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Sample records for binge drinking up-regulates

  1. Binge Drinking

    Medline Plus

    Full Text Available ... Chronic Disease Prevention and Health Promotion (NCCDPHP) Injury, Violence & Safety Featured Videos Binge Drinking Binge Drinking A ... Safe Teen Drivers Break the Silence: Stop the Violence Break the Silence: Stop the Violence Binge Drinking ...

  2. Binge Drinking

    Medline Plus

    Full Text Available ... for Chronic Disease Prevention and Health Promotion (NCCDPHP) Injury, Violence & Safety Featured Videos Binge Drinking Binge Drinking A Time To Act A Time To Act Injury Prevention Research Injury Prevention Research In the Swim ...

  3. Binge Drinking

    Medline Plus

    Full Text Available ... and HIV/AIDS - and discusses effective community prevention strategies such as increasing alcohol excise taxes. The video ... Alcohol & Public Health Binge Drinking Factsheet Effective Prevention Strategies Send Us Feedback What do you think of ...

  4. Binge Drinking

    Centers for Disease Control (CDC) Podcasts

    2010-04-13

    This podcast explores the health risks of binge drinking and discusses effective community strategies to prevent it.  Created: 4/13/2010 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/13/2010.

  5. Binge Drinking

    Medline Plus

    Full Text Available ... to Improve Systemic Analysis (10:45) Take 3 Teen Pregnancy The Immunization Baby Book The Story of Folic ... the health risks of binge drinking - including unintended pregnancy, sexually transmitted diseases, injury, car ... Teen Drivers Safe Teen Drivers Break the Silence: Stop ...

  6. Binge Drinking

    Centers for Disease Control (CDC) Podcasts

    2010-10-05

    This podcast is based on the October, 2010 CDC Vital Signs report which indicates that drinking too much, including binge drinking, causes more than 79,000 deaths in the U.S. each year and is the third leading preventable cause of death.  Created: 10/5/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 10/5/2010.

  7. Binge Drinking

    Science.gov (United States)

    ... drinking. When someone drinks too much and gets alcohol poisoning, it affects the body's involuntary reflexes — including breathing and the ... For Kids For Parents MORE ON THIS TOPIC Alcohol Coping ... College Prom Pressure Abusive Relationships Dealing With Addiction I Think I May Have ...

  8. Binge drinking in pregnancy

    DEFF Research Database (Denmark)

    Kesmodel, Ulrik Schiøler

    2001-01-01

    % and 86%. The proportion of women who reported binge drinking depended on the definition of pregnancy, but the proportion peaked in week 3 measured from the last menstrual period and thereafter declined to approximately 1 percent in week 7. On the basis of this 1998 study, it is suggested that most human...... studies on binge drinking in pregnancy may have failed to find any association because of methodological problems. It is suggested that future studies should take into account the number of binge episodes as well as the time of binge drinking. This information may easily be obtained from most pregnant...

  9. Binge Drinking PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2010-10-05

    This PSA is based on the October, 2010 CDC Vital Signs report which indicates that drinking too much, including binge drinking, causes more than 79,000 deaths in the U.S. each year and is the third leading preventable cause of death.  Created: 10/5/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 10/5/2010.

  10. Women, Girls, and Binge Drinking

    Centers for Disease Control (CDC) Podcasts

    2013-08-01

    Bob Brewer, CDC's Alcohol Program Director, goes on the air to discuss the problem of binge drinking among women and girls.  Created: 8/1/2013 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 8/1/2013.

  11. Binge drinking, drinking frequency, and risk of ischaemic heart disease

    DEFF Research Database (Denmark)

    Skov-Ettrup, Lise; Eliasen, Marie; Ekholm, Ola

    2011-01-01

    INTRODUCTION: Light-to-moderate alcohol drinking is associated with a decreased risk of ischaemic heart disease (IHD). However, drinking heavily and in binges has been suggested to increase IHD risk. This complexity makes the issue of binge drinking within the light-to-moderate alcohol range...

  12. Binge Drinking in Young Adults: Data, Definitions and Determinants

    Science.gov (United States)

    Courtney, Kelly E.; Polich, John

    2009-01-01

    Binge drinking is an increasingly important topic in alcohol research, but the field lacks empirical cohesion and definitional precision. The present review summarizes findings and viewpoints from the scientific binge-drinking literature. Epidemiological studies quantify the seriousness of alcohol-related problems arising from binge drinking, with…

  13. Binge Drinking Effects on EEG in Young Adult Humans

    Directory of Open Access Journals (Sweden)

    Kelly E. Courtney

    2010-05-01

    Full Text Available Young adult (N = 96 university students who varied in their binge drinking history were assessed by electroencephalography (EEG recording during passive viewing. Groups consisted of male and female non-binge drinkers (>1 to 5/4 drinks/ounces in under two hours, low-binge drinkers (5/4–7/6 drinks/ounces in under two hours, and high-binge drinkers (≥ 10 drinks/ounces in under two hours, who had been drinking alcohol at their respective levels for an average of 3 years. The non- and low-binge drinkers exhibited less spectral power than the high-binge drinkers in the delta (0–4 Hz and fast-beta (20–35 Hz bands. Binge drinking appears to be associated with a specific pattern of brain electrical activity in young adults that may reflect the future development of alcoholism.

  14. Binging at the campus: Motivations and impulsivity influence binge drinking profiles in university students.

    Science.gov (United States)

    Lannoy, Séverine; Billieux, Joël; Poncin, Marie; Maurage, Pierre

    2017-01-26

    This study explored the involvement of two key psychological factors, drinking motives and impulsivity traits, in binge drinking. On the basis of a large screening phase (N=4424), 867 binge drinkers were selected and were first compared with 924 non-binge drinkers. Then, a cluster analysis was performed, focusing on the binge drinker sample, to explore the respective involvement of four drinking motives (DMQ-R model) and four impulsivity facets (UPPS model) in this habit. Centrally, the cluster analysis identified three clusters of binge drinkers presenting distinct psychological characteristics and alcohol consumption patterns: emotional, recreational, and hazardous binge drinkers. Hazardous binge drinkers were characterized by strong drinking motives but moderate impulsivity. Binge drinking should thus no more be considered as a unitary drinking pattern but rather as a habit encompassing a variety of psychological profiles. Moreover, risky drinking habits in young people might be mainly related to disproportionate drinking motives. Future studies should thus consider binge drinking heterogeneity, and prevention programs focusing on drinking motivations should be developed.

  15. Determinants for binge drinking among adolescents in Denmark

    DEFF Research Database (Denmark)

    Pedersen, Maria; Kragh Andersen, Per; Sabroe, Svend

    2014-01-01

    Background and Objective: Binge drinking is a relatively common behavior among adolescents in Denmark. The aim of this study is to assess whether peer alcohol drinking, mothers’ and fathers’ attitudes toward alcohol drinking, and the adolescents’ own financial situations (e.g., the presence...... of pocket money) predict binge drinking among adolescents in Denmark. Methods: This study is based on the Danish data from the European School Survey Project on Alcohol and Other Drugs, which took place in 2011. This cross-sectional survey obtained data from 2765 adolescents who were in grade 9 in Denmark...... at that time. Logistic regression was used to assess the association between the outcome variable of binge drinking and the exposure variables of alcohol-drinking peers, pocket money, and mother’s/father’s approval of intoxication. Results: The risk of binge drinking increased with the number of alcohol...

  16. Energy Drinks and Binge Drinking Predict College Students' Sleep Quantity, Quality, and Tiredness.

    Science.gov (United States)

    Patrick, Megan E; Griffin, Jamie; Huntley, Edward D; Maggs, Jennifer L

    2016-05-16

    This study examines whether energy drink use and binge drinking predict sleep quantity, sleep quality, and next-day tiredness among college students. Web-based daily data on substance use and sleep were collected across four semesters in 2009 and 2010 from 667 individuals for up to 56 days each, yielding information on 25,616 person-days. Controlling for average levels of energy drink use and binge drinking (i.e., 4+ drinks for women, 5+ drinks for men), on days when students consumed energy drinks, they reported lower sleep quantity and quality that night, and greater next-day tiredness, compared to days they did not use energy drinks. Similarly, on days when students binge drank, they reported lower sleep quantity and quality that night, and greater next-day tiredness, compared to days they did not binge drink. There was no significant interaction effect between binge drinking and energy drink use on the outcomes.

  17. Binge Drinking and Occupation, North Dakota, 2004–2005

    Directory of Open Access Journals (Sweden)

    Dwayne W. Jarman, DVM, MPH

    2007-10-01

    Full Text Available IntroductionBinge drinking is a leading cause of preventable death and results in employee absenteeism and lost productivity. Knowledge about the prevalence of binge drinking among employees of different occupations is limited.MethodsWe assessed the prevalence of binge drinking (i.e., consuming five or more drinks per occasion during the previous 30 days by primary occupation using data from the 2004–2005 North Dakota Behavioral Risk Factor Surveillance System. We used logistic regression to assess the association between binge drinking and primary occupation.ResultsOverall, 24.1% (95% confidence interval [CI], 22.5–25.7 of North Dakota workers reported binge drinking. The prevalence was highest among farm or ranch employees (45.3%; 95% CI, 28.3–63.4, food or drink servers (33.4%; 95% CI, 23.9–44.4, and farm or ranch owners (32.5%; 95% CI, 26.3–39.4. The prevalence was lowest among health care workers (13.2%; 95% CI, 10.3–16.8. Compared with health care workers, the adjusted odds of binge drinking were highest among farm or ranch employees (adjusted odds ratio [AOR], 2.2; 95% CI, 0.9–5.5, food or drink servers (AOR, 2.1; 95% CI, 1.1–4.0, and farm or ranch owners (AOR, 1.7; 95% CI, 1.1–2.6. Health insurance coverage was lowest among employees in occupations with the highest prevalence of binge drinking.ConclusionWe found occupational differences in the prevalence of binge drinking among employees in North Dakota. Many occupational categories had a high prevalence of binge drinking. We recommend the implementation of both employer-sponsored and population-based interventions to reduce binge drinking among North Dakota workers, particularly because employees in occupations with the highest rates of binge drinking had the lowest rates of health insurance coverage.

  18. Binge Drinking – Nationwide Problem, Local Solutions

    Centers for Disease Control (CDC) Podcasts

    2012-01-03

    This podcast is based on the January 2012 CDC Vital Signs report. One in six adults binge drinks about four times a month. It's a problem nationwide but community-based strategies, such as reducing access to alcohol and increasing the price, can prevent binge drinking.  Created: 1/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 1/3/2012.

  19. The relationship between age at drinking onset and subsequent binge drinking among women

    DEFF Research Database (Denmark)

    Eliasen, Marie; Kaer, Susanne K; Munk, Christian;

    2009-01-01

    BACKGROUND: To examine the association between age at drinking onset and subsequent binge drinking, and to examine whether there are differences in this association between four countries. METHODS: The data consisted of 68,539 women aged 18-47 years randomly selected from the general population...... in Denmark, Iceland, Norway and Sweden. Frequency of binge drinking, defined as consuming >6 U of alcohol at the same occasion once or more per month, and age at drinking debut were assessed through a questionnaire survey. RESULTS: Overall, 12-26% reported binge drinking once or more per month in the four...... countries. Median age for starting drinking was 16 years in all four countries. Women who started drinking at 14 years or younger were significantly more likely to binge drink than women who started drinking at 19 years or older with adjusted odds ratios of 2.9 (95% confidence intervals 2.3-3.7), 2.8 (2...

  20. Binge Drinking Among Women and Girls PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-01-08

    This 60 second public service announcement is based on the January 2013 CDC Vital Signs report, which presents information about binge drinking among women and girls. Binge drinking is defined for women as four or more drinks in a short period of time. It puts women and girls at greater risk for breast cancer, sexual assault, heart disease, and unintended pregnancy.  Created: 1/8/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 1/8/2013.

  1. Trajectories of binge drinking and personality change across emerging adulthood.

    Science.gov (United States)

    Ashenhurst, James R; Harden, Kathryn P; Corbin, William R; Fromme, Kim

    2015-12-01

    College students binge drink more frequently than the broader population, yet most individuals "mature out" of binge drinking. Impulsivity and sensation seeking traits are important for understanding who is at risk for maintaining binge drinking across college and the transition to adult roles. We use latent class growth analysis (LCGA) to examine longitudinal binge-drinking trajectories spanning from the end of high school through 2 years after college (M ages = 18.4 to 23.8). Data were gathered over 10 waves from students at a large Southwestern university (N = 2,245). We use latent factor models to estimate changes in self-reported impulsive (IMP) and sensation-seeking (SS) personality traits across 2 time periods-(a) the end of high school to the end of college and (b) the 2-year transition out of college. LCGA suggested 7 binge-drinking trajectories: frequent, moderate, increasing, occasional, low increasing, decreasing, and rare. Models of personality showed that from high school through college, change in SS and IMP generally paralleled drinking trajectories, with increasing and decreasing individuals showing corresponding changes in SS. Across the transition out of college, only the increasing group demonstrated a developmentally deviant increase in IMP, whereas all other groups showed normative stability or decreases in both IMP and SS. These data indicate that "late bloomers," who begin binge drinking only in the later years of college, are a unique at-risk group for drinking associated with abnormal patterns of personality maturation during emerging adulthood. Our results indicate that personality targeted interventions may benefit college students.

  2. Alcohol Use and Binge Drinking Among Women of Childbearing Age: United States, 2011-2013

    Science.gov (United States)

    ... and Mortality Weekly Report ( MMWR ) MMWR Share Compartir Alcohol Use and Binge Drinking Among Women of Childbearing ... 44 years (N = 198,098) who reported any alcohol use or binge drinking, † by selected characteristics — Behavioral ...

  3. Does binge drinking during early pregnancy increase the risk of psychomotor deficits?

    DEFF Research Database (Denmark)

    Kesmodel, Ulrik Schiøler; Bay, Bjørn; Wimberley, Theresa;

    2013-01-01

    BACKGROUND: The potential effects of binge drinking during pregnancy on child motor function have only been assessed in a few, small studies. We aimed to examine the effects of binge alcohol consumption during early pregnancy, including number of binge episodes and timing of binge drinking...... environment, postnatal parental smoking, health status, participation in organized sport, and indicators for hearing and vision impairment. RESULTS: There were no systematic or significant differences in motor function between children of mothers reporting isolated episodes of binge drinking and children...... of mothers with no binge episodes. No association was observed with respect to the number of binge episodes (maximum of 12) and timing of binge drinking. CONCLUSIONS: In this study, we found no systematic association between isolated episodes of binge drinking during early pregnancy and child motor function...

  4. Binge drinking among adolescents: prevalence, risk practices and related variables.

    Science.gov (United States)

    Golpe, Sandra; Isorna, Manuel; Barreiro, Carmen; Braña, Teresa; Rial, Antonio

    2017-01-12

    According to the last Survey on Drug Use among Secondary School Students (ESTUDES 2014-2015), consumption levels of alcohol and other substances have decreased in the last years in Spain. However, available data on binge drinking remain worrying, given the negative consequences related with this pattern. The aim of this paper is to analyse binge drinking among adolescents, providing updated data on prevalence in addition to information about the consequences and some predictive factors of binge drinking. A correlational method was used for this purpose, comprised of administering a survey to Compulsory Secondary School, High School and Vocational Training students. Based on a sample of 3,419 Galician adolescents aged between 12 and 18 years (M = 14.57; SD = 1.76), the results show that binge drinking is a common and global practice, with few socio-demographic differences but related with a wide range of risk practices. Furthermore, variables such as consumption expectancies, consumption by family and friends, as well as curfew time and allowance money have been identified as interesting predictive factors that should be taken into account at the preventive level.

  5. Characteristics of women who binge drink before and after they become aware of their pregnancy

    DEFF Research Database (Denmark)

    Strandberg-Larsen, Katrine; Rod Nielsen, Naja; Nybo Andersen, Anne-Marie;

    2008-01-01

    Background Consumption of high doses of alcohol on a single occasion (binge drinking) may harm the developing foetus and pregnant women are advised to avoid binge drinking while pregnant. We present characteristics of Danish women who binge drank in the pre-and post recognised part of their pregn...

  6. Binge drinking in pregnancy and risk of fetal death

    DEFF Research Database (Denmark)

    Strandberg-Larsen, Katrine; Nielsen, Naja Rod; Grønbaek, Morten;

    2008-01-01

    episodes was related to the risk of early (at or before 12 completed weeks) or late (13-21 completed weeks) spontaneous abortion. However, three or more binge episodes showed an adjusted hazard ratio of 1.56 (95% confidence interval 1.01-2.40) for stillbirth (22 or more completed weeks) relative...... pregnancy is associated with an increased risk of stillbirth, but neither frequency nor timing of binge drinking was associated with an increased risk of spontaneous abortion in clinically recognized pregnancies....

  7. The Utility of a Gender-Specific Definition of Binge Drinking on the AUDIT

    Science.gov (United States)

    Olthuis, Janine V.; Zamboanga, Byron L.; Ham, Lindsay S.; Van Tyne, Kathryne

    2011-01-01

    Objective: Although binge drinking is commonly defined as the consumption of at least 5 drinks in 1 sitting for men and 4 for women, the Alcohol Use Disorders Identification Test (AUDIT) defines binge drinking as the consumption of 6 or more drinks in 1 sitting for both men and women. This study examined the effect of using gender-specific binge…

  8. Quantitative and qualitative assessment of university students' definitions of binge drinking.

    Science.gov (United States)

    Bonar, Erin E; Young, Kathleen M; Hoffmann, Erica; Gumber, Shinakee; Cummings, Jeremy P; Pavlick, Michelle; Rosenberg, Harold

    2012-06-01

    This study was designed to assess undergraduates' (N = 424) definitions of binge drinking and to evaluate whether the number of drinks they said comprise a binge varied as a function of beverage type, respondent gender, and respondent binge drinking status. When asked to designate the specific number of drinks that comprise a binge for each of four beverage types, students reported that the number of beers constituting a binge was significantly larger than the number of glasses of wine, shots of hard liquor, and servings of any combination of alcoholic beverage types; men reported that a larger number of drinks constitute a binge than did women; and those who had engaged in 3 or more binges in the past 2 weeks reported that more drinks comprise a binge than those who had binged less often. Responses to an open-ended question asking their definition of a binge revealed that students sometimes characterize a binge in terms of motivations for and unhealthy consequences of drinking, in addition to defining a binge as comprising consumption of a large amount of alcohol in a limited (though often unspecified) time period. Furthermore, students attributed their open-ended definitions of binge drinking to informal sources of information and observation of others' drinking almost as often as they did to school-based or media-based sources. This suggests that educators might look for innovative ways to use both formal and informal social networking, and video illustrations of restrained drinking, as ways to influence young people's views of binge drinking.

  9. Binge drinking: Burden of liver disease and beyond.

    Science.gov (United States)

    Llerena, Susana; Arias-Loste, María Teresa; Puente, Angela; Cabezas, Joaquín; Crespo, Javier; Fábrega, Emilio

    2015-11-28

    The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts (in the form of violence or traffic accidents) and its organic impact (affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.

  10. Binge drinking: Burden of liver disease and beyond

    Institute of Scientific and Technical Information of China (English)

    Susana; Llerena; María; Teresa; Arias-Loste; Angela; Puente; Joaquín; Cabezas; Javier; Crespo; Emilio; Fábrega

    2015-01-01

    The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts(in the form of violence or traffic accidents) and its organic impact(affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.

  11. Personality-Targeted Interventions Delay the Growth of Adolescent Drinking and Binge Drinking

    Science.gov (United States)

    Conrod, Patricia J.; Castellanos, Natalie; Mackie, Clare

    2008-01-01

    Background: Personality factors are implicated in the vulnerability to adolescent alcohol misuse. This study examined whether providing personality-targeted interventions in early adolescence can delay drinking and binge drinking in high-risk youth. Methods: A randomised control trial was carried out with 368 adolescents recruited from years 9 and…

  12. Do women give the same information on binge drinking during pregnancy when asked repeatedly?

    DEFF Research Database (Denmark)

    Strandberg-Larsen, K; Andersen, Anne-Marie Nybo; Olsen, Jørn;

    2006-01-01

    OBJECTIVE: To study if pregnant women give the same answers to questions on frequency and timing of binge drinking when asked more than once during and after pregnancy. DESIGN: Cohort study.Setting:The Danish National Birth Cohort. SUBJECTS: The study is based on 76 307 pregnant women with repeated...... information on binge drinking during the early part of pregnancy and 8933 pregnant women with information on binge drinking during pregnancy weeks 30-36, obtained while pregnant and 6 months after delivery. RESULTS: More women reported binge drinking, if the interview took place close to the period...... in question. As the report of binge drinking was highest in the first of two interviews referring to the same period, as well as women who participated in the first interview in pregnancy week 12 or earlier reported more binge drinking compared to women who participated in the interview later in pregnancy...

  13. Binge drinking among Arab/Chaldeans: an exploratory study.

    Science.gov (United States)

    Arfken, Cynthia L; Owens, Darlene; Said, Manal

    2012-01-01

    Focus groups were conducted with young Arab/Chaldeans (N = 82) from different ethno-religious groups (Chaldeans, Orthodox Christians, and Muslims) to explore the potential risk and the protective factors associated with the high level of binge (or episodic heavy) drinking among Arab/Chaldeans reported by general population surveys. Most of the participants were aware of and knowledgeable about the problem in their community. Themes identified as contributory factors consistent across ethno-religious groups included the availability of alcohol, the importance of family, conformity to group behavior, and social reasons. Differences included the context for drinking and gender roles. These findings can be used to tailor culturally appropriate interventions.

  14. Prevalence of binge drinking and associated behaviours among 3286 college students in France.

    OpenAIRE

    2016-01-01

    Background Studies conducted on characteristics of binge drinking and associated behaviours in college student populations are scarce especially in France. Hence, it is important to identify risk factors for binge drinking at university, especially those which may be changed. The aim of this study was to assess the prevalence of binge drinking and associated behaviours across a large sample of college students in Upper Normandy (France). Methods A cross sectional study was performed between N...

  15. Personality factors and styles among college students who binge eat and drink.

    Science.gov (United States)

    Rush, Christina C; Becker, Sara J; Curry, John F

    2009-03-01

    Elevated rates of comorbidity between binge eating and alcohol use problems have been widely documented. Prior studies have examined specific personality traits associated with the co-occurrence of these problems. The current study explores comprehensive personality factors that are associated with the co-occurrence of binge eating and binge drinking among a diverse sample of 208 college undergraduates. Using the Five Factor Model of personality, the authors assessed both comprehensive personality factors and style of impulse control, a personality style defined by different combinations of neuroticism and conscientiousness. On the basis of responses to a screening instrument, college students were assigned to one of four groups: binge eat, binge drink, binge eat and drink, and non-binge. The binge eat and drink group reported a higher level of neuroticism than did students in the binge drink and non-binge groups. Additionally, the binge eat and drink group was more likely to report an undercontrolled style of impulse control than were other groups. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  16. Effects of message framing in anti-binge drinking PSAs: the moderating role of counterfactual thinking.

    Science.gov (United States)

    Baek, Tae Hyun; Shen, Lijiang; Reid, Leonard N

    2013-01-01

    This experiment examined the interaction effects of message framing and counterfactual thinking on attitudes toward binge drinking and behavioral intentions. Data from a 2 (message framing: gain vs. loss) × 2 (counterfactual thinking priming: additive vs. subtractive) between-subjects factorial design showed that a gain-framed message resulted in lower binge drinking intentions than did a loss-framed message after subjects engaged in additive counterfactual thinking. The effects of a loss-framed message on binge drinking intentions occurred when subtractive counterfactual thinking was induced. Theoretical and practical implications for anti-binge drinking public service announcements are discussed.

  17. The social image of drinking - mass media campaigns may inadvertently increase binge drinking.

    Science.gov (United States)

    Zimmermann, Friederike; Kohlmann, Karoline; Monter, Anne; Ameis, Nina

    2016-11-23

    Mass media campaigns that promote responsible drinking are rarely tested for their usefulness in reducing heavy alcohol consumption. Existing campaigns that appeal to responsible drinking while simultaneously displaying young people in social drinking situations may even have paradoxical effects. To examine such possible effects, we drew on a real-world media campaign, which we systematically modified on the basis of recent prototype research. We pilot tested questionnaires (using n = 41 participants), developed two different sets of posters in the style of an existing campaign (n = 39) and investigated their effectiveness (n = 102). In the main study, young men were randomly assigned to one of three conditions: sociable or unsociable binge drinker prototype condition or a control group. Outcome variables were intention, behavioural willingness, attitude, subjective norm, self-efficacy, prototype evaluation and prototype similarity with respect to binge drinking. Binge drinking as a habit was included to control for the fact that habitual drinking in social situations is hard to overcome and poses a particular challenge to interventions. The manipulation check showed that the experimental variation (sociable vs. unsociable drinker prototype condition) was successful. Results of the main study showed that the sociable drinker prototype condition resulted in a higher willingness and - for those with less of a habit - a higher intention to binge drink the next weekend. The unsociable drinker prototype condition had no effects. The results imply that the social components of mass media campaigns might inadvertently exacerbate binge drinking in young men. We therefore advocate against campaigns including aspects of alcohol consumption that might be positively associated with drinker prototype perception. Finally, we provide suggestions for future research.

  18. Conditional covariation of binge drinking with predictors of college students' cheating.

    Science.gov (United States)

    Bichler, Gisela; Tibbetts, Stephen G

    2003-12-01

    Recent research has identified a variety of significant predictors of academic dishonesty, but virtually no studies have examined the conditional relation of binge drinking and students' cheating. Using a survey sample of 289 college students, this study tested the mediating relations of binge drinking with the correlation of independent variables--including opportunity, strain, and self-control--on self-reported academic dishonesty. Low self-control had a stronger correlation with students' cheating behaviors for those who were heavy binge drinkers (beta = -.52) than for students who were nonbingers (beta = -.38). Differential relations were found for other key variables, namely, opportunity and strain, at varying severities of binge drinking.

  19. Changing arenas of underage adolescent binge drinking in Swedish small towns

    Directory of Open Access Journals (Sweden)

    Ander Birgitta

    2015-09-01

    Full Text Available AIM – The study explores arenas of adolescent binge drinking in small Swedish towns and the meanings these have for young persons. The focus is thus on space and place, and on the geography of underage drinking.

  20. Predicting Binge Drinking in College Students: Rational Beliefs, Stress, or Loneliness?

    Science.gov (United States)

    Chen, Yixin; Feeley, Thomas Hugh

    2015-01-01

    We proposed a conceptual model to predict binge-drinking behavior among college students, based on the theory of planned behavior and the stress-coping hypothesis. A two-wave online survey was conducted with predictors and drinking behavior measured separately over 2 weeks' time. In the Wave 1 survey, 279 students at a public university in the United States answered questions assessing key predictors and individual characteristics. In the Wave 2 survey, 179 participants returned and reported their drinking behavior over 2 weeks' time. After conducting a negative binomial regression, we found that more favorable attitude toward drinking and less perceived control of drinking at Wave 1 were associated with more binge drinking at Wave 2; subjective norm at Wave 1 was not a significant predictor of binge drinking at Wave 2; students with higher stress at Wave 1 engaged in more binge drinking at Wave 2, but those with higher loneliness did not. Implications of findings are discussed.

  1. Patterns of binge drinking at an international nightlife resort

    DEFF Research Database (Denmark)

    Tutenges, Sébastien; Hesse, Morten

    2008-01-01

    AIMS: The aim of this study was to compare the patterns of substance use in young Danes while holidaying in the Bulgarian holiday resort of Sunny Beach (SB) to their patterns of substance use in Denmark. METHODS: Data were collected from visitors to SB in 2007 (n = 1011). Information on alcohol a...... nightlife resorts provide a context for excess in drug use and alcohol use. Alcohol poses a potentially severe threat to the short- and long-term health of young tourists, but little attention has been paid to form interventions targeting binge drinking in nightlife resorts....

