink, Remco H S

    2015-01-01

    We previously demonstrated that acute inhibition of voltage-gated calcium channels (VGCCs) is a common mode of action for (sub)micromolar concentrations of chemicals, including insecticides. However, since human exposure to chemicals is usually chronic and repeated, we investigated if selected insec

  19. Inhibition of voltage-gated calcium channels after subchronic and repeated exposure of PC12 cells to different classes of insecticides

    NARCIS (Netherlands)

    Meijer, Marieke; Brandsema, Joske A R; Nieuwenhuis, Desirée; Wijnolts, Fiona M J; Dingemans, Milou M L|info:eu-repo/dai/nl/304834564; Westerink, Remco H S|info:eu-repo/dai/nl/239425952

    2015-01-01

    We previously demonstrated that acute inhibition of voltage-gated calcium channels (VGCCs) is a common mode of action for (sub)micromolar concentrations of chemicals, including insecticides. However, since human exposure to chemicals is usually chronic and repeated, we investigated if selected insec

  20. Anti-Inflammatory and Antioxidant Effects of Repeated Exposure to Cruciferous Allyl Nitrile in Sensitizer-Induced Ear Edema in Mice.

    Science.gov (United States)

    Tanii, Hideji; Sugitani, Kayo; Saijoh, Kiyofumi

    2016-02-29

    Skin sensitizers induce allergic reactions through the induction of reactive oxygen species. Allyl nitrile from cruciferous vegetables has been reported to induce antioxidants and phase II detoxification enzymes in various tissues. We assessed the effects of repeated exposure to allyl nitrile on sensitizer-induced allergic reactions. Mice were dosed with allyl nitrile (0-200 µmol/kg), and then received a dermal application of 1 of 3 sensitizers on the left ear or 1 of 2 vehicles on the right ear. Quantitative assessment of edema was carried out by measuring the difference in weight between the portions taken from the right and left ears. We tested enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) in ears. Repeated exposure to allyl nitrile reduced edemas induced by glutaraldehyde and by 2, 4-dinitrochlorobenzene (DNCB), but not by formaldehyde. The repeated exposure decreased levels of TBARS, a marker of oxidative stress, induced by glutaraldehyde and by DNCB, but not by formaldehyde. Allyl nitrile elevated SOD levels for the 3 sensitizers, and CAT levels for formaldehyde and DNCB. Allyl nitrile also increased GPx levels for formaldehyde and DNCB, but not for glutaraldehyde. The reduced edemas were associated with changes in oxidative stress levels and antioxidant enzymes. Repeated exposure to allyl nitrile reduced allergic reactions induced by glutaraldehyde and by DNCB, but not by formaldehyde. This reduction was associated with changes in ROS levels and antioxidant enzyme activities.

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

    Science.gov (United States)

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

    1994-04-01

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

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

    Science.gov (United States)

    Paul, A P; Medina, A E

    2012-09-27

    Neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF-) or control Green Fluorescent Protein (GFP). After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF- or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Fetal alcohol exposure and IQ at age 8: evidence from a population-based birth-cohort study.

    Directory of Open Access Journals (Sweden)

    Sarah J Lewis

    Full Text Available Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother's intake but also by genetic variants carried by both the mother and the fetus. Associations between children's cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child's cognitive score (measured by the Weschler Intelligence Scale at age 8.We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1-6 units alcohol per week during pregnancy (per allele effect estimates were -1.80 (95% CI= -2.63 to -0.97 p=0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI= -1.05 to 1.36 p=0.80, p-value for interaction  =0.009. A further genetic variant associated with alcohol metabolism in mothers was associated with their child's IQ, but again only among mothers who drank during pregnancy.

  4. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  5. Cholinesterase inhibition and depression of the photic after discharge of flash evoked potentials following acute or repeated exposures to a mixture of carbaryl and propoxur.

    Science.gov (United States)

    Mwanza, Jean-Claude; Lyke, Danielle F; Hertzberg, Richard C; Haber, Lynne; Kohrman-Vincent, Melissa; Li, Ruosha; Pan, Yi; Lyles, Robert H; Simmons, Jane Ellen; Macmillan, Denise K; Zehr, R Dan; Swank, Adam E; Herr, David W

    2012-06-01

    Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had

  6. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5‐year‐old children

    National Research Council Canada - National Science Library

    Falgreen Eriksen, H‐L; Mortensen, EL; Kilburn, T; Underbjerg, M; Bertrand, J; Støvring, H; Wimberley, T; Grove, J; Kesmodel, US

    2012-01-01

    ..., Støvring H, Wimberley T, Grove J, Kesmodel U. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5‐year‐old children. BJOG 2012;119:1191–1200. Objective...

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Effects of short-term repeated exposure to different flooring surfaces on the behavior and physiology of dairy cattle.

    Science.gov (United States)

    Schütz, K E; Cox, N R

    2014-05-01

    during the stand-off period. We observed no major effect of the repeated stand-off exposure. In summary, adding rubber matting onto concrete surfaces for stand-off purposes is beneficial for animal welfare. A well-managed wood chip surface offered the best welfare for dairy cows removed from pasture, and the findings of this study confirm that a concrete surface decreases the welfare of cows removed from pasture.

  9. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    Science.gov (United States)

    2011-01-01

    Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. Conclusions The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing

  10. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    Directory of Open Access Journals (Sweden)

    Mortensen Alicja

    2011-06-01

    Full Text Available Abstract Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs and silver acetate (AgAc to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP. The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM, nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. Conclusions The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver

  11. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate.

    Science.gov (United States)

    Loeschner, Katrin; Hadrup, Niels; Qvortrup, Klaus; Larsen, Agnete; Gao, Xueyun; Vogel, Ulla; Mortensen, Alicja; Lam, Henrik Rye; Larsen, Erik H

    2011-06-01

    The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing selenium and sulfur in the

  12. A review of the reporting and handling of missing data in cohort studies with repeated assessment of exposure measures

    Directory of Open Access Journals (Sweden)

    Karahalios Amalia

    2012-07-01

    Full Text Available Abstract Background Retaining participants in cohort studies with multiple follow-up waves is difficult. Commonly, researchers are faced with the problem of missing data, which may introduce biased results as well as a loss of statistical power and precision. The STROBE guidelines von Elm et al. (Lancet, 370:1453-1457, 2007; Vandenbroucke et al. (PLoS Med, 4:e297, 2007 and the guidelines proposed by Sterne et al. (BMJ, 338:b2393, 2009 recommend that cohort studies report on the amount of missing data, the reasons for non-participation and non-response, and the method used to handle missing data in the analyses. We have conducted a review of publications from cohort studies in order to document the reporting of missing data for exposure measures and to describe the statistical methods used to account for the missing data. Methods A systematic search of English language papers published from January 2000 to December 2009 was carried out in PubMed. Prospective cohort studies with a sample size greater than 1,000 that analysed data using repeated measures of exposure were included. Results Among the 82 papers meeting the inclusion criteria, only 35 (43% reported the amount of missing data according to the suggested guidelines. Sixty-eight papers (83% described how they dealt with missing data in the analysis. Most of the papers excluded participants with missing data and performed a complete-case analysis (n = 54, 66%. Other papers used more sophisticated methods including multiple imputation (n = 5 or fully Bayesian modeling (n = 1. Methods known to produce biased results were also used, for example, Last Observation Carried Forward (n = 7, the missing indicator method (n = 1, and mean value substitution (n = 3. For the remaining 14 papers, the method used to handle missing data in the analysis was not stated. Conclusions This review highlights the inconsistent reporting of missing data in cohort studies and the continuing

  13. A review of the reporting and handling of missing data in cohort studies with repeated assessment of exposure measures.

    Science.gov (United States)

    Karahalios, Amalia; Baglietto, Laura; Carlin, John B; English, Dallas R; Simpson, Julie A

    2012-07-11

    Retaining participants in cohort studies with multiple follow-up waves is difficult. Commonly, researchers are faced with the problem of missing data, which may introduce biased results as well as a loss of statistical power and precision. The STROBE guidelines von Elm et al. (Lancet, 370:1453-1457, 2007); Vandenbroucke et al. (PLoS Med, 4:e297, 2007) and the guidelines proposed by Sterne et al. (BMJ, 338:b2393, 2009) recommend that cohort studies report on the amount of missing data, the reasons for non-participation and non-response, and the method used to handle missing data in the analyses. We have conducted a review of publications from cohort studies in order to document the reporting of missing data for exposure measures and to describe the statistical methods used to account for the missing data. A systematic search of English language papers published from January 2000 to December 2009 was carried out in PubMed. Prospective cohort studies with a sample size greater than 1,000 that analysed data using repeated measures of exposure were included. Among the 82 papers meeting the inclusion criteria, only 35 (43%) reported the amount of missing data according to the suggested guidelines. Sixty-eight papers (83%) described how they dealt with missing data in the analysis. Most of the papers excluded participants with missing data and performed a complete-case analysis (n=54, 66%). Other papers used more sophisticated methods including multiple imputation (n=5) or fully Bayesian modeling (n=1). Methods known to produce biased results were also used, for example, Last Observation Carried Forward (n=7), the missing indicator method (n=1), and mean value substitution (n=3). For the remaining 14 papers, the method used to handle missing data in the analysis was not stated. This review highlights the inconsistent reporting of missing data in cohort studies and the continuing use of inappropriate methods to handle missing data in the analysis. Epidemiological journals

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

    Science.gov (United States)

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

    2016-06-01

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

  15. Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

    Science.gov (United States)

    Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L

    2017-08-01

    Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes.NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal

  16. Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure

    Directory of Open Access Journals (Sweden)

    Liang-En Chen

    2016-01-01

    Full Text Available Repeated high sustained positive Gz (+Gz exposures are known for the harmful pathophysiological impact on the brain of rats, which is reflected as the interruption of normal performance of learning and memory. Interestingly, extract of Ginkgo biloba (EGb has been reported to have neuroprotective effects and cognition-enhancing effects. In this study, we are interested in evaluating the protective effects of EGb toward the learning and memory abilities. Morris Water Maze Test (MWM was used to evaluate the cognitive function, and the physiological status of the key components in central cholinergic system was also investigated. Our animal behavioral tests indicated that EGb can release the learning and memory impairment caused by repeated high sustained +Gz. Administration of EGb to rats can diminish some of the harmful physiological effects caused by repeated +Gz exposures. Moreover, EGb administration can increase the biological activities of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px but reduce the production of malondialdehyde (MDA. Taken together, our study showed that EGb can ameliorate the impairment of learning and memory abilities of rats induced by repeated high sustained +Gz exposure; the underlying mechanisms appeared to be related to the signal regulation on the cholinergic system and antioxidant enzymes system.

  17. The impact of sensory integration therapy on gross motor function in children after prenatal exposure to alcohol

    Directory of Open Access Journals (Sweden)

    Jacek Wilczyński

    2015-03-01

    Full Text Available Introduction : In Poland there are 900 cases of full-blown foetal alcohol syndrome (FAS in neonates per year, and in 9000 children there are some symptoms of it. Aim of the research : To analyse the impact of sensory integration (SI therapy on gross motor skills function in children after prenatal exposure to alcohol. Material and methods: The study was conducted on a group of 20 children aged 4–5 years with information from an interview about prenatal exposure to alcohol. The diagnosis of sensory integration disorder consisted of two 60-minute diagnostics meetings. Twelve trials with clinical observations were performed by Ayres: finger to nose, cocontraction, prone extension posture, flexed position supine, asymmetrical tonic neck reflex (ATOS, symmetrical tonic neck reflex (STOS, muscle tension, Schilder test, dynamic balance, static balance, gravitational insecurity, and trunk stabilisation. The therapeutic program included: normalisation of the vestibular and proprioceptive system, normalisation of the touch system, strengthening muscle tension, development of motion planning, development of oculomotor performance, development of motor coordination, hand therapy, integration of ATOS, STOS, development of locomotion and balance functions, and improving efficiency of gross and small motor skills. Results and conclusions : High efficiency of SI therapy has been shown in children after prenatal exposure to alcohol on the example of gross motor skills. Positive effects of SI therapy have been shown for tests: finger to nose, in the erect position on the stomach, the flexural position on the back, ATOS, STOS, Schilder test, dynamic balance, static balance, and the uncertainty of gravity and trunk stabilisation. Only cocontraction and muscle tension tests showed no efficacy of SI therapy. The a-Cronbach position analysis showed high reliability of the performed tests both before and after the therapy. It is advisable to continue the study on a

  18. Childhood trauma exposure and alcohol dependence severity in adulthood: mediation by emotional abuse severity and neuroticism.