  2. Beyond inhibition: a dual-process perspective to renew the exploration of binge drinking.

    Science.gov (United States)

    Lannoy, Séverine; Billieux, Joël; Maurage, Pierre

    2014-01-01

    Binge drinking is a widespread alcohol-consumption pattern in youth and is linked to cognitive consequences, mostly for executive functions. However, other crucial factors remain less explored in binge drinking and notably the emotional-automatic processes. Dual-process model postulates that addictive disorders are not only due to impaired reflective system (involved in deliberate behaviors), but rather to an imbalance between under-activated reflective system and over-activated affective-automatic one (involved in impulsive behaviors). This proposal has been confirmed in alcohol-dependence, but has not been tested in binge drinking. The observation of comparable impairments in binge drinking and alcohol-dependence led to the "continuum hypothesis," suggesting similar deficits across different alcohol-related disorders. In this perspective, applying the dual-process model to binge drinking might renew the understanding of this continuum hypothesis. A three-axes research agenda will be proposed, exploring: (1) the affective-automatic system in binge drinking; (2) the systems' interactions and imbalance in binge drinking; (3) the evolution of this imbalance in the transition between binge drinking and alcohol-dependence.

  3. Beyond inhibition: A dual-process perspective to renew the exploration of binge drinking.

    Directory of Open Access Journals (Sweden)

    Severine eLannoy

    2014-06-01

    Full Text Available Binge drinking is a widespread alcohol-consumption pattern in youth and is linked to cognitive consequences, mostly for executive functions. However, other crucial factors remain less explored in binge drinking and notably the emotional-automatic processes. Dual-process model postulates that addictive disorders are not only due to impaired reflective system (involved in deliberate behaviours, but rather to an imbalance between under-activated reflective system and over-activated affective-automatic one (involved in impulsive behaviours. This proposal has been confirmed in alcohol-dependence, but has not been tested in binge drinking. The observation of comparable impairments in binge-drinking and alcohol-dependence led to the continuum hypothesis, suggesting similar deficits across different alcohol-related disorders. In this perspective, applying the dual-process model to binge drinking might renew the understanding of this continuum hypothesis. A three-axes research agenda will be proposed, exploring: (1 the affective-automatic system in binge drinking; (2 the systems’ interactions and imbalance in binge drinking; (3 the evolution of this imbalance in the transition between binge drinking and alcohol-dependence.

  4. Evolution of the binge drinking pattern in college students: neurophysiological correlates.

    Science.gov (United States)

    López-Caneda, Eduardo; Rodríguez Holguín, Socorro; Corral, Montserrat; Doallo, Sonia; Cadaveira, Fernando

    2014-08-01

    It is well known that alcohol impairs response inhibition and that adolescence is a critical period of neuromaturation where cognitive processes such as inhibitory control are still developing. In recent years, growing evidence has shown the negative consequences of alcohol binge drinking on the adolescent and young human brain. However, the effects of cessation of binge drinking on brain function remain unexplored. The objective of the present study was to examine brain activity during response execution and inhibition in young binge drinkers in relation to the progression of their drinking habits over time. Event-related potentials (ERPs) elicited by a Go/NoGo task were recorded twice within a 2-year interval in 57 undergraduate students (25 controls, 22 binge drinkers, and 10 ex-binge drinkers) with no personal or family history of alcoholism or psychopathological disorders. The results showed that the amplitude of NoGo-P3 over the frontal region correlated with an earlier age of onset of regular drinking as well as with greater quantity and speed of alcohol consumption. Regression analysis showed that NoGo-P3 amplitude was significantly predicted by the speed of alcohol intake and the age of onset of regular drinking. The group comparisons showed that, after maintaining a binge drinking pattern for at least 2 years, binge drinkers displayed significantly larger NoGo-P3 amplitudes than controls, whereas ex-binge drinkers were in an intermediate position between the two other groups (with no significant differences with respect to controls or binge drinkers). These findings suggest that binge drinking in young people may impair the neural functioning related to inhibitory processes, and that the cessation of binge drinking may act as a brake on the neurophysiological impairments related to response inhibition.

  5. Perceptions and practices of student binge drinking: an observational study of residential college students.

    Science.gov (United States)

    Clinkinbeard, Samantha S; Johnson, Michael A

    2013-01-01

    Professionals have debated the use of the term binge drinking over the past couple of decades, yet little attention has been paid to college student perceptions. We explored how students at one university qualitatively defined binge drinking; whether their own definitions coincided with those adopted by researchers; and whether students' own definitions varied according to their behavior. The most common definition provided by students included a description of the consumption of a large, non-specific, amount of alcohol. Only half of the students who, by standard definition, participated in binge drinking in the previous 30 days actually identified their behavior as such. Finally, binge drinkers were more likely to define binge drinking in an extreme manner such that it results in vomiting or blacking out.

  6. Vital Signs – Binge Drinking Among Women and Girls

    Centers for Disease Control (CDC) Podcasts

    2013-01-08

    This podcast is based on the January 2013 CDC Vital Signs report, which presents information about binge drinking among women and girls. Binge drinking is defined for women as four or more drinks in a short period of time. It puts women and girls at greater risk for breast cancer, sexual assault, heart disease, and unintended pregnancy.  Created: 1/8/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 1/8/2013.

  7. Binge Drinking and Rape: A Prospective Examination of College Women with a History of Previous Sexual Victimization

    Science.gov (United States)

    McCauley, Jenna L.; Calhoun, Karen S.; Gidycz, Christine A.

    2010-01-01

    The current study prospectively examined the longitudinal relationships between binge drinking behavior and rape experiences among a multisite sample of college women with a history of prior attempted or completed rape (N = 228). Rates of binge drinking among this high-risk sample were high. Prospective analyses indicated that binge drinking…

  8. The effect of alcohol binge drinking in early pregnancy on child’s general intelligence

    DEFF Research Database (Denmark)

    Kesmodel, Ulrik Schiøler; Eriksen, Hanne-Lise Falgreen; Underbjerg, Mette;

    2012-01-01

    Please cite this paper as: Kesmodel U, Falgreen Eriksen H, Underbjerg M, Kilburn T, Støvring H, Wimberley T, Mortensen E. The effect of alcohol binge drinking in early pregnancy on general intelligence in children. BJOG 2012;119:1222-1231. Objective  To examine the effects of binge alcohol...... consumption during early pregnancy, including the number of binge episodes and the timing of binge drinking, on general intelligence in 5-year-old children. Design  Follow-up study. Setting  Neuropsychological testing in four Danish cities 2003-2008. Population  A cohort of 1617 women and their children......, home environment, postnatal parental smoking, health status, and indicators for hearing and vision impairment. Main outcome measure  WPPSI-R. Results  There were no systematic or significant differences in general intelligence between children of mothers reporting binge drinking and children of mothers...

  9. Evaluating a selective prevention programme for binge drinking among young adolescents: study protocol of a randomized controlled trial

    NARCIS (Netherlands)

    Lammers, J.; Goossens, F.; Lokman, S.; Monshouwer, K.; Lemmers, L.; Conrod, P.; Wiers, R.; Engels, R.; Kleinjan, M.

    2011-01-01

    Background In comparison to other Europe countries, Dutch adolescents are at the top in drinking frequency and binge drinking. A total of 75% of the Dutch 12 to 16 year olds who drink alcohol also engage in binge drinking. A prevention programme called Preventure was developed in Canada to prevent a

  10. Evaluating a selective prevention programme for binge drinking among young adolescents: Study protocol of a randomized controlled trial

    NARCIS (Netherlands)

    Lammers, J.; Goossens, F.; Lokman, S.; Monshouwer, K.; Lemmers, A.C.J.; Conrod, P.; Wiers, R.W.H.J.; Engels, R.C.M.E.; Kleinjan, M.

    2011-01-01

    Background In comparison to other Europe countries, Dutch adolescents are at the top in drinking frequency and binge drinking. A total of 75% of the Dutch 12 to 16 year olds who drink alcohol also engage in binge drinking. A prevention programme called Preventure was developed in Canada to prevent a

  11. Binge drinking and alcohol-related problems among U.S.-born Asian Americans.

    Science.gov (United States)

    Iwamoto, Derek; Takamatsu, Stephanie; Castellanos, Jeanett

    2012-07-01

    Binge drinking (five drinks or more in a 2-h sitting for men or four or more drinks in a 2-h sitting for women) and alcohol-related problems are a growing problem among Asian American young adults. The current study examines the sociocultural (i.e., generational status and ethnic identity) determinants of binge drinking and alcohol-related problems across U.S.-born, young-adult, Asian American ethnic groups. Data were collected from 1,575 Asian American undergraduates from a public university in Southern California. Chinese Americans consisted of the largest Asian ethnicity in the study, followed by Vietnamese, Filipino, Korean, South Asian, Japanese, Multi-Asian, and "other Asian American." Participants completed a web-based assessment of binge drinking, alcohol-related problems, ethnic identity, descriptive norms (i.e., perceived peer drinking norms), and demographic information. An analysis of variance was used to determine potential gender and ethnic differences in binge drinking and alcohol-related problems. Negative binomial regression was selected to examine the relationship between the predictors and outcomes in our model. There were no gender differences between Asian American men and women in regards to binge drinking; however, men reported more alcohol-related problems. Japanese Americans reported the highest number of binge-drinking episodes and alcohol-related problems, followed by Filipino and Multi-Asian Americans (e.g., Chinese and Korean). Living off-campus; higher scores in descriptive norms; Greek status; and belonging to the ethnic groups Japanese, Filipino, Multi-Asian, Korean, and South Asian increased the risk of engaging in binge drinking. Quantity of alcohol consumed, Greek status, gender, Filipino, South Asian, other Asian, and lower ethnic identity scores were related to alcohol-related problems. Using one of the largest samples collected to date on sociocultural determinants and drinking among U.S.-born Asian American young adults, the

  12. Binge drinking and blood pressure: cross-sectional results of the HAPIEE study.

    Directory of Open Access Journals (Sweden)

    Andrzej Pajak

    Full Text Available OBJECTIVES: To investigate whether binge drinking pattern influences blood pressure independently from drinking volume or whether it modifies the effect of volume of drinking. METHODS: We used cross-sectional data from population samples of 7559 men and 7471 women aged 45-69 years in 2002-05, not on antihypertensive medication, from Russia, Poland and Czech Republic. Annual alcohol intake, drinking frequency and binge drinking (≥ 100 g in men and ≥ 60 g in women in one session at least once a month were estimated from graduated frequency questionnaire. Blood pressure was analysed as continuous variables (systolic and diastolic pressure and a binary outcome (≥ 140/90 mm Hg. RESULTS: In men, annual alcohol intake and drinking frequency were strongly associated with blood pressure. The odds ratio of high blood pressure for binge drinking in men was 1.62 (95% CI 1.45-1.82 after controlling for age, country, body mass index, education and smoking; additional adjustment for annual alcohol intake reduced it to 1.20 (1.03-1.39. In women, the fully adjusted odds ratio of high blood pressure for binge drinking was 1.31 (1.05-1.63. Binge drinking did not modify the effect of annual alcohol intake. Consuming alcohol as wine, beer or spirits had similar effects. CONCLUSIONS: The results suggest that the independent long-term effect of binge drinking was modest, that binge drinking did not modify the effect of alcohol intake, and that different alcoholic beverages had similar effects on blood pressure.

  13. Binge Drinking – Nationwide Problem, Local Solutions PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2012-01-03

    This 60 second PSA is based on the January 2012 CDC Vital Signs report. One in six adults binge drinks about four times a month. It's a problem nationwide but community-based strategies, such as reducing access to alcohol and increasing the price, can prevent binge drinking.  Created: 1/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 1/3/2012.

  14. Binge-drinking in Britain as a social and cultural phenomenon: the development of a grounded theoretical model.

    Science.gov (United States)

    Van Wersch, Anna; Walker, Wendy

    2009-01-01

    Techniques and procedures of Strauss and Corbin's grounded theory were used to develop a conditional matrix on binge-drinking in Britain, reflecting data of 32 participants, aged between 22 and 58. The core category was 'binge-drinking as a social and cultural phenomenon'. Results show the value of binge-drinking as an enjoyable way of socializing and counter-balancing the demands of daily hassles and routines. Intervening and contextual factors indicate fluctuations in binge-drinking behaviour and the social and cultural constraints that may operate, such as 'no drink-driving', 'not when the next day is a work day' and 'not on one's own'.

  15. 'Let's get wasted': A discourse analysis of teenagers' talk about binge drinking.

    Science.gov (United States)

    Chainey, Timothy A; Stephens, Christine

    2016-05-01

    Teenage binge drinking is a significant health issue. To explore teenagers talk about binge drinking, four peer-group interviews were conducted with 20 teenagers, aged 16-18 years, with experience of excessive alcohol use. A discourse analysis showed that a 'drinking is cool' discourse constructed 'getting wasted' as an integral part of social life, while a 'drinking as a social lubricant' discourse described the behavioural functions of alcohol use. Participants also actively resisted an 'alcohol is bad' discourse, which acknowledges the risks of alcohol use. The findings illustrate how teenagers use these resources in sophisticated ways to position the teen drinker positively and negatively.

  16. Predictors of weekly alcohol drinking and alcohol-related problems in binge-drinking undergraduates.

    Science.gov (United States)

    Motos Sellés, Patricia; Cortés Tomás, María Teresa; Giménez Costa, José Antonio; Cadaveira Mahía, Fernando

    2015-06-17

    The important implications generated by binge drinking among university students justify the interest to determine which factors predict its occurrence. Specifically, this study aims to assess the role of personality and drinking onset in predicting weekly alcohol consumption, and the impact of the whole set of variables in predicting the number of consequences associated with consumption in undergraduates. Two hundred and thirteen freshmen who were intensive consumers (binge drinkers) from the University Complutense of Madrid were evaluated. All of them filled in a self-registration of consumption, the BIS-11, the NEO-FFI and the IECI consequences associated with intake. The hierarchical regression analysis shows that the drinking onset appears to be a relevant predictor variable in explaining weekly consumption and the number of consequences. The same can be said of the weekly consumption variable with regard to the number of consequences. In general, the influence of personality is quite limited. It is interesting to point out that responsibility and impulsivity, along with age, explain most of the weekly consumption behavior among males. With respect to the consequences of consumption, only impulsivity and neuroticism contribute to explain them, but with less strength than age and weekly consumption. Our results justify the need to plan tighter interventions and consider new predictors that help to explain further weekly consumption in women.

  17. Components of Negative Affect as Moderators of the Relationship between Early Drinking Onset and Binge-Drinking Behavior

    Science.gov (United States)

    McNamara, Robert S.; Swaim, Randall C.; Rosen, Lee A.

    2010-01-01

    This study examines the moderating effects of negative affect on the relationship between early drinking onset and binge-drinking behavior. Six hundred and thirty-five eleventh- and twelfth-grade students completed the American Drug and Alcohol Survey and reported on a variety of measures, including items assessing anxiety, anger, depression, age…

  18. Desire thinking as a predictor of craving and binge drinking: A longitudinal study.

    Science.gov (United States)

    Martino, Francesca; Caselli, Gabriele; Felicetti, Federica; Rampioni, Margherita; Romanelli, Pierluigi; Troiani, Lorena; Sassaroli, Sandra; Albery, Ian P; Spada, Marcantonio M

    2017-01-01

    Desire thinking is a conscious and voluntary cognitive process orienting to prefigure images, information and memories about positive target-related experience. Desire thinking has been found to be associated with both craving and alcohol use in clinical and non-clinical populations, however its role in predicting craving and problematic drinking patterns has never been investigated using a longitudinal design. The central aim of the present study was to explore the role of desire thinking at Time 2 (3months post-baseline) in predicting craving and binge drinking and Time 3 (6months post-baseline), controlling for levels of both these constructs and Time 1 (baseline). One hundred and thirty three non-hazardous drinkers were assessed on craving and binge drinking at Times 1 and 3, and on desire thinking at Time 2. Findings showed that desire thinking at Time 2 predicted craving and binge drinking at Time 3, controlling for craving and binge drinking at Time 1. Furthermore, the imaginal prefiguration component of desire thinking at Time 2 was found to mediate the relationship between craving at Times 1 and 3; conversely the verbal perseveration component of desire thinking at Time 2 was found to mediate the relationship between binge drinking at Times 1 and 3. The implications of these findings are discussed.

  19. Binge Drinking and Risky Sex among College Students. NBER Working Paper No. 15953

    Science.gov (United States)

    DeSimone, Jeffrey S.

    2010-01-01

    This study examines the relationship between binge drinking and sexual behavior in nationally representative data on age 18-24 four-year college students. For having sex, overall or without condoms, large and significant positive associations are eliminated upon holding constant proxies for time-invariant sexual activity and drinking preferences.…

  20. Predicting Binge Drinking in College Students: Rational Beliefs, Stress, or Loneliness?

    Science.gov (United States)

    Chen, Yixin; Feeley, Thomas Hugh

    2015-01-01

    We proposed a conceptual model to predict binge-drinking behavior among college students, based on the theory of planned behavior and the stress-coping hypothesis. A two-wave online survey was conducted with predictors and drinking behavior measured separately over 2 weeks' time. In the Wave 1 survey, 279 students at a public university in the…

  1. A Discrepancy of Definitions: Binge Drinking and Female Students at an Australian University

    Science.gov (United States)

    Murugiah, Sera

    2012-01-01

    Women are more vulnerable to the effects of alcohol than men. They get intoxicated more quickly and have a higher blood alcohol level than men, even when body weight and alcohol consumption are the same. Despite this we are seeing a convergence of the drinking patterns of young women and young men, including binge drinking. In this research, 20…

  2. Integrated smoking cessation and binge drinking intervention for young adults: a pilot efficacy trial.

    Science.gov (United States)

    Ames, Steven C; Pokorny, Steven B; Schroeder, Darrell R; Tan, Winston; Werch, Chudley E

    2014-05-01

    Alcohol consumption is strongly associated with cigarette smoking in young adults. The primary aim of this investigation was to complete a pilot evaluation of the efficacy of an integrated intervention that targets both cigarette smoking and binge drinking on the cigarette smoking and binge behavior of young adults at 6-month follow-up. Participants were 95 young adult (M=24.3; SD=3.5 years) smokers (≥1 cigarettes per day) who binge drink (≥1 time per month) and who were randomly assigned to standard treatment (n=47) involving six individual treatment visits plus eight weeks of nicotine patch therapy or the identical smoking cessation treatment integrated with a binge drinking intervention (integrated intervention; n=48). Using an intent-to-treat analysis for tobacco abstinence, at both 3 month end of treatment and 6 month follow-up, more participants who received integrated intervention were biochemically confirmed abstinent from tobacco than those who received standard treatment at 3 months (19% vs. 9%, p=0.06) and 6 months (21% vs. 9%, p=0.05). At 6 months, participants who completed the study and who received integrated intervention consumed fewer drinks per month (psmoking cessation and reduces binge drinking compared to standard treatment.

  3. Gender roles and binge drinking among Latino emerging adults: a latent class regression analysis.

    Science.gov (United States)

    Vaughan, Ellen L; Wong, Y Joel; Middendorf, Katharine G

    2014-09-01

    Gender roles are often cited as a culturally specific predictor of drinking among Latino populations. This study used latent class regression to test the relationships between gender roles and binge drinking in a sample of Latino emerging adults. Participants were Latino emerging adults who participated in Wave III of the National Longitudinal Study of Adolescent Health (N = 2,442). A subsample of these participants (n = 660) completed the Bem Sex Role Inventory--Short. We conducted latent class regression using 3 dimensions of gender roles (femininity, social masculinity, and personal masculinity) to predict binge drinking. Results indicated a 3-class solution. In Class 1, the protective personal masculinity class, personal masculinity (e.g., being a leader, defending one's own beliefs) was associated with a reduction in the odds of binge drinking. In Class 2, the nonsignificant class, gender roles were not related to binge drinking. In Class 3, the mixed masculinity class, personal masculinity was associated with a reduction in the odds of binge drinking, whereas social masculinity (e.g., forceful, dominant) was associated with an increase in the odds of binge drinking. Post hoc analyses found that females, those born outside the United States, and those with greater English language usage were at greater odds of being in Class 1 (vs. Class 2). Males, those born outside the United States, and those with greater Spanish language usage were at greater odds of being in Class 3 (vs. Class 2). Directions for future research and implications for practice with Latino emerging adults are discussed.

  4. Challenging the Collegiate Rite of Passage: A Campus-Wide Social Marketing Media Campaign To Reduce Binge Drinking.

    Science.gov (United States)

    Glider, Peggy; Midyett, Stephen J.; Mills-Novoa, Beverly; Johannessen, Koreen; Collins, Carolyn

    2001-01-01

    A social marketing media campaign, based on a normative social influence model and focused on normative messages regarding binge drinking, has yielded positive preliminary results of an overall 29.2 percent decrease in binge drinking rates over a three-year period. Two surveys provided information on student knowledge, perceptions, and behaviors…

  5. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    Science.gov (United States)

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.

  6. Predictors of binge drinking in adolescents: ultimate and distal factors - a representative study

    Directory of Open Access Journals (Sweden)

    Donath Carolin

    2012-04-01

    Full Text Available Abstract Background As epidemiological surveys have shown, binge drinking is a constant and wide-spread problem behavior in adolescents. It is not rare to find that more than half of all adolescents engage in this behavior when assessing only the last 4 weeks of time independent of the urbanity of the region they live in. There have been several reviews on predictors of substance consumption in adolescents in general, but there has been less high quality research on predictors of binge drinking, and most studies have not been theoretically based. The current study aimed to analyze the ultimate and distal factors predicting substance consumption according to Petraitis' theory of triadic influence. We assessed the predictive value of these factors with respect to binge drinking in German adolescents, including the identification of influence direction. Methods In the years 2007/2008, a representative written survey of N = 44,610 students in the 9th grade of different school types in Germany was carried out (net sample. The return rate of questionnaires was 88% regarding all students whose teachers or school directors had agreed to participate in the study. In this survey, prevalence of binge drinking was investigated as well as potential predictors from the social/interpersonal, the attitudinal/environmental, and the intrapersonal fields (3 factors of Petraitis. In a multivariate logistic regression analysis, these variables were included after testing for multicollinearity in order to assess their ability to predict binge drinking. Results Prevalence of binge drinking in the last 30 days was 52.3% for the surveyed adolescents with a higher prevalence for boys (56.9% than for girls (47.5%. The two most influential factors found to protect against binge drinking with p p Conclusions Whereas some of the risk and protective factors for binge drinking are not surprising since they are known for substance abuse in general, there are two points that

  7. The Role of Positive Alcohol Expectancies in Underage Binge Drinking among College Students

    Science.gov (United States)

    McBride, Nicole M.; Barrett, Blake; Moore, Kathleen A.; Schonfeld, Lawrence

    2014-01-01

    Objective: This study explored associations between positive alcohol expectancies, and demographics, as well as academic status and binge drinking among underage college students. Participants: A sample of 1,553 underage college students at 3 public universities and 1 college in the Southeast who completed the Core Alcohol and Drug Survey in the…

  8. Associations between Responsible Beverage Service Laws and Binge Drinking and Alcohol-Impaired Driving

    Science.gov (United States)

    Linde, Ann C.; Toomey, Traci L.; Wolfson, Julian; Lenk, Kathleen M.; Jones-Webb, Rhonda; Erickson, Darin J.

    2016-01-01

    We explored potential associations between the strength of state Responsible Beverage Service (RBS) laws and self-reported binge drinking and alcohol-impaired driving in the U.S. A multi-level logistic mixed-effects model was used, adjusting for potential confounders. Analyses were conducted on the overall BRFSS sample and drinkers only. Seven…

  9. Experiential Learning in Marketing Communications Courses: The Demarketing of College Binge-Drinking

    Science.gov (United States)

    Rozensher, Susan G.; Seal, David S.

    2009-01-01

    The experiential learning approach has been gathering substantial momentum and support in educational circles. In the team-based experiential learning project presented here, which effectively integrated theory and application, students were charged with creating an integrated marketing communications plan to demarket binge drinking on the college…

  10. Adverse Childhood Experiences and Risk of Binge Drinking and Drunkenness in Middle-Aged Finnish Men

    Directory of Open Access Journals (Sweden)

    Laura Kauhanen

    2011-01-01

    Full Text Available Objective. The purpose of this study was to investigate associations between adverse childhood experiences and binge drinking and drunkenness in adulthood using both historical and recalled data from childhood. Methods. Data on childhood adverse experiences were collected from school health records and questionnaires completed in adulthood. Adulthood data were obtained from the baseline examinations of the male participants (n=2682 in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD in 1984–1989 from eastern Finland. School health records from the 1930s to 1950s were available for a subsample of KIHD men (n=952. Results. According to the school health records, men who had adverse childhood experiences had a 1.51-fold (95% CI 1.05 to 2.18 age- and examination-year adjusted odds of binge drinking in adulthood. After adjustment for socioeconomic position in adulthood or behavioural factors in adulthood, the association remained unchanged. Adjustment for socioeconomic position in childhood attenuated these effects. Also the recalled data showed associations with adverse childhood experiences and binge drinking with different beverages. Conclusions. Our findings suggest that childhood adversities are associated with increased risk of binge drinking in adulthood.

  11. Binge drinking and psychoactive drug use in a cohort of European youths

    Directory of Open Access Journals (Sweden)

    Roberta Siliquini

    2012-02-01

    Full Text Available Background. TEN-D by Night is an international, multicentre, cross-sectional portal survey conducted on a large sample of young people in six European countries. This paper aims to investigate the alcohol and psychoactive drug consumption of this sample, with a focus on the prevalence of binge drinking and the poly-drug habits of the TEN-D cohort. Design and Methods. The study population consisted of 4695 young people attending recreational sites on weekend nights. The intervention included two questionnaires and two psychoactive substance detection tests performed at the entry and exit of the recreational sites. A multivariate logistic regression model was used to predict the probability of binge drinking. Results. Binge drinking was reported by 20% of the males and 13% of the females (P=0.001 before entry into the recreational sites and by 18% of the males and 11% of the females before entry into the clubs (P<0.001. Poly-drug use was reported by 71% of the males and 66% of the females. Living with a parent (OR 1.57; P=0.01, seeking employment (OR 1.66; P=0.005 and cannabis consumption (several times per month and several times per week, OR 1.94 and 3.66, respectively, P<0.05 were associated with binge drinking. Conclusions. Our survey showed that it is possible to identify individuals and groups at higher risk of binge drinking. This identification would allow for a focus on specific targets and would facilitate the redesign of prevention programmes. The increased use of psychoactive substances among youths should be studied extensively to promote successful prevention campaigns.

  12. Adolescent but not adult ethanol binge drinking modulates cocaine withdrawal symptoms in mice

    Science.gov (United States)

    Aguilar, Maria A.; Giménez-Gómez, Pablo; Miñarro, José; Rodríguez-Arias, Marta

    2017-01-01

    Background Ethanol (EtOH) binge drinking is an increasingly common behavior among teenagers that induces long-lasting neurobehavioral alterations in adulthood. An early history of EtOH abuse during adolescence is highly correlated with cocaine addiction in adulthood. Abstinence of cocaine abuse can cause psychiatric symptoms, such as anxiety, psychosis, depression, and cognitive impairments. This study assessed the consequences of adolescent exposure to EtOH on the behavioral alterations promoted by cocaine withdrawal in adulthood. Methods We pretreated juvenile (34–47 days old) or adult (68–81 days old) mice with EtOH (1.25 g/kg) following a binge-drinking pattern. Then, after a three-week period without drug delivery, they were subjected to a chronic cocaine treatment in adulthood and tested under cocaine withdrawal by the ensuing paradigms: open field, elevated plus maze, prepulse inhibition, tail suspension test, and object recognition. Another set of mice were treated with the same EtOH binge-drinking procedure during adolescence and were tested immediately afterwards under the same behavioral paradigms. Results Adolescent EtOH pretreatment undermined the anxiogenic effects observed after cocaine abstinence, reduced prepulse inhibition, and increased immobility scores in the tail suspension test following cocaine withdrawal. Moreover, the memory deficits evoked by these substances when given separately were enhanced in cocaine-withdrawn mice exposed to EtOH during adolescence. EtOH binge drinking during adolescence also induced anxiety, depressive symptoms, and memory impairments when measured immediately afterwards. In contrast, neither EtOH nor cocaine alone or in combination altered any of these behaviors when given in adulthood. Conclusions EtOH binge drinking induces short- and long-term behavioral alterations and modulates cocaine withdrawal symptoms when given in adolescent mice. PMID:28291777

  13. Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats.

    Directory of Open Access Journals (Sweden)

    Nicholas W Gilpin

    Full Text Available Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (~postnatal days 28-42 in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF cell in the lateral portion of the central amygdala (CeA, a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity, an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects

  14. Stress and binge drinking: A toxic combination for the teenage brain.

    Science.gov (United States)

    Goldstein, Aaron; Déry, Nicolas; Pilgrim, Malcolm; Ioan, Miruna; Becker, Suzanna

    2016-09-01

    Young adult university students frequently binge on alcohol and have high stress levels. Based on findings in rodents, we predicted that heavy current alcohol use and elevated stress and depression scores would be associated with deficits on high interference memory tasks, while early onset, prolonged binge patterns would lead to broader cognitive deficits on tests of associative encoding and executive functions. We developed the Concentration Memory Task, a novel computerized version of the Concentration card game with a high degree of interference. We found that young adults with elevated stress, depression, and alcohol consumption scores were impaired in the Concentration Memory Task. We also analyzed data from a previous study, and found that higher alcohol consumption scores were associated with impaired performance on another high interference memory task, based on Kirwan and Stark's Mnemonic Similarity Test. On the other hand, adolescent onset of binge drinking predicted poorer performance on broader range of memory tests, including a more systematic test of spatial recognition memory, and an associative learning task. Our results are broadly consistent with findings in rodents that acute alcohol and stress exposure suppress neurogenesis in the adult hippocampus, which in turn impairs performance in high interference memory tasks, while adolescent onset binge drinking causes more extensive brain damage and cognitive deficits.

  15. Alcohol availability and neighborhood poverty and their relationship to binge drinking and related problems among drinkers in committed relationships.

    Science.gov (United States)

    McKinney, Christy M; Chartier, Karen G; Caetano, Raul; Harris, T Robert

    2012-09-01

    The authors examined the relationship of alcohol outlet density (AOD) and neighborhood poverty with binge drinking and alcohol-related problems among drinkers in married and cohabitating relationships and assessed whether these associations differed across sex. A U.S. national population couples survey was linked to U.S. Census data on AOD and neighborhood poverty. The 1,784 current drinkers in the survey reported on their binge drinking, alcohol-related problems, and other covariates. AOD was defined as the number of alcohol outlets per 10,000 persons and was obtained at the zip code level. Neighborhood poverty was defined as having a low (poverty at the census tract level. We used logistic regression for survey data to estimate odds ratios and 95% confidence intervals and tested for differences of associations by sex. Associations of neighborhood poverty with binge drinking were stronger for male than for female drinkers. The association of neighborhood poverty with alcohol-related problems was also stronger for men than for women. We observed no relationships between AOD and binge drinking or alcohol-related problems in this couples survey. Efforts to reduce binge drinking or alcohol-related problems among partners in committed relationships may have the greatest impact if targeted to male drinkers living in high-poverty neighborhoods. Binge drinking and alcohol-related problems, as well as residence in an impoverished neighborhood are risk factors for intimate partner violence (IPV) and other relationship conflicts.

  16. Alcohol, binge drinking and associated mental health problems in young urban Chileans.

    Directory of Open Access Journals (Sweden)

    Amanda J Mason-Jones

    Full Text Available To explore the link between alcohol use, binge drinking and mental health problems in a representative sample of adolescent and young adult Chileans.Age and sex-adjusted Odds Ratios (OR for four mental wellbeing measures were estimated with separate conditional logistic regression models for adolescents aged 15-20 years, and young adults aged 21-25 years, using population-based estimates of alcohol use prevalence rates from the Chilean National Health Survey 2010.Sixty five per cent of adolescents and 85% of young adults reported drinking alcohol in the last year and of those 83% per cent of adolescents and 86% of young adults reported binge drinking in the previous month. Adolescents who reported binging alcohol were also more likely, compared to young adults, to report being always or almost always depressed (OR 12.97 [95% CI, 1.86-19.54] or to feel very anxious in the last month (OR 9.37 [1.77-19.54]. Adolescent females were more likely to report poor life satisfaction in the previous year than adolescent males (OR 8.50 [1.61-15.78], feel always or almost always depressed (OR 3.41 [1.25-9.58]. Being female was also associated with a self-reported diagnosis of depression for both age groups (adolescents, OR 4.74 [1.49-15.08] and young adults, OR 4.08 [1.65-10.05].Young people in Chile self-report a high prevalence of alcohol use, binge drinking and associated mental health problems. The harms associated with alcohol consumption need to be highlighted through evidence-based prevention programs. Health and education systems need to be strengthened to screen and support young people. Focussing on policy initiatives to limit beverage companies targeting alcohol to young people will also be needed.

  17. Association between Acculturation and Binge Drinking among Asian-Americans: Results from the California Health Interview Survey

    Directory of Open Access Journals (Sweden)

    Monideepa B. Becerra

    2013-01-01

    Full Text Available Objective. Evaluate the association between acculturation and binge drinking among six Asian-American subgroups. Methods. A cross-sectional analysis of public access adult portion of 2007, 2009, and 2011/2012 California Health Interview Survey data was conducted. Univariate and multivariable logistic regression analyses were utilized with any binge drinking in the past year as the outcome variable and language spoken at home and time in USA as proxy measures of acculturation. Results. A total of 1,631 Asian-Americans (N=665,195 were identified as binge drinkers. Binge drinking was positively associated with being first generation South Asian (OR=3.05, 95% CI=1.55, 5.98 and monolingual (English only Vietnamese (OR=3.00; 95% CI=1.58, 5.70, especially among females. Other factors associated with increased binge drinking were being female (Chinese only, not being current married (South Asian only, and being an ever smoker (all subgroups except South Asians. Conclusion. First generation South Asians and linguistically acculturated Vietnamese, especially females, are at an increased risk of binge drinking. Future studies and preventive measures should address the cultural basis of such health risk behaviors among Asian-American adults.

  18. Child abuse and neglect: Relations to adolescent binge drinking in the National Longitudinal Study of Adolescent Health (AddHealth) Study

    OpenAIRE

    Shin, Sunny Hyucksun; Edwards, Erika M.; Heeren, Timothy

    2008-01-01

    The purpose of this study was to examine the relationship between child maltreatment and adolescent binge drinking. Given that many victimized children have been maltreated in multiple ways, we examine the effects of co-occurrence of multiple types of maltreatment on adolescent binge drinking. We used the National Longitudinal Study of Adolescent Health (AddHealth), which included a nationally representative sample of adolescents (n = 12,748). Adolescent binge drinking was defined as five or ...

  19. The Influence of a Web-Based Course on Alcohol Consumption and Binge Drinking Behavior among First Year Students

    Science.gov (United States)

    Robinson, Lillian D.

    2011-01-01

    Underage drinking and risky alcohol consumption are issues that have garnered a great deal of national and local attention and subsequently many prevention efforts. The consumption of alcohol and binge drinking by minors jeopardizes not only their quality of life and academic success, but also places the individual and others at an increased risk…

  20. University Binge Drinking Patterns and Changes in Patterns of Alcohol Consumption among Chinese Undergraduates in a Hong Kong University

    Science.gov (United States)

    Kim, Jean H.; Chan, Karli W. C.; Chow, Julie K. W.; Fung, K. P.; Fong, Ben Y. F.; Cheuk, Ka Kin; Griffiths, Sian M.

    2009-01-01

    Objective: To examine patterns of binge drinking and changes in drinking patterns among Chinese university students. Participants and Methods: Responses to an anonymous questionnaire were compared between a random sample of 411 second year Chinese undergraduate students in 2006 and 2,630 first year students from the previous year. Students…

  1. Binge drinking during pregnancy and risk of seizures in childhood: a study based on the Danish National Birth Cohort

    DEFF Research Database (Denmark)

    Sun, Yuelian; Strandberg-Larsen, Katrine; Vestergaard, Mogens;

    2009-01-01

    Seizures are often found in children with fetal alcohol syndrome, but it is not known whether binge drinking during pregnancy by nonalcoholic women is associated with an increased risk of seizure disorders in children. The authors conducted a population-based cohort study of 80,526 liveborn...... singletons in the Danish National Birth Cohort (1996-2002). Information on maternal binge drinking (intake of > or = 5 drinks on a single occasion) was collected in 2 computer-assisted telephone interviews during pregnancy. Children were followed for up to 8 years. Information on neonatal seizures, epilepsy......, and febrile seizures was retrieved from the Danish National Hospital Register. Results showed that exposure to binge drinking episodes during pregnancy was not associated with an increased risk of seizure disorders in children, except for those exposed at 11-16 gestational weeks. These children had a 3...

  2. Evaluating a selective prevention programme for binge drinking among young adolescents: study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Wiers Reinout

    2011-02-01

    Full Text Available Abstract Background In comparison to other Europe countries, Dutch adolescents are at the top in drinking frequency and binge drinking. A total of 75% of the Dutch 12 to 16 year olds who drink alcohol also engage in binge drinking. A prevention programme called Preventure was developed in Canada to prevent adolescents from binge drinking. This article describes a study that aims to assess the effects of this selective school-based prevention programme in the Netherlands. Methods A randomized controlled trial is being conducted among 13 to 15-year-old adolescents in secondary schools. Schools were randomly assigned to the intervention and control conditions. The intervention condition consisted of two 90 minute group sessions, carried out at the participants' schools and provided by a qualified counsellor and a co-facilitator. The intervention targeted young adolescents who demonstrated personality risk for alcohol abuse. The group sessions were adapted to four personality profiles. The control condition received no further intervention above the standard substance use education sessions provided in the Dutch national curriculum. The primary outcomes will be the percentage reduction in binge drinking, weekly drinking and drinking-related problems after three specified time periods. A screening survey collected data by means of an Internet questionnaire. Students have completed, or will complete, a post-treatment survey after 2, 6, and 12 months, also by means of an online questionnaire. Discussion This study protocol presents the design and current implementation of a randomized controlled trial to evaluate the effectiveness of a selective alcohol prevention programme. We expect that a significantly lower number of adolescents will binge drink, drink weekly, and have drinking-related problems in the intervention condition compared to the control condition, as a result of this intervention. Trial registration This trial is registered in the Dutch

  3. Alcohol consumption and binge drinking in early pregnancy. A cross-sectional study with data from the Copenhagen Pregnancy Cohort

    DEFF Research Database (Denmark)

    Iversen, Mette Langeland; Sørensen, Nina Olsén; Broberg, Lotte

    2015-01-01

    . Since the introduction of the recommendation of total abstinence, no studies have examined pre-pregnancy lifestyle and reproductive risk factors associated with this behaviour in a Danish context. The aims of this study were therefore to describe the prevalence of weekly alcohol consumption and binge...... drinking in early pregnancy among women living in the capital of Denmark. Secondly to identify pre-pregnancy lifestyle and reproductive risk factors associated with binge drinking during early pregnancy. METHODS: Data were collected from September 2012 to August 2013 at the Department of Obstetrics......BACKGROUND: Since 2007 the Danish Health and Medicines Authority has advised total alcohol abstinence from the time of trying to conceive and throughout pregnancy. The prevalence of binge drinking among pregnant Danish women has nevertheless been reported to be up to 48 % during early pregnancy...

  4. An Interactive Text Message Intervention to Reduce Binge Drinking in Young Adults: A Randomized Controlled Trial with 9-Month Outcomes.

    Directory of Open Access Journals (Sweden)

    Brian Suffoletto

    Full Text Available Binge drinking is associated with numerous negative consequences. The prevalence and intensity of binge drinking is highest among young adults. This randomized trial tested the efficacy of a 12-week interactive text message intervention to reduce binge drinking up to 6 months after intervention completion among young adults.Young adult participants (18-25 y; n = 765 drinking above the low-risk limits (AUDIT-C score >3/4 women/men, but not seeking alcohol treatment, were enrolled from 4 Emergency Departments (EDs in Pittsburgh, PA. Participants were randomized to one of three conditions in a 2:1:1 allocation ratio: SMS Assessments + Feedback (SA+F, SMS Assessments (SA, or control. For 12 weeks, SA+F participants received texts each Thursday querying weekend drinking plans and prompting drinking limit goal commitment and each Sunday querying weekend drinking quantity. SA+F participants received tailored feedback based on their text responses. To contrast the effects of SA+F with self-monitoring, SA participants received texts on Sundays querying drinking quantity, but did not receive alcohol-specific feedback. The control arm received standard care. Follow-up outcome data collected through web-based surveys were provided by 78% of participants at 3- months, 63% at 6-months and 55% at 9-months. Multiple imputation-derived, intent-to-treat models were used for primary analysis. At 9-months, participants in the SA+F group reported greater reductions in the number of binge drinking days than participants in the control group (incident rate ratio [IRR] 0.69; 95% CI .59 to.79, lower binge drinking prevalence (odds ratio [OR] 0.52; 95% CI 0.26 to 0.98], less drinks per drinking day (beta -.62; 95% CI -1.10 to -0.15 and lower alcohol-related injury prevalence (OR 0.42; 95% CI 0.21 to 0.88. Participants in the SA group did not reduce drinking or alcohol-related injury relative to controls. Findings were similar using complete case analyses.An interactive

  5. Binge Drinking among Men Who Have Sex with Men and Transgender Women in San Salvador: Correlates and Sexual Health Implications.

    Science.gov (United States)

    Peacock, Erin; Andrinopoulos, Katherine; Hembling, John

    2015-08-01

    High rates of heavy alcohol use among men who have sex with men (MSM) and transgender women (TW) have been linked to increased vulnerability for HIV and poor mental health. While theories explaining elevated drinking levels among sexual minorities have been forwarded, few investigations have assessed the potential pathways using empirical data, particularly with an explicit focus on self-stigma and among MSM and TW in low- and middle-income countries. This study examined the relationship between stigma-related stress (specifically, self-stigma and concealment of one's sexual orientation) and binge drinking in a sample of MSM and TW (n = 670) in San Salvador, El Salvador, recruited using respondent-driven sampling. Levels of alcohol consumption among participants were high: only 39 % of the sample did not drink alcohol or did not binge drink, while 34 % engaged in binge drinking at least weekly. Among MSM, high self-stigma was associated with binge drinking at least weekly (adjusted relative risk ratio (aRRR) = 2.1, p sexual orientation to multiple types of people was associated with binge drinking less than weekly (aRRR = 2.9 for disclosure to one-two types of people, p types of people, p sexual health outcomes, including high number of lifetime partners (adjusted odds ratio (aOR) = 1.7, p sexual risk behavior and was actually associated with increased intention to test for HIV in the next 12 months (aOR = 2.8, p sexual orientation to multiple types of people may be more engaged with the sexual minority community, likely in bars and other venues where permissive norms for alcohol use prevail. That this frequency of binge drinking does not appear to be associated with increased sexual risk behavior (and may even be associated with increased intention to test for HIV in the next 12 months) lends further support to the suggestion that these individuals with healthy concepts of the self (as indicated by high levels of disclosure and low

  6. Alcohol consumption and binge drinking in adolescents: comparison of different migration backgrounds and rural vs. urban residence - a representative study

    Directory of Open Access Journals (Sweden)

    Bleich Stefan

    2011-02-01

    Full Text Available Abstract Background Binge drinking is a constant problem behavior in adolescents across Europe. Epidemiological investigations have been reported. However, epidemiological data on alcohol consumption of adolescents with different migration backgrounds are rare. Furthermore representative data on rural-urban comparison concerning alcohol consumption and binge drinking are lacking. The aims of the study are the investigation of alcohol consumption patterns with respect to a urban-rural differences and b differences according to migration background. Methods In the years 2007/2008, a representative written survey of N = 44,610 students in the 9th. grade of different school types in Germany was carried out (net sample. The return rate of questionnaires was 88% regarding all students whose teachers respectively school directors had agreed to participate in the study. Weighting factors were specified and used to make up for regional and school-type specific differences in return rates. 27.4% of the adolescents surveyed have a migration background, whereby the Turkish culture is the largest group followed by adolescents who emigrated from former Soviet Union states. The sample includes seven large cities (over 500,000 inhabitants (12.2%, independent smaller cities ("urban districts" (19.0% and rural areas ("rural districts" (68.8%. Results Life-time prevalence for alcohol consumption differs significantly between rural (93.7% and urban areas (86.6% large cities; 89.1% smaller cities with a higher prevalence in rural areas. The same accounts for 12-month prevalence for alcohol consumption. 57.3% of the rural, re-spectively 45.9% of the urban adolescents engaged in binge drinking in the 4 weeks prior to the survey. Students with migration background of the former Soviet Union showed mainly drinking behavior similar to that of German adolescents. Adolescents with Turkish roots had engaged in binge drinking in the last four weeks less frequently than

  7. Binge Drinking

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  19. Binge Drinking

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  1. Binge Drinking

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  2. A self-administered Timeline Followback to measure variations in underage drinkers' alcohol intake and binge drinking.

    Science.gov (United States)

    Collins, R Lorraine; Kashdan, Todd B; Koutsky, James R; Morsheimer, Elizabeth T; Vetter, Charlene J

    2008-01-01

    Underage drinkers typically have not developed regular patterns of drinking and so are likely to exhibit situational variation in alcohol intake, including binge drinking. Information about such variation is not well captured by quantity/frequency (QF) measures, which require that drinkers blend information over time to derive a representative estimate of "typical" drinking. The Timeline Followback (TLFB) method is designed to retrospectively capture situational variations in drinking during a specific period of time. We compared our newly-developed Self-administered TLFB (STLFB) measure to a QF measure for reporting alcohol intake. Our sample of 429 (men=204; women=225) underage (i.e., age 18-20 years) drinkers completed the two drinking measures and reported on alcohol problems. The STLFB and QF measures converged in assessing typical daily intake, but the STLFB provided more information about situational variations in alcohol use and better identification of regular versus intermittent binge drinkers. Regular binge drinkers reported more alcohol problems. The STLFB is an easy-to-administer measure of variations in alcohol intake, which can be useful for understanding drinking behavior.

  3. Child abuse and neglect: relations to adolescent binge drinking in the national longitudinal study of Adolescent Health (AddHealth) Study.

    Science.gov (United States)

    Shin, Sunny Hyucksun; Edwards, Erika M; Heeren, Timothy

    2009-03-01

    The purpose of this study was to examine the relationship between child maltreatment and adolescent binge drinking. Given that many victimized children have been maltreated in multiple ways, we examine the effects of co-occurrence of multiple types of maltreatment on adolescent binge drinking. We used the National Longitudinal Study of Adolescent Health (AddHealth), which included a nationally representative sample of adolescents (n=12,748). Adolescent binge drinking was defined as five or more drinks in a row at least 2-3 times per month in the past year. Among those reporting any maltreatment, 12.4% reported binge drinking compared to 9.9% among those reporting no maltreatment. Logistic regression models found that child maltreatment is a robust risk factor for adolescent binge drinking controlling for parental alcoholism. In particular, all types of or combinations of types of maltreatment were strongly associated with adolescent binge drinking, controlling for age, gender, race, parental alcoholism and monitoring. Research examining the effect of childhood maltreatment on later alcohol abuse needs to recognize the clustering effects of multiple types of childhood maltreatment on alcohol problems.

  4. Is alcohol binge drinking in early and late pregnancy associated with behavioural and emotional development at age 7 years?

    DEFF Research Database (Denmark)

    Niclasen, Janni; Andersen, Anne-Marie Nybo; Strandberg-Larsen, Katrine

    2014-01-01

    The purpose of this study was to investigate associations of maternal binge drinking in early and late pregnancy with child behavioural and emotional development at age seven. It was hypothesised that late exposure is associated with more negative outcomes than early exposure. Differences were....../internalising scores and above cutoff hyperactivity/inattention, conduct, emotional and peer problems scores. Only women with full information concerning binge drinking from the three interviews, together with full-scale SDQ information on their children at age seven and being term-born, were included in the study (N...... = 37,315). After adjustment for maternal education, psychiatric diagnoses, age and smoking, children exposed to binge drinking in early and late pregnancy had significantly higher mean externalizing scores at age seven than unexposed children, an effect albeit much less for early binge drinking...

  5. Personality and alcohol metacognitions as predictors of weekly levels of alcohol use in binge drinking university students.

    Science.gov (United States)

    Clark, Ailsa; Tran, Cathy; Weiss, Alexander; Caselli, Gabriele; Nikčević, Ana V; Spada, Marcantonio M

    2012-04-01

    This study investigated the relative contribution of the Big 5 personality factors and alcohol metacognitions in predicting weekly levels of alcohol use in binge drinking university students. No research to date has investigated whether either of these constructs predicts levels of weekly alcohol use in binge drinkers. A sample of university students (n=142) who were classified as binge drinkers were administered the following self-report instruments: NEO-Five Factor Inventory (NEO-FFI; Costa & McCrae, 1992), Positive Alcohol Metacognitions Scale (PAMS; Spada & Wells, 2008), Negative Alcohol Metacognitions Scale (NAMS; Spada & Wells, 2008), and Khavari Alcohol Test (KAT; Khavari & Farber, 1978). Pearson product-moment correlations showed that weekly levels of alcohol use were negatively correlated with agreeableness and conscientiousness and positively correlated with positive alcohol metacognitions about cognitive self-regulation, negative alcohol metacognitions about uncontrollability and negative alcohol metacognitions about cognitive harm. A hierarchical regression analysis revealed that conscientiousness and positive alcohol metacognitions about cognitive self-regulation were the only two significant predictors of weekly levels of alcohol use when controlling for gender. These findings show that being male, low on conscientiousness and high on positive alcohol metacognitions about cognitive self-regulation raises the risk for increased weekly levels of alcohol use in binge drinking university students. The implications of these findings are discussed.

  6. OPRM1 and Diagnosis-Related Posttraumatic Stress Disorder in Binge-Drinking Patients Living with HIV

    Science.gov (United States)

    Nugent, Nicole R.; Lally, Michelle A.; Brown, Larry; Knopik, Valerie S.; McGeary, John E.

    2013-01-01

    Posttraumatic stress disorder (PTSD) has been linked to numerous negative outcomes in persons living with HIV (PLH) and there is evidence that PTSD symptoms may play a role in maintaining alcohol use problems. The opioid receptor mu-1 (OPRM1) gene may play a role in both PTSD and alcohol use. We examined the association between PTSD and drinking motives as well as variation in the OPRM1 as a predictor of both PTSD and drinking motives in a sample of 201 PLH reporting recent binge drinking. Self-reported PTSD symptom severity was significantly associated with drinking motives for coping, enhancement, and socialization. OPRM1 variation was associated with decreased PTSD symptom severity as well as enhancement motives for drinking. PMID:22143634

  7. Is there an association between traumatic dental injury and social capital, binge drinking and socioeconomic indicators among schoolchildren?

    Directory of Open Access Journals (Sweden)

    Haroldo Neves de Paiva

    Full Text Available Traumatic dental injury is defined as trauma caused by forces on a tooth with variable extent and severity. The aim of the present study was to investigate the prevalence of traumatic dental injury and its association with overjet, lip protection, sex, socioeconomic status, social capital and binge drinking among 12-year-old students.A cross-sectional study was conducted with a sample of 633 12-year-old students. Data were collected through a clinical exam and self-administered questionnaires. Socioeconomic status was determined based on mother's schooling and household income. The Social Capital Questionnaire for Adolescent Students and Alcohol Use Disorders Identification Test (AUDIT-C were used to measure social capital and binge drinking, respectively.The prevalence of traumatic dental injury was 29.9% (176/588. Traumatic dental injury was more prevalent among male adolescents (p = 0.010, those with overjet greater than 5 mm (p < 0.001 and those with inadequate lip protection (p < 0.001. In the multiple logistic regression analysis, overjet [OR = 3.80 (95% CI: 2.235-6.466, p < 0.0001], inadequate lip protection [OR = 5.585 (95% CI: 3.654-8.535, p < 0.0001] and binge drinking [OR = 1.93 (95% CI: 1.21-3.06, p = 0.005] remained significantly associated with traumatic dental injury.The present findings suggest that a high level of total social capital and trust are not associated with TDI in adolescents, unlike binge drinking. The effects of social and behavioral factors on TDI are not well elucidated. Therefore, further research involving other populations and a longitudinal design is recommended.

  8. Ceramide metabolism analysis in a model of binge drinking reveals both neuroprotective and toxic effects of ethanol

    Science.gov (United States)

    Bae, Mihyun; Bandaru, Veera Venkata Ratnam; Patel, Neha; Haughey, Norman J.

    2014-01-01

    Binge drinking is a common form of alcohol abuse that involves repeated rounds of intoxication followed by withdrawal. The episodic effects of binge drinking and withdrawal on brain resident cells are thought to contribute to neural remodeling and neurological damage. However, the molecular mechanisms for these neurodegenerative effects are not understood. Ethanol (EtOH) regulates the metabolism of ceramide, a highly bioactive lipid that is enriched in brain. We used a mouse model of binge drinking to determine the effects of EtOH intoxication and withdrawal on brain ceramide metabolism. Intoxication and acute alcohol withdrawal were each associated with distinct changes in ceramide regulatory genes and metabolic products. EtOH intoxication was accompanied by decreased concentrations of multiple ceramides, coincident with reductions in the expression of enzymes involved in the production of ceramides, and increased expression of ceramide degrading enzymes. EtOH withdrawal was associated with specific increases in ceramide C16:0, C18:0 and C20:0 and increased expression of enzymes involved with ceramide production. These data suggest that EtOH intoxication may evoke a ceramide phenotype that is neuroprotective, while EtOH withdrawal results in a metabolic shift that increases the production of potentially toxic ceramide species. PMID:25060779

  9. Binge-like ingestion of a combination of an energy drink and alcohol leads to cognitive deficits and motivational changes.

    Science.gov (United States)

    Takahashi, Tatiane T; Vendruscolo, Leandro F; Takahashi, Reinaldo N

    2015-09-01

    The combination of alcohol with an energy drink (ED) is believed to contribute to risky alcohol-drinking behaviors, such as binge drinking. However, the long-term effects on cognition and reward function that are caused by the repeated binge-like ingestion of alcohol and EDs are still poorly known. The present study examined the effects of a history of repeated exposure to alcohol and/or an ED on short-term memory and alcohol-seeking behavior. Male Wistar rats were given daily intragastric administration of alcohol (3.4g/kg) combined or not with an ED (10.71ml/kg) for 6 consecutive days. The rats were tested for locomotion 15min after the first intragastric treatment. Short-term memory was assessed in the novel object recognition and social discrimination tests 2-3days after the last intragastric administration. The rewarding effect of alcohol was tested 1-3weeks following the last intragastric administration in a conditioned place preference paradigm. The acute binge-like ingestion of alcohol decreased locomotor activity, whereas the combination of alcohol and an ED increased locomotion in the first minutes of assessment. Alcohol exposure produced cognitive deficits in both the object recognition and social discrimination tests, and adding the ED to the alcohol solution did not modify these effects. The combination of alcohol and the ED increased alcohol-induced conditioned place preference. Thus, a history of binge-like alcohol exposure combined with the ED caused subsequent cognitive deficits and increased alcohol seeking behavior, and such behavioral effects might contribute to the progression to alcohol abuse disorders.

  10. Drug use, binge drinking and attempted suicide among homeless and potentially homeless youth.

    Science.gov (United States)

    Sibthorpe, B; Drinkwater, J; Gardner, K; Bammer, G

    1995-06-01

    In order to assess the need for drug-related services for at-risk youth, a survey was conducted among young people aged 12-17 years who, owing to severe family discord, were currently living away from home (homeless) or had experienced periods away from home in the past 12 months (potentially homeless). Prevalence of use and of potentially harmful levels of use of alcohol and other licit and illicit drugs were higher than in a comparative population. Of the 155 people interviewed, 54% reported past physical abuse, 28% reported past sexual abuse, and 73% had a family alcohol or other drug history. Of the total, 62% had been in a youth refuge at some time in the past 12 months. Twenty four per cent had been to hospital as a result of alcohol or other drug use and 45% had attempted suicide. Female sex and an interaction between sexual abuse and binge drinking predicted suicide attempts. This study points to the need for a comprehensive approach to interventions for troubled youth which gives greater recognition to mental health issues related to family circumstances, including abuse.