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    Schwandt, Melanie L; Heilig, Markus; Hommer, Daniel W; George, David T; Ramchandani, Vijay A

    2013-06-01

    Childhood trauma has been linked with a number of negative outcomes later in life, including alcohol dependence (AD). Previous studies have suggested a mediating role for neuroticism in the relationship between childhood trauma and psychopathology. In this study, we investigate the prevalence of multiple types of childhood trauma in treatment-seeking alcohol-dependent patients, and the associations between childhood trauma and AD severity using multiple mediation analysis. The prevalence of 5 types of childhood trauma-emotional abuse, sexual abuse, physical abuse, emotional neglect, and physical neglect-was assessed in treatment-seeking alcohol-dependent patients (n = 280) and healthy controls (n = 137) using the Childhood Trauma Questionnaire. Multiple mediation analyses were used to model associations between childhood trauma measures and alcohol-related outcomes, primarily the severity of AD in the alcohol-dependent sample. Childhood trauma was significantly more prevalent and more severe in the alcohol-dependent subjects. In addition, childhood trauma was found to influence AD severity, an effect that was mediated by neuroticism. When individual trauma types were examined, emotional abuse was found to be the primary predictor of AD severity, both directly and through the mediating effects of the impulsivity subfacet of neuroticism. Physical abuse also had a moderate direct effect on AD severity. Mediation analysis did not reveal any association between childhood trauma and Alcohol Use Disorders Identification Test score in the nondependent control sample. Childhood trauma is highly prevalent in treatment-seeking alcoholics and may play a significant role in the development and severity of AD through an internalizing pathway involving negative affect. Our findings suggest that alcoholics with a history of childhood emotional abuse may be particularly vulnerable to severe dependence. Copyright © 2012 by the Research Society on Alcoholism.

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

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    Morgan L Kleiber

    2014-06-01

    Full Text Available There is abundant evidence that prenatal alcohol exposure leads to a range of behavioural 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.

  20. Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE): A Pilot Study in Alcohol-dependent Women.

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    Persson, Anna; Back, Sudie E; Killeen, Therese K; Brady, Kathleen T; Schwandt, Melanie L; Heilig, Markus; Magnusson, Åsa

    Posttraumatic stress disorder (PTSD) and substance use disorders are highly comorbid. Effective treatments are largely lacking. This pilot study evaluated the safety and feasibility of a novel intervention, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), in preparation for a randomized controlled trial. Twenty-two treatment-seeking women with current DSM-IV-TR PTSD and alcohol dependence (AD) were recruited. Participants received COPE. Safety and feasibility were evaluated, as were efficacy-related outcomes: PTSD and depression symptom severity, alcohol use, craving, and dependence severity. No adverse events occurred. COPE was implemented in routine clinical practice. Among the assessed women, 95.8% were eligible to participate. Treatment attendance and completion were higher than in previous studies. Post treatment, all efficacy-related outcomes, including PTSD and depression symptom severity, alcohol use, craving, and dependence severity, were significantly reduced. COPE was safe and feasible to use. Concerns that trauma-focused, exposure-based therapy might promote relapse in this population appear unwarranted. Our findings provide initial evidence suggestive of COPE efficacy for comorbid PTSD and AD in women. These results provide a strong rationale for investigating the efficacy of COPE for comorbid PTSD and AD in women in a randomized controlled trial.

  1. Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol

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    De Giorgio Andrea

    2012-07-01

    Full Text Available Abstract Background Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder. Methods Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal day 60. The spatial distribution of parvalbumin interneurons was studied using Voronoi spatial tessellation and their dendritic trees were completely reconstructed. Results Parvalbumin interneurons of ethanol-treated animals showed a clustered spatial distribution similar to that observed in control animals. The dendritic tree of parvalbumin interneurons was significantly reduced in ethanol-treated animals, as compared with controls. Conclusions Striatal parvalbumin interneurons are crucial components of the brain network serving motor control. Therefore, the shrinkage of their dendrites could contribute to the motor and cognitive symptoms observed in fetal alcohol spectrum disorder.

  2. DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

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    Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

    2011-01-01

    Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in

  3. Single-session alcohol sclerotherapy in symptomatic benign hepatic cysts performed with a time of exposure to alcohol of 10 min: initial results.

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    Larssen, Trond B; Rosendahl, Karen; Horn, Arild; Jensen, Dag K; Rørvik, Jarle

    2003-12-01

    The aim of this study was to evaluate the 1-year results of single-session sclerotherapy of symptomatic benign non-parasitic liver cysts performed with maximum 10 min time of ethanol exposure. During the period 1995-1999, 15 symptomatic liver cysts in nine patients--eight women and one man--were treated with 10 min time of exposure to ethanol. Ultrasound-guided puncture combined with fluoroscopy was used for catheter placement. Alcohol sclerotherapy was performed with a maximum volume of ethanol 96% of 10% of the cyst volume, never exceeding 100 ml. At follow-up the patients were examined with liver function tests, ultrasound or CT examination, clinical examination, and interview by a gastrointestinal surgeon. Ten cysts in seven patients (six women and one man; age range 44-61 years, median age 58 years), who had a follow-up of at least 1 year, were included. The original cyst volumes were 30-4110 ml (median 392 ml). After a follow-up period of 12-47 months (median 23 months), cyst volumes were 0-523 ml (median 21.5 ml) with a reduction of the median cyst volume by 95% ( p<0,005). All patients experienced relief of their clinical symptoms. Except for pain, no complications were observed. Sclerotherapy using only one session and maximum 10 min time of exposure to ethanol represents an effective treatment of symptomatic liver cysts.

  4. Single-session alcohol sclerotherapy in symptomatic benign hepatic cysts performed with a time of exposure to alcohol of 10 min: initial results

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    Larssen, Trond B.; Rosendahl, Karen; Jensen, Dag K.; Roervik, Jarle [Department of Radiology, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen (Norway); Horn, Arild [Department of Surgery, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen (Norway)

    2003-12-01

    The aim of this study was to evaluate the 1-year results of single-session sclerotherapy of symptomatic benign non-parasitic liver cysts performed with maximum 10 min time of ethanol exposure. During the period 1995-1999, 15 symptomatic liver cysts in nine patients - eight women and one man - were treated with 10 min time of exposure to ethanol. Ultrasound-guided puncture combined with fluoroscopy was used for catheter placement. Alcohol sclerotherapy was performed with a maximum volume of ethanol 96% of 10% of the cyst volume, never exceeding 100 ml. At follow-up the patients were examined with liver function tests, ultrasound or CT examination, clinical examination, and interview by a gastrointestinal surgeon. Ten cysts in seven patients (six women and one man; age range 44-61 years, median age 58 years), who had a follow-up of at least 1 year, were included. The original cyst volumes were 30-4110 ml (median 392 ml). After a follow-up period of 12-47 months (median 23 months), cyst volumes were 0-523 ml (median 21.5 ml) with a reduction of the median cyst volume by 95% (p<0,005). All patients experienced relief of their clinical symptoms. Except for pain, no complications were observed. Sclerotherapy using only one session and maximum 10 min time of exposure to ethanol represents an effective treatment of symptomatic liver cysts. (orig.)

  5. 'Just a pinch of salt'. An experimental comparison of the effect of repeated exposure and flavor-flavor learning with salt or spice on vegetable acceptance in toddlers.

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    Bouhlal, Sofia; Issanchou, Sylvie; Chabanet, Claire; Nicklaus, Sophie

    2014-12-01

    Children's vegetable intake is below the recommended amounts. No studies to date have tested the relevance of using salt or spices to increase children's vegetable acceptance. Our objective was to compare the effect of repeated exposure (RE) and of flavor-flavor learning (FFL) on toddlers' acceptance of a non-familiar vegetable. Two unconditioned stimuli were used: salt and a salt-associated spice. Toddlers attending six nurseries were assigned to 3 groups in a between subject design. Groups were exposed 8 times to a basic salsify puree (0.2% salt w/w; RE group; n = 47), a salty salsify puree (0.5% salt w/w; FFL-Salt group; n = 54) or a spiced salsify puree (0.2% salt and 0.02% nutmeg w/w; FFL-Nutmeg group; n = 50). Acceptance (intake and liking) of the target vegetable (basic salsify puree) and of a control vegetable (carrot puree) was evaluated at pre-exposure, at each exposure of the learning period, at post-exposure, and at 1, 3 and 6 months after exposure. In all groups, intake of the target vegetable increased from pre- to post-exposure. This increase was significantly higher in the RE group (64 ± 11 g) than in the FFL-Salt group (23 ± 11 g) and marginally higher than in the FFL-Nutmeg group (36 ± 11 g). No difference between groups was observed on the increase in liking of the target vegetable from pre- to post-exposure. The increase of the target vegetable intake was still observed after 6 months for all groups. Thus, repeated exposure appears to be the simplest choice to increase vegetable intake on the short and long term in toddlers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

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    Bertholet Jean-Yves

    2005-04-01

    Full Text Available Abstract Background The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J. Results Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype at adult age. Conclusion Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures or involve different animal models.

  7. Repeated exposure to cat urine induces complex behavioral, hormonal, and c-fos mRNA responses in Norway rats ( Rattus norvegicus)

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    Yin, Baofa; Gu, Chen; Lu, Yi; Hegab, Ibrahim M.; Yang, Shengmei; Wang, Aiqin; Wei, Wanhong

    2017-08-01

    Prey species show specific adaptations that allow recognition, avoidance, and defense against predators. This study was undertaken to investigate the processing of a chronic, life-threatening stimulus to Norway rats ( Rattus norvegicus). One hundred forty-four Norway rats were tested by repeated presentation of cat urine for 1 h at different days in a defensive withdrawal apparatus. Rats exposed to urine for short periods showed significantly larger defensive behavioral and medial hypothalamic c-fos messenger RNA (mRNA) responses than other groups. These defensive responses habituated shortly after the presentation of cat urine. Serum levels of adrenocorticotropic hormone and corticosterone increased significantly when animals were repeatedly exposed to cat urine. However, the hormonal responses took longer to habituate than the behavioral and molecular responses did. We conclude that the behavioral and c-fos mRNA responses are "primed" for habituation to repeated exposures to cat urine, while the hormonal responses show "resistance." The results support our hypothesis that the strongest anti-predator responses at three levels would occur during short-term exposure to cat urine and that these responses would subsequently disappear on prolonged exposure. This study assists understanding the way in which the different levels of defensive responses are integrated and react during chronic stress.

  8. Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test.