  11. Binge drinking during adolescence and young adulthood is associated with deficits in verbal episodic memory

    Science.gov (United States)

    Cadaveira, Fernando; Caamaño-Isorna, Francisco; Rodríguez-Holguín, Socorro

    2017-01-01

    Binge drinking (BD), a harmful pattern of alcohol consumption, is common during adolescence. Young adults with alcohol use disorders exhibit hippocampal alterations and episodic memory deficits. However, it is not known how these difficulties progress in community BD adolescents. Our objective was to analyze the relationship between BD trajectory and verbal episodic memory during the developmental period spanning from adolescence and to early adulthood. An initial sample of 155 male and female first-year university students with no other risk factors were followed over six years. Participants were classified as stable non-BDs, stable BDs and ex-BDs according to the third AUDIT item. At baseline, participants comprised 36 ♂/ 40 ♀ non-BDs (18.58 years), 40 ♂/ 39 ♀ BDs (18.87 years), and at the third follow-up, they comprised 8 ♂/ 8 ♀ stable non-BDs (25.49 years), 2 ♂/ 2 ♀ stable BDs (25.40) and 8 ♂/ 12 ♀ ex-BDs (24.97 years). Episodic memory was assessed four times with the Logical Memory subtest (WMS-III) and the Rey Auditory Verbal Learning Test (RAVLT). Generalized linear mixed models were applied. The results showed that, relative to non-BDs, stable BDs presented difficulties in immediate and delayed recall in the Logical Memory subtest. These difficulties remained stable over time. The short-term ex-BDs continued to display difficulties in immediate and delayed recall in the Logical Memory subtest, but long-term ex-BDs did not. The effects were not influenced by age of alcohol onset, frequency of cannabis use, tobacco use or psychopathological distress. In conclusion, BD during adolescence and young adulthood is associated with episodic memory deficits. Abandoning the BD pattern may lead to partial recovery. These findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol. PMID:28152062

  12. Binge drinking during adolescence and young adulthood is associated with deficits in verbal episodic memory.

    Science.gov (United States)

    Carbia, Carina; Cadaveira, Fernando; Caamaño-Isorna, Francisco; Rodríguez-Holguín, Socorro; Corral, Montse

    2017-01-01

    Binge drinking (BD), a harmful pattern of alcohol consumption, is common during adolescence. Young adults with alcohol use disorders exhibit hippocampal alterations and episodic memory deficits. However, it is not known how these difficulties progress in community BD adolescents. Our objective was to analyze the relationship between BD trajectory and verbal episodic memory during the developmental period spanning from adolescence and to early adulthood. An initial sample of 155 male and female first-year university students with no other risk factors were followed over six years. Participants were classified as stable non-BDs, stable BDs and ex-BDs according to the third AUDIT item. At baseline, participants comprised 36 ♂/ 40 ♀ non-BDs (18.58 years), 40 ♂/ 39 ♀ BDs (18.87 years), and at the third follow-up, they comprised 8 ♂/ 8 ♀ stable non-BDs (25.49 years), 2 ♂/ 2 ♀ stable BDs (25.40) and 8 ♂/ 12 ♀ ex-BDs (24.97 years). Episodic memory was assessed four times with the Logical Memory subtest (WMS-III) and the Rey Auditory Verbal Learning Test (RAVLT). Generalized linear mixed models were applied. The results showed that, relative to non-BDs, stable BDs presented difficulties in immediate and delayed recall in the Logical Memory subtest. These difficulties remained stable over time. The short-term ex-BDs continued to display difficulties in immediate and delayed recall in the Logical Memory subtest, but long-term ex-BDs did not. The effects were not influenced by age of alcohol onset, frequency of cannabis use, tobacco use or psychopathological distress. In conclusion, BD during adolescence and young adulthood is associated with episodic memory deficits. Abandoning the BD pattern may lead to partial recovery. These findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol.

  13. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on behaviour in 5-year-old children: a prospective cohort study on 1628 children

    DEFF Research Database (Denmark)

    Skogerbø, Åshild; Kesmodel, Ulrik Schiøler; Denny, Clark

    2013-01-01

    To examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on behaviour in children at the age of 5 years.......To examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on behaviour in children at the age of 5 years....

  14. Under the Influence: The Binge Drinking Epidemic on College Campuses. Hearing before the Committee on Governmental Affairs. United States Senate, One Hundred Seventh Congress, Second Session (May 15, 2002).

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Senate Committee on Governmental Affairs.

    A hearing was held to explore the problem of binge drinking on campus and to consider possible responses to this problem. Following an opening statement by Senator Joseph Lieberman, a panel of witness who have done research and work in the field gave testimony. These witnesses commented on the problem of binge drinking: (1) Raynard S. Kingston,…

  15. CDC Vital Signs: Binge Drinking a Serious, Under-Recognized Problem Among Women and Girls

    Science.gov (United States)

    ... community is affected by alcohol’s price and availability. Underage drinking is affected by exposure to alcohol marketing. Underage drinking is also influenced by adult drinking, and youth ...

  16. Short-Term Prospective Effects of Impulsivity on Binge Drinking: Mediation by Positive and Negative Drinking Consequences

    Science.gov (United States)

    Park, Aesoon; Kim, Jueun; Gellis, Les A.; Zaso, Michelle J.; Maisto, Stephen A.

    2014-01-01

    Objective: Although the association of impulsivity with diverse alcohol outcomes has been documented, the mechanisms by which impulsivity predicts drinking over time remain to be fully characterized. The authors examined whether positive drinking consequences, but not negative drinking consequences, mediated the association between impulsivity and…

  17. Binge Drinking Associations with Patrons' Risk Behaviors and Alcohol Effects after Leaving a Nightclub: Sex Differences in the "Balada com Ciencia" Portal Survey Study in Brazil.

    Directory of Open Access Journals (Sweden)

    Zila M Sanchez

    Full Text Available The purpose of the present study was to investigate the potential associations of binge drinking detected at the exit of nightclubs and risk behaviors and alcohol effects just after leaving the venue in a representative sample of Brazilian nightclub patrons according to sex. For this purpose, a portal survey study called Balada com Ciência was conducted in 2013 in the megacity of São Paulo, Brazil, using a two-stage cluster sampling survey design. Individual-level data were collected in 2422 subjects at the entrance and 1822 subjects at the exit of 31 nightclubs, and breath alcohol concentration (BrAC was measured using a breathalyzer. The following day, 1222 patrons answered an online follow-up survey that included questions about risk behaviors and alcohol effects practiced just after leaving the nightclub. Weighted logistic regressions were used to analyze binge drinking associated with risk behaviors by sex. For both sexes, the most prevalent risk behaviors practiced after leaving a nightclub were drinking and driving (men=27.9%; women=20.4%, the use of illicit drugs (men=15.8%; women=9.4% and risky sexual behavior (men=11.4%; women=6.8%. The practice of binge drinking increased the behavior of illicit drug use after leaving the nightclub by 2.54 times [95% CI: 1.26-5.09] among men who drank and increased the risk of an episode of new alcohol use by 5.80 times [95% CI: 1.50-22.44] among women who drank. Alcoholic blackouts were more prevalent among men [OR=8.92; 95% CI: 3.83-20.80] and women [OR= 5.31; 95% CI: 1.68-16.84] whose BrAC was equivalent to binge drinking compared with patrons with a lower BrAC. Public policies aiming to reduce patrons' BrAC at the exit of nightclubs, such as staff training in responsible beverage service and legislation to prevent alcohol sales to drunk individuals, would be useful to protect patrons from the risk behaviors associated with binge drinking in nightclubs.

  18. Binge Drinking Associations with Patrons' Risk Behaviors and Alcohol Effects after Leaving a Nightclub: Sex Differences in the "Balada com Ciência" Portal Survey Study in Brazil.

    Science.gov (United States)

    Sanchez, Zila M; Ribeiro, Karen J; Wagner, Gabriela A

    2015-01-01

    The purpose of the present study was to investigate the potential associations of binge drinking detected at the exit of nightclubs and risk behaviors and alcohol effects just after leaving the venue in a representative sample of Brazilian nightclub patrons according to sex. For this purpose, a portal survey study called Balada com Ciência was conducted in 2013 in the megacity of São Paulo, Brazil, using a two-stage cluster sampling survey design. Individual-level data were collected in 2422 subjects at the entrance and 1822 subjects at the exit of 31 nightclubs, and breath alcohol concentration (BrAC) was measured using a breathalyzer. The following day, 1222 patrons answered an online follow-up survey that included questions about risk behaviors and alcohol effects practiced just after leaving the nightclub. Weighted logistic regressions were used to analyze binge drinking associated with risk behaviors by sex. For both sexes, the most prevalent risk behaviors practiced after leaving a nightclub were drinking and driving (men=27.9%; women=20.4%), the use of illicit drugs (men=15.8%; women=9.4%) and risky sexual behavior (men=11.4%; women=6.8%). The practice of binge drinking increased the behavior of illicit drug use after leaving the nightclub by 2.54 times [95% CI: 1.26-5.09] among men who drank and increased the risk of an episode of new alcohol use by 5.80 times [95% CI: 1.50-22.44] among women who drank. Alcoholic blackouts were more prevalent among men [OR=8.92; 95% CI: 3.83-20.80] and women [OR= 5.31; 95% CI: 1.68-16.84] whose BrAC was equivalent to binge drinking compared with patrons with a lower BrAC. Public policies aiming to reduce patrons' BrAC at the exit of nightclubs, such as staff training in responsible beverage service and legislation to prevent alcohol sales to drunk individuals, would be useful to protect patrons from the risk behaviors associated with binge drinking in nightclubs.

  19. An examination of pathways from childhood maltreatment to adolescent binge drinking.

    Science.gov (United States)

    Shin, Sunny Hyucksun; Hong, Hyokyoung Grace; Wills, Thomas A

    2012-01-01

    Considerable clinical and empirical evidence has accumulated over the past decades indicating that there is a strong association between childhood maltreatment and heavy episodic drinking in adolescence, but there is a paucity of empirically based knowledge about the processes linking the association. The aim of this paper is to examine mechanisms that might account for the association between childhood maltreatment and heavy episodic drinking in adolescence. Using a nationally representative sample of adolescents (ages ranging 12-21; N = 6,337), this study examined the role of individual self-regulatory processes in the associations, controlling for age, gender, race/ethnicity, peer substance use, parental alcoholism, and parent-child conflict. Factor analyses were used to test the measurement structure of self-regulatory processes. Findings confirmed the association between childhood maltreatment and heavy episodic drinking in adolescence. Structural modeling analyses indicated indirect effects for childhood maltreatment primarily through poor self-regulatory processes and peer substance use. Implications for future research are discussed.

  20. The Effects of Low to Moderate Alcohol Consumption and Binge Drinking in Early Pregnancy on Executive Function in Five-Year-Old Children

    DEFF Research Database (Denmark)

    Skogerbø, Åshild; Kesmodel, Ulrik Schiøler; Wimberley, Theresa

    2012-01-01

    from the Danish National Birth Cohort. Methods  Participants were sampled based on maternal alcohol drinking patterns during early pregnancy. When the children were 5 years old, the parent and teacher forms of the Behaviour Rating Inventory of Executive Function (BRIEF) were completed by the mothers......Please cite this paper as: SkogerbøÅ, Kesmodel U, Wimberley T, Støvring H, Bertrand J, Landrø N, Mortensen E. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on executive function in 5-year-old children. BJOG 2012;119:1201-1210. Objective  To examine...... the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on children's executive functions at the age of 5 years. Design  Follow-up study. Setting  Neuropsychological testing in four Danish cities 2003-2008. Population  A cohort of 1628 women and their children sampled...

  1. Adolescent binge drinking increases expression of the danger signal receptor agonist HMGB1 and Toll-like receptors in the adult prefrontal cortex.

    Science.gov (United States)

    Vetreno, R P; Crews, F T

    2012-12-13

    Adolescence is a critical developmental stage of life during which the prefrontal cortex (PFC) matures, and binge drinking and alcohol abuse are common. Recent studies have found that ethanol increases neuroinflammation via upregulated high-mobility group box 1 (HMGB1) signaling through Toll-like receptors (TLRs). HMGB1/TLR 'danger signaling' induces multiple brain innate immune genes that could alter brain function. To determine whether adolescent binge drinking persistently increases innate immune gene expression in the PFC, rats (P25-P55) were exposed to adolescent intermittent ethanol (AIE [5.0 g/kg, 2-day on/2-day off schedule]). On P56, HMGB1/TLR danger signaling was assessed using immunohistochemistry (i.e., +immunoreactivity [+IR]). In a separate group of subjects, spatial and reversal learning on the Barnes maze was assessed in early adulthood (P64-P75), and HMGB1/TLR danger signaling was measured using immunohistochemistry for +IR and RT-PCR for mRNA in adulthood (P80). Immunohistochemical assessment at P56 and 24 days later at P80 revealed increased frontal cortical HMGB1, TLR4, and TLR3 in the AIE-treated rats. Adolescent intermittent ethanol treatment did not alter adult spatial learning on the Barnes maze, but did cause reversal learning deficits and increased perseverative behavior. Barnes maze deficits correlated with the expression of danger signal receptors in the PFC. Taken together, these findings provide evidence that adolescent binge drinking leads to persistent upregulation of innate immune danger signaling in the adult PFC that correlates with adult neurocognitive dysfunction.

  2. The Effects of Low to Moderate Alcohol Consumption and Binge Drinking in Early Pregnancy on Selective and Sustained Attention in Five-Year-Old Children

    DEFF Research Database (Denmark)

    Underbjerg, Mette; Kesmodel, Ulrik Schiøler; Landrø, Nils Inge

    2012-01-01

    Please cite this paper as: Underbjerg M, Kesmodel U, Landrø N, Bakketeig L, Grove J, Wimberley T, Kilburn T, Svaerke C, Thorsen P, Mortensen E. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on selective and sustained attention in 5-year-old children. BJOG...... consumption, age, body mass index (BMI), parity, home environment, postnatal smoking in the home, child's health status, and indicators for hearing and vision impairments. Main outcome measures  TEACh-5 attention scores. Results  There were no significant effects on test performance in children of mothers...

  3. Is Binge Drinking Prevalent in Greece after the Emergence of the Economic Crisis? Assessment of This Idea Using the Theory of Planned Behavior

    Directory of Open Access Journals (Sweden)

    George Vlontzos

    2017-01-01

    Full Text Available This paper aims to evaluate the impact of the ongoing economic crisis in Greece on alcohol consumption and binge drinking. For this reason, the Theory of Planned Behavior is being applied by using a sample of nearly 900 questionnaires. The questionnaire consists of parts trying to identify the attitude of the interviewees towards alcohol, their subjective norms of social environment, and the perceived behavioral control. This research has been implemented on a national level. The most important finding is the considerable difference in alcohol consumption compared with other countries faced similar negative economic situations. Drinking is considered as a source of pleasure and socializing. The participants’ perception is that family environment and friends are not considering drinking as a non-desirable way of entertainment. As one of the major results of the survey, drinking was found to not be driven by a necessity to overcome problems related to it, which is the main difference with previous studies in others countries, like Argentina, Russia, USA, etc.

  4. Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking.

    Science.gov (United States)

    McClintick, Jeanette N; McBride, William J; Bell, Richard L; Ding, Zheng-Ming; Liu, Yunlong; Xuei, Xiaoling; Edenberg, Howard J

    2015-02-01

    Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5-3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system.

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

    Science.gov (United States)

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

    2015-11-01

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

  6. Future-oriented emotions in the prediction of binge-drinking intention and expectation: the role of anticipated and anticipatory emotions.

    Science.gov (United States)

    Carrera, Pilar; Caballero, Amparo; Muñoz, Dolores

    2012-06-01

    The Theory of Planned Behavior (TPB) offers a parsimonious explanation of purposive behavior, but in the study of healthy and risk behaviors its sufficiency may be questioned. Working with binge-drinking, a very common risk behavior in Spanish undergraduate students, we used two strategies for improving predictions from TPB: using behavioral intention (BI) and behavioral expectation (BE) as proximal antecedents of behaviors and adding as new predictors two future-oriented emotions (anticipated and anticipatory). Hierarchical regression analyses show that while anticipated emotions improved TPB explanations of BI, anticipatory emotions improved the explanations of BE. The present results show the influence of future emotions in the prediction of behavioral intention and behavioral expectation.

  7. Binge Drinking of Ethanol during Adolescence Induces Oxidative Damage and Morphological Changes in Salivary Glands of Female Rats

    Science.gov (United States)

    Fagundes, Nathalia Carolina Fernandes; Fernandes, Luanna Melo Pereira; Paraense, Ricardo Sousa de Oliveira; Teixeira, Francisco Bruno; Alves-Junior, Sergio Melo; Pinheiro, João de Jesus Viana; Crespo-López, Maria Elena

    2016-01-01

    This study investigates morphological and biochemistry effects of binge ethanol consumption in parotid (PG) and submandibular (SG) salivary glands of rats from adolescence to adulthood. Female Wistar rats (n = 26) received ethanol at 3 g/kg/day (20% w/v) for 3 consecutive days/week from the 35th until the 62nd day of life. Animals were treated in two periods: 1 week (G1) and 4 weeks (G2), with a control (treated with distilled water) and an ethanol group to each period. In morphological analysis, morphometric and immunohistochemistry evaluation for smooth muscle actin (αSMA), cytokeratin-18 (CK-18), and vimentin (VIM) were made. Biochemical changes were analyzed by concentration of nitrites and levels of malondialdehyde (MDA). The difference between groups in each analysis was evaluated by Mann-Whitney U test or Student's t-test (p ≤ 0.05). PG showed, at one week of ethanol exposure, lower CK-18 and α-SMA expression, as well as MDA levels. After four weeks, lower CK-18 and higher MDA levels were observed in PG exposed to ethanol, in comparison to control group. SG showed lower α-SMA expression after 1 and 4 weeks of ethanol exposure as well as higher MDA levels after 1 week. Ethanol binge consumption during adolescence promotes tissue and biochemical changes with only one-week binge in acinar and myoepithelial PG cells. PMID:27579155

  8. Neuropeptide Y (NPY) in the central nucleus of the amygdala (CeA) does not affect ethanol-reinforced responding in binge-drinking, nondependent rats.

    Science.gov (United States)

    Henderson, Angela N; Czachowski, Cristine L

    2012-03-01

    The central nucleus of the amygdala (CeA) has been implicated as having a significant role in mediating alcohol-drinking behavior. Neuropeptide Y (NPY) has been investigated as a potential pharmacotherapeutic due to its ability to attenuate ethanol intake, particularly when administered into the CeA. Previous research suggests, though the evidence is somewhat conflicting, that the efficacy of NPY is contingent upon genetic background and/or prior history of ethanol dependence in rats. However, studies looking at the effects of NPY in nonselected animals lacking a history of ethanol dependence have two factors that could impact the interpretation of the results: ethanol history/selection AND relatively low baseline ethanol intakes as compared to ethanol-dependent and/or genetically selected controls. The purpose of the present study was to generate higher baseline ethanol intakes upon which to examine the effects of NPY on ethanol and sucrose drinking in nonselected rats using a binge drinking model. Long Evans rats were trained to complete a single response requirement resulting in access to either 2% sucrose (Sucrose Group) or 2% sucrose/10% ethanol (Ethanol Group) for a 20-min drinking session. On treatment days, rats were bilaterally microinjected into the CeA with aCSF or one of three doses of NPY (0.25μg, 0.50μg, or 1.00μg/.5μL). Subjects in the Ethanol Group were consuming an average of 1.2g/kg of ethanol (yielding BELs of ~90mg%) during the 20min access period following aCSF treatments. The results revealed that NPY had no effect on either sucrose or ethanol consumption or on appetitive responding (latency to respond). Overall, the findings indicate that even a history of binge-like ethanol consumption is not sufficient to recruit CeA NPY activity, and are consistent with previous studies showing that the role of NPY in regulating ethanol reinforcement in the CeA may be contingent upon a prior history of ethanol dependence.

  9. Binge Eating Disorder

    Science.gov (United States)

    ... Our ePublications > Binge eating disorder fact sheet ePublications Binge eating disorder fact sheet Print this fact sheet Binge eating disorder fact sheet (PDF, 211 KB) Related information Anorexia ...

  10. Ethanol inhibits LPS-induced signaling and modulates cytokine production in peritoneal macrophages in vivo in a model for binge drinking

    Directory of Open Access Journals (Sweden)

    Pruett Stephen B

    2009-09-01

    Full Text Available Abstract Background Previous reports indicate that ethanol, in a binge drinking model in mice, inhibits the production of pro-inflammatory cytokines in vivo. However, the inhibition of signaling through TLR4 has not been investigated in this experimental model in vivo. Considering evidence that signaling can be very different in vitro and in vivo, the present study was conducted to determine if effects of ethanol on TLR4 signaling reported for cells in culture or cells removed from ethanol treated mice and stimulated in culture also occur when ethanol treatment and TLR4 activation occur in vivo. Results Phosphorylated p38, ERK, and c-Jun (nuclear were quantified with kits or by western blot using samples taken 15, 30, and 60 min after stimulation of peritoneal macrophages with lipopolysaccharide in vivo. Effects of ethanol were assessed by administering ethanol by gavage at 6 g/kg 30 min before administration of lipopolysaccharide (LPS. Cytokine concentrations in the samples of peritoneal lavage fluid and in serum were determined at 1, 2, and 6 hr after lipopolysaccharide administration. All of these data were used to measure the area under the concentration vs time curve, which provided an indication of the overall effects of ethanol in this system. Ethanol suppressed production of most pro-inflammatory cytokines to a similar degree as it inhibited key TLR4 signaling events. However, NF-κB (p65 translocation to the nucleus was not inhibited by ethanol. To determine if NF-κB composed of other subunits was inhibited, transgenic mice with a luciferase reporter were used. This revealed a reproducible inhibition of NF-κB activity, which is consistent with the observed inhibition of cytokines whose expression is known to be NF-κB dependent. Conclusion Overall, the effects of ethanol on signalling in vivo were similar to those reported for in vitro exposure to ethanol and/or lipopolysaccharide. However, inhibition of the activation of NF-κB was

  11. Biomarkers of Alcohol Binge - drinking Induced Brain Damage in Mice%急性暴饮性饮酒对小鼠脑损伤生物标志物的影响

    Institute of Scientific and Technical Information of China (English)

    赵美清; 冯利东

    2012-01-01

    Objective To study oxyradical - related biomarkers for binge - drinking inducing alcohol - induced brain damage in mice. Methods A binge drinking model was created with a single dose of alcohol that was administered by gavage to mice. Blood alcohol levels were monitored and the brain biopsy Was performed for the pathological examination, and compared with the normal control group. The activity of SOD and the level of MDA in the mice brain were measured between the two groups of animals. Results There was no observable microscopic change in the brain after a single dose of alcohol exposure. However, the activity of SOD in the mice brain decreased and the level of MDA increased dramatically (P<0. 01). Conclusion A single dose of alcohol binge - drinking can cause oxyradical-related biomarkers change in brain which expressed as increased oxygen radicals and decreased degradation enzymes of peroxides, resulting in brain damage.%目的 研究急性暴饮性饮酒对小鼠脑组织中氧自由基相关生物学标志物的影响.方法 首先建立急性暴饮性饮酒的小鼠动物模型,检测其血液中乙醇的浓度,进行大脑病理解剖学检查,并与正常对照组比较;然后测定该动物模型以及正常动物脑组织中超氧化物歧化酶(SOD)的活性以及丙二醛(MDA)的含量水平.结果 在单次乙醇胃灌注小鼠大脑并没有观察到明显的显微镜下病理学变化,然而单次乙醇胃灌注可以使小鼠脑组织中SOD的活力显著降低(P<0.01);而使MDA含量水平显著升高(P<0.01).结论 一次性大量饮酒可以导致小鼠大脑氧自由基相关生物学标志物水平的变化,表现为降低降解自由基酶的活力和升高氧自由基的水平,从而可能造成脑损伤.

  12. Exercise enhances hippocampal recovery following binge ethanol exposure.

    Directory of Open Access Journals (Sweden)

    Mark E Maynard

    Full Text Available Binge drinking damages the brain, and although a significant amount of recovery occurs with abstinence, there is a need for effective strategies to maximize neurorestoration. In contrast to binge drinking, exercise promotes brain health, so the present study assessed whether it could counteract ethanol-induced damage by augmenting natural self-repair processes following one or more binge exposures. Adult female rats were exposed to 0 (control, 1 or 2 binges, using an established 4-day model of binge-induced neurodegeneration. Half of the animals in each group remained sedentary, or had running wheel access beginning 7 days after the final binge, and were sacrificed 28 days later. To assess binge-induced hippocampal damage and exercise restoration, we quantified volume of the dentate gyrus and number of granule neurons. We found that a single binge exposure significantly decreased the volume of the dentate gyrus and number of granule neurons. A second binge did not exacerbate the damage. Exercise completely restored baseline volume and granule neuron numbers. To investigate a potential mechanism of this restoration, we administered IdU (a thymidine analog in order to label cells generated after the first binge. Previous studies have shown that neurogenesis in the dentate gyrus is decreased by binge alcohol exposure, and that the hippocampus responds to this insult by increasing cell genesis during abstinence. We found increased IdU labeling in binge-exposed animals, and a further increase in binged animals that exercised. Our results indicate that exercise reverses long-lasting hippocampal damage by augmenting natural self-repair processes.

  13. Binge Eating Disorder

    Science.gov (United States)

    ... Events Upcoming and past meetings Follow Us Social media, RSS feeds, and more Follow Us ... and Facts for Binge Eating Disorder Symptoms and Causes of Binge Eating Disorder Diagnosis and Treatment of ...

  14. Alcohol drinking pattern during pregnancy and risk of infant mortality

    DEFF Research Database (Denmark)

    Strandberg-Larsen, Katrine; Grønboek, Morten; Andersen, Anne-Marie Nybo;

    2009-01-01

    The safety of small amounts of alcohol drinking and occasional binge-level drinking during pregnancy remains unsettled. We examined the association of maternal average alcohol intake and binge drinking (>or=5 drinks per sitting) with infant mortality, both in the neonatal and postneonatal period....

  15. A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males

    Science.gov (United States)

    Stacey, David; Lourdusamy, Anbarasu; Ruggeri, Barbara; Maroteaux, Matthieu; Jia, Tianye; Cattrell, Anna; Nymberg, Charlotte; Banaschewski, Tobias; Bhattacharyya, Sohinee; Band, Hamid; Barker, Gareth; Bokde, Arun; Buchel, Christian; Carvalho, Fabiana; Conrod, Patricia; Desrivieres, Sylvane; Easton, Alanna; Fauth-Buehler, Mira; Fernandez-Medarde, Alberto; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavanh, Hugh; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Rotter, Andrea; Santos, Eugenio; Smolka, Michael; Sommer, Wolfgang; Mameli, Manuel; Spanagel, Rainer; Girault, Jean-Antoine; Mueller, Christian; Schumann, Gunter

    2016-01-01

    Background The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2−/− mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning. Methods Transcriptomic data from the nucleus accumbens (NAcc) of male Rasgrf2−/− mice and wild-type controls were analyzed by weighted gene coexpression network analysis (WGCNA). We performed follow-up genetic association tests in humans using a sample of male adolescents from the IMAGEN study characterized for binge drinking (n = 905) and ventral striatal activation during an fMRI reward task (n = 608). Results The WGCNA analyses using accumbal transcriptomic data revealed 37 distinct “modules,” or functionally related groups of genes. Two of these modules were significantly associated with Rasgrf2 knockout status: M5 (p < 0.001) and M6 (p < 0.001). In follow-up translational analyses we found that human orthologues for the M5 module were significantly (p < 0.01) enriched with genetic association signals for binge drinking in male adolescents. Furthermore, the most significant locus, originating from the EH-domain containing 4 (EHD4) gene (p < 0.001), was also significantly associated with altered ventral striatal activity in male adolescents performing an fMRI reward task (pempirical < 0.001). Limitations It was not possible to determine the extent to which the M5 module was dysregulated in Rasgrf2−/− mice by perturbed mesolimbic

  16. Co-Occurring Physical Fighting and Suicide Attempts among U.S. High School Students: Examining Patterns of Early Alcohol Use Initiation and Current Binge Drinking

    Directory of Open Access Journals (Sweden)

    Monica H Swahn

    2013-08-01

    Full Text Available Introduction: A growing body of empirical research documents a significant co-occurrence of suicide attempts and interpersonal violence among youth. However, the potential role of early alcohol use initiation and current heavy alcohol use as correlates of this comorbidity has not been examined in a nationally representative sample of high school students.Methods: We based our analyses on cross-sectional data from the 2009 Youth Risk Behavior Survey, which includes a nationally representative sample (n=16,410 of high school students in grades 9 through 12 in the United States. Multinomial logistic regression analyses were conducted to test the associations between measures of alcohol use (early alcohol use initiation and heavy drinking and comorbid suicidal and violent behavior while controlling for potential confounders.Results: Among high school students, 3.6% reported comorbid physical fighting and suicide attempt in the past year. Early alcohol use (prior to age 13 and heavy drinking (5 or more drinks in a row were strongly associated with comorbid reports of physical fighting and suicide attempts (Adj. odds ratio [OR]=3.12; 95% confidence interval [CI]:2.49-3.89 and (Adj. OR=3.45; 95%CI:2.63-4.52.Conclusion: These findings underscore the importance of both early alcohol use initiation and heavy drinking as statistically significant correlates of comorbid fighting and suicide attempts among youth. While future research is needed to determine the temporal ordering between problem drinking and violent or suicidal behaviors, existing prevention programs may benefit from including components aimed at reducing and delaying alcohol use. [West J Emerg Med. 2013;14(4:341–346.

  17. Binge Eating Disorder

    Directory of Open Access Journals (Sweden)

    Senol Turan

    2015-12-01

    Full Text Available Binge Eating Disorder, characterized by frequent and persistent overeating episodes that are accompanied by feeling of loss of control over eating without regular compensatory behaviors and was identified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as a new eating disorder category. Binge Eating Disorder is the most common eating disorder among adults. Binge Eating Disorder is associated with significant morbidity, including medical complications related to obesity, eating disorder psychopathology, psychiatric comorbidity; reduced quality of life, and impaired social functioning. Current treatments of Binge Eating Disorder include pharmacotherapy, psychotherapy and bariatric surgery. In this review, the definition, epidemiology, etiology, clinical features, and also mainly treatment of Binge Eating Disorder are discussed.

  18. Driven to Drink

    Institute of Scientific and Technical Information of China (English)

    FRANCISCO; LITTLE

    2006-01-01

    Where I come from drinking is a way of life. Around the braai (barbeque) watching sport, at the pool in fact any occasion is a good enough excuse to down a few frosties and have a rip. Often, drinking back home does not include any food, apart from the odd peanuts or crisps. It develops from youth into the rowdy binges

  19. Quit Binging (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-01-15

    Too many people are overindulging in alcohol and putting themselves at risk for death from alcohol poisoning. In this podcast, Dr. Dafna Kanny discusses the dangers of binge drinking, including alcohol poisoning death.  Created: 1/15/2015 by MMWR.   Date Released: 1/15/2015.

  20. Learning Bing maps API

    CERN Document Server

    Sinani, Artan

    2013-01-01

    This is a practical, hands-on guide with illustrative examples, which will help you explore the vast universe of Bing maps.If you are a developer who wants to learn how to exploit the numerous features of Bing Maps then this book is ideal for you. It can also be useful for more experienced developers who wish to explore other areas of the APIs. It is assumed that you have some knowledge of JavaScript, HTML, and CSS. For some chapters a working knowledge of .Net and Visual Studio is also needed.

  1. Comparing the AUDIT and 3 Drinking Indices as Predictors of Personal and Social Drinking Problems in Freshman First Offenders

    Science.gov (United States)

    O'Hare, Thomas

    2005-01-01

    The current study of 376 college freshman adjudicated the first time for breaking university drinking rules tested the predictive power of four alcohol consumption and problem drinking indices--recent changes in drinking (the Alcohol Change Index: ACI), heavy drinking, binge drinking index, and the Alcohol Use Disorders Identification Test (AUDIT)…

  2. Binge eating disorder

    DEFF Research Database (Denmark)

    Schousboe, Birgitte Hartvig; Waaddegaard, Mette

    2011-01-01

    Binge eating disorder kaldes også bulimi uden opkastning eller den tredje spiseforstyrrelse. Det er en udbredt, men mindre kendt spiseforstyrrelse end anoreksi og bulimi. Patienterne er ofte overvægtige og har ikke kompenserende adfærd over for overspisningen i form af opkastning eller brug af...

  3. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

    Science.gov (United States)

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas.

  4. Alcohol binge drinking during pregnancy and cryptorchidism

    DEFF Research Database (Denmark)

    Strandberg-Larsen, Katrine; Jensen, Morten Søndergaard; Ramlau-Hansen, Cecilia Høst;

    2009-01-01

    Recent studies have suggested gestational weeks 8-14 as a time window of particular importance to the intrauterine development of the male genitalia, and prenatal exposure to alcohol is under suspicion as a risk factor for cryptorchidism. We examined if prenatal exposure to alcohol, and especially...

  5. Underage College Students' Drinking Behavior, Access to Alcohol, and the Influence of Deterrence Policies: Findings from the Harvard School of Public Health College Alcohol Study.

    Science.gov (United States)

    Wechsler, Henry; Lee, Jae Eun; Nelson, Toben F.; Kuo, Meichun

    2002-01-01

    Used data from college alcohol surveys conducted between 1993-01 to compare underage students' and older students' drinking behaviors, access to alcohol, and exposure to prevention. While underage drinking rates decreased, binge drinking rates remained constant. Underage students' frequent binge drinking and related problems increased. College…

  6. Functional and structural brain connectivity of young binge drinkers: a follow-up study

    Science.gov (United States)

    Correas, A.; Cuesta, P.; López-Caneda, E.; Rodríguez Holguín, S.; García-Moreno, L. M.; Pineda-Pardo, J. A.; Cadaveira, F.; Maestú, F.

    2016-01-01

    Adolescence is a period of ongoing brain maturation characterized by hierarchical changes in the functional and structural networks. For this reason, the young brain is particularly vulnerable to the toxic effects of alcohol. Nowadays, binge drinking is a pattern of alcohol consumption increasingly prevalent among adolescents. The aim of the present study is to evaluate the evolution of the functional and anatomical connectivity of the Default Mode Network (DMN) in young binge drinkers along two years. Magnetoencephalography signal during eyes closed resting state as well as Diffusion Tensor Imaging (DTI) were acquired twice within a 2-year interval from 39 undergraduate students (22 controls, 17 binge drinkers) with neither personal nor family history of alcoholism. The group comparison showed that, after maintaining a binge drinking pattern along at least two years, binge drinkers displayed an increased brain connectivity of the DMN in comparison with the control group. On the other hand, the structural connectivity did not show significant differences neither between groups nor over the time. These findings point out that a continued pattern of binge drinking leads to functional alterations in the normal brain maturation process, even before anatomical changes can be detected. PMID:27506835

  7. Bing and Neel Syndrome

    Directory of Open Access Journals (Sweden)

    S. Jennane

    2012-01-01

    Full Text Available Introduction. We report the case of a Bing and Neel syndrome revealed by an isolated left ptosis. Case Report. a 57-year-old man was followed up since October 2003 for a typical Waldenström’s macroglobulinemia. A first complete remission was obtained with chlorambucil. In August 2004, he relapsed. A second complete remission was obtained with RFC chemotherapy regimen (rituximab, fludarabine, and cyclophosphamide. In October 2009, the patient presented with an isolated left ptosis revealing a Bing and Neel syndrome. The diagnosis was suspected on MRI and confirmed by the detection in the CSF of a monoclonal IgM similar to the one found in the plasma. A quite good partial remission has been obtained after one course of RDHAP (rituximab, dexamethasone, cytarabine, and cisplatin and 3 courses of RDHOx (rituximab, dexamethasone, cytarabine, and oxaliplatin, in addition to ten intrahectal chemotherapy injections. The treatment was followed by intensification and autologous stem cell transplantation. At D58, the patient died due to a septic shock. Conclusion. BNS is a rare and potentially treatable complication of WM. It should be considered in patients with neurologic symptoms and a history of WM.

  8. Nutraceutical up-regulation of serotonin paradoxically induces compulsive behavior

    Science.gov (United States)

    The role of diet in either the etiology or treatment of complex mental disorder is highly controversial in psychiatry. However, physiological mechanisms by which diet can influence brain chemistry – particularly that of serotonin – are well established. Here we show that dietary up-regulation of br...

  9. Drinking pattern and blood pressure.

    Science.gov (United States)

    Seppä, K; Laippala, P; Sillanaukee, P

    1994-03-01

    Large amounts of alcohol are known to increase blood pressure. There is little evidence about the effect of binge drinking of alcohol on blood pressure, although this is the dominant style of alcohol drinking in several countries. The purpose of the present study was to examine the relationship between binge drinking and blood pressure using daily heavy drinkers as a reference group. We examined 260 consecutive nonalcoholic 40- and 45-year-old men participating in a health screening. There were 37 teetotalers, 147 social drinkers, 62 weekend heavy drinkers attending the health screening 2 to 7 days after binge drinking, and 14 men who drank heavily every day. Group division was made using self-reported alcohol consumption and a structured alcohol questionnaire. Blood pressure was measured manually by a mercury manometer. BMDP statistical software was used in the statistical analysis of the material. The diastolic blood pressure of weekend heavy drinkers (mean intake during the weekend, 289 g) did not differ from that found in teetotalers but systolic blood pressure was slightly higher (5 mm Hg, P = .04). In contrast, daily heavy drinkers (mean intake during the weekend [Friday to Saturday], 151 g) had significantly higher systolic (8 mm Hg, P = .04) and diastolic (6 mm Hg, P = .05) blood pressure values than teetotalers. We conclude that different drinking habits seem to have different effects on blood pressure, those of daily heavy drinking being more prominent than those of weekend heavy drinking.

  10. A mouse model for binge-level methamphetamine use

    Directory of Open Access Journals (Sweden)

    Shkelzen Shabani

    2016-11-01

    Full Text Available Binge/crash cycles of methamphetamine (MA use are frequently reported by individuals suffering from MA use disorders. An MA binge is self-reported as multiple daily doses that commonly accumulate to 800 mg/day (~10 mg/kg/day for a 170 pound human. A genetic animal model with a similar vulnerability to binge-level MA intake is missing. We used selectively bred MA high drinking (MAHDR and low drinking (MALDR mouse lines to determine whether several procedural variations would result in binge-level MA intake. Data were also collected in two progenitor populations of the MA drinking lines, the DBA/2J (D2 strain and the F2 cross of the D2 and C57BL/6J strains. The impact of 3 factors was examined: (1 concentration of MA in the two-bottle choice procedure used for selective breeding; (2 ratio of bottles containing MA vs. water, and (3 length of the withdrawal (or abstinence period between MA drinking sessions. When MA concentration was progressively increased every 4 days in 20 mg/l amounts from 20 to 140 mg/l, maximum intake in MALDR mice was 1.1 mg/kg, whereas MAHDR mice consumed as much as 14.6 mg/kg. When these concentrations were tested in a multiple bottle choice procedure, the highest ratio of MA to water bottles (3:1 was associated with escalated MA intake of up to 29.1 mg/kg in MAHDR mice and 12.0 mg/kg in F2 mice; MALDR mice did not show a ratio-dependent escalation in MA intake. Finally, MAHDR and D2 mice were offered 3 bottles of MA vs. water at increasing concentrations from 20 to 80 mg/l, and tested under an intermittent 6-h withdrawal period, which was lengthened to 30 hours (D2 mice or to 30 or 78 hours (MAHDR. D2 and MAHDR mice initially consumed similar amounts of 14-16 mg/kg MA, but D2 mice reduced their MA intake 3-fold after introduction of 30-h abstinence periods, whereas MAHDR mice retained their high level of intake regardless of withdrawal period. MAHDR mice provide a genetic model of binge-level MA intake appropriate for the

  11. Investigating the Reinforcing Value of Binge Anticipation

    Science.gov (United States)

    Pearson, Carolyn M.; Chester, David S.; Powell, David; Wonderlich, Stephen A.; Smith, Gregory T.

    2017-01-01

    Binge eating is a hallmark feature of several types of eating disorders, including bulimia nervosa, anorexia nervosa (binge/purge type), and binge-eating disorder, and is associated with numerous harmful consequences. For decades, researchers have sought to understand what maintains and reinforces this behavior in the face of such profound negative consequences. In this context, researchers have focused on the binge-eating behavior itself, and given little consideration to what may be a crucial part of the process: anticipating or planning binge-eating episodes. In this article, we discuss binge anticipation, its potential reinforcing value, and methodologies which would allow researchers to investigate this potentially critical process in individuals who binge eat. PMID:27184737

  12. Recovery from Binge Eating Disorder

    Science.gov (United States)

    Krentz, Adrienne; Chew, Judy; Arthur, Nancy

    2005-01-01

    The purpose of this study was to characterize the psychological processes of recovery from binge eating disorder (BED). A model was developed by asking the research question, "What is the experience of recovery for women with BED?" Unstructured interviews were conducted with six women who met the DSM-IV criteria for BED, and who were recovered…

  13. Inflammation-related genes up-regulated in schizophrenia brains

    Directory of Open Access Journals (Sweden)

    Kreuger Johan

    2007-09-01

    Full Text Available Abstract Background Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment. Methods We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received. Results Using global and high-resolution mRNA quantification techniques, we show that genes involved in immune response (GO:0006955 are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia (p-values from qPCR ≤ 0.01. These four genes were co-expressed in both schizophrenic subjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-α, IFN-α and IFN-γ. Conclusion Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia.

  14. Drinking Patterns and Behavioral Consequences: A Cross-Sectional Study Among Romanian University Students

    Directory of Open Access Journals (Sweden)

    Adriana Nasui Bogdana

    2016-03-01

    Full Text Available Alcohol/binge drinking among university students has become a major public health problem. Many of young students will be exposed to substantial changes in living arrangements, socialization groups and social activities during the transitional period.

  15. Integrating Underage Drinking and Drug Use Prevention

    Science.gov (United States)

    Wolfsberg, Jeffrey S.

    2006-01-01

    During the year 2004, 20% of eighth-graders and 60.3% of twelfth-graders reported that they had gotten drunk at least once over the course of just one year, according to the National Institute of Drug Abuse (NIDA). Of the 10.7 million underage youth who drink, 7.2 million or 31% of all high school students binge drink with a frequency of at least…

  16. Binge Eating Disorder and Youth.

    Science.gov (United States)

    Lipsky, Rachele K; McGuinness, Teena M

    2015-08-01

    Children and adolescents who eat unusually large amounts of food, feel guilty about it, and try to hide their overeating may be struggling with binge eating disorder (BED), a condition associated with suicidal ideation and other eating disorders. Although BED is new to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, the syndrome is becoming increasingly recognized. The study of BED in children and adolescents is in its natal phase, but the importance of recognition and possible treatment strategies are discussed in the current article along with psychiatric nursing implications.

  17. Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.

    Directory of Open Access Journals (Sweden)

    Ryan P Vetreno

    Full Text Available During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55 treatment led to persistent, global reductions of choline acetyltransferase (ChAT expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70 produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28-P48 and adult (P70-P90 binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity.

  18. Cannabinoid CB1 receptor inhibition blunts adolescent-typical increased binge alcohol and sucrose consumption in male C57BL/6J mice.

    Science.gov (United States)

    Agoglia, Abigail E; Holstein, Sarah E; Eastman, Vallari R; Hodge, Clyde W

    2016-04-01

    Increased binge alcohol consumption has been reported among adolescents as compared to adults in both humans and rodent models, and has been associated with serious long-term health consequences. However, the neurochemical mechanism for age differences in binge drinking between adolescents and adults has not been established. The present study was designed to evaluate the mechanistic role of the cannabinoid CB1 receptor in adolescent and adult binge drinking. Binge consumption was established in adolescent and adult male C57BL/6J mice by providing access to 20% alcohol or 1% sucrose for 4h every other day. Pretreatment with the CB1 antagonist/inverse agonist AM-251 (0, 1, 3, and 10mg/kg) in a Latin square design dose-dependently reduced adolescent alcohol consumption to adult levels without altering adult intake. AM-251 (3mg/kg) also reduced adolescent but not adult sucrose consumption. Adolescent reductions in alcohol and sucrose were not associated with alterations in open-field locomotor activity or thigmotaxis. These findings point to age differences in CB1 receptor activity as a functional mediator of adolescent-typical increased binge drinking as compared to adults. Developmental alterations in endocannabinoid signaling in the adolescent brain may therefore be responsible for the drinking phenotype seen in this age group.

  19. Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

    Science.gov (United States)

    Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa

    2015-01-01

    Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

  20. Treatment of binge eating disorder.

    Science.gov (United States)

    Wilson, G Terence

    2011-12-01

    The two specialty psychological therapies of CBT and IPT remain the treatments of choice for the full range of BED patients, particularly those with high levels of specific eating disorder psychopathology such as overvaluation of body shape and weight. They produce the greatest degree of remission from binge eating as well as improvement in specific eating disorder psychopathology and associated general psychopathology such as depression. The CBT protocol evaluated in the research summarized above was the original manual from Fairburn and colleagues. Fairburn has subsequently developed a more elaborate and sophisticated form of treatment, namely, enhanced CBT (CBT-E) for eating disorders. Initial research suggests that CBT-E may be more effective than the earlier version with bulimia nervosa and Eating Disorder Not Otherwise Specified patients. CBT-E has yet to be evaluated for the treatment of BED, although it would currently be the recommended form of CBT. Of relevance in this regard is that the so-called broad form of the new protocol includes 3 optional treatment modules that could be used to address more complex psychopathology in BED patients. One of the modules targeted at interpersonal difficulties is IPT, as described earlier in this chapter. Thus, the broader protocol could represent a combination of the two currently most effective therapies for BED. Whether this combined treatment proves more effective than either of the components alone, particularly for a subset of BED patients with more complex psychopathology, remains to be tested. CBT-E also includes a module designed to address what Fairburn terms “mood intolerance” (problems in coping with negative affect) that can trigger binge eating and purging. The content and strategies of this mood intolerance module overlap with the emotional regulation and distress tolerance skills training of Linehan's dialectical behavior therapy (DBT). Two randomized controlled trials have tested the efficacy of an

  1. Energy drink use, problem drinking and drinking motives in a diverse sample of Alaskan college students

    Directory of Open Access Journals (Sweden)

    Monica C. Skewes

    2013-08-01

    Full Text Available Background. Recent research has identified the use of caffeinated energy drinks as a common, potentially risky behaviour among college students that is linked to alcohol misuse and consequences. Research also suggests that energy drink consumption is related to other risky behaviours such as tobacco use, marijuana use and risky sexual activity. Objective. This research sought to examine the associations between frequency of energy drink consumption and problematic alcohol use, alcohol-related consequences, symptoms of alcohol dependence and drinking motives in an ethnically diverse sample of college students in Alaska. We also sought to examine whether ethnic group moderated these associations in the present sample of White, Alaska Native/American Indian and other ethnic minority college students. Design. A paper-and-pencil self-report questionnaire was completed by a sample of 298 college students. Analysis of covariance (ANCOVA was used to examine the effects of energy drink use, ethnic group and energy drink by ethnic group interactions on alcohol outcomes after controlling for variance attributed to gender, age and frequency of binge drinking. Results. Greater energy drink consumption was significantly associated with greater hazardous drinking, alcohol consequences, alcohol dependence symptoms, drinking for enhancement motives and drinking to cope. There were no main effects of ethnic group, and there were no significant energy drink by ethnic group interactions. Conclusion. These findings replicate those of other studies examining the associations between energy drink use and alcohol problems, but contrary to previous research we did not find ethnic minority status to be protective. It is possible that energy drink consumption may serve as a marker for other health risk behaviours among students of various ethnic groups.

  2. Fox reimbedding and Bing submanifolds

    CERN Document Server

    Nakamura, Kei

    2012-01-01

    Let M be an orientable closed connected 3-manifold. We introduce the notion of amalgamated Heegaard genus of M with respect to a closed separating 2-manifold F, and use it to show that the following two statements are equivalent: (i) a compact connected 3-manifold Y can be embedded in M so that the exterior of the image of Y is a union of handlebodies; and (ii) a compact connected 3-manifold Y can be embedded in M so that every knot in M can be isotoped to lie within the image of Y . Our result can be regarded as a common generalization of the reimbedding theorem by Fox [Fox48] and the characterization of 3-sphere by Bing [Bin58], as well as more recent results of Hass and Thompson [HT89] and Kobayashi and Nishi [KN94].

  3. Den tredje spiseforstyrrelse - Binge Eating Disorder

    DEFF Research Database (Denmark)

    Schousboe, Birgitte Hartvig

    2010-01-01

    Mennesker med Binge Eating Disorder indtager større mængder mad uden at være sultne. Overspisningen kan dulme svære følelser, men medfører typisk ekstremt ubehag og skam. Mennesker, der lider af spiseforstyrrelsen Binge Eating Disorder (i daglig tale kaldet BED), har ofte problemer med overvægt, og...

  4. Concordance of Bing Doubles and Boundary Genus

    Science.gov (United States)

    Livingston, Charles; van Cott, Cornelia A.

    2011-11-01

    Cha and Kim proved that if a knot K is not algebraically slice, then no iterated Bing double of K is concordant to the unlink. We prove that if K has nontrivial signature $\\sigma$, then the n-iterated Bing double of K is not concordant to any boundary link with boundary surfaces of genus less than $2^{n-1}\\sigma$. The same result holds with $\\sigma$ replaced by $2\\tau$, twice the Ozsvath-Szabo knot concordance invariant.

  5. Examining associations between adolescent binge eating and binge eating in parents and friends

    Science.gov (United States)

    Goldschmidt, Andrea B.; Wall, Melanie M.; Choo, Tse-Hwei J.; Bruening, Meg; Eisenberg, Marla E.; Neumark-Sztainer, Dianne

    2014-01-01

    Objective Binge eating is prevalent among adolescents, but little is known about how parents and friends may influence such behaviors. This study examined associations between adolescent binge eating behaviors, and similar behaviors in their parents and friends. Method Participants were 2,770 target adolescent boys and girls who had at least one friend and/or parent who also participated. Logistic regression, stratified by gender, examined associations between parents’ and friends’ self-reported binge eating, and similar behaviors in target adolescents. Results Girls’ binge eating was associated with their male friends’ (odds ratio=2.33; p=.03) and fathers’ binge eating (odds ratio=3.38; p=.02), but not with their female friends’ or mothers’ binge eating (p>.05). For boys, binge eating was not associated with parents’ or friends’ behavior. Discussion Adolescent girls’ binge eating is associated with similar behaviors in their other-sex parents and friends. Results should be replicated, and mechanisms explaining this relation should be further explored. PMID:24105696

  6. Energy Drink Use Among Ohio Appalachian Smokers.

    Science.gov (United States)

    Davison, Genevieve; Shoben, Abigail; Pasch, Keryn E; Klein, Elizabeth G

    2016-10-01

    Caffeine-containing energy drinks have emerged as a public health concern due to their association with caffeine toxicity and alcohol use. Despite the fact that previous research has linked caffeine use in the form of coffee drinking to smoking, there is little research examining the association between energy drinks and smoking. The present study examines demographic and behavioral factors associated with energy drink use among a sample of rural Ohio Appalachian smokers. It was hypothesized that male gender, young age (21-30 years.) and alcohol use would be associated with energy drink use. A sample of adult smokers (n = 298) from Ohio Appalachian counties were interviewed regarding demographic and behavioral factors. Logistic regression analysis was used to assess the association between these factors and energy drink use. Seventy percent of Ohio Appalachian smokers studied had ever used an energy drink and 40 % had used an energy drink in the past month. Young age, male gender, and single marital status were associated with higher odds of ever having used an energy drink. Young age, and binge drinking were associated with higher odds of past 30-day use while abstinence from drinking was associated with lower odds of past 30-day use. Ohio Appalachian adult smokers had higher rates of energy drink use compared to previous estimates of ever or past month use found in other studies. The combined use of caffeine, nicotine, and alcohol warrants attention due to potential for health risk.

  7. Insights revealed by rodent models of sugar binge eating.

    Science.gov (United States)

    Murray, Susan M; Tulloch, Alastair J; Chen, Eunice Y; Avena, Nicole M

    2015-12-01

    Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study.

  8. Understanding Eating Disorders, Anorexia, Bulimia, and Binge-Eating

    Science.gov (United States)

    ... Javascript on. Photo: iStock Eating disorders, such as anorexia nervosa, bulimia nervosa, and binge eating , are among ... There are three main types of eating disorders: anorexia nervosa, bulimia nervosa, and binge-eating disorder. People ...

  9. College Drinking

    Science.gov (United States)

    ... the widespread availability of alcohol, inconsistent enforcement of underage drinking laws, and limited interactions with parents and other ... BAC) Increases, So Does Impairment / Women and Alcohol / Underage Drinking / College Drinking / Older Adults and Drinking Spring 2014 ...

  10. Prevalence and correlates of binge eating in seasonal affective disorder

    OpenAIRE

    2014-01-01

    Eating pathology in Seasonal Affective Disorder (SAD) may be more severe than hyperphagia during winter. Although research has documented elevated rates of subclinical binge eating in women with SAD, the prevalence and correlates of BED in SAD remain largely uncharacterized. We examined the prevalence and correlates of binge eating, weekly binge eating with distress, and BED as defined by the DSM-IV-TR in SAD. We also tested whether binge eating exhibits a seasonal pattern among individuals w...

  11. Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ΔFosB in mice.

    Science.gov (United States)

    Sajja, Ravi Kiran; Rahman, Shafiqur

    2013-06-01

    Chronic administration of ethanol induces persistent accumulation of ΔFosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ΔFosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ΔFosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ΔFosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ΔFosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ΔFosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction.

  12. Evaluation of Extinction as a Functional Treatment for Binge Eating

    Science.gov (United States)

    Bosch, Amanda; Miltenberger, Raymond G.; Gross, Amy; Knudson, Peter; Breitwieser, Carrie Brower

    2008-01-01

    Binge eating is a serious behavior problem exhibited by individuals diagnosed with binge eating disorder and bulimia nervosa. Binge eating is thought to be maintained by automatic negative reinforcement in the form of relief from negative emotional responding. Current treatments produce only moderate abstinence, perhaps because they do not attempt…

  13. The Motivations and Experiences of Underage Female Students Who Choose to Abstain from Drinking in College

    Science.gov (United States)

    Gravelle, Deborah

    2012-01-01

    For decades, research has been conducted regarding alcohol consumption and behaviors, binge drinking, alcohol prevention, and education programs; however, there is limited research investigating a student's decision not to drink. In particular, there is minimal research on the experiences of underage female college students who have chosen to…

  14. Student Drinking: New Strategies but No Magic Bullet

    Science.gov (United States)

    Gilroy, Marilyn

    2009-01-01

    More than 1,700 students between the ages of 18 and 24 die each year from alcohol-related causes, according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA). These students succumb to alcohol poisoning, cardiac arrest, or injuries from falls off dorm room balconies or other heights on campus. The problem of binge drinking, defined…

  15. Topiramate: use in binge eating disorder?

    Directory of Open Access Journals (Sweden)

    Mauro Gentile

    2012-01-01

    Full Text Available Introduction: Topiramate was serendipitously synthesized in 1979 during research aimed at developing a fructose-1,6-diphosphatase inhibitor that might be used in the treatment of diabetes mellitus. Some investigators have suggested it might be used in the treatment of binge eating disorder (BED. The aim of this review was to evaluate current knowledge and opinions on this topic. Materials and methods: We conducted a search of five electronic databases (PubMed, Embase, Nice, Cochrane, Cinahl using the search strategy ‘‘topiramate’’ AND ‘‘binge’’, ‘‘binge eating disorder.’’ No time limits were applied, and only reports of randomized controlled trials were included in our analysis. Results: In clinical studies, topiramate use has been associated with significant weight loss mediated by reductions in the frequency of bingeing episodes. The most common side effects of the drug are paresthesias, but nephrolithiasis, oligohydrosis, and dizziness have also been described. Conclusions: Available data are limited, but the literature we reviewed suggests that topiramate can be useful in the medical treatment of BED, reducing both body weight and binge episodes. Side effects are not negligible. Before topiramate can be regarded as a good tool for the treatment of BED, further data must be obtained from longer, methodologically correct studies of larger populations.