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    Desikan, Anita; Wills, Derek N; Ehlers, Cindy L

    2014-07-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. Studies in animal models have demonstrated that alcohol exposure during adolescence can cause a modification in some aspects of behavioral development, causing the "adolescent phenotype" to be retained into adulthood. However, the "adolescent phenotype" has not been studied for a number of behavioral tests. The objective of the present study was to investigate the ontogeny of behaviors over adolescence/young adulthood in the light/dark box, open field conflict and forced swim test in male Wistar rats. These data were compared to previously published data from rats that received intermittent alcohol vapor exposure during adolescence (AIE) to test whether they retained the "adolescent phenotype" in these behavioral tests. Three age groups of rats were tested (post-natal day (PD) 34-42; PD55-63; PD69-77). In the light/dark box test, younger rats escaped the light box faster than older adults, whereas AIE rats returned to the light box faster and exhibited more rears in the light than controls. In the open field conflict test, both younger and AIE rats had shorter times to first enter the center, spent more time in the center of the field, were closer to the food, and consumed more food than controls. In the forced swim test no clear developmental pattern emerged. The results of the light/dark box and the forced swim test do not support the hypothesis that adolescent ethanol vapor exposure can "lock-in" all adolescent phenotypes. However, data from the open field conflict test suggest that the adolescent and the AIE rats both engaged in more "disinhibited" and food motivated behaviors. These data suggest that, in some behavioral tests, AIE may result in a similar form of behavioral disinhibition to what is seen in adolescence.

  9. Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area.

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    Sotomayor-Zárate, Ramón; Abarca, Jorge; Araya, Katherine A; Renard, Georgina M; Andrés, María E; Gysling, Katia

    2015-11-01

    A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems. Cocaine (10mg/Kg i.p.) induced an increase of VTA DA extracellular levels in control rats. However, this effect was not observed in repeated stress rats. Considering the evidence relating stress with CRF, we decided to perfuse CRF and CP-154526 (selective antagonist of CRF1 receptor) in the VTA of control and repeated stress rats, respectively. We observed that perfusion of 20μM CRF inhibited the increase of VTA DA extracellular levels induced by cocaine in control rats. Interestingly, we observed that in the presence of 10μM CP-154526, cocaine induced a significant increase of VTA DA extracellular levels in repeated stress rats. Regarding the role of VTA GABA neurotransmission, cocaine administration induced a significant increase in VTA GABA extracellular levels only in repeated stress rats. Consistently, cocaine was able to increase VTA DA extracellular levels in repeated stress rats when 100μM bicuculline, an antagonist of GABAA receptor, was perfused intra VTA. Thus, both CRF and GABA systems are involved in the lack of response to cocaine in the VTA of repeated stress rats. It is tempting to suggest that the loss of response in VTA dopaminergic neurons to cocaine, after repeated stress, is due to an interaction between CRF and GABA systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Alteration of brain levels of neurotransmitters and amino acids in male F344 rats induced by three-week repeated inhalation exposure to 1-bromopropane.

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    Suda, Megumi; Honma, Takeshi; Miyagawa, Muneyuki; Wang, Rui-Sheng

    2008-08-01

    The present study investigated the effects of 1-bromopropane (1BP) on brain neuroactive substances of rats to determine the extent of its toxicity to the central nervous system (CNS). We measured the changes in neurotransmitters (acetylcholine, catecholamine, serotonin and amino acids) and their metabolites or precursors in eight brain regions after inhalation exposure to 1BP at 50 to 1,000 ppm for 8 h per day for 7 d per week for 3 wk. Rats were sacrificed at 2 h (Case 1), or at 19 h (Case 2) after the end of exposure. In Case 1, the level of 5-hydroxyindoleacetic acid (5HIAA) was lowered in some brain regions by 1BP exposure. The decrease of 5HIAA in the frontal cortex was statistically significant at 50 ppm 1BP exposure. In Case 2, gamma-amino butyric acid (GABA) and taurine were decreased in many brain regions of exposed rats, and a significant decrease of taurine in the midbrain occurred at 50 ppm 1BP exposure. In both cases of 2-h and 19-h intervals from the end of exposure to sacrifice, aspartate and glutamine levels were elevated in many brain regions, but the acetylcholine level did not change in any brain region. Three-week repeated exposure to 1BP produced significantly changes in amino acid contents of rat brains, particularly at 1,000 ppm.

  11. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol.

    Science.gov (United States)

    Kaphalia, Bhupendra S; Bhopale, Kamlesh K; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J; Ansari, G A Shakeel

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH(-)) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH(-) and hepatic ADH-normal (ADH(+)) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼1.5-fold greater in ADH(-) vs. ADH(+) deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH(-) deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2009-01-01

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

  13. Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

    Science.gov (United States)

    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.

  14. Histopathology of repeated, intermittent exposure of chloramine-T to walleye (Sander vitreum) and (Ictalurus punctalus) channel catfish

    Science.gov (United States)

    Gaikowski, M.P.; Densmore, Christine L.; Blazer, V.S.

    2009-01-01

    Chloramine-T (Cl-T) has been used safely and effectively to control bacterial gill disease in salmonids at a maximum exposure regimen of up to four consecutive, once-daily exposures administered for 60??min at 20??mg/L. However, data to document safe treatment concentrations of Cl-T are lacking for freshwater-reared fish other than salmonids. We report the histopathology resultant from the administration of 12 consecutive, once-daily, 180-min static immersion baths of 0, 20, 50, or 80??mg Cl-T/L to walleye (20????C) and channel catfish (27????C). Twelve fish of each species were euthanized immediately before the first exposure (initial controls) and then after the twelfth exposure and 7 and 14??days after the twelfth exposure. Only initial controls and fish euthanized immediately after the twelfth exposure were processed for histological review because of the general lack of exposure-related lesions in exposed fish. The only exposure-related histological changes were in the spleen where significantly greater erythrocyte swelling and necrosis was observed in channel catfish exposed at 80??mg/L relative to exposure at 0??mg/L; similar histological changes were insignificant for walleye, though there appeared to be a shift in the general category of histological change with degenerative changes (necrosis, etc.) observed following exposure at 50 or 80??mg/L compared to the inflammatory and hemodynamic changes (congestion, leukocyte infiltrate, etc.) observed in walleye exposed at 0 or 20??mg/L. The only significant change in peripheral blood cytology was that walleye fingerlings exposed at 80??mg/L had significantly fewer mature red blood cells and significantly more immature red blood cells per oil-immersion field than controls. The histopathological changes observed following exposure to Cl-T under an exaggerated exposure regimen suggest that walleye or channel catfish therapeutically exposed to Cl-T will not have treatment-related histological changes.

  15. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

    Directory of Open Access Journals (Sweden)

    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  16. GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure

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    Wu Meei-Maan

    2010-08-01

    Full Text Available Abstract Background Arsenic is a strong stimulus of heme oxygenase (HO-1 expression in experimental studies in response to oxidative stress caused by a stimulus. A functional GT-repeat polymorphism in the HO-1 gene promoter was inversely correlated to the development of coronary artery disease in diabetics and development of restenosis following angioplasty in patients. The role of this potential vascular protective factor in carotid atherosclerosis remains unclear. We previously reported a graded association of arsenic exposure in drinking water with an increased risk of carotid atherosclerosis. In this study, we investigated the relationship between HO-1 genetic polymorphism and the risk of atherosclerosis related to arsenic. Methods Three-hundred and sixty-seven participants with an indication of carotid atherosclerosis and an additional 420 participants without the indication, which served as the controls, from two arsenic exposure areas in Taiwan, a low arsenic-exposed Lanyang cohort and a high arsenic-exposed LMN cohort, were studied. Carotid atherosclerosis was evaluated using a duplex ultrasonographic assessment of the extracranial carotid arteries. Allelic variants of (GTn repeats in the 5'-flanking region of the HO-1 gene were identified and grouped into a short (S allele ( Results Analysis results showed that arsenic's effect on carotid atherosclerosis differed between carriers of the class S allele (OR 1.39; 95% CI 0.86-2.25; p = 0.181 and non-carriers (OR 2.65; 95% CI 1.03-6.82; p = 0.044 in the high-exposure LMN cohort. At arsenic exposure levels exceeding 750 μg/L, difference in OR estimates between class S allele carriers and non-carriers was borderline significant (p = 0.051. In contrast, no such results were found in the low-exposure Lanyang cohort. Conclusions This exploratory study suggests that at a relatively high level of arsenic exposure, carriers of the short (GTn allele (

  17. Field study of the urinary excretion of ethoxyacetic acid during repeated daily exposure to the ethyl ether of ethylene glycol and the ethyl ether of ethylene glycol acetate.

    Science.gov (United States)

    Veulemans, H; Groeseneken, D; Masschelein, R; Van Vlem, E

    1987-06-01

    The urinary excretion of ethoxyacetic acid (EAA) was studied in a group of five women daily exposed to the ethyl ether of ethylene glycol (EGEE) and the ethyl ether of ethylene glycol acetate (EGEE-Ac) during 5 d of normal production and 7 d after a 12-d production stop. The mean combined exposure concentration of EGEE and EGEE-Ac (expressed in equivalent weight of EGEE) was 14.0 mg/m3 with occasional slight excursions above the current Belgian occupational exposure limit. The daily combined exposure profiles for EGEE and EGEE-Ac were rather constant during the first observation period, but they tended to decrease during the last week. The urinary EAA excretion clearly increased during the work week. Over the weekends the elimination was far from complete, and even after a prolonged nonexposure period of 12 d traces of the metabolite were still detectable. Based on the observations from the first period, a good linear correlation (r = 0.92) was found between the average exposure over 5 d (14.4 mg/m3) and the EAA excretion at the end of the week (105.7 mg/g creatinine). An EAA estimate of 150 +/- 35 mg/g was found to correspond with repeated 5-d full-shift exposures to the respective occupational exposure limit of EGEE (19 mg/m3) or EGEE-Ac (27 mg/m3).

  18. Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design

    Science.gov (United States)

    Mauritz, Maria W.; Van Gaal, Betsie G. I.; Jongedijk, Ruud A.; Schoonhoven, Lisette; Nijhuis-van der Sanden, Maria W. G.; Goossens, Peter J. J.

    2016-01-01

    Background In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the

  19. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

    Science.gov (United States)

    Gershkovich, Pavel; Wasan, Kishor M; Ribeyre, Charles; Ibrahim, Fady; McNeill, John H

    2015-01-01

    Purpose: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored. PMID:26322116

  20. Allergic inflammation in the upper respiratory tract of the rat upon repeated inhalation exposure to the contact allergen dinitrochlorobenzene (DNCB).

    NARCIS (Netherlands)

    Triel, J.J. van; Arts, J.H.; Muijser, H.; Kuper, C.F.

    2010-01-01

    Previously, the contact allergen dinitrochlorobenzene (DNCB) was identified as a sensitizer by inhalation in BALB/c mice; in addition, DNCB induced a lymphocytic infiltrate in the larynx of dermally sensitized Th1-prone Wistar rats upon a single inhalation challenge. In the present study, repeated

  1. Repeated exposure to heat stress results in a diaphragm phenotype that resists ventilator-induced diaphragm dysfunction.

    Science.gov (United States)

    Yoshihara, Toshinori; Ichinoseki-Sekine, Noriko; Kakigi, Ryo; Tsuzuki, Takamasa; Sugiura, Takao; Powers, Scott K; Naito, Hisashi

    2015-11-01

    Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against CMV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.

  2. Allergic inflammation in the upper respiratory tract of the rat upon repeated inhalation exposure to the contact allergen dinitrochlorobenzene (DNCB).

    NARCIS (Netherlands)

    Triel, J.J. van; Arts, J.H.; Muijser, H.; Kuper, C.F.

    2010-01-01

    Previously, the contact allergen dinitrochlorobenzene (DNCB) was identified as a sensitizer by inhalation in BALB/c mice; in addition, DNCB induced a lymphocytic infiltrate in the larynx of dermally sensitized Th1-prone Wistar rats upon a single inhalation challenge. In the present study, repeated i

  3. Detection of local inflammation induced by repeated exposure to contact allergens by use of IVIS SpectrumCT analyses

    DEFF Research Database (Denmark)

    Nielsen, Morten M; Schmidt, Jonas Damgård; Christensen, Jan P

    2017-01-01

    BACKGROUND: Contact allergy is characterized by local skin inflammation that, in some cases, can result in systemic immune activation. OBJECTIVES: To investigate whether IVIS SpectrumCT analyses can be used to detect the immune response induced by contact allergens. METHODS: Mice were repeatedly ...