  16. Integrative Response Therapy for Binge Eating Disorder

    Science.gov (United States)

    Robinson, Athena

    2013-01-01

    Binge eating disorder (BED), a chronic condition characterized by eating disorder psychopathology and physical and social disability, represents a significant public health problem. Guided self-help (GSH) treatments for BED appear promising and may be more readily disseminable to mental health care providers, accessible to patients, and…

  17. DMPD: Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15331118 Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. Wu...e-associated up-regulation in macrophage PGE2 synthesis. PubmedID 15331118 Title Mechanism of age-associated... up-regulation in macrophage PGE2 synthesis. Authors Wu D, Meydani SN. Publicatio

  18. Underage Drinking

    Science.gov (United States)

    ... 10/17. Drinking patterns vary by age and gender As adolescents get older, they tend to drink ... clear rules against drinking, as well as improve communication between children and parents about alcohol. The Role ...

  19. Drinking Motives

    DEFF Research Database (Denmark)

    Grunert, Klaus G; Rosendahl, Jacob; Andronikidis, Andreas I.

    2013-01-01

    This chapter presents an analysis of what consumer in Europe drink and why they drink what they drink. The concept of drinking motives is developed and defined, and analysis of data on drinking motives shows that these can be grouped into two major classes: self-expressive and functional. This di......This chapter presents an analysis of what consumer in Europe drink and why they drink what they drink. The concept of drinking motives is developed and defined, and analysis of data on drinking motives shows that these can be grouped into two major classes: self-expressive and functional....... This distinction is universal and henceapplies across Europe. However, the importance of self-expressive as compared to functional motives, as well as the way in which these relate to different beverages, does differ across Europe. Both dimensions are relevant for the motives for drinking non-alcoholic drinks...

  20. Evidence that Melanocortin Receptor Agonist Melanotan-II Synergistically Augments the Ability of Naltrexone to Blunt Binge-Like Ethanol Intake in Male C57BL/6J Mice

    Science.gov (United States)

    Navarro, Montserrat; Carvajal, Francisca; Lerma-Cabrera, Jose Manuel; Cubero, Inmaculada; Picker, Mitchell J.; Thiele, Todd E.

    2015-01-01

    Background The non-selective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent pre-clinical evidence shows that MC receptor (MCR) agonists reduce excessive ethanol drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and opioid systems in the modulation of pain, drug tolerance, and food intake. Method In the present report, a mouse model of binge ethanol drinking was employed to determine if the MCR agonist, melanotan-II (MTII), would improve the effectiveness of NAL in reducing excessive binge-like ethanol drinking when these drugs were co-administered prior to ethanol access. Results Both NAL and MTII blunt binge-like ethanol drinking and associated blood ethanol levels, and when administered together, a low dose of MTII (0.26 mg/kg) produces a 7.6-fold increase in the effectiveness of NAL in reducing binge-like ethanol drinking. Using isobolographic analysis, it is demonstrated that MTII increases the effectiveness of NAL in a synergistic manner. Conclusions The current observations suggest that activators of MC signaling may represent a new approach to treating alcohol abuse disorders, and a way to potentially improve existing NAL-based therapies. PMID:26108334

  1. Impaired up-regulation of type II corticosteroid receptors in hippocampus of aged rats.

    Science.gov (United States)

    Eldridge, J C; Fleenor, D G; Kerr, D S; Landfield, P W

    1989-01-30

    Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment.

  2. Microarray and KOG analysis of Acanthamoeba healyi genes up-regulated by mouse-brain passage.

    Science.gov (United States)

    Moon, Eun-Kyung; Xuan, Ying-Hua; Kong, Hyun-Hee

    2014-08-01

    Long-term cultivation in a laboratory could reduce the virulence of Acanthamoeba. To identify virulence factors of Acanthamoeba, the authors compared the transcription profiles of long-term cultivated Acanthamoeba healyi (OLD) and three times mouse-brain passaged A. healyi (MBP) using microarray analysis and eukaryotic orthologous group (KOG) assignments. Microarray analysis revealed that 601 genes were up-regulated by mouse-brain passage. The results of real-time PCR of 8 randomly selected genes up-regulated in the MBP strain confirmed microarray analysis findings. KOG assignments showed relatively higher percentages of the MBP strain up-regulated genes in T article (signal transduction mechanism), O article (posttranslational modification, protein turnover, chaperones), C article (energy production and conversion), and J article (translation, ribosomal structure and biogenesis). In particular, the MBP strain showed higher expressions of cysteine protease and metalloprotease. A comparison of KOG assignments by microarray analysis and previous EST (expressed sequence tags) analysis showed similar populations of up-regulated genes. These results provide important information regarding the identification of virulence factors of pathogenic Acanthamoeba.

  3. Up-regulated miR-145 expression inhibits porcine preadipocytes differentiation by targeting IRS1.

    Science.gov (United States)

    Guo, Yunxue; Chen, Yaosheng; Zhang, Yun; Zhang, Yue; Chen, Luxi; Mo, Delin

    2012-01-01

    Generally, most miRNAs that were up-regulated during differentiation promoted adipogenesis, but our research indicated that up-regulation of miR-145 in porcine preadipocytes did not promote but inhibit adipogenesis. In this study, miR-145 was significantly up-regulated during porcine dedifferentiated fat (DFAT) cells differentiation. In miR-145 overexpressed DFAT cells, adipogenesis was inhibited and triglycerides accumulation was decreased after hormone stimulation (P<0.05). Furthermore, up-regulation of miR-145 expression repressed induction of mRNA levels of adipogenic markers, such as CCAAT/enhancer-binding protein α (C/EBPα), and peroxisome proliferator-activated receptor γ2 (PPARγ2). These effects caused by miR-145 overexpression were mediated by Insulin receptor substrate 1 (IRS1) as a mechanism. These data suggested that induced miR-145 expression during differentiation could inhibit adipogenesis by targeting IRS1, and miR-145 may be novel agent for adipose tissue engineering.

  4. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R.; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A.; Bielenberg, Diane R.

    2017-01-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

  5. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

  6. MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xiumei Xie

    2012-03-01

    Full Text Available Muramyldipeptide (MDP, the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2. Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.

  7. MDP up-regulates the gene expression of type I interferons in human aortic endothelial cells.

    Science.gov (United States)

    Lv, Qingshan; Yang, Mei; Liu, Xueting; Zhou, Lina; Xiao, Zhilin; Chen, Xiaobin; Chen, Meifang; Xie, Xiumei; Hu, Jinyue

    2012-03-23

    Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs) with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF) 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.

  8. Bing Xin:The Teller of Tales

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AT 9 p.m. on February 28, 1999,contemporary Chinese masterand famous writer Bing Xinpassed away quietly. As she wrote in herwill, "I quietly came into the world and Iwill leave it the same way." The entireliterary circle as well as other membersof society attended her funeral to mournher passing. Thousands of fire-red rosesencircled her. Several generations of herreaders came from all parts of thecountry to pay tribute to the centenarian

  9. Binge Eating Disorder and Body Uneasiness

    OpenAIRE

    Massimo Cuzzolaro; Maurizio Bellini; Lorenzo Donini; Chiara Santomassimo

    2008-01-01

    Debate continues regarding the nosological status of binge eating disorder (BED) and the specific diagnostic criteria, including whether, like anorexia nervosa and bulimia nervosa, it should be characterized by body image disturbances in addition to abnormal eating behaviour. The aims of this article are: a) to concisely review the main points of the literature that has developed on diagnosis and treatment (especially pharmacological) of BED and b) to present the results of an original resear...

  10. Hepatotoxicity of piperazine designer drugs: up-regulation of key enzymes of cholesterol and lipid biosynthesis.

    Science.gov (United States)

    Arbo, Marcelo Dutra; Melega, Simone; Stöber, Regina; Schug, Markus; Rempel, Eugen; Rahnenführer, Jörg; Godoy, Patricio; Reif, Raymond; Cadenas, Cristina; de Lourdes Bastos, Maria; Carmo, Helena; Hengstler, Jan G

    2016-12-01

    The piperazine derivatives most frequently consumed for recreational purposes are 1-benzylpiperazine, 1-(3,4-methylenedioxybenzyl) piperazine, 1-(3-trifluoromethylphenyl) piperazine and 1-(4-methoxyphenyl) piperazine. Generally, they are consumed as capsules, tablets or pills but also in powder or liquid forms. Currently, the precise mechanism by which piperazine designer drugs induce hepatotoxicity and whether they act by a common pathway is unclear. To answer this question, we performed a gene array study with rat hepatocytes incubated with the four designer drugs. Non-cytotoxic concentrations were chosen that neither induce a decrease in reduced glutathione or ATP depletion. Analysis of the gene array data showed a large overlap of gene expression alterations induced by the four drugs. This 'piperazine designer drug consensus signature' included 101 up-regulated and 309 down-regulated probe sets (p cholesterol biosynthesis represented a dominant overrepresented motif. Key enzymes of cholesterol biosynthesis up-regulated by all four piperazine drugs include sterol C4-methyloxidase, isopentyl-diphosphate-Δ-isomerase, Cyp51A1, squalene epoxidase and farnesyl diphosphate synthase. Additionally, glycoprotein transmembrane nmb, which participates in cell adhesion processes, and fatty acid desaturase 1, an enzyme that regulates unsaturation of fatty acids, were also up-regulated by the four piperazine designer drugs. Regarding the down-regulated probe sets, only one gene was common to all four piperazine derivatives, the betaine-homocysteine-S-methyltransferase 2. Analysis of transcription factor binding sites of the 'piperazine designer drug consensus signature' identified the sterol regulatory element binding protein (SREBP-1) as strongly overrepresented in the up-regulated genes. SREBP transcription factors are known to regulate multiple genes of cholesterol metabolism. In conclusion, the present study shows that piperazine designer drugs act by up-regulating key

  11. The emerging role of m-TOR up-regulation in brain Astrocytoma.

    Science.gov (United States)

    Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

    2017-05-01

    The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

  12. Sucrose prevents up-regulation of senescence-associated genes in carnation petals.

    Science.gov (United States)

    Hoeberichts, Frank A; van Doorn, Wouter G; Vorst, Oscar; Hall, Robert D; van Wordragen, Monique F

    2007-01-01

    cDNA microarrays were used to characterize senescence-associated gene expression in petals of cut carnation (Dianthus caryophyllus) flowers, sampled from anthesis to the first senescence symptoms. The population of PCR fragments spotted on these microarrays was enriched for flower-specific and senescence-specific genes, using subtractive hybridization. About 90% of the transcripts showed a large increase in quantity, approximately 25% transiently, and about 65% throughout the 7 d experiment. Treatment with silver thiosulphate (STS), which blocks the ethylene receptor and prevented the normal senescence symptoms, prevented the up-regulation of almost all of these genes. Sucrose treatment also considerably delayed visible senescence. Its effect on gene expression was very similar to that of STS, suggesting that soluble sugars act as a repressor of ethylene signal transduction. Two fragments that encoded a carnation EIN3-like (EIL) protein were isolated, some of which are key transcription factors that control ethylene response genes. One of these (Dc-EIL3) was up-regulated during senescence. Its up-regulation was delayed by STS and prevented by sucrose. Sucrose, therefore, seems to repress ethylene signalling, in part, by preventing up-regulation of Dc-EIL3. Some other transcription factors displayed an early increase in transcript abundance: a MYB-like DNA binding protein, a MYC protein, a MADS-box factor, and a zinc finger protein. Genes suggesting a role in senescence of hormones other than ethylene encoded an Aux/IAA protein, which regulate transcription of auxin-induced genes, and a cytokinin oxidase/dehydrogenase, which degrades cytokinin. Taken together, the results suggest a master switch during senescence, controlling the co-ordinated up-regulation of numerous ethylene response genes. Dc-EIL3 might be (part of) this master switch.

  13. Dietary restraint moderates genetic risk for binge eating.

    Science.gov (United States)

    Racine, Sarah E; Burt, S Alexandra; Iacono, William G; McGue, Matt; Klump, Kelly L

    2011-02-01

    Dietary restraint is a prospective risk factor for the development of binge eating and bulimia nervosa. Although many women engage in dietary restraint, relatively few develop binge eating. Dietary restraint may increase susceptibility for binge eating only in individuals who are at genetic risk. Specifically, dietary restraint may be a behavioral exposure factor that activates genetic predispositions for binge eating. We investigated this possibility in 1,678 young adolescent and adult same-sex female twins from the Minnesota Twin Family Study and the Michigan State University Twin Registry. Twin moderation models were used to examine whether levels of dietary restraint moderate genetic and environmental influences on binge eating. Results indicated that genetic and nonshared environmental factors for binge eating increased at higher levels of dietary restraint. These effects were present after controlling for age, body mass index, and genetic and environmental overlap among dietary restraint and binge eating. Results suggest that dietary restraint may be most important for individuals at genetic risk for binge eating and that the combination of these factors could enhance individual differences in risk for binge eating.

  14. Prevalence and correlates of binge eating in seasonal affective disorder.

    Science.gov (United States)

    Donofry, Shannon D; Roecklein, Kathryn A; Rohan, Kelly J; Wildes, Jennifer E; Kamarck, Marissa L

    2014-06-30

    Eating pathology in Seasonal Affective Disorder (SAD) may be more severe than hyperphagia during winter. Although research has documented elevated rates of subclinical binge eating in women with SAD, the prevalence and correlates of binge eating disorder (BED) in SAD remain largely uncharacterized. We examined the prevalence and correlates of binge eating, weekly binge eating with distress, and BED as defined by the DSM-IV-TR in SAD. We also tested whether binge eating exhibits a seasonal pattern among individuals with BED. Two samples were combined to form a sample of individuals with SAD (N=112). A third sample included non-depressed adults with clinical (n=12) and subclinical (n=11) BED. All participants completed the Questionnaire of Eating and Weight Patterns-Revised (QEWP-R) and modified Seasonal Pattern Assessment Questionnaire (M-SPAQ). In the SAD sample, 26.5% reported binge eating, 11.6% met criteria for weekly binge eating with distress, and 8.9% met criteria for BED. Atypical symptom severity predicted binge eating and BED. In the BED sample, 30% endorsed seasonal worsening of mood, and 26% reported a winter pattern of binge eating. The spectrum of eating pathology in SAD includes symptoms of BED, which are associated with atypical depression symptoms, but typical depression symptoms.

  15. Lisdexamfetamine Dimesylate Effects on Binge Eating Behaviour and Obsessive-Compulsive and Impulsive Features in Adults with Binge Eating Disorder.

    Science.gov (United States)

    McElroy, Susan L; Mitchell, James E; Wilfley, Denise; Gasior, Maria; Ferreira-Cornwell, M Celeste; McKay, Michael; Wang, Jiannong; Whitaker, Timothy; Hudson, James I

    2016-05-01

    In a published 11-week, placebo-controlled trial, 50 and 70 mg/d lisdexamfetamine dimesylate (LDX), but not 30 mg/d LDX, significantly reduced binge eating days (primary endpoint) in adults with binge eating disorder (BED). This report provides descriptions of LDX effects on secondary endpoints (Binge Eating Scale [BES]; Three-Factor Eating Questionnaire [TFEQ]; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE]; and the Barratt Impulsiveness Scale, version 11 [BIS-11]) from that study. Week 11 least squares mean treatment differences favoured all LDX doses over placebo on the BES (p ≤ 0.03), TFEQ Disinhibition and Hunger subscales (all p binge eating severity and obsessive-compulsive and impulsive features of BED in addition to binge eating days.

  16. Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.

    Science.gov (United States)

    Gondré-Lewis, Marjorie C; Warnock, Kaitlin T; Wang, Hong; June, Harry L; Bell, Kimberly A; Rabe, Holger; Tiruveedhula, Veera Venkata Naga Phani Babu; Cook, James; Lüddens, Hartmut; Aurelian, Laure; June, Harry L

    2016-01-01

    Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the

  17. Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats.

    Science.gov (United States)

    Sinclair, Elaine B; Culbert, Kristen M; Gradl, Dana R; Richardson, Kimberlei A; Klump, Kelly L; Sisk, Cheryl L

    2015-12-01

    Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague-Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial prefrontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex

  18. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Science.gov (United States)

    Banerjee, Atrayee; Abdelmegeed, Mohamed A; Jang, Sehwan; Song, Byoung-Joon

    2015-01-01

    The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  19. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  20. SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation

    DEFF Research Database (Denmark)

    Petersson, Stine Juhl; Jørgensen, Louise Helskov; Andersen, Ditte C;

    2013-01-01

    , Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen......Skeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up......-regulated during skeletal muscle disease, but its function remains elusive. In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6...

  1. Identification of up-regulated genes in human uterine leiomyoma by suppression subtractive hybridization

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In searching for differentially expressed genes in human uterine leiomyomas (ULs), suppression sub-tractive hybridization was used to construct an UL up-regulated library, which turned out to represent 88genes. After two rounds of screening by reverse Northern analysis, twenty genes were proved to be up-regulated, including seventeen known genes and three genes with unknown function. All these genes werefirstly associated with UL. Three genes with notable difference were selected for Northern confirmationOur results proved the authenticity of the twenty genes. One gene named Phospholipase A2 (PLA2) showedup-regulation in 4/6 of the patients and investigation of tissue distribution indicated that it had obviousexpression in prostate, testis, liver, heart and skeletal muscle.

  2. Up-regulation of cyclooxygenase-2 by product-prostaglandin E2

    Science.gov (United States)

    Tjandrawinata, R. R.; Hughes-Fulford, M.

    1997-01-01

    The development of prostate cancer has been linked to high level of dietary fat intake. Our laboratory investigates the connection between cancer cell growth and fatty acid products. Studying human prostatic carcinoma PC-3 cells, we found that prostaglandin E2 (PGE2) increased cell growth and up-regulated the gene expression of its own synthesizing enzyme, cyclooxygenase-2 (COX-2). PGE2 increased COX-2 mRNA expression dose-dependently with the highest levels of stimulation seen at the 3-hour period following PGE2 addition. The NSAID flurbiprofen (5 microM), in the presence of exogenous PGE2, inhibited the up-regulation of COX-2 mRNA and cell growth. These data suggest that the levels of local intracellular PGE2 play a major role in the growth of prostate cancer cells through an activation of COX-2 gene expression.

  3. Influence of Apoptin on Up-regulation of the Expression of Bad and Bax

    Institute of Scientific and Technical Information of China (English)

    GUO Tai; YANG Qian

    2005-01-01

    The chicken anemia virus protein, apoptin, which manifests selectivity and specificity to tumor cells, induces a p53-independent and Bcl-2-insensitive type of apoptosis in various human tumor cells. In this study, the apoptin gene was cloned from the total DNA of chicken anemia virus, and the recombinant vector was constructed. We used oligonucleotide microarray to study the changes of four genes, including Bcl-2, Bcl-xL, Bad and Bax. The post-transfection with the recombinant was also studied. The pro-apoptotic genes(Bad and Bax) and anti-apoptosis genes(Bcl-2 and Bcl-xL) were up-regulated in contrast to the controls. According to the published data, either Bcl-2 or Bcl-xL can form non-functional heterodimers by Bad and Bax binding together, resulting in blocking partly the release of cytochrome c from mitochondria. However, apoptosis could be inhibited by neither the endogenous Bcl-xL nor Bcl-2 over-expression. The experiments show that the apoptin-induced apoptotic pathway is related to the up-regulation of Bad and Bax. Bad was up-regulated by apoptin; then this up-regulated product of Bad was in favor of displacing Bax from binding to Bcl-xL or Bcl-2. Consequently, Bax exerted a pro-apoptotic dysfunction to mitochondria, thereby inducing the release of cytochrome c. Finally, apoptin induced the apoptosis of HHCC cells. These results indicate that the oligonucleotide microarray can reveal the genes related to the apoptosis induced by apoptin in HHCC cells.

  4. Gene up-regulation in response to predator kairomones in the water flea, Daphnia pulex

    Directory of Open Access Journals (Sweden)

    Okada Yasukazu

    2010-04-01

    Full Text Available Abstract Background Numerous cases of predator-induced polyphenisms, in which alternate phenotypes are produced in response to extrinsic stimuli, have been reported in aquatic taxa to date. The genus Daphnia (Branchiopoda, Cladocera provides a model experimental system for the study of the developmental mechanisms and evolutionary processes associated with predator-induced polyphenisms. In D. pulex, juveniles form neckteeth in response to predatory kairomones released by Chaoborus larvae (Insecta, Diptera. Results Previous studies suggest that the timing of the sensitivity to kairomones in D. pulex can generally be divided into the embryonic and postembryonic developmental periods. We therefore examined which of the genes in the embryonic and first-instar juvenile stages exhibit different expression levels in the presence or absence of predator kairomones. Employing a candidate gene approach and identifying differentially-expressed genes revealed that the morphogenetic factors, Hox3, extradenticle and escargot, were up-regulated by kairomones in the postembryonic stage and may potentially be responsible for defense morph formation. In addition, the juvenile hormone pathway genes, JHAMT and Met, and the insulin signaling pathway genes, InR and IRS-1, were up-regulated in the first-instar stage. It is well known that these hormonal pathways are involved in physiological regulation following morphogenesis in many insect species. During the embryonic stage when morphotypes were determined, one of the novel genes identified by differential display was up-regulated, suggesting that this gene may be related to morphotype determination. Biological functions of the up-regulated genes are discussed in the context of defense morph formation. Conclusions It is suggested that, following the reception of kairomone signals, the identified genes are involved in a series of defensive phenotypic alterations and the production of a defensive phenotype.

  5. Binge or control? : assessment of the validity, treatment and underlying mechanisms of Binge Eating Disorder

    NARCIS (Netherlands)

    Dingemans, Alexandra

    2009-01-01

    This thesis focuses on patients with Binge Eating Disorder. The thesis consists of three parts. In the first part the validity of the diagnosis of BED will be discussed. The results of two literature reviews and an empirical cross-sectional study suggested that BED is a distinct eating disorder and

  6. Moclobemide up-regulates proliferation of hippocampal progenitor cells in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-fengLI; You-zhiZHANG; Yan-qinLIU; Heng-linWANG; LiYUAN; Zhi-puLUO

    2004-01-01

    AIM: To explore the action mechanism of antidepressants. METHODS: The PC 12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA)600 μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10 μnol/L, the percentage in S-phase increased. Furthermore,the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40 mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION:Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.

  7. Up-regulation of miR-98 and unraveling regulatory mechanisms in gestational diabetes mellitus

    Science.gov (United States)

    Cao, Jing-Li; Zhang, Lu; Li, Jian; Tian, Shi; Lv, Xiao-Dan; Wang, Xue-Qin; Su, Xing; Li, Ying; Hu, Yi; Ma, Xu; Xia, Hong-Fei

    2016-01-01

    MiR-98 expression was up-regulated in kidney in response to early diabetic nephropathy in mouse and down-regulated in muscle in type 2 diabetes in human. However, the expression prolife and functional role of miR-98 in human gestational diabetes mellitus (GDM) remained unclear. Here, we investigated its expression and function in placental tissues from GDM patients and the possible molecular mechanisms. The results showed that miR-98 was up-regulated in placentas from GDM patients compared with normal placentas. MiR-98 over-expression increased global DNA methylational level and miR-98 knockdown reduced global DNA methylational level. Further investigation revealed that miR-98 could inhibit Mecp2 expression by binding the 3′-untranslated region (UTR) of methyl CpG binding protein 2 (Mecp2), and then led to the expression dysregulation of canonical transient receptor potential 3 (Trpc3), a glucose uptake related gene. More importantly, in vivo analysis found that the expression level of Mecp2 and Trpc3 in placental tissues from GDM patients, relative to the increase of miR-98, was diminished, especially for GDM patients over the age of 35 years. Collectively, up-regulation of miR-98 in the placental tissues of human GDM is linked to the global DNA methylation via targeting Mecp2, which may imply a novel regulatory mechanism in GDM. PMID:27573367

  8. General up regulation of Spodoptera frugiperda trypsins and chymotrypsins allows its adaptation to soybean proteinase inhibitor.

    Science.gov (United States)

    Brioschi, Daniela; Nadalini, Larissa D; Bengtson, Mario H; Sogayar, Mari Cleide; Moura, Daniel S; Silva-Filho, Marcio C

    2007-12-01

    The existence of a diverse serine proteinase gene family in lepidopteran insects suggests they play a significant role in the insect adaptation to plant proteinase inhibitors. These proteinases have been shown to be involved in the process of proteolytic digestion in insect larvae. We carried out a selective transcriptome study of midguts from Spodoptera frugiperda larvae fed on a diet supplemented with soybean proteinase inhibitor (SPI). Using subtracted cDNA libraries made of gut-expressed transcripts, a total of 2100 partial sequences were obtained, of those 38% were related to digestive process. Two large and diverse groups of chymotrypsins and trypsins were obtained, and some of these proteinase-encoding genes were further characterized by quantitative RT-PCR. The transcription analyses revealed two groups: one group of genes constitutively expressed in the control larvae that is up regulated by introducing SPI to the diet, and a second group that is absent in the control but is induced by the SPI-rich diet. This observation suggests that adaptation of S. frugiperda to SPI involves de novo synthesis and also up regulation of existing enzymes. Proteases from intestines of larvae reared on a diet with SPI showed insensitivity to the inhibitor. The proteases were also insensitive to a broad-spectrum potato proteinase inhibitor preparation. We propose that adaptation of S. frugiperda to SPI follows a "shotgun" approach, based on a general up regulation of a large set of endoproteinases.

  9. Gene expression profiling identifies a set of transcripts that are up-regulated inhuman testicular seminoma.

    Science.gov (United States)

    Yamada, Shigeyuki; Kohu, Kazuyoshi; Ishii, Tomohiko; Ishidoya, Shigeto; Ishidoya, Shigeru; Hiramatsu, Masayoshi; Kanto, Satoru; Fukuzaki, Atsushi; Adachi, Yutsu; Endoh, Mareyuki; Moriya, Takuya; Sasaki, Hiroki; Satake, Masanobu; Arai, Yoichi

    2004-10-31

    Seminoma constitutes one subtype of human testicular germ cell tumors and is uniformly composed of cells that are morphologically similar to the primordial germ cells and/or the cells in the carcinoma in situ. We performed a genome-wide exploration of the genes that are specifically up-regulated in seminoma by oligonucleotide-based microarray analysis. This revealed 106 genes that are significantly and consistently up-regulated in the seminomas compared to the adjacent normal tissues of the testes. The microarray data were validated by semi-quantitative RT-PCR analysis. Of the 106 genes, 42 mapped to a small number of specific chromosomal regions, namely, 1q21, 2p23, 6p21-22, 7p14-15, 12pll, 12p13, 12q13-14 and 22q12-13. This list of up-regulated genes may be useful in identifying the causative oncogene(s) and/or the origin of seminoma. Furthermore, immunohistochemical analysis revealed that the seminoma cells specifically expressed the six gene products that were selected randomly from the list. These proteins include CCND2 and DNMT3A and may be useful as molecular pathological markers of seminoma.

  10. Moclobemide up-regulates proliferation of hippocampal progenitor cells in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-feng LI; You-zhi ZHANG; Yan-qin LIU; Heng-lin WANG; Li YUAN; Zhi-pu LUO

    2004-01-01

    AIM: To explore the action mechanism of antidepressants. METHODS: The PC12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA)600 μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10 μmol/L, the percentage in S-phase increased. Furthermore,the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION:Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.

  11. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression.