  4. Effects of repeated hyperbaric nitrogen-oxygen exposures on the striatal dopamine release and on motor disturbances in rats.

    Science.gov (United States)

    Lavoute, Cécile; Weiss, Michel; Rostain, Jean-Claude

    2005-09-14

    Previous studies have demonstrated disruptions of motor activities and a decrease of extracellular dopamine level in the striatum of rats exposed to high pressure of nitrogen. Men exposed to nitrogen pressure develop also motor and cognitive disturbances related to inert gas narcosis. After repetitive exposures, adaptation to narcosis was subjectively reported. To study the effects of repetitive exposures to hyperbaric nitrogen-oxygen, male Sprague-Dawley rats were implanted in the striatum with multifiber carbon dopamine-sensitive electrodes. After recovery from surgery, free-moving rats were exposed for 2 h up to 3 MPa of nitrogen-oxygen mixture before and after one daily exposure to 1 MPa of nitrogen-oxygen, for 5 consecutive days. Dopamine release was measured by differential pulse voltammetry and motor activities were quantified using piezo-electric captor. At the first exposure to 3 MPa, the striatal dopamine level decreased during the compression (-15%) to reach -20% during the stay at 3 MPa. Motor activities were increased during compression (+15%) and the first 60 min at constant pressure (+10%). In contrast, at the second exposure to 3 MPa, an increase of dopamine of +15% was obtained during the whole exposure. However, total motor activities remained unchanged as compared to the first exposure. Our results confirm that nitrogen exposure at 3 MPa led to a decreased striatal dopamine release and increased motor disturbances in naïve rats. Repetitive exposures to 1 MPa of nitrogen induced a reversal effect on the dopamine release which suggests a neurochemical change at the level of the neurotransmitter regulation processes of the basal ganglia. In contrast, motor activity remained quantitatively unchanged, thus suggesting that dopamine is not involved alone in modulating these motor disturbances.

  5. The effects of chronic cadmium exposure on repeat swimming performance and anaerobic metabolism in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis)

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, Jessie L.; McGeer, James C., E-mail: jmcgeer@wlu.ca

    2016-04-15

    Highlights: • Exposure to 18 nM waterborne Cd induced plasma Ca loss that recovered by day 30 for lake whitefish but not brown trout. • Ucrit measured after an initial swim to 85% of Ucrit and a 30 min rest period was reduced in 18 nM Cd exposed fish compared to controls. • Swimming to 85% of Ucrit resulted in decreased muscle glycogen and increased lactate that was not recovered in the 30 min recovery period. • Second swim impairment is not related to metabolic processes in white muscle. - Abstract: This study investigates the effect of chronic Cd exposure on the ability to perform repeat swim challenges in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). Fish were exposed to waterborne Cd (18 nM) in moderately hard water (120 mg L{sup −1} CaCO{sub 3}) for 30 days. This level of exposure has been shown to cause sublethal physiological disruption and acclimation responses but no impairment of sustained swimming capacity (U{sub crit}) in single swim challenges. Swim trials were done over the course of the exposure and each one consisted of an initial swim to 85% of the U{sub crit} of control fish, a 30 min recovery period and finally a second swim challenge to determine U{sub crit}. Plasma and tissue samples were collected before and after each of the swim periods. As expected from previous studies, Cd exposure resulted in significant accumulation of Cd in gills, liver and kidney but not in white muscle. Exposure also induced a loss of plasma Ca followed by subsequent recovery (in lake whitefish but not brown trout) with few mortalities (100% survival for lake whitefish and 93% for brown trout). Both control and exposed fish swam to 85% of the single swim U{sub crit} and no differences in performance were seen. The Ucrit of unexposed controls in the second swim challenges were not different from the single swim Ucrit. However, second swim performance was significantly reduced in Cd exposed fish, particularly after a week of exposure

  6. Graphomotor skills in children with prenatal alcohol exposure and fetal alcohol spectrum disorder: A population-based study in remote Australia.

    Science.gov (United States)

    Doney, Robyn; Lucas, Barbara R; Jirikowic, Tracy; Tsang, Tracey W; Watkins, Rochelle E; Sauer, Kay; Howat, Peter; Latimer, Jane; Fitzpatrick, James P; Oscar, June; Carter, Maureen; Elliott, Elizabeth J

    2017-02-01

    Few studies have examined graphomotor skills in children with prenatal alcohol exposure (PAE) or fetal alcohol spectrum disorder (FASD). Graphomotor skills were assessed in 108 predominantly Australian Aboriginal children aged 7.5-9.6 years in remote Western Australia using clinical observations (pencil grasp; writing pressure) and standardised assessment tools (the Evaluation Tool of Children's Handwriting; and the Miller Function and Participation Scales - The Draw-a-Kid Game). Skills were compared between children (i) without PAE, (ii) PAE but not FASD and (iii) FASD. Most children used a transitional pencil grasp and exerted heavy handwriting pressure (83.3% and 30.6% of the cohort). The percentage of letters (M = 62.9%) and words (M = 73.3%) written legibly was low. Children with FASD were more likely than children without PAE to use a cross-thumb grasp (P = 0.027), apply heavy writing pressure (P = 0.036), be unable to write a sentence (P = 0.041) and show poorer word legibility (P = 0.041). There were no significant differences between groups for drawing outcomes, although some children with FASD drew pictures that appeared delayed for their age. There were no significant differences between children without PAE and those with PAE but who were not diagnosed with FASD. Overall, graphomotor skills were poor in this cohort, but children with FASD performed significantly worse than children without PAE. Findings suggest the need for improved occupational therapy services for children in remote regions and evaluation of graphomotor skills in children with PAE. © 2016 Occupational Therapy Australia.

  7. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats

    Science.gov (United States)

    ALLEN, Camryn D.; LEE, Soon; KOOB, George F.; RIVIER, Catherine

    2011-01-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration. PMID:21300146

  8. Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available The abuse of psychostimulants, such as methamphetamine (METH, is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to naïve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr as well as decreased dopamine transporter (DAT level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.

  9. Repeated measures of inflammation, blood pressure, and heart rate variability associated with personal traffic exposures in healthy adults

    Science.gov (United States)

    BACKGROUND: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic lo...

  10. Repeated measures of inflammation, blood pressure, and heart rate variability associated with personal traffic exposures in healthy adults

    Science.gov (United States)

    BACKGROUND: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic lo...

  11. The effect of sensory-nutrient congruency on food intake after repeated exposure: do texture and/or energy density matter?

    Science.gov (United States)

    Hogenkamp, P S

    2014-09-01

    Sensory properties guide the amount that people eat. In particular, food texture plays an important role in a food's 'expected satiation', which in turn affects the food-related decision making process. One hypothesis is that incongruent pairing of a textural cue with a post-ingestive outcome compromises this process, leading to poor energy compensation. Several studies examined the effect of both energy density and sensory characteristics (i.e. increased creaminess and thickness) on expectations, subjective appetite and food intake. To add to this literature, a re-analysis of data assessed whether the effect of sensory-nutrient pairings on energy intake compensation persisted after repeated exposure to a food. In this cross-over design, 27 participants consumed two preloads with 'congruent' (low-energy/liquid; high-energy/semi-solid) and two preloads with 'incongruent' (low-energy/semi-solid; high-energy/liquid) texture-nutrient combinations for nine subsequent meals, during which ad libitum intake was measured. Intake at first exposure did not differ between the low-energy (280±150kcal) and high-energy preloads (292±183kcal) in the incongruent conditions. By contrast, it was greater after the low-energy (332±203kcal) than after the high-energy (236±132kcal) preload in the congruent conditions (energy∗incongruent/congruent, p=0.04). Post-exposure, this pattern changed: intake depended on the energy density of the preloads in all conditions, and was greater after low-energy preloads (day∗energy∗incongruent/congruent-interaction for breakfast: p=0.02). Thus, manipulating the sensory properties of a food influenced energy compensation and meal size, but only at initial exposure. Repeated exposure 'corrected' the initial lack of compensation observed in conditions with incongruent sensory-nutrient pairings.

  12. Comparative systems toxicology analysis of cigarette smoke and aerosol from a candidate modified risk tobacco product in organotypic human gingival epithelial cultures: A 3-day repeated exposure study.

    Science.gov (United States)

    Zanetti, Filippo; Titz, Bjoern; Sewer, Alain; Lo Sasso, Giuseppe; Scotti, Elena; Schlage, Walter K; Mathis, Carole; Leroy, Patrice; Majeed, Shoaib; Torres, Laura Ortega; Keppler, Brian R; Elamin, Ashraf; Trivedi, Keyur; Guedj, Emmanuel; Martin, Florian; Frentzel, Stefan; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2017-03-01

    Smoking is one of the major lifestyle-related risk factors for periodontal diseases. Modified risk tobacco products (MRTP) offer a promising alternative in the harm reduction strategy for adult smokers unable to quit. Using a systems toxicology approach, we investigated and compared the exposure effects of a reference cigarette (3R4F) and a heat-not-burn technology-based candidate MRTP, the Tobacco Heating System (THS) 2.2. Human gingival epithelial organotypic cultures were repeatedly exposed (3 days) for 28 min at two matching concentrations of cigarette smoke (CS) or THS2.2 aerosol. Results showed only minor histopathological alterations and minimal cytotoxicity upon THS2.2 aerosol exposure compared to CS (1% for THS2.2 aerosol vs. 30% for CS, at the high concentration). Among the 14 proinflammatory mediators analyzed, only 5 exhibited significant alterations with THS2.2 exposure compared with 11 upon CS exposure. Transcriptomic and metabolomic analysis indicated a general reduction of the impact in THS2.2 aerosol-exposed samples with respect to CS (∼79% lower biological impact for the high THS2.2 aerosol concentration compared to CS, and 13 metabolites significantly perturbed for THS2.2 vs. 181 for CS). This study indicates that exposure to THS2.2 aerosol had a lower impact on the pathophysiology of human gingival organotypic cultures than CS. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function

    Directory of Open Access Journals (Sweden)

    P. Gautam

    2014-01-01

    Full Text Available 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.

  14. Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design

    Directory of Open Access Journals (Sweden)

    Maria W. Mauritz

    2016-09-01

    Full Text Available Background: In the Netherlands, most patients with severe mental illness (SMI receive flexible assertive community treatment (FACT provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1 PTSD and dissociative symptoms changes and (2 changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25 with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results

  15. The effects of chronic cadmium exposure on repeat swimming performance and anaerobic metabolism in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis).

    Science.gov (United States)

    Cunningham, Jessie L; McGeer, James C

    2016-04-01

    This study investigates the effect of chronic Cd exposure on the ability to perform repeat swim challenges in brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis). Fish were exposed to waterborne Cd (18nM) in moderately hard water (120mgL(-1) CaCO3) for 30 days. This level of exposure has been shown to cause sublethal physiological disruption and acclimation responses but no impairment of sustained swimming capacity (Ucrit) in single swim challenges. Swim trials were done over the course of the exposure and each one consisted of an initial swim to 85% of the Ucrit of control fish, a 30min recovery period and finally a second swim challenge to determine Ucrit. Plasma and tissue samples were collected before and after each of the swim periods. As expected from previous studies, Cd exposure resulted in significant accumulation of Cd in gills, liver and kidney but not in white muscle. Exposure also induced a loss of plasma Ca followed by subsequent recovery (in lake whitefish but not brown trout) with few mortalities (100% survival for lake whitefish and 93% for brown trout). Both control and exposed fish swam to 85% of the single swim Ucrit and no differences in performance were seen. The Ucrit of unexposed controls in the second swim challenges were not different from the single swim Ucrit. However, second swim performance was significantly reduced in Cd exposed fish, particularly after a week of exposure where 31% and 38% reductions were observed for brown trout and lake whitefish respectively. Swimming to 85% Ucrit resulted in metabolic expenditure with little recovery after 30min. Few differences were observed between control and Cd exposed fish with the exception of a reduction in resting white muscle ATP stores of Cd exposed fish after 1 week of exposure. The results show that chronic sublethal Cd exposure results in an impairment of swimming ability in repeat swim challenges but this impairment is generally not related to metabolic processes

  16. Reactive Oxygen Species-mediated Loss of Phenotype of Parvalbumin Interneurons Contributes to Long-term Cognitive Impairments After Repeated Neonatal Ketamine Exposures.

    Science.gov (United States)

    Zhang, Hui; Sun, Xiao-Ru; Wang, Jing; Zhang, Zhen-Zhen; Zhao, Hong-Ting; Li, Hui-Hui; Ji, Mu-Huo; Li, Kuan-Yu; Yang, Jian-Jun

    2016-11-01

    Ketamine, a common anesthetic used for pediatric patients, has been shown to induce neurotoxicity and alter adolescent behaviors in rats when administered during neonatal period. However, the mechanisms underlying this kind of neurotoxicity remain largely to be determined. Herein, we studied whether the reactive oxygen species (ROS) due to the increased NOX2 mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Sprague-Dawley male rat pups received a daily administration of ketamine intraperitoneally (75 mg/kg) from postnatal day 6 (P6) to P8 for three consecutive days. For the interventional study, pups were treated with a NADPH oxidase inhibitor, apocynin (Apo). Learning and memory abilities were tested by the open field, fear conditioning, and Morris water maze on P40, P42-44, and P50-56, respectively. For histological and biochemical assays, a separate cohort of rats was killed on P9 or P60, and the brain tissues were harvested. Our results showed the upregulation of 8-OHdG and gp91/NOX2 and downregulation of PV and glutamic acid decarboxylase 67 (GAD67) after repeated ketamine exposures, which co-occurred with the long-term cognitive impairments as evidenced by the decreased freezing time to context. However, Apo treatment attenuated these abnormalities. Our results suggest that oxidative damage, probably due to the increased NOX2, mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Moreover, the inhibition of NADPH oxidase may protect against cognitive dysfunction.

  17. Exposure to ambient air particulate matter and non-alcoholic fatty liver disease

    National Research Council Canada - National Science Library

    Tarantino, Giovanni; Capone, Domenico; Finelli, Carmine

    2013-01-01

    The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters < 2.5 mm (PM2.5...

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

    Science.gov (United States)

    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.

  19. Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease.

    Science.gov (United States)

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

    2009-12-01

    Owing 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 particulate matter (CAPs) or filtered air for 6 weeks, progression of NAFLD was evaluated by standardized histological assessment of hepatic inflammation and fibrosis. In mice fed HFC, 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 scores of (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). In conclusion, ambient PM(2.5) exposure may be a significant risk factor for NAFLD progression.

  20. Ventilatory long-term facilitation is evident after initial and repeated exposure to intermittent hypoxia in mice genetically depleted of brain serotonin.

    Science.gov (United States)

    Hickner, Stephen; Hussain, Najaah; Angoa-Perez, Mariana; Francescutti, Dina M; Kuhn, Donald M; Mateika, Jason H

    2014-02-01

    Our study was designed to determine if central nervous system (CNS) serotonin is required for the induction of ventilatory long-term facilitation (LTF) in intact, spontaneously breathing mice. Nineteen tryptophan hydroxylase 2-deficient (Tph2(-/-)) mice, devoid of serotonin in the CNS, and their wild-type counterparts (Tph2(+/+)) were exposed to intermittent hypoxia each day for 10 consecutive days. The ventilatory response to intermittent hypoxia was greater in the Tph2(+/+) compared with the Tph2(-/-) mice (1.10 ± 0.10 vs. 0.77 ± 0.01 ml min(-1)·percent(-1) oxygen; P ≤ 0.04). Ventilatory LTF, caused by increases in breathing frequency, was evident in Tph2(+/+) and Tph2(-/-) mice following exposure to intermittent hypoxia each day; however, the magnitude of the response was greater in the Tph2(+/+) compared with the Tph2(-/-) mice (1.11 ± 0.02 vs. 1.05 ± 0.01 normalized to baseline on each day; P ≤ 0.01). The magnitude of ventilatory LTF increased significantly from the initial to the finals days of the protocol in the Tph2(-/-) (1.06 ± 0.02 vs. 1.11 ± 0.03 normalized to baseline on the initial days; P ≤ 0.004) but not in the Tph2(+/+) mice. This enhanced response was mediated by increases in tidal volume. Body temperature and metabolic rate did not account for differences in the magnitude of ventilatory LTF observed between groups after acute and repeated daily exposure to intermittent hypoxia. We conclude that ventilatory LTF, after acute exposure to intermittent hypoxia, is mediated by increases in breathing frequency and occurs in the absence of serotonin, although the magnitude of the response is diminished. This weakened response is enhanced following repeated daily exposure to intermittent hypoxia, via increases in tidal volume, to a similar magnitude evident in Tph2(+/+) mice. Thus the magnitude of ventilatory LTF following repeated daily exposure to intermittent hypoxia is not dependent on the presence of CNS serotonin.

  1. Chronic Alcohol Exposure Decreases 53BP1 Protein Levels Leading to a Defective DNA Repair in Cultured Primary Cortical Neurons.

    Science.gov (United States)

    Romero, Ana M; Palanca, Ana; Ruiz-Soto, Maria; Llorca, Javier; Marín, María P; Renau-Piqueras, Jaime; Berciano, Maria T; Lafarga, Miguel

    2016-01-01

    Chronic alcohol consumption may cause neurodevelopmental and neurodegenerative disorders. Alcohol neurotoxicity is associated with the production of acetaldehyde and reactive oxygen species that induce oxidative DNA damage. However, the molecular mechanisms by which ethanol disturbs the DNA damage response (DDR), resulting in a defective DNA repair, remain unknown. Here, we have used cultured primary cortical neurons exposed to 50 or 100 mM ethanol for 7 days to analyze the ethanol-induced DDR. Ethanol exposure produced a dose-dependent generation of double strand breaks and the formation of DNA damage foci immunoreactive for the histone γH2AX, a DNA damage marker, and for the ubiquitylated H2A, which is involved in chromatin remodeling at DNA damage sites. Importantly, these DNA damage foci failed to recruit the protein 53BP1, a crucial DNA repair factor. This effect was associated with a drop in 53BP1 mRNA and protein levels and with an inhibition of global transcription. Moreover, ethanol-exposed neurons treated with ionizing radiation (2 Gy) also failed to recruit 53BP1 at DNA damage foci and exhibited a greater vulnerability to DNA lesions than irradiated control neurons. Our results support that defective DNA repair, mediated by the deficient expression and recruitment of 53BP1 to DNA damage sites, represents a novel mechanism involved in ethanol neurotoxicity. The design of therapeutic strategies that increase or stabilize 53BP1 levels might potentially promote DNA repair and partially compensate alcohol neurotoxicity.

  2. [Diagnosis of fetal alcohol spectrum disorders].

    Science.gov (United States)

    van Wieringen, Hester; Letteboer, Tom G W; Pereira, Rob Rodrigues; de Ruiter, Sanne; Balemans, Walter A F; Lindhout, Dick

    2010-01-01

    Prenatal alcohol exposure may cause decreased growth of the child, congenital abnormalities, specific facial characteristics, and, most importantly, mental retardation and behavioural disorders, all known as fetal alcohol spectrum disorders (FASD). A significant number of pregnant women in the Netherlands drink alcohol, but the prevalence of FASD in our country is unknown. Repeated and high peak blood alcohol concentrations, for example in the case of binge drinking by the mother, result in more severe abnormalities; a safe limit for alcohol consumption in pregnancy cannot be defined. In 2007 and 2008, Dutch paediatricians reported a total of 56 diagnosed cases of FASD, mostly adopted and foster children. Possibly the condition has not always been diagnosed. Use of international guidelines for diagnosis by the medical profession may improve detection. The guidelines of the Canadian Public Health Agency provide a useful and generally accepted classification, with strict cut-off points to avoid overdiagnosis; attention should always be paid to the broad differential diagnosis.

  3. In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra

    2013-01-01

    J mice were exposed four times during gestation by intratracheal instillation of 67μg/animal of nanosized carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female offspring were raised to maturity and mated with unexposed CBA males. Expanded simple tandem repeat (ESTR) germline...... mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring....

  4. Enhanced hepatotoxicity induced by repeated exposure to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin in combination in male rats

    Institute of Scientific and Technical Information of China (English)

    Yimei Wang; Chunfeng Lu; Zhiguo Sheng; Gang Liu; Ze Fu; Benzhan Zhu; Shuangqing Peng

    2011-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are among persistent polyhalogenated aromatic hydrocarbons that exist as complex mixtures in the environment worldwide. The present study was attempted to investigate the hepatotoxicity following repeated exposure to TCDD and PCBs in combination in male rats, and to reveal the involvement of potential mechanisms. Male Sprague-Dawley rats were exposed to TCDD (10 μg/kg) and Aroclor 1254 (10 mg/kg, a representative mixture of PCBs) alone or in combination by intragastric administration. After 12-day exposure, all treatments produced significant hepatotoxicity as characterized by changes of plasma biochemistry and histopathological changes. These effects were more prominent in the combined group. Furthermore, all treatments induced hepatic cytochrome P450 1A1 (CYP1A1) expression, and the maximal level of CYP1A1 expression was observed in the combined group, as in the case of the most severe hepatotoxicity evoked by the combined exposure.These findings indicated that the hepatotoxicity induced by TCDD and Aroclor 1254 might be ascribed to the high expression of hepatic CYP1A1. The present study demonstrates the enhanced hepatotoxicity after exposure to TCDD and PCBs in combination in rats.

  5. An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)-oxide using a repeated measurements sampling design.

    Science.gov (United States)

    Fustinoni, S; Campo, L; Manini, P; Buratti, M; Waidyanatha, S; De Palma, G; Mutti, A; Foa, V; Colombi, A; Rappaport, S M

    2008-09-01

    The aim of this work was to investigate urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We obtained three or four air and urine samples from each exposed worker (eight reinforced plastics workers and 13 varnish workers), one air and urine samples from 22 control workers (automobile mechanics) and one blood sample from all subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.2 mg m(-3) and 133 microg m(-3) for reinforced plastics workers, 3.4 mg m(-3) and 12 microg m(-3) for varnish workers, and <0.3 mg m(-3) and <5 microg m(-3) for controls. Urinary levels of styrene, mandelic acid, phenylglyoxylic acid, phenylglycine (PHG), 4-vinylphenol (VP) and mercapturic acids (M1+M2), as well as cysteinyl adducts of serum albumin (but not those of haemoglobin) were significantly associated with exposure status (controlsexposure, suggestive of saturable metabolism. Levels of the protein adducts were not associated with exposure to either Sty or StyOX among exposed subjects.

  6. Physical Activity- and Alcohol-dependent Association Between Air Pollution Exposure and Elevated Liver Enzyme Levels: An Elderly Panel Study.

    Science.gov (United States)

    Kim, Kyoung-Nam; Lee, Hyemi; Kim, Jin Hee; Jung, Kweon; Lim, Youn-Hee; Hong, Yun-Chul

    2015-05-01

    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. 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. 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 liver enzyme levels in the elderly. These adverse effects can be reduced by exercising regularly and abstinence from alcohol.