    Science.gov (United States)

    Paradisi, Andrea; Maisse, Carine; Coissieux, Marie-May; Gadot, Nicolas; Lépinasse, Florian; Delloye-Bourgeois, Céline; Delcros, Jean-Guy; Svrcek, Magali; Neufert, Clemens; Fléjou, Jean-François; Scoazec, Jean-Yves; Mehlen, Patrick

    2009-10-06

    Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, which show a major increased risk for colorectal cancer. While the understanding of the molecular pathogenesis of IBD has recently improved, the mechanisms that link these chronic inflammatory states to colorectal cancer development are in large part unknown. One of these mechanisms is NF-kappaB pathway activation which in turn may contribute to tumor formation by providing anti-apoptotic survival signals to the epithelial cells. Based on the observation that netrin-1, the anti-apoptotic ligand for the dependence receptors DCC and UNC5H is up-regulated in colonic crypts in response to NF-kappaB, we show here that colorectal cancers from inflammatory bowel diseases patients have selected up-regulation of netrin-1. Moreover, we demonstrate that this inflammation-driven netrin-1 up-regulation is causal for colorectal cancer development as interference with netrin-1 autocrine loop in a mouse model for ulcerative colitis-associated colorectal cancer, while showing no effect on inflammation, inhibits colorectal cancer progression.

  12. Rapid Response to Treatment for Binge Eating Disorder

    Science.gov (United States)

    Grilo, Carlos M.; Masheb, Robin M.; Wilson, Terence G.

    2006-01-01

    The authors examined rapid response among 108 patients with binge eating disorder (BED) who were randomly assigned to 1 of 4 16-week treatments: fluoxetine, placebo, cognitive-behavioral therapy (CBT) plus fluoxetine, or CBT plus placebo. Rapid response, defined as 65% or greater reduction in binge eating by the 4th treatment week, was determined…

  13. De oorsprong van Art Nouveau - Het Bing imperium

    NARCIS (Netherlands)

    Weisberg, Gabriel P.; Becker, Edwin; Posseme, Evelyne

    2004-01-01

    The opening of Sigmund Bing's gallery L'Art Nouveau had been an eagerly expected event in the Paris art world throughout the latter half of 1895, since Bing first announced that he would be soon exhibiting artistic furniture. The doors finally opened on 26 December 1895 as visitors poured in at 22 R

  14. College Student Binge Eating: Insecure Attachment and Emotion Regulation

    Science.gov (United States)

    Han, Suejung; Pistole, M. Carole

    2014-01-01

    Because college students who have accomplished developmental tasks less effectively may be at risk for detrimental behavior such as binge eating, we examined emotion regulation as a mediator of attachment insecurity and binge eating. Based on undergraduate and graduate student responses to a Web-based survey ("N" = 381), structural…

  15. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

  16. Drinking Water

    Science.gov (United States)

    ... the safest water supplies in the world, but drinking water quality can vary from place to place. It ... water supplier must give you annual reports on drinking water. The reports include where your water came from ...

  17. Binge Abstinence is Associated with Reduced Energy Intake After Treatment in Patients with Binge Eating Disorder and Obesity

    Science.gov (United States)

    Masheb, Robin M.; Dorflinger, Lindsey M.; Rolls, Barbara J.; Mitchell, Diane C.; Grilo, Carlos M.

    2016-01-01

    Objective Binge eating disorder (BED) is strongly associated with obesity and related medical and psychiatric morbidities. Cognitive behavioral therapy (CBT) has consistently been shown to reduce binge eating frequency and improve psychological functioning, as well as to produce abstinence rates of roughly 50%. This study examined the relationship between binge abstinence and dietary and psychological outcomes after CBT for BED. Methods Fifty adult patients with BED received 6-month treatments using a combination of CBT and dietary counseling. Trained interviewers conducted two 24-hour dietary recall interviews on randomly selected days at baseline and at 6 months. Results Participants had significant reductions in energy, macronutrient, and sugar intake and an increase in fruit intake. They reported significant reductions in BMI and binge eating frequency (from mean = 14.24 to mean = 1.90 binge eating episodes during the previous 28 days), as well as improvements in psychological functioning. Those who became binge abstinent reported eating roughly 400 fewer calories per day and experienced greater improvements in psychological functioning than those who did not. Conclusions Findings from this study suggest that individuals who achieve complete cessation from binge eating have significantly improved dietary and psychological outcomes that could potentially improve weight status, compared with those who continue to binge eat post-treatment. PMID:27797154

  18. Improving prediction of binge episodes by modelling chronicity of dietary restriction.

    Science.gov (United States)

    Holmes, Millicent; Fuller-Tyszkiewicz, Matthew; Skouteris, Helen; Broadbent, Jaclyn

    2014-11-01

    This study evaluates the influences of chronicity of, and time lag between, dietary restriction and binge outcome for predicting binge episode onset. Sixty-two women aged 18 to 40 years old completed an online survey at random intervals seven times daily for a 7-day period. Participants self-reported engagement in dietary restriction and/or binging, and temptation to binge. Consecutive instances of reported dietary restriction better predicted subsequent binges than single instances. As the time lag between the first report of dietary restriction and binge onset increased, a clear linear trend emerged, such that the value of restriction for predicting binges increased with the number of consecutive assessments in which they reported dietary restriction. A similar pattern was found when predicting temptation to binge. Present findings suggest that duration of restriction is a crucial determinant of binge onset. These findings have implications for clinical practice by highlighting the time course from dietary restriction to binging.

  19. The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

    Directory of Open Access Journals (Sweden)

    Carlos A. Rubio

    2014-01-01

    Full Text Available The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014 exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days, by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease, collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention.

  20. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

    Directory of Open Access Journals (Sweden)

    Kuznitzky Raquel

    2004-04-01

    Full Text Available Abstract Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD. Results Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008, but not between CCL21 and the number of infiltrating cells in the lesions. Conclusions These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells.

  1. Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers.

    Science.gov (United States)

    Brody, Arthur L; Mukhin, Alexey G; La Charite, Jaime; Ta, Karen; Farahi, Judah; Sugar, Catherine A; Mamoun, Michael S; Vellios, Evan; Archie, Meena; Kozman, Maggie; Phuong, Jonathan; Arlorio, Franca; Mandelkern, Mark A

    2013-06-01

    One-third of smokers primarily use menthol cigarettes and usage of these cigarettes leads to elevated serum nicotine levels and more difficulty quitting in standard treatment programmes. Previous brain imaging studies demonstrate that smoking (without regard to cigarette type) leads to up-regulation of β(2)*-containing nicotinic acetylcholine receptors (nAChRs). We sought to determine if menthol cigarette usage results in greater nAChR up-regulation than non-menthol cigarette usage. Altogether, 114 participants (22 menthol cigarette smokers, 41 non-menthol cigarette smokers and 51 non-smokers) underwent positron emission tomography scanning using the α(4)β(2)* nAChR radioligand 2-[(18)F]fluoro-A-85380 (2-FA). In comparing menthol to non-menthol cigarette smokers, an overall test of 2-FA total volume of distribution values revealed a significant between-group difference, resulting from menthol smokers having 9-28% higher α(4)β(2)* nAChR densities than non-menthol smokers across regions. In comparing the entire group of smokers to non-smokers, an overall test revealed a significant between-group difference, resulting from smokers having higher α(4)β(2)* nAChR levels in all regions studied (36-42%) other than thalamus (3%). Study results demonstrate that menthol smokers have greater up-regulation of nAChRs than non-menthol smokers. This difference is presumably related to higher nicotine exposure in menthol smokers, although other mechanisms for menthol influencing receptor density are possible. These results provide additional information about the severity of menthol cigarette use and may help explain why these smokers have more trouble quitting in standard treatment programmes.

  2. BLT2 up-regulates interleukin-8 production and promotes the invasiveness of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Hyunju Kim

    Full Text Available BACKGROUND: The elevated production of interleukin (IL-8 is critically associated with invasiveness and metastatic potential in breast cancer cells. However, the intracellular signaling pathway responsible for up-regulation of IL-8 production in breast cancer cells has remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report that the expression of BLT2 is markedly up-regulated in the highly aggressive human breast cancer cell lines MDA-MB-231 and MDA-MB-435 compared with MCF-10A immortalized human mammary epithelial cells, as determined by RT-PCR, real-time PCR and FACS analysis. Blockade of BLT2 with BLT2 siRNA knockdown or BLT2 inhibitor treatment downregulated IL-8 production and thereby diminished the invasiveness of aggressive breast cancer cells, analyzed by Matrigel invasion chamber assays. We further characterized the downstream signaling mechanism by which BLT2 stimulates IL-8 production and identified critical mediatory roles for the generation of reactive oxygen species (ROS and the consequent activation of the transcription factor NF-κB. Moreover, blockade of BLT2 suppressed the formation of metastatic lung nodules by MDA-MB-231 cells in both experimental and orthotopic metastasis models. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrates that a BLT2-ROS-NF-κB pathway up-regulates IL-8 production in MDA-MB-231 and MDA-MB-435 cells, thereby contributing to the invasiveness of these aggressive breast cancer cells. Our findings provide insight into the molecular mechanism of invasiveness in breast cancer.

  3. Up-regulation of the adrenomedullin system mediates hypotension and hypoaldosteronism induced by simulated microgravity.

    Science.gov (United States)

    Andreis, Paola G; Rossi, Gian Paolo; Bova, Sergio; Neri, Giuliano; Nussdorfer, Gastone G; Mazzocchi, Giuseppina

    2004-04-01

    We recently demonstrated that prolonged simulated microgravity (SMG) induced hypotension and hypoaldosteronism in rats, and gathered preliminary evidence for an involvement of circulating adrenomedullin (AM). Thus, we aimed to investigate whether short-term SMG elicits the same effects, and whether up-regulation of adrenal AM system plays a relevant role. Rats were exposed for 8 days to SMG in the form of hindlimb unweighting, and then, along with control animals, were given an intraperitoneal injection of AM22-52 and/or angiotensin-II (Ang-II) (100 nmoles/kg) or the saline vehicle. Systolic blood pressure (SBP) was measured by tail-cuff sphygmomanometry. The adrenal expression of AM was assayed by semiquantitative RT-PCR. The plasma concentrations of aldosterone (PAC) and AM, and adrenal AM content were measured by RIA. Short-term SMG induced significant decreases in SBP and PAC. Conversely, both the plasma and adrenal levels of AM, and adrenal AM mRNA were enhanced in SMG-exposed animals. The SMG-induced hypotension and hypoaldosteronism were reversed by AM22-52, an AM-receptor antagonist, thereby demonstrating a causal link between these effects and the up-regulation of AM system. SMG hampered SBP and PAC responses to Ang-II; the co-administration of AM22-52 restored these responses. These findings accord well with the known ability of AM to counteract the effects of Ang-II on both blood vessels and adrenocortical cells. Taken together, our findings allow us to conclude that up-regulation of the adrenal AM system i) occurs early and takes part in the adaptative changes occurring during SMG conditions; and ii) may account for both hypotension and hypoaldosteronism on returning to the normogravitational environment.

  4. Mung bean decreases plasma cholesterol by up-regulation of CYP7A1.

    Science.gov (United States)

    Yao, Yang; Hao, Liu; Shi, Zhenxing; Wang, Lixia; Cheng, Xuzhen; Wang, Suhua; Ren, Guixing

    2014-06-01

    Our results affirmed that supplementation of 1 or 2% mung bean could decrease plasma total cholesterol and triacylglycerol level. Mung bean increased mRNA 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Most importantly, mung bean increased not only the protein level of cholesterol-7α-hydroxylase (CYP7A1) but also mRNA CYP7A1. It was concluded that the hypocholesterolemic activity of mung bean was most probable mediated by enhancement of bile acid excretion and up-regulation of CYP7A1.

  5. Up-Regulated Production and Activation of the Complement System in Alzheimer’s Disease Brain

    OpenAIRE

    Yasojima, Koji; Schwab, Claudia; McGeer, Edith G.; McGeer, Patrick L.

    1999-01-01

    We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer’s disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated in affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense a...

  6. Utilization of Wind Turbines for Up-regulation of Power Grids

    DEFF Research Database (Denmark)

    Juelsgaard, Morten; Bendtsen, Jan Dimon; Wisniewski, Rafal

    2013-01-01

    This work considers the use of wind turbines for aiding up-regulation of an electrical grid, by employing temporary overproduction with respect to available power. We present a simple model describing a turbine, and show how the possible period of overproduction can be maximized by solving a series...... of convex problems, where the load is distributed among several turbines in a farm. Thereafter, we present an optimization scheme that guarantees a lower limit for the overproduction period and subsequently propose an adaptive implementation that is robust against parameter uncertainties....

  7. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    ALG-2 was isolated in a screen for proteins involved in programmed cell death and is the first Ca(2+)-binding protein found to be directly involved in apoptosis. We have generated polyclonal antibodies that are suitable for detecting ALG-2 using different immunological methods. Three commercial......, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...

  8. Body dissatisfaction and dietary restraint influence binge eating behavior.

    Science.gov (United States)

    Andrés, Ana; Saldaña, Carmina

    2014-11-01

    As binge eating is a common behavior throughout the general population, we hypothesized that body dissatisfaction would produce binge eating via its prediction of dieting. Six hundred eight individuals were nonrandomly recruited from the community. The mean age and body mass index of participants were 34.76 years (SD, 14.41) and 27.82 kg/m(2) (SD, 9.54), respectively. Participants were asked to complete several self-report questionnaires, which included measures of dieting status, binge eating behavior, body dissatisfaction, overvaluation of weight and shape, and self-esteem. The results showed that dieting was a common behavior; 38.1% of participants reported dieting during the past year. Binge eating during the previous 6 months was reported by 9.9% of the sample and was associated with a higher body mass index as well as more frequent dieting. A model including dieting status, overvaluation of weight and shape, shape satisfaction, and self-esteem showed the best fit for the prediction of binge eating behavior. Moreover, those who dieted and overvalued their weight and shape were 2.01 and 2.31 times more likely, respectively, to binge eat. Structural equation modeling revealed that body dissatisfaction caused dietary restraint, thus triggering binge eating. Both dieting and overvaluation of weight and shape are important risk factors for the development of binge eating disorders. Dieting and binge eating are common behaviors that represent a risk for the development of both excess weight and eating disorders. The structural model proposed in this study could be beneficial in understanding this causal relationship.

  9. Drinking Places: Young People and Cultures of Alcohol Consumption in Rural Environments

    Science.gov (United States)

    Valentine, Gill; Holloway, Sarah; Knell, Charlotte; Jayne, Mark

    2008-01-01

    This paper focuses on the contemporary British moral panic about young people and the consumption of alcohol in public space. Most of this public debate has focused on binge drinking in urban areas as a social problem. Here, we consider instead the role of alcohol in rural communities, and in particular alcohol consumption in domestic and informal…

  10. Socioeconomic Differences in Alcohol-Specific Parenting Practices and Adolescents’ Drinking Patterns

    NARCIS (Netherlands)

    Spijkerman, R.; Eijnden, R.J.J.M. van den; Huiberts, A.M.P.

    2008-01-01

    The aim of this study was to investigate to what extent alcohol-specific parenting practices relate to adolescents’ alcohol use, binge drinking, and alcohol-related problems, and whether these associations are moderated by socioeconomic status (SES), i.e. parents’ education level and family income.

  11. Up-regulation of -opioid receptors in the spinal cord of morphine-tolerant rats

    Indian Academy of Sciences (India)

    Subrata Basu Ray; Himanshu Gupta; Yogendra Kumar Gupta

    2004-03-01

    Though morphine remains the most powerful drug for treating pain, its effectiveness is limited by the development of tolerance and dependence. The mechanism underlying development of tolerance to morphine is still poorly understood. One of the factors could be an alteration in the number of m-receptors within specific parts of the nervous system. However, reports on changes in the -opioid receptor density in the spinal cord after chronic morphine administration are conflicting. Most of the studies have used subcutaneously implanted morphine pellets to produce tolerance. However, it does not simulate clinical conditions, where it is more common to administer morphine at intervals, either by injections or orally. In the present study, rats were made tolerant to morphine by injecting increasing doses of morphine (10–50 mg/kg, subcutaneously) for five days. In vitro tissue autoradiography for localization of -receptor in the spinal cord was done using [3H]-DAMGO. As compared to the spinal cord of control rats, the spinal cord of tolerant rats showed an 18.8% increase or up-regulation in the density of -receptors in the superficial layers of the dorsal horn. This up-regulation of -receptors after morphine tolerance suggests that a fraction of the receptors have been rendered desensitized, which in turn could lead to tolerance.

  12. Neural cell 3D microtissue formation is marked by cytokines' up-regulation.

    Directory of Open Access Journals (Sweden)

    Yinzhi Lai

    Full Text Available Cells cultured in three dimensional (3D scaffolds as opposed to traditional two-dimensional (2D substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate. Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue.

  13. Salvianolic acid B inhibits mitochondrial dysfunction by up-regulating mortalin

    Science.gov (United States)

    Liu, Yunxia; Hu, Yingying; E, Qiukai; Zuo, Ji; Yang, Ling; Liu, Wen

    2017-01-01

    Salvianolic acid B is an antioxidative ingredient derived from Radix Salviae miltiorrhizae that has been widely used to treat liver diseases. However, the therapeutic mechanism underlying Salvianolic acid B has remained largely unknown. Our studies verified that Salvianolic acid B efficiently blocked mitochondrial deformation and dysfunction induced by H2O2 in the human hepatocyte cell line HL7702. Mortalin, a mitochondrial molecular chaperone, maintains mitochondrial morphology stabilization and function integrity. Previous results showed that mortalin overexpression has been observed in hematoma carcinoma cells and that mortalin maintains mitochondrial homeostasis and antagonizes oxidative stress damage. We found that Salvianolic acid B significantly up-regulated mortalin protein expression levels. In addition, Salvianolic acid B lost the function of preventing mitochondrial deformation and dysfunction induced by oxidative stress under mortalin knockdown conditions. We further found that mortalin overexpression increases the mRNA expression of mitofusin-related factor Mfn1 and mitofission-related factor hFis1. In conclusion, Salvianolic acid B maintains the mitochondrial structure stabilization and functional integrity by up-regulating mortalin, which may be associated with increased mitofusin factor Mfn1 and reduced mitofission factor hFis1. PMID:28251987

  14. N-glycoprotein analysis discovers new up-regulated glycoproteins in colorectal cancer tissue.

    Science.gov (United States)

    Nicastri, Annalisa; Gaspari, Marco; Sacco, Rosario; Elia, Laura; Gabriele, Caterina; Romano, Roberto; Rizzuto, Antonia; Cuda, Giovanni

    2014-11-07

    Colorectal cancer is one of the leading causes of death due to cancer worldwide. Therefore, the identification of high-specificity and -sensitivity biomarkers for the early detection of colorectal cancer is urgently needed. Post-translational modifications, such as glycosylation, are known to play an important role in cancer progression. In the present work, we used a quantitative proteomic technique based on (18)O stable isotope labeling to identify differentially expressed N-linked glycoproteins in colorectal cancer tissue samples compared with healthy colorectal tissue from 19 patients undergoing colorectal cancer surgery. We identified 54 up-regulated glycoproteins in colorectal cancer samples, therefore potentially involved in the biological processes of tumorigenesis. In particular, nine of these (PLOD2, DPEP1, SE1L1, CD82, PAR1, PLOD3, S12A2, LAMP3, OLFM4) were found to be up-regulated in the great majority of the cohort, and, interestingly, the association with colorectal cancer of four (PLOD2, S12A2, PLOD3, CD82) has not been hitherto described.

  15. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats

    Science.gov (United States)

    Hoffman, Gloria E.; Koban, Michael

    2016-01-01

    A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC), would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD) because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness. PMID:27997552

  16. Substance P stimulates differentiation of mice osteoblast through up-regulating Osterix expression

    Institute of Scientific and Technical Information of China (English)

    SUN Hai-biao; CHEN Jun-chang; Qiang; GUO Min-feng; ZHANG Hua-ping

    2010-01-01

    Objective:To investigate the molecular pathway of substance P(SP)to induce osteoblastic differentiation.Methods:Mesenchymal stem cells were isolated and cultured.The cultures were divided into four groups with Group A(control group)cultured without any factors,Group B cultured with SP,Group C cultured with SP and SP receptor neurokinin-1(NK_1)antagonist,and Group D cultured with SP NK_1 antagonist respectively to induce osteoblastic cells differentiation.Osterix gene expression was detected by reverse transcription-polymerase chain reaction(RT-PCR)for three times after 1-2 weeks of cultivation and the results were analyzed by one-way analysis of variance(ANOVA).Results:The log phase of bone marrow stromal cells appeared at 4-6 days.ALP staining revealed that the majority of cells,more than 95%,were positive and small bluepurple granules were found in the cytoplasm.And Group B,treated with SP,showed a higher level of ALP activity than the other three groups.Meanwhile,RT-PCR found that Osterix expression in Group B was obviously up-regulated,compared with other groups.But Osterix expression in Group D had no remarkable differences,compared with the controls.Conclusions:SP can up-regulate Osterix gene expression to stimulate differentiation of mesenchymal stem cells into osteoblastic cells at the final stage.The regulatory effect of SP on Osterix expression was dependant on SP NK_1 receptors.

  17. Midazolam inhibits the hypoxia-induced up-regulation of erythropoietin in the central nervous system.

    Science.gov (United States)

    Matsuyama, Tomonori; Tanaka, Tomoharu; Tatsumi, Kenichiro; Daijo, Hiroki; Kai, Shinichi; Harada, Hiroshi; Fukuda, Kazuhiko

    2015-08-15

    Erythropoietin (EPO), a regulator of red blood cell production, is endogenously expressed in the central nervous system. It is mainly produced by astrocytes under hypoxic conditions and has proven to have neuroprotective and neurotrophic effects. In the present study, we investigated the effect of midazolam on EPO expression in primary cultured astrocytes and the mouse brain. Midazolam was administered to 6-week-old BALB/c male mice under hypoxic conditions and pregnant C57BL/6N mice under normoxic conditions. Primary cultured astrocytes were also treated with midazolam under hypoxic conditions. The expression of EPO mRNA in mice brains and cultured astrocytes was studied. In addition, the expression of hypoxia-inducible factor (HIF), known as the main regulator of EPO, was evaluated. Midazolam significantly reduced the hypoxia-induced up-regulation of EPO in BALB/c mice brains and primary cultured astrocytes and suppressed EPO expression in the fetal brain. Midazolam did not affect the total amount of HIF proteins but significantly inhibited the nuclear expression of HIF-1α and HIF-2α proteins. These results demonstrated the suppressive effects of midazolam on the hypoxia-induced up-regulation of EPO both in vivo and in vitro.

  18. Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation.

    Science.gov (United States)

    Wang, Wuyang; Gao, Qiong; Yang, Meimei; Zhang, Xiaoli; Yu, Lu; Lawas, Maria; Li, Xinran; Bryant-Genevier, Marthe; Southall, Noel T; Marugan, Juan; Ferrer, Marc; Xu, Haoxing

    2015-03-17

    Upon nutrient starvation, autophagy digests unwanted cellular components to generate catabolites that are required for housekeeping biosynthesis processes. A complete execution of autophagy demands an enhancement in lysosome function and biogenesis to match the increase in autophagosome formation. Here, we report that mucolipin-1 (also known as TRPML1 or ML1), a Ca(2+) channel in the lysosome that regulates many aspects of lysosomal trafficking, plays a central role in this quality-control process. By using Ca(2+) imaging and whole-lysosome patch clamping, lysosomal Ca(2+) release and ML1 currents were detected within hours of nutrient starvation and were potently up-regulated. In contrast, lysosomal Na(+)-selective currents were not up-regulated. Inhibition of mammalian target of rapamycin (mTOR) or activation of transcription factor EB (TFEB) mimicked a starvation effect in fed cells. The starvation effect also included an increase in lysosomal proteostasis and enhanced clearance of lysosomal storage, including cholesterol accumulation in Niemann-Pick disease type C (NPC) cells. However, this effect was not observed when ML1 was pharmacologically inhibited or genetically deleted. Furthermore, overexpression of ML1 mimicked the starvation effect. Hence, lysosomal adaptation to environmental cues such as nutrient levels requires mTOR/TFEB-dependent, lysosome-to-nucleus regulation of lysosomal ML1 channels and Ca(2+) signaling.

  19. Salvianolic acid B inhibits mitochondrial dysfunction by up-regulating mortalin.

    Science.gov (United States)

    Liu, Yunxia; Hu, Yingying; E, Qiukai; Zuo, Ji; Yang, Ling; Liu, Wen

    2017-03-02

    Salvianolic acid B is an antioxidative ingredient derived from Radix Salviae miltiorrhizae that has been widely used to treat liver diseases. However, the therapeutic mechanism underlying Salvianolic acid B has remained largely unknown. Our studies verified that Salvianolic acid B efficiently blocked mitochondrial deformation and dysfunction induced by H2O2 in the human hepatocyte cell line HL7702. Mortalin, a mitochondrial molecular chaperone, maintains mitochondrial morphology stabilization and function integrity. Previous results showed that mortalin overexpression has been observed in hematoma carcinoma cells and that mortalin maintains mitochondrial homeostasis and antagonizes oxidative stress damage. We found that Salvianolic acid B significantly up-regulated mortalin protein expression levels. In addition, Salvianolic acid B lost the function of preventing mitochondrial deformation and dysfunction induced by oxidative stress under mortalin knockdown conditions. We further found that mortalin overexpression increases the mRNA expression of mitofusin-related factor Mfn1 and mitofission-related factor hFis1. In conclusion, Salvianolic acid B maintains the mitochondrial structure stabilization and functional integrity by up-regulating mortalin, which may be associated with increased mitofusin factor Mfn1 and reduced mitofission factor hFis1.

  20. Utrophin up-regulation by an artificial transcription factor in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Elisabetta Mattei

    Full Text Available Duchenne Muscular Dystrophy (DMD is a severe muscle degenerative disease, due to absence of dystrophin. There is currently no effective treatment for DMD. Our aim is to up-regulate the expression level of the dystrophin related gene utrophin in DMD, complementing in this way the lack of dystrophin functions. To this end we designed and engineered several synthetic zinc finger based transcription factors. In particular, we have previously shown that the artificial three zinc finger protein named Jazz, fused with the appropriate effector domain, is able to drive the transcription of a test gene from the utrophin promoter "A". Here we report on the characterization of Vp16-Jazz-transgenic mice that specifically over-express the utrophin gene at the muscular level. A Chromatin Immunoprecipitation assay (ChIP demonstrated the effective access/binding of the Jazz protein to active chromatin in mouse muscle and Vp16-Jazz was shown to be able to up-regulate endogenous utrophin gene expression by immunohistochemistry, western blot analyses and real-time PCR. To our knowledge, this is the first example of a transgenic mouse expressing an artificial gene coding for a zinc finger based transcription factor. The achievement of Vp16-Jazz transgenic mice validates the strategy of transcriptional targeting of endogenous genes and could represent an exclusive animal model for use in drug discovery and therapeutics.

  1. Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury

    Institute of Scientific and Technical Information of China (English)

    Lauren M Aleksunes; Michael Goedken; José E Manautou

    2006-01-01

    AIM: To investigate the expression and activity of NAD(P)H quinone oxidoreductase 1 (NQO1) in human liver specimens obtained from patients with liver damage due to acetaminophen (APAP) overdose or primary biliary cirrhosis (PBC).METHODS: NQO1 activity was determined in cytosol from normal, APAP and PBC liver specimens. Western blot and immunohistochemical staining were used to determine patterns of NQO1 expression using a specific antibody against NQO1.RESULTS: NQO1 protein was very low in normal human livers. In both APAP and PBC livers, there was strong induction of NQO1 protein levels on Western blot.Correspondingly, significant up-regulation of enzyme activity (16- and 22-fold, P< 0.05) was also observed in APAP and PBC livers, respectively. Immunohistochemical analysis highlighted injury-specific patterns of NQO1 staining in both APAP and PBC livers.CONCLUSION: These data demonstrate that NQO1 protein and activity are markedly induced in human livers during both APAP overdose and PBC. Up-regulation of this cytoprotective enzyme may represent an adaptive stress response to limit further disease progression by detoxifying reactive species.

  2. Neurobiological features of binge eating disorder.

    Science.gov (United States)

    Balodis, Iris M; Grilo, Carlos M; Potenza, Marc N

    2015-12-01

    Biobehavioral features associated with binge-eating disorder (BED) have been investigated; however, few systematic reviews to date have described neuroimaging findings from studies of BED. Emerging functional and structural studies support BED as having unique and overlapping neural features as compared with other disorders. Neuroimaging studies provide evidence linking heightened responses to palatable food cues with prefrontal areas, particularly the orbitofrontal cortex (OFC), with specific relationships to hunger and reward-sensitivity measures. While few studies to date have investigated non-food-cue responses; these suggest a generalized hypofunctioning in frontostriatal areas during reward and inhibitory control processes. Early studies applying neuroimaging to treatment efforts suggest that targeting neural function underlying motivational processes may prove important in the treatment of BED.