  7. Association between secondhand smoke exposure at home and cigarette gifting and sharing in Zhejiang, China: a repeat cross-sectional study.

    Science.gov (United States)

    Xu, Yue; Xu, ShuiYang; Wu, QingQing; Guo, YuJie

    2016-03-03

    The aims of the current study were to assess the prevalence of household cigarette gifting and sharing, and to evaluate the relationship between secondhand smoke (SHS) exposure, and cigarette gifting and sharing, in Zhejiang, China. A repeat cross-sectional design. 10 sites in 5 cities in Zhejiang, China. Two surveys were conducted with adults in Zhejiang, China, in 2010 (N=2112) and 2012 (N=2279), respectively. At both waves, the same questionnaire was used; respondents were asked questions on residence, number of family smokers, indoor smoking rules, household income and cigarette gifting and sharing. The findings revealed that more than half of respondents' families (54.50% in 2010, 52.79% in 2012) reported exposure to SHS. Many families (54.73% in 2010, 47.04% in 2012) shared cigarettes with others, and a minority (14.91% in 2010, 14.17% in 2012) reported their family giving cigarettes as a gift. There was a significant decrease in cigarette sharing from 2010 to 2012, irrespective of household with SHS exposure status; and the cigarette gifting was significantly decreased in household without SHS exposure. Compared to households without SHS exposure, the prevalence of cigarette gifting and sharing in households with SHS exposure was more obvious. Encouraging and promoting a smoke-free household environment is necessary to change public smoking customs in Zhejiang, China. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Alcoholic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

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

    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.

  9. Physical Activity- and Alcohol-dependent Association Between Air Pollution Exposure and Elevated Liver Enzyme Levels: An Elderly Panel Study

    Science.gov (United States)

    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

  10. Prenatal alcohol exposure, adaptive function, and entry into adult roles in a prospective study of young adults.

    Science.gov (United States)

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

    2015-01-01

    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. 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 =5 9) 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 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats.

    Science.gov (United States)

    Wang, Yujie; Wu, Changyi; Han, Bin; Xu, Fei; Mao, Mingfeng; Guo, Xiangyang; Wang, Jun

    2016-07-01

    Propofol is one of the most widely used intravenous anesthetics. However, repeated exposure to propofol may cause neurodegeneration in the developing brain. Dexmedetomidine (Dex), an α2 adrenoceptor agonist, has been previously demonstrated to provide neuroprotection against neuroapoptosis and neurocognitive impairments induced by several anesthetics. Thus, the current study aimed to investigate the effect of Dex on neonatal propofol-induced neuroapoptosis and juvenile spatial learning/memory deficits. Propofol (30 mg/kg) was intraperiotoneally administered to 7‑day‑old Sprague Dawley rats (n=75) three times each day at 90 min intervals for seven consecutive days with or without Dex (75 µg/kg) treatment 20 min prior to propofol injection. Following repeated propofol exposure, reduced Akt and GSK‑3β phosphorylation, increased cleaved caspase‑3 expression levels, an increased Bax/Bcl‑2 ratio, and increased terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling (TUNEL)‑positive cells in the CA1 hippocampal subregion were observed. Morris Water Maze testing at postnatal day 29 also demonstrated spatial learning and memory deficits following propofol treatment compared with the control group. Notably, these changes were significantly attenuated by Dex pretreatment. The results of the current study demonstrated that Dex ameliorates the neurocognitive impairment induced by repeated neonatal propofol challenge in rats, partially via its anti‑apoptotic action and normalization of the disruption to the PI3K/Akt/GSK‑3β signaling pathway. The present study provides preliminary evidence demonstrating the safety of propofol on the neonatal brain and the potential use of dexmedetomidine pretreatment in pediatric patients.

  12. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    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

  13. Eosinophilia and biotoxin exposure in bottlenose dolphins (Tursiops truncatus) from a coastal area impacted by repeated mortality events

    Energy Technology Data Exchange (ETDEWEB)

    Schwacke, Lori H., E-mail: Lori.Schwacke@noaa.gov [National Oceanic and Atmospheric Administration, National Ocean Service, Center for Human Health Risks, 331 Fort Johnson Road, Charleston, SC 29412 (United States); Twiner, Michael J. [National Oceanic and Atmospheric Administration, National Ocean Service, Center for Coastal Environmental Health and Biomolecular Research, 219 Fort Johnson Road, Charleston, SC 29412 (United States); De Guise, Sylvain [University of Connecticut, Department of Pathobiology and Veterinary Science, 61 North Eagleville Road, U-89, Storrs, CT 06269 (United States); Balmer, Brian C.; Wells, Randall S. [Chicago Zoological Society, c/o Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Townsend, Forrest I. [Bayside Hospital for Animals, 251 N.E. Racetrack Road, Fort Walton Beach, FL 32547 (United States); Rotstein, David C. [National Oceanic and Atmospheric Administration, National Marine Fisheries Service, Office of Protected Resources, Marine Mammal Health and Stranding Response Program, 1315 East West Highway, Silver Spring, MD 20910 (United States); Varela, Rene A. [Ocean Embassy Inc, 6433 Pinecastle Blvd, Ste 2, Orlando, FL 32809 (United States); Hansen, Larry J. [National Oceanic and Atmospheric Administration, National Marine Fisheries Service Southeast Fisheries Science Center,101 Pivers Island Road, Beaufort, NC 28516 (United States); Zolman, Eric S. [National Oceanic and Atmospheric Administration, National Ocean Service, Center for Coastal Environmental Health and Biomolecular Research, 219 Fort Johnson Road, Charleston, SC 29412 (United States); Spradlin, Trevor R. [National Oceanic and Atmospheric Administration, National Marine Fisheries Service, Office of Protected Resources, Marine Mammal Health and Stranding Response Program, 1315 East West Highway, Silver Spring, MD 20910 (United States); and others

    2010-08-15

    Bottlenose dolphins (Tursiops truncatus) inhabiting coastal waters in the northern Gulf of Mexico have been impacted by recurrent unusual mortality events over the past few decades. Several of these mortality events along the Florida panhandle have been tentatively attributed to poisoning from brevetoxin produced by the dinoflagellate Karenia brevis. While dolphins in other regions of the Florida coast are often exposed to K. brevis blooms, large-scale dolphin mortality events are relatively rare and the frequency and magnitude of die-offs along the Panhandle raise concern for the apparent vulnerability of dolphins in this region. We report results from dolphin health assessments conducted near St. Joseph Bay, Florida, an area impacted by 3 unusual die-offs within a 7-year time span. An eosinophilia syndrome, manifested as an elevated blood eosinophil count without obvious cause, was observed in 23% of sampled dolphins. Elevated eosinophil counts were associated with decreased T-lymphocyte proliferation and increased neutrophil phagocytosis. In addition, indication of chronic low-level exposure to another algal toxin, domoic acid produced by the diatom Pseudo-nitzschia spp., was determined. Previous studies of other marine mammal populations exposed recurrently to Pseudo-nitzschia blooms have suggested a possible link between the eosinophilia and domoic acid exposure. While the chronic eosinophilia syndrome could over the long-term produce organ damage and alter immunological status and thereby increase vulnerability to other challenges, the significance of the high prevalence of the syndrome to the observed mortality events in the St. Joseph Bay area is unclear. Nonetheless, the unusual immunological findings and concurrent evidence of domoic acid exposure in this sentinel marine species suggest a need for further investigation to elucidate potential links between chronic, low-level exposure to algal toxins and immune health.

  14. Effects of repeated prenatal glucocorticoid exposure on long-term potentiation in the juvenile guinea-pig hippocampus.

    Science.gov (United States)

    Setiawan, Elaine; Jackson, Michael F; MacDonald, John F; Matthews, Stephen G

    2007-06-15

    Synthetic glucocorticoids (sGCs) are routinely used to treat women at risk of preterm labour to promote fetal lung maturation. There is now strong evidence that exposure to excess glucocorticoid during periods of rapid brain development has permanent consequences for endocrine function and behaviour in the offspring. Prenatal exposure to sGC alters the expression of N-methyl-D-aspartate receptor (NMDA-R) subunits in the fetal and neonatal hippocampus. Given the integral role of the NMDA-R in synaptic plasticity, we hypothesized that prenatal sGC exposure will have effects on hippocampal long-term potentiation (LTP) after birth. Further, this may occur in either the presence or absence of elevated cortisol concentrations, in vitro. Pregnant guinea-pigs were injected with betamethasone (Beta, 1 mg kg(-1)) or vehicle on gestational days (gd) 40, 41, 50, 51, 60 and 61 (term approximately 70 days), a regimen comparable to that given to pregnant women. On postnatal day 21, LTP was examined at Schaffer collateral synapses in the CA1 region of hippocampal slices prepared from juvenile animals exposed to betamethasone or vehicle, in utero. Subsequently, the acute glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-dependent effects of cortisol (0.1-10 microM; bath applied 30 min before LTP induction) were examined. There was no effect of prenatal sGC treatment on LTP under basal conditions. The application of 10 microM cortisol depressed excitatory synaptic transmission in all treatment groups regardless of sex. Similarly, LTP was depressed by 10 microM cortisol in all groups, with the exception of Beta-exposed females, in which LTP was unaltered. Hippocampal MR and GR protein levels were increased in Beta-exposed females, but not in any other prenatal treatment group. This study reveals sex-specific effects of prenatal exposure to sGC on LTP in the presence of elevated cortisol, a situation that would occur in vivo during stress.

  15. A momentary exposures analysis of proximity to alcohol outlets and risk for assault.

    Science.gov (United States)

    Morrison, Christopher N; Dong, Beidi; Branas, Charles C; Richmond, Therese S; Wiebe, Douglas J

    2017-02-01

    This study estimated, with high spatial and temporal specificity, individuals' risk of being assaulted relative to their momentary proximity to alcohol outlets during daily activities. Case-control study. Philadelphia, PA, USA. Cases were 194 non-gun assault victims and 135 gun assault victims aged between 10 and 24 years. Age-matched controls (n = 274) were selected using random-digit dialing. Participants described minute-by-minute movements (i.e. activity paths) during the course of the day of the assault (cases) or a recent randomly selected day within 3 days of interview (controls). The dependent measure was being an assault case compared with a non-assault control. The main independent measures were participants' momentary proximity to alcohol outlets. The units of analysis were 10-minute segments beginning at 4:00 a.m. Proximity to bars and restaurants was associated with decreased odds of non-gun assault before 1 p.m. [e.g. 7 a.m. to 9:59 a.m.: odds ratio (OR) = 0.78; 95% confidence interval (CI) = 0.64, 0.94; P = 0.008], and increased odds after 7 p.m. (e.g. 1 a.m. to 3:59 a.m.: OR = 1.96; 95% CI = 1.24, 3.09; P = 0.004). Proximity to beer stores was associated with increased odds before 1 p.m. (e.g. 7 a.m. to 9:59 a.m.: OR = 2.34; 95% CI = 1.58, 3.46; P Proximity to alcohol outlets was mostly unrelated to risks for gun assault. Individuals in areas with greater densities of bars and restaurants and beer stores appear to be at increased risk for non-gun assault at times when these outlets are likely to be patronized most heavily. © 2016 Society for the Study of Addiction.

  16. Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

    Directory of Open Access Journals (Sweden)

    C.C. Justo

    2010-07-01

    Full Text Available Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD, increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL from postnatal day (PND 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39, the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg or MPD (10 mg/kg; MPD pretreated rats received MPD (10 mg/kg. Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood. To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg or nicotine (0.4 mg/kg. All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

  17. Alcoholism and Alcohol Abuse

    Science.gov (United States)

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

  18. Decreased extracellular adenosine levels lead to loss of hypoxia-induced neuroprotection after repeated episodes of exposure to hypoxia.

    Directory of Open Access Journals (Sweden)

    Mei Cui

    Full Text Available Achieving a prolonged neuroprotective state following transient ischemic attacks (TIAs is likely to effectively reduce the brain damage and neurological dysfunction associated with recurrent stroke. HPC is a phenomenon in which advanced exposure to mild hypoxia reduces the stroke volume produced by a subsequent TIA. However, this neuroprotection is not long-lasting, with the effects reaching a peak after 3 days. Therefore, in this study, we investigated the use of multiple episodes of hypoxic exposure at different time intervals to induce longer-term protection in a mouse stroke model. C57BL/6 mice were subjected to different hypoxic preconditioning protocols: a single episode of HPC or five identical episodes at intervals of 3 days (E3d HPC or 6 days (E6d HPC. Three days after the last hypoxic exposure, temporary middle cerebral artery occlusion (MCAO was induced. The effects of these HPC protocols on hypoxia-inducible factor (HIF regulated gene mRNA expression were measured by quantitative PCR. Changes in extracellular adenosine concentrations, known to exert neuroprotective effects, were also measured using in vivo microdialysis and high pressure liquid chromatography (HPLC. Neuroprotection was provided by E6d HPC but not E3d HPC. HIF-regulated target gene expression increased significantly following all HPC protocols. However, E3d HPC significantly decreased extracellular adenosine and reduced cerebral blood flow in the ischemic region with upregulated expression of the adenosine transporter, equilibrative nucleoside transporter 1 (ENT1. An ENT1 inhibitor, propentofylline increased the cerebral blood flow and re-established neuroprotection in E3d HPC. Adenosine receptor specific antagonists showed that adenosine mainly through A1 receptor mediates HPC induced neuroprotection. Our data indicate that cooperation of HIF-regulated genes and extracellular adenosine is necessary for HPC-induced neuroprotection.

  19. Prevention of diabetes in NOD mice by repeated exposures to a contact allergen inducing a sub-clinical dermatitis

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Buschard, Karsten; Hansen, Axel Jacob Kornerup

    2010-01-01

    Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect...... of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two...

  20. Operant alcohol self-administration in dependent rats: focus on the vapor model.

    Science.gov (United States)

    Vendruscolo, Leandro F; Roberts, Amanda J

    2014-05-01

    Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be.

  1. Mechanisms of adaptation from a multiple to a single step recovery strategy following repeated exposure to forward loss of balance in older adults.

    Directory of Open Access Journals (Sweden)

    Christopher P Carty

    Full Text Available When released from an initial, static, forward lean angle and instructed to recover with a single step, some older adults are able to meet the task requirements, whereas others either stumble or fall. The purpose of the present study was to use the concept of margin of stability (MoS to investigate balance recovery responses in the anterior-posterior direction exhibited by older single steppers, multiple steppers and those that are able to adapt from multiple to single steps following exposure to repeated forward loss of balance. One hundred and fifty-one healthy, community dwelling, older adults, aged 65-80 years, participated in the study. Participants performed four trials of the balance recovery task from each of three initial lean angles. Balance recovery responses in the anterior-posterior direction were quantified at three events; cable release (CR, toe-off (TO and foot contact (FC, for trials performed at the intermediate lean angle. MoS was computed as the anterior-posterior distance between the forward boundary of the Base of Support (BoS and the vertical projection of the velocity adjusted centre of mass position (XCoM. Approximately one-third of participants adapted from a multiple to a single step recovery strategy following repeated exposure to the task. MoS at FC for the single and multiple step trials in the adaptation group were intermediate between the exclusively single step group and the exclusively multiple step group, with the single step trials having a significant, 3.7 times higher MoS at FC than the multiple step trials. Consistent with differences between single and multiple steppers, adaptation from multiple to single steps was attributed to an increased BoS at FC, a reduced XCoM at FC and an increased rate of BoS displacement from TO to FC. Adaptations occurred within a single test session and suggest older adults that are close to the threshold of successful recovery can rapidly improve dynamic stability following

  2. Acute Onset of Vancomycin Anaphylaxis With Disseminated Intravascular Coagulation in an Orthopedic Patient Despite Prior Repeated Exposure.

    Science.gov (United States)

    Adams, Brock; Roboubi, Babak; Henshaw, Robert

    2015-12-01

    Vancomycin is a glycopeptide antibiotic that exhibits bactericidal activity against gram-positive cocci. It is commonly recommended for surgical prophylaxis in cases of suspected bacterial resistance or penicillin allergy. There are 2 main types of hypersensitivity reactions associated with vancomycin. Red man syndrome is an anaphylactoid reaction caused by direct release of histamine. The second is an anaphylactic reaction, which is an immunoglobulin E-mediated response. We present the case of a 55-year-old woman with a history of metastatic giant cell tumor of the right proximal tibia. She had undergone multiple surgeries for this and other nonorthopedic conditions. The patient received vancomycin for the majority of these procedures and extended courses of vancomycin on 2 separate occasions. In the present case, the patient was taken to the operating room for a prosthetic infection, and vancomycin was given after cultures were taken. The patient immediately developed signs consistent with anaphylaxis and disseminated intravascular coagulation. This was treated acutely with hemodynamic resuscitation, replacement of blood components, steroids, and repeated boluses of epinephrine. She recovered and was taken back to the operating room during that same admission without incident. The patient has since been treated with systemic daptomycin and a tobramycin cement spacer without further incident.

  3. Repeated sedimentation and exposure of glacial Lake Missoula sediments: A lake-level history at Garden Gulch, Montana, USA

    Science.gov (United States)

    Smith, Larry N.

    2017-01-01

    Glaciolacustrine sediments record lake transgression, regression, and subaerial modification of the silty lake-bottom of glacial Lake Missoula in the Clark Fork River valley. The sequence preserved at Garden Gulch, MT documents lake-level fluctuations at >65% of its full-pool volume. Twelve sedimentary cycles fine upwards from (1) very fine-grained sandy silt to (2) silt with climbing ripples to (3) rhythmically laminated silt and some clay. The cycles are fine-grained turbidites capped locally by thin layers of angular gravel derived from local bedrock outcrops. The gravels appear to be the toes of mass wasting lobes carried onto the exposed lakebed surface during repeated lake-level lowerings. Periglacial wedges, small rotational faults, involutions, and clastic dikes deform the tops of eleven cycles. The wedges are 10-30 cm wide, penetrate 30-70 cm deep, are spaced seven cycles. The Garden Gulch section may represent as few as seven and as many as twelve substantial fillings and partial to complete drainings of glacial Lake Missoula.

  4. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

    Science.gov (United States)

    Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    2016-01-01

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  5. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.

    Science.gov (United States)

    Pavón, Francisco Javier; Marco, Eva María; Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

    Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

  6. Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa).

    Science.gov (United States)

    Zuccolo, Luisa; DeRoo, Lisa A; Wills, Andrew K; Davey Smith, George; Suren, Pål; Roth, Christine; Stoltenberg, Camilla; Magnus, Per

    2016-12-23

    Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

  7. Removal and environmental exposure of alcohol ethoxylates in US sewage treatment.

    Science.gov (United States)

    Morrall, S W; Dunphy, J C; Cano, M L; Evans, A; McAvoy, D C; Price, B P; Eckhoff, W S

    2006-05-01

    Alcohol ethoxylates (AE) are a common nonionic surfactant employed in consumer and industrial detergents worldwide. Commercial AE are typically complex mixtures composed of > 100 homologous compounds with varying alkyl chain lengths and varying numbers of ethylene oxide (EO) units. Recent improvements in analytical methodology have enabled accurate measurement of the entire AE mixture in sewage treatment plant (STP) influents and effluents, including alkyl chain lengths from 12 to 18 carbons with a range of ethoxylation from 0 to 18 EO units. These improved analytical methods were used to measure AE concentrations at nine sites representative of sewage treatment processes and geographical locations. These new data will make possible a more accurate assessment of environmental risk for AE in the United States. The results indicate that all AE homologues are effectively removed (> 99%) in the most common treatment types. Individual STP total AE effluent concentrations ranged from a low of 0.92 microg/L for activated sludge to a high of 15.6 microg/L for a trickling filter process. For the purpose of representing a national average distribution, an average-flow-weighted wastewater treatment plant effluent concentration was determined for each AE component. The total-flow-weighted average AE effluent concentration was 3.64 microg/L.

  8. Repeated inhalation exposure to octamethylcyclotetrasiloxane produces hepatomegaly, transient hepatic hyperplasia, and sustained hypertrophy in female Fischer 344 rats in a manner similar to phenobarbital.

    Science.gov (United States)

    McKim, J M; Kolesar, G B; Jean, P A; Meeker, L S; Wilga, P C; Schoonhoven, R; Swenberg, J A; Goodman, J I; Gallavan, R H; Meeks, R G

    2001-04-15

    Octamethylcyclotetrasiloxane (D4) has been described as a phenobarbital-like inducer of hepatic enzymes. Phenobarbital (PB) and phenobarbital-like chemicals induce transient hepatic and thyroid hyperplasia and sustained hypertrophy in rats and mice. The extent to which these processes are involved with D4-induced hepatomegaly is not known. The present study has evaluated the effects of repeated inhalation exposure to D4 vapors on hepatic and thyroid cell proliferation and hypertrophy with respect to time and exposure concentration. Female Fischer 344 rats were exposed via whole body inhalation to 0 ppm D4, 700 ppm D4 vapors (6 h/day; 5 days/week), or 0.05% PB in drinking water over a 4-week period. Incorporation of 5'-bromo-2-deoxyuridine (BrdU) and the abundance of proliferating cell nuclear antigen were used as indicators of cell proliferation. Designated animals from each treatment group were euthanized on study days 6, 13, and 27. The effect of D4 exposure concentration on hepatic cell proliferation was evaluated at 0, 7, 30, 70, 150, 300, or 700 ppm. Liver-to-body weight ratios in animals exposed to 700 ppm D4 were increased 18, 20, and 22% over controls while PB-treated animals showed increases of 33, 27, and 27% over controls on days 6, 13, and 27 respectively. Hepatic incorporation of BrdU following exposure to D4 was highest on day 6 (labeling index = 15-22%) and was at or below control values by day 27. This pattern of transient hyperplasia was observed in all hepatic lobes examined and was similar to the pattern observed following treatment with PB.

  9. Disposition of Lead (Pb) in Saliva and Blood of Sprague-Dawley Rats Following a Single or Repeated Oral Exposure to Pb-Acetate

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Lin, Yuehe; Weitz, Karl K.; Wu, Hong; Gies, Richard A.; Moore, Dean A.; Yantasee, Wassana

    2006-05-01

    Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100 mg Pb-acetate/kg body weight in rats or {approx}1-week after 5 sequential daily oral gavage doses of 1, 10, or 100 mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and ?-amylase activity were also determined. At specified times post-dosing groups of animals were anethetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to PB-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r2=0.922) between the average Pb concentrations in these biological matrices which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24 hr post-dosing and a decrease in ?-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These

  10. Development of immunity against viral and bacterial antigens after repeated exposures to suberythemal doses of ultraviolet light

    Directory of Open Access Journals (Sweden)

    S. A. Snopov

    2012-01-01

    Full Text Available The effects of ultraviolet (UV radiation on human infectious immunity are not well studied. On the one hand, solar and artificial UU sources have been shown to change cytokine levels in human skin, lymphocyte subpopulation counts in parepheral blood, lymphocyte DNA synthesis and prolifarative response to mitogens. On the other hand, there are just only one or two observations suggesting an influence of UV radiation on human infection course. For instance, UV irradiations have been reported to induce a reccurence of orofacial vesicular lesions caused by herpes siplex virus. Moreover, there is a lack of data concerning immune effects of suberythtemal doses of UV in spite of a long history of using them by Russian prophylactic medicine. In this work we questioned whether such suberythemal UV exposures can affect the immune responses of children to infectious conjunctivitis, to simultaneous measles and polio vaccinations and to simultaneous polio and diphtheria-tetanus vaccinations. In peripheral blood of vaccinated children we examined leukocyte counts (monocytes, neutrophils, eosinophils, lymphocytes, percentages of lymphocyte subpopulations (CD3+, CD20+, CD4+, CD8+, CD25+, HLADR+, concentrations of cytokines (IL-1 beta, TNF-alpha, IFN- amma и IL-10, DNA-synthetic activity of lymphocytes and titres of antibodies against measles and diphtheria toxin. We observed no local or systemic reactions to the vaccines in the UV-group while a moderate rise in body temperature occured in several children from unexposed group. In the blood of childeren from UV-group we found increases in CD25+ и HLADR+ cell percentages, IL- 1 beta and IL-10 concentrations, PWMinduced DNA synthesis in mononuclears, and no decreases in formation of antibodies against measles and diphreria. We concluded that suberythemal UV exposures of children modulated their further responses to imminisations perhaps through the activation of a T helper 2-like

  11. Greater sensitivity to novelty in rats is associated with increased motor impulsivity following repeated exposure to a stimulating environment: implications for the etiology of impulse control deficits.

    Science.gov (United States)

    Ferland, Jacqueline-Marie N; Zeeb, Fiona D; Yu, Katrina; Kaur, Sukhbir; Taves, Matthew D; Winstanley, Catharine A

    2014-12-01

    Heightened motor impulsivity and increased novelty-seeking commonly co-occur in psychiatric disorders, including drug addiction. However, the relationship between these two phenomena remains unclear. One-time tests of novelty sensitivity commonly used in preclinical experiments, such as the open-field or novel-object test, fail to capture the fact that novelty-seekers repeatedly experience novel, stimulating situations. The present study therefore investigated whether repeated exposure to a novel, stimulating environment (SE) altered impulsive action. Male Long-Evans rats were trained to perform the five-choice serial reaction time task (5CSRTT) which measures motor impulsivity in the form of premature responding as well as attention and motivation. Animals were then exposed to a novel SE (1 h/day for 16 days) immediately prior to the 5CSRTT. Significant increases in premature responding were observed in a subgroup of reactive animals termed high responders (HR-SE). These rats were not more impulsive at baseline, and levels of impulsivity normalised once exposure to the SE was discontinued. No other aspect of 5CSRTT performance was affected by the SE challenge. We also determined that HR-SE rats were hyperactive in a novel environment. Biochemical analyses revealed changes in gene and protein expression within the dorsal hippocampus of HR-SE rats, including decreases in mRNA encoding the dopamine D1 receptor and brain-derived neurotrophic factor. These results indicate a novel mechanism by which impulsivity and novelty-reactivity interact that may enhance addiction vulnerability synergistically. Furthermore, studying such context-induced impulsivity may provide insight into the process by which environmental load precipitates psychiatric symptoms in impulse control disorders.

  12. Effects of repeated low-dose exposure of the nerve agent VX on monoamine levels in different brain structures in mice.

    Science.gov (United States)

    Graziani, S; Christin, D; Daulon, S; Breton, P; Perrier, N; Taysse, L

    2014-05-01

    In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 μg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30% inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed.

  13. Trends in toxic alcohol exposures in the United States from 2000 to 2013: a focus on the use of antidotes and extracorporeal treatments.

    Science.gov (United States)

    Ghannoum, Marc; Hoffman, Robert S; Mowry, James B; Lavergne, Valery

    2014-01-01

    Morbidity and mortality from toxic alcohols like ethylene glycol and methanol remain prevalent worldwide. The introduction of fomepizole, a potent blocker of alcohol dehydrogenase, has modified current practice over the last 15 years. The aim of the study was to describe the characteristics of toxic alcohol poisoning reported to US poison centers, the trends in the incidence of antidote use and hemodialysis treatment, as well as the related mortality. A retrospective study of all electronic entries from the AAPCC National Poison Data System database, from the years 2000 to 2013 was reviewed. When considering all exposures, the great majority of patients had a benign outcome. Major effects (e.g., life threatening) occurred in 2.1% and 4.9% of methanol and ethylene glycol cases, respectively. Mortality rates were similar for both toxic alcohols, approximately 0.6%. When only considering ingestions reported to healthcare facilities, a major effect was reported in 9.5% and 20.5%, and the mortality rate was 2.9% and 2.4% for methanol and ethylene glycol exposures, respectively, and remained constant over time. The use of fomepizole increased statistically over the study period while that of ethanol decreased, until it became proportionally negligible by 2012-2013. The use of hemodialysis significantly decreased in "Early" ethylene glycol exposures during the study period. Similar to other reports, it appears that the use of fomepizole has largely supplanted ethanol as the antidote of choice in toxic alcohol exposures and may decrease the requirements for hemodialysis in patients poisoned with ethylene glycol who have no acidosis and normal kidney function.

  14. Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun Oularbi

    2014-04-01

    Full Text Available Lambda-cyhalothrin (LCT is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administered orally over 28 days. The effects of the insecticide on various biochemical parameters were evaluated at 14 and 28 days. Histopathological studies were carried out in the kidneys and adrenal glands at the end of the experiment. Lambda-cyhalothrin, as a pyrethroid insecticide, induced significant increases (P≤0.05 in plasma urea, creatinine, uric acid and glucose concentrations, and alanine aminotransferase and aspartate aminotransferase activities after 14 and 28 days. In the rat plasma samples after 28 days, residual concentrations of LCT 1R, cis,

  15. Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee.

    Science.gov (United States)

    Whittemore, A S; Wu, M L; Paffenbarger, R S; Sarles, D L; Kampert, J B; Grosser, S; Jung, D L; Ballon, S; Hendrickson, M

    1988-12-01

    Vaginal exposures to talc and other particulates may play an etiologic role in epithelial ovarian cancer. Surgical sterilization may protect against ovarian cancer by blocking entry of such particulates into the peritoneal cavity. The authors assessed histories of talcum powder use, tubal sterilization, and hysterectomy with ovarian conservation in 188 women in the San Francisco Bay Area with epithelial ovarian cancers diagnosed in 1983-1985 and in 539 control women. To investigate the roles of blood-borne environmental exposures on ovarian cancer risk, they assessed lifetime consumption of coffee, tobacco, and alcohol in these women. Of the 539 controls, 280 were hospitalized women without overt cancer, and 259 were chosen from the general population by random digit telephone dialing. Ninety-seven (52%) of the cancer patients habitually used talcum powder on the perineum, compared with 247 (46%) of the controls. Adjusted for parity, the relative risk (RR) = 1.40, p = 0.06. There were no statistically significant trends with increasing frequency or duration of talc use, and patients did not differ from controls in use of talc on sanitary pads and/or contraceptive diaphragms. Fewer ovarian cancer patients (7%) than controls (13%) reported prior fallopian tube ligation (RR, adjusted for parity, = 0.56, p = 0.06), and fewer patients (20%) than controls (28%) reported prior hysterectomy (RR = 0.66, p = 0.05). The protective effect of hysterectomy was confined to those who underwent this surgery 10 or more years prior to interview and to those who had not undergone prior tubal sterilization. Consumption of cigarettes and alcohol did not differ between cases and controls. By contrast, 11 (6%) cases never regularly consumed coffee, compared with 31 (11%) hospital controls and 26 (10%) population controls (RR, adjusted for smoking, = 2.2, p = 0.03, for the comparison using all controls). Overall, ovarian cancer risk among women who had drunk coffee for more than 40 years

  16. Prenatal alcohol exposure affects progenitor cell numbers in olfactory bulbs and dentate gyrus of vervet monkeys

    DEFF Research Database (Denmark)

    Burke, Mark W; Inyatkin, Alexey; Ptito, Maurice

    2016-01-01

    cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts...... vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years......). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group...

  17. INFLUENCE OF MORINGA OLEIFERA (DRUM-STICK FRUIT EXTRACT ON HAEMATOLOGICAL PROFILE FOLLOWING REPEATED EXPOSURE TO LOW LEVELS OF ARSENIC THROUGH FEED ON RATS

    Directory of Open Access Journals (Sweden)

    Vaibhav R. Pachade

    2012-01-01

    Full Text Available Effect of Moringa oleifera fruits hot methanolic extract (MFE, if any, in minimizing the adverse reactions of repeated exposure to arsenic trioxide (AT in feed was investigated in Wistar rats with reference to haematological profile. Three groups of rats each containing 10 (5male+5female were used. The group I served as negative control. Rats of group II were fed arsenic trioxide (AT alone @ 100 ppm in feed while those of group III simultaneously received AT (@100 ppm and MFE (50 mg/kg/day for 28 days. Blood samples were collected from retroorbital plexus for estimation of hematological parameters (haemoglobin, PCV, TEC, MCH, MCHC, MCV of different groups on 0 day, 15th day and 29th day respectively. Exposure to AT through feed in group II resulted in significant (P<0.05 decrease in haemoglobin, TEC and MCHC, accompanied by increased MCV, with no significant alteration of PCV or MCH of the rats. While rats of group III treated with AT (@100 ppm and MFE (50 mg/kg/day also resulted in same consequences as it was in group II but it was slightly less than that of group II suggesting of mild non significant protective effect.

  18. Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation.

    Science.gov (United States)

    Zhou, Wei; Tian, Dongdong; He, Jun; Wang, Yimei; Zhang, Lijun; Cui, Lan; Jia, Li; Zhang, Li; Li, Lizhong; Shu, Yulei; Yu, Shouzhong; Zhao, Jun; Yuan, Xiaoyan; Peng, Shuangqing

    2016-04-12

    Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the increased lung cancer risk in populations, but the mechanisms underlying PM-associated carcinogenesis are not yet clear. Previous studies have indicated that aberrant epigenetic alterations, such as genome-wide DNA hypomethylation and gene-specific DNA hypermethylation contribute to lung carcinogenesis. And silence or mutation of P53 tumor suppressor gene is the most prevalent oncogenic driver in lung cancer development. To explore the effects of PM2.5 on global and P53 promoter methylation changes and the mechanisms involved, we exposed human bronchial epithelial cells (BEAS-2B) to low concentrations of PM2.5 for 10 days. Our results indicated that PM2.5-induced global DNA hypomethylation was accompanied by reduced DNMT1 expression. PM2.5 also induced hypermethylation of P53 promoter and inhibited its expression by increasing DNMT3B protein level. Furthermore, ROS-induced activation of Akt was involved in PM2.5-induced increase in DNMT3B. In conclusion, our results strongly suggest that repeated exposure to PM2.5 induces epigenetic silencing of P53 through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation, which not only provides a possible explanation for PM-induced lung cancer, but also may help to identify specific interventions to prevent PM-induced lung carcinogenesis.

  19. Repeated inhalation exposure of rats to an anionic high molecular weight polymer aerosol: application of prediction models to better understand pulmonary effects and modes of action.

    Science.gov (United States)

    Pauluhn, Jürgen

    2014-08-01

    Opposed to the wealth of information available for kinetic lung overload-related effects of poorly-soluble, low-toxicity particles (PSP), only limited information is available on biodegradable high molecular weight (HMW) organic polymers (molecular weight >20,000 Da). It is hypothesized that such types of polymers may exert a somewhat similar volume displacement-related mode of action in alveolar macrophages as PSP; however, with a differing biokinetics of the material retained in the lung. This polyurethane polymer was examined in single and 2-/13-week repeated exposure rat inhalation bioassays. The design of studies was adapted to that commonly applied for PSP. Rats were nose-only exposed for 6h/day for the respective study durat