  3. [The treatment of binge eating disorder - a review].

    Science.gov (United States)

    Papp, Ildikó; Szumska, Irena; Túry, Ferenc

    2015-01-01

    The binge eating disorder is a relatively new type of eating disorders, which was first described in 1992, and became a distinct nosological entity in the system of DSM-5 in 2013. Its central symptom is the binge, which is not followed by compensatory behaviours as in bulimia nervosa. Therefore, the patients are generally obese. The prevalence of the disorder is 1-3% in the general population, but much higher in help-seeking obese subjects. The two main goals of the therapy is body weight reduction, and the cessation of binges. In the pharmacotherapy of binge eating disorder the antidepressants are recommended mainly in the case of unsuccessful psychotherapy, and in treating comorbid depression. In the field of psychotherapy data are available mainly on the effectiveness of cognitive behavioural therapy, dialectic behaviour therapy, behavioural weight loss, and interpersonal therapy. Effectivity studies on new therapeutic methods and treatment combinations are needed as well as long term follow-up studies.

  4. Negative emotional expectancies and readiness to change among college student binge drinkers.

    Science.gov (United States)

    McNally, A M; Palfai, T P

    2001-01-01

    While expectancies are considered to be an important cognitive variable in the etiology and maintenance of substance use, less is known about their role in attitudes toward addictive behavior change. It has recently been suggested that negative alcohol expectancies, in particular, might play a fundamental role in motivation to change. Among a population of college student binge drinkers, the differential ability of positive and negative expectancies to predict total readiness to change (RTC) scores was examined. Hierarchical regression analyses revealed that controlling for level of consumption and number of drinking-related problems, negative and not positive expectancies significantly predicted RTC. In an examination of expectancy subtypes, negative emotional expectancies emerged as the only significant predictor of change motivation. Possible explanations for the findings and implications for interventions with undergraduate heavy drinkers are discussed.

  5. Systemisk/Narrativ gruppebehandling af Binge Eating Disorder

    DEFF Research Database (Denmark)

    Schousboe, Birgitte Hartvig

    2010-01-01

    Artiklen beskriver gruppeterapi på systemisk/narrativt grundlag til patienter med Binge Eating Disorder (BED). Den beskriver, hvordan en problemmættet historie omkring BED-gruppen blev dekonstrueret ved at ændre behandlingens udformning og eksperimentere med socialkonstruktionistiske ideer og......, hvilket har fremmet konsolideringen af foretrukne historier i gruppens refleksioner og styrket terapeuternes evne til at facilitere processen. Nøgleord: Binge Eating Disorder, systemisk narrativ terapi, grupppe...

  6. Daily variations in cortisol levels and binge eating disorder.

    Science.gov (United States)

    Sitton, Sarah; Porn, Patricia M; Shaeffer, Stephanie

    2002-12-01

    Morning and afternoon levels of cortisol for 73 volunteers (67 women and 6 men) were compared in relation to their Binge Eating Disorder scores, Body Mass Indexes, and self-reports of mood and hunger. Cortisol level was not significantly correlated with binge eating or mood or hunger for either time period. However, it was inversely related to body mass, with lower cortisol levels associated with greater body mass.

  7. Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity.

    Science.gov (United States)

    Sun, Xinjuan; Chen, Jin'an; Zhang, Jie; Wang, Wei; Sun, Jinshan; Wang, Aiping

    2016-03-01

    To determine the role of maggot debridement therapy (MDT) on diabetic foot wound healing, we compared growth related factors in wounds before and after treatment. Furthermore, we utilized human umbilical vein endothelial cells (HUVECs) to explore responses to maggot excretions/secretions on markers of angiogenesis and proliferation. The results showed that there was neo-granulation and angiogenesis in diabetic foot wounds after MDT. Moreover, significant elevation in CD34 and CD68 levels was also observed in treated wounds. In vitro, ES increased HUVEC proliferation, improved tube formation, and increased expression of vascular endothelial growth factor receptor 2 in a dose dependent manner. These results demonstrate that MDT and maggot ES can promote diabetic foot wound healing by up-regulating endothelial cell activity.

  8. Neuronal changes resulting in up-regulation of alpha-1 adrenoceptors after peripheral nerve injury

    Institute of Scientific and Technical Information of China (English)

    Peter D.Drummond

    2014-01-01

    Under normal conditions, the sympathetic neurotransmitter noradrenaline inhibits the pro-duction and release of pro-inlfammatory cytokines. However, after peripheral nerve and tissue injury, pro-inflammatory cytokines appear to induce the expression of the alpha1A-adreno-ceptor subtype on immune cells and perhaps also on other cells in the injured tissue. In turn, noradrenaline may act on up-regulated alpha1-adrenoceptors to increase the production of the pro-inflammatory cytokine interleukin-6. In addition, the release of inflammatory mediators and nerve growth factor from keratinocytes and other cells may augment the expression of al-pha1-adrenoceptors on peripheral nerve ifbers. Consequently, nociceptive afferents acquire an abnormal excitability to adrenergic agents, and inlfammatory processes build. These mechanisms could contribute to the development of sympathetically maintained pain in conditions such as post-herpetic neuralgia, cutaneous neuromas, amputation stump pain and complex regional pain syndrome.

  9. HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer.

    Science.gov (United States)

    Wang, Yue; Cai, Xiaoli; Zhang, Shuqin; Cui, Ming; Liu, Fabao; Sun, Baodi; Zhang, Weiying; Zhang, Xiaodong; Ye, Lihong

    2017-03-11

    The oncoprotein hepatitis B X-interacting protein (HBXIP) results in the dysregulation of lipid metabolism to enhance the development of breast cancer. Acyl-CoA synthetase long-chain family member 1 (ACSL1) is required for thioesterification of long-chain fatty acids into their acyl-CoA derivatives. In this study, we present a hypothesis that HBXIP might be involved in the regulation of ACSL1 in breast cancer. Interestingly, we found that the overexpression of HBXIP was able to up-regulate ACSL1 at the levels of mRNA and protein in a dose-dependent manner in breast cancer cells. Conversely, silencing of HBXIP led to the opposite results. Mechanistically, HBXIP as a coactivator interacted with transcriptional factor Sp1 through binding to the promoter of ACSL1 by ChIP assays analysis, leading to the transcription of ACSL1 in breast cancer cells. Immunohistochemistry staining revealed that the positive rate of ACSL1 was 71.4% (35/49) in clinical breast cancer tissues, HBXIP 79.6% (39/49), in which the positive rate of ACSL1 was 76.9% (30/39) in the HBXIP-positive specimens. But, few positive rate of ACSL1 10% (1/10) was observed in normal breast tissues. The mRNA levels of ACSL1 were significantly higher in clinical breast cancer tissues than those in their corresponding peritumor tissues. The mRNA levels of ACSL1 were positively associated with those of HBXIP in clinical breast cancer tissues. Thus, we conclude that the oncoprotein HBXIP is able to up-regulate ACSL1 through activating the transcriptional factor Sp1 in breast cancer.

  10. Low-level laser irradiation stimulates tenocyte migration with up-regulation of dynamin II expression.

    Directory of Open Access Journals (Sweden)

    Wen-Chung Tsai

    Full Text Available Low-level laser therapy (LLLT is commonly used to treat sports-related tendinopathy or tendon injury. Tendon healing requires tenocyte migration to the repair site, followed by proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of laser on tenocyte migration. Furthermore, the correlation between this effect and expression of dynamin 2, a positive regulator of cell motility, was also investigated. Tenocytes intrinsic to rat Achilles tendon were treated with low-level laser (660 nm with energy density at 1.0, 1.5, and 2.0 J/cm(2. Tenocyte migration was evaluated by an in vitro wound healing model and by transwell filter migration assay. The messenger RNA (mRNA and protein expressions of dynamin 2 were determined by reverse transcription/real-time polymerase chain reaction (real-time PCR and Western blot analysis respectively. Immunofluorescence staining was used to evaluate the dynamin 2 expression in tenocytes. Tenocytes with or without laser irradiation was treated with dynasore, a dynamin competitor and then underwent transwell filter migration assay. In vitro wound model revealed that more tenocytes with laser irradiation migrated across the wound border to the cell-free zone. Transwell filter migration assay confirmed that tenocyte migration was enhanced dose-dependently by laser. Real-time PCR and Western-blot analysis demonstrated that mRNA and protein expressions of dynamin 2 were up-regulated by laser irradiation dose-dependently. Confocal microscopy showed that laser enhanced the expression of dynamin 2 in cytoplasm of tenocytes. The stimulation effect of laser on tenocytes migration was suppressed by dynasore. In conclusion, low-level laser irradiation stimulates tenocyte migration in a process that is mediated by up-regulation of dynamin 2, which can be suppressed by dynasore.

  11. Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is a progressive and lethal disorder characterized by fibroproliferation and excessive accumulation of extracellular matrix in the lung. METHODS AND FINDINGS: Using oligonucleotide arrays, we identified osteopontin as one of the genes that significantly distinguishes IPF from normal lungs. Osteopontin was localized to alveolar epithelial cells in IPF lungs and was also significantly elevated in bronchoalveolar lavage from IPF patients. To study the fibrosis-relevant effects of osteopontin we stimulated primary human lung fibroblasts and alveolar epithelial cells (A549 with recombinant osteopontin. Osteopontin induced a significant increase of migration and proliferation in both fibroblasts and epithelial cells. Epithelial growth was inhibited by the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS and antibody to CD44, while fibroproliferation was inhibited by GRGDS and antibody to alphavbeta3 integrin. Fibroblast and epithelial cell migration were inhibited by GRGDS, anti-CD44, and anti-alphavbeta3. In fibroblasts, osteopontin up-regulated tissue inhibitor of metalloprotease-1 and type I collagen, and down-regulated matrix metalloprotease-1 (MMP-1 expression, while in A549 cells it caused up-regulation of MMP-7. In human IPF lungs, osteopontin colocalized with MMP-7 in alveolar epithelial cells, and application of weakest link statistical models to microarray data suggested a significant interaction between osteopontin and MMP-7. CONCLUSIONS: Our results provide a potential mechanism by which osteopontin secreted from the alveolar epithelium may exert a profibrotic effect in IPF lungs and highlight osteopontin as a potential target for therapeutic intervention in this incurable disease.

  12. Up-regulation of GLT-1 severely impairs LTD at mossy fibre--CA3 synapses.

    Science.gov (United States)

    Omrani, Azar; Melone, Marcello; Bellesi, Michele; Safiulina, Victoria; Aida, Tomomi; Tanaka, Kohishi; Cherubini, Enrico; Conti, Fiorenzo

    2009-10-01

    Glutamate transporters are responsible for clearing synaptically released glutamate from the extracellular space. By this action, they maintain low levels of ambient glutamate, thus preventing excitotoxic damage, and contribute to shaping synaptic currents. We show that up-regulation of the glutamate transporter GLT-1 by ceftriaxone severely impaired mGluR-dependent long-term depression (LTD), induced at rat mossy fibre (MF)-CA3 synapses by repetitive stimulation of afferent fibres. This effect involved GLT-1, since LTD was rescued by the selective GLT-1 antagonist dihydrokainate (DHK). DHK per se produced a modest decrease in fEPSP amplitude that rapidly regained control levels after DHK wash out. Moreover, the degree of fEPSP inhibition induced by the low-affinity glutamate receptor antagonist gamma-DGG was similar during basal synaptic transmission but not during LTD, indicating that in ceftriaxone-treated rats LTD induction did not alter synaptic glutamate transient concentration. Furthermore, ceftriaxone-induced GLT-1 up-regulation significantly reduced the magnitude of LTP at MF-CA3 synapses but not at Schaffer collateral-CA1 synapses. Postembedding immunogold studies in rats showed an increased density of gold particles coding for GLT-1a in astrocytic processes and in mossy fibre terminals; in the latter, gold particles were located near and within the active zones. In both CEF-treated and untreated GLT-1 KO mice used for verifying the specificity of immunostaining, the density of gold particles in MF terminals was comparable to background levels. The enhanced expression of GLT-1 at release sites may prevent activation of presynaptic receptors, thus revealing a novel mechanism by which GLT-1 regulates synaptic plasticity in the hippocampus.

  13. Up-regulated expression of extracellular matrix remodeling genes in phagocytically challenged trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Kristine M Porter

    Full Text Available BACKGROUND: Cells in the trabecular meshwork (TM, the tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic function in TM cells is thought to play an important role in the normal functioning of the outflow pathway. Dysfunction of phagocytosis could lead to abnormalities of outflow resistance and increased intraocular pressure (IOP. However, the molecular mechanisms triggered by phagocytosis in TM cells are completely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profile analysis of human TM cells phagocytically challenged to E. coli or pigment under physiological and oxidative stress environment were performed using Affymetrix U133 plus 2.0 array and analyzed with Genespring GX. Despite the differential biological response elicited by E. coli and pigment particles, a number of genes, including MMP1, MMP3, TNFSF11, DIO2, KYNU, and KCCN2 showed differential expression with both phagocytic ligands in all conditions. Data was confirmed by qPCR in both human and porcine TM cells. Metacore pathway analysis and the usage of recombinant adenovirus encoding the dominant negative mutant of IkB identified NF-κB as a transcription factor mediating the up-regulation of at least MMP1 and MMP3 in TM cells with phagocytosis. In-gel zymography demonstrated increased collagenolytic and caseinolytic activities in the culture media of TM cells challenge to E. coli. In addition, collagenolytic I activity was further confirmed using the self-quenched fluorescent substrate DQ-Collagen I. CONCLUSIONS/SIGNIFICANCE: Here we report for the first time the differential gene expression profile of TM cells phagocytically challenged with either E. coli or pigment. Our data indicate a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

  14. Alcohol drinking, consumption patterns and breast cancer among Danish nurses: a cohort study

    DEFF Research Database (Denmark)

    Mørch, Lina S; Johansen, Ditte; Thygesen, Lau C;

    2007-01-01

    BACKGROUND: The aim of this study was to analyse the impact of alcohol intake and drinking pattern on the risk of breast cancer. METHODS: A total of 17 647 nurses were followed from 1993 until the end of 2001. At baseline participants completed a questionnaire on alcohol intake and other lifestyle...... alcohol consumers, weekly alcohol intake increased the risk of breast cancer with 2% for each additional drink consumed. Weekend consumption increased the risk with 4% for each additional drink consumed friday through sunday. Binge drinking of 4-5 drinks the latest weekday increased risk with 55......%, compared with consumption of one drink. A possible threshold in risk estimates was found for consumption above 27 drinks per week. CONCLUSIONS: For alcohol consumption above the intake most frequently reported, the risk of breast cancer is increased. The risk is minor for moderate levels but increases...

  15. Insecticide-Mediated Up-Regulation of Cytochrome P450 Genes in the Red Flour Beetle (Tribolium castaneum

    Directory of Open Access Journals (Sweden)

    Xiao Liang

    2015-01-01

    Full Text Available Some cytochrome P450 (CYP genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively, permethrin (2.00- and 2.03-fold and lambda-cyhalothrin (1.73- and 1.81-fold, whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.

  16. Insecticide-mediated up-regulation of cytochrome P450 genes in the red flour beetle (Tribolium castaneum).

    Science.gov (United States)

    Liang, Xiao; Xiao, Da; He, Yanping; Yao, Jianxiu; Zhu, Guonian; Zhu, Kun Yan

    2015-01-19

    Some cytochrome P450 (CYP) genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR) revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively), permethrin (2.00- and 2.03-fold) and lambda-cyhalothrin (1.73- and 1.81-fold), whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold) when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.

  17. Drinking cholera

    DEFF Research Database (Denmark)

    Grant, Stephen Lawrence; Tamason, Charlotte Crim; Hoque, Bilqis Amin

    2015-01-01

    beconducive to V. cholerae survival. Furthermore, salinity levels of participant’s drinking water sourceswere all well below the levels required for optimal survival of V. cholerae. Respondents explainedthat they preferred less salty and more aesthetically pleasing drinking water. Conclusion: Theoretically, V...

  18. Alcohol consumption in university students: the role of reasons for drinking, coping strategies, expectancies, and personality traits.

    Science.gov (United States)

    Williams, A; Clark, D

    1998-01-01

    Despite the popularity of the social learning perspective of alcohol abuse, there have been limited efforts devoted to developing comprehensive models that delineate the roles of the constituent components of this approach. In the present study, we determined whether reasons for drinking, coping strategies, alcohol expectancies, and personality traits predict binge drinking and alcohol consumption levels in university students. Escape drinking was the sole positive direct predictor of binge drinking. Social drinking predicted alcohol consumption and thereby exerted an indirect influence on binge drinking. Alcohol expectancies played a significant role in the model but only by influencing reasons for drinking. Although the use of alcohol and/or drugs to cope predicted alcohol consumption, none of a variety of other coping strategies exerted a significant influence in the model. Stress responsivity-related personality traits played a significant role, primarily via an influence on alcohol expectancies. These findings provide support for the social learning perspective of alcohol abuse and offer further insight into the factors that contribute to the development of risky alcohol consumption patterns.

  19. EGF up-regulates miR-31 through the C/EBPβ signal cascade in oral carcinoma.

    Directory of Open Access Journals (Sweden)

    Wen-Cheng Lu

    Full Text Available Oral squamous cell carcinoma (OSCC is one of the most prevalent carcinomas worldwide. MicroRNAs (miRNAs are short, non-coding RNAs that regulate gene expression and modulate physiological or pathological processes including OSCC carcinogenesis. miR-31 has been found to be up-regulated in OSCC and to act as an oncogenic miRNA. However, the molecular mechanism underlying miR-31 up-regulation in OSCC is still obscure. The activation of epidermal growth factor receptor (EGFR signaling axis plays key roles in driving oral carcinogenesis. Our screening identified that there is up-regulation of miR-31, miR-181b and miR-222 in OSCC cells following EGF treatment. Subsequent analysis showed that EGF treatment led to AKT activation, which then resulted in miR-31 up-regulation. Moreover, EGF treatment and the AKT activation induced by exogenous expression up-regulated C/EBPβ expression. The miR-31 up-regulation induced by EGF was abrogated by AKT inhibition or by the knockdown of C/EBPβ expression. In OSCC cell subclones stably overexpressing the functional isoform of C/EBPβ, miR-31 expression was up-regulated. Curcumin is a natural ingredient exhibiting anti-cancer potential. It was found that curcumin attenuated AKT activation and the up-regulation of C/EBPβ and miR-31 caused by EGF stimulation in OSCC cells. Lastly, concordance across the expression of EGFR, the expression of C/EBPβ and the expression of miR-31 in OSCC tissues was found. This study describes a novel scenario where the up-regulation of miR-31 expression in OSCC is, at least in part, a consequence of EGFR oncogenic activation. Although the AKT activation and C/EBPβ expression after EGF treatment might not be directly linked, both events are the crucial mediators underlying miR-31 up-regulation in the EGFR signaling axis.

  20. Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.

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    Takeshi Chiyomaru

    Full Text Available Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs. In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1 and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as 'Pathways in cancer', 'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3' UTR of several target genes (such as RAC1, EGFR and EP300 that are components of 'Pathways in cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.

  1. Hydrogen sulfide inhibits development of atherosclerosis through up-regulating protein S-nitrosylation.

    Science.gov (United States)

    Lin, Yan; Chen, Yulong; Zhu, Ninghong; Zhao, Sihai; Fan, Jianglin; Liu, Enqi

    2016-10-01

    Hydrogen sulfide (H2S) is an important gaseous signaling molecule that serves many important regulatory roles in physiological and pathophysiological conditions. H2S exerts an anti-atherosclerotic effect through mediating the biological functions of nitric oxide (NO). However, its mechanism of action is unclear. The purpose of this study is to explore the effect mechanism of H2S on the development of atherosclerosis with regard to protein S-nitrosylation. A total of 45 male apoE(-/-) mice were randomly divided into three groups. Atherosclerosis was induced by Western diet (21% fat and 0.15% cholesterol) with/without administration of a H2S donor (NaHS) or an endogenous cystathionine γ-lyase inhibitor (d, l-propargylglycine) for 12 weeks. After 12 weeks, plasma lipid and plasma NO levels were measured. Aortic gross lesion area and histopathological features of aortic lesion were determined. Additionally, the level of S-nitrosylated proteins in vascular smooth muscle cells (VSMCs) was detected using immunofluorescence in aorta. Rat VSMCs were performed in an in vitro experiment. Inducible nitric oxide synthase (iNOS) protein expression, NO generation, protein S-nitrosylation, and cell proliferation and migration were measured. We found that H2S significantly reduced the aortic atherosclerotic lesion area (P=0.006) and inhibited lipid and macrophage accumulation (P=0.004, P=0.002) and VSMC proliferation (P=0.019) in apoE(-/-) mice. H2S could up-regulate levels of plasma NO and protein S-nitrosylation in aorta VSMCs. However, d, l- propargylglycine had the opposite effect, increasing the lesion area and the content of lipids and macrophages in the lesions of apoE(-/-) mice and down-regulating plasma NO levels and protein S-nitrosylation in aorta VSMCs. In vitro experiments, H2S could significantly reverse the reduction of iNOS expression and NO generation induced by oxidized low-density lipoprotein in VSMCs. Moreover, H2S could increase the protein S

  2. Exercise-induced up-regulation of MMP-1 and IL-8 genes in endurance horses

    Directory of Open Access Journals (Sweden)

    Silvestrelli Maurizio

    2009-06-01

    Full Text Available Abstract Background The stress response is a critical factor in the training of equine athletes; it is important for performance and for protection of the animal against physio-pathological disorders. In this study, the molecular mechanisms involved in the response to acute and strenuous exercise were investigated using peripheral blood mononuclear cells (PBMCs. Results Quantitative real-time PCR (qRT-PCR was used to detect modifications in transcription levels of the genes for matrix metalloproteinase-1 (MMP-1 and interleukin 8 (IL-8, which were derived from previous genome-wide expression analysis. Significant up-regulation of these two genes was found in 10 horses that had completed a race of 90–120 km in a time-course experimental design. Conclusion These results suggest that MMP-1 and IL-8 are both involved in the exercise-induced stress response, and this represents a starting point from which to understand the adaptive responses to this phenomenon.

  3. FOXO3-mediated up-regulation of Bim contributes to rhein-induced cancer cell apoptosis.

    Science.gov (United States)

    Wang, Jiao; Liu, Shu; Yin, Yancun; Li, Mingjin; Wang, Bo; Yang, Li; Jiang, Yangfu

    2015-03-01

    The anthraquinone compound rhein is a natural agent in the traditional Chinese medicine rhubarb. Preclinical studies demonstrate that rhein has anticancer activity. Treatment of a variety of cancer cells with rhein may induce apoptosis. Here, we report that rhein induces atypical unfolded protein response in breast cancer MCF-7 cells and hepatoma HepG2 cells. Rhein induces CHOP expression, eIF2α phosphorylation and caspase cleavage, while it does not induce glucose-regulated protein 78 (GRP78) expression in both MCF-7 and HepG2 cells. Meanwhile, rhein inhibits thapsigargin-induced GRP78 expression and X box-binding protein 1 splicing. In addition, rhein inhibits Akt phosphorylation and stimulates FOXO transactivation activity. Rhein induces Bim expression in MCF-7 and HepG2 cells, which can be abrogated by FOXO3a knockdown. Knockdown of FOXO3a or Bim abrogates rhein-induced caspase cleavage and apoptosis. The chemical chaperone 4-phenylbutyrate acid antagonizes the induction of FOXO activation, Bim expression and caspase cleavage by rhein, indicating that protein misfolding may be involved in triggering these deleterious effects. We conclude that FOXO3a-mediated up-regulation of Bim is a key mechanism underlying rhein-induced cancer cells apoptosis.

  4. Schisandra polysaccharide increased glucose consumption by up-regulating the expression of GLUT-4.

    Science.gov (United States)

    Jin, Dun; Zhao, Ting; Feng, Wei-Wei; Mao, Guang-Hua; Zou, Ye; Wang, Wei; Li, Qian; Chen, Yao; Wang, Xin-Tong; Yang, Liu-Qing; Wu, Xiang-Yang

    2016-06-01

    In our previous study, a polysaccharide was extracted from Schisandra Chinensis (Trucz.) Baill and found with anti-diabetic effects. The aim of this study was to investigate the anti-diabetic effects of the low weight molecular polysaccharide (SCPP11) purified from crude Schisandra polysaccharide and illustrate the underlying mechanism in buffalo rat liver cells. The insulin resistance model of BRL cells was established by incubating with insulin solution for 24h. The effects of SCPP11 on regulating related protein and mRNA expression in an insulin and AMPK signal pathway were investigated by western blot and RT-PCR analysis. SCPP11 showed no cytotoxicity to BRL cells and could improve the glucose consumption in BRL cells. SCPP11 increased the protein expression of Akt, p-AMPK and GLUT-4 in BRL cells. Moreover, SCPP11 could enhance the mRNA expression levels of IRS-1, PI3K, Akt, GLUT-4, AMPKα and PPAR-γ in BRL cells at the same time. In conclusion, SCPP11 possessed effects in improving glucose consumption by up-regulating the expression of GLUT-4 which might occur via insulin and AMPK signal pathway and could be a potential functional food to prevent and mitigate the insulin resistance condition.

  5. Up-regulated production and activation of the complement system in Alzheimer's disease brain.

    Science.gov (United States)

    Yasojima, K; Schwab, C; McGeer, E G; McGeer, P L

    1999-03-01

    We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer's disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated in affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense accumulations of plaques and tangles, C1q mRNA was increased 11- to 80-fold over control levels, and C9 mRNA 10- to 27-fold. These levels were substantially higher than in the livers of the same cases. Western blot analysis of AD hippocampus established the presence of all of the native complement proteins as well as their activation products C4d, C3d, and the membrane attack complex. These data indicate that high levels of complement are being produced in affected areas of AD brain, that full activation of the classical complement pathway is continuously taking place, and that this activation may be contributing significantly to AD pathology.

  6. Cloning and characterization of an up-regulated GA 20-oxidase gene in hybrid maize

    Institute of Scientific and Technical Information of China (English)

    Jinkun Du; Yingyin Yao; Zhongfu Ni; Qixin Sun

    2009-01-01

    Previous studies revealed that GA content and metabolism are positively correlated with a faster shoot growth rate of hybrid, and recently, genes participating in both GA biosynthesis and GA response pathways were also found to be differentially expressed between wheat hybrid and its parental inbreds. In this study, an up-regulated GA 20-oxidase gene in a maize hybrid, designated ZmGA20, was cloned. ZmGA20 contains an open reading frame (ORF) encoding 391 amino acid residues. BLASTX searches in GenBank revealed that the ZmGA20 is homologous to the sequences of GA20ox proteins from different species, and analysis also indicated that ZmGA20 had typical features of GA 20-oxidase proteins, including a "LPWKET" sequence. Semi-quantitative RT-PCR analysis showed that ZmGA20 was expressed in different tissues and/or organs. The expression level of ZmGA20 in the hybrid was higher than that in two parents (in roots, leaves, stems and embryo, and ears). The abundance of ZmGA20 transcript was equal to that of the highly expressed parents, which provided molecular evidence for the observed GA content heterosis in maize hybrids.

  7. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

    Science.gov (United States)

    Fey, Theres; Schubert, Kai Michael; Schneider, Holger; Fein, Evelyn; Kleinert, Eike; Pohl, Ulrich; Dendorfer, Andreas

    2016-08-01

    Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

  8. Up-Regulation of CCR5 and CXCR4 Expression on Human Monocytes by Interferon Gamma

    Institute of Scientific and Technical Information of China (English)

    陆韵; 刘祖强; 陈应华

    2003-01-01

    Chemokine receptors, mainly CCR5 and CXCR4, have been proved to be the important coreceptors in HIV-1 entry.HIV-1 disease progression is, in general, characterized by an initial predominance of CCR5 using macrophage tropic, non-syncytium-inducing (NSI) isolates, switching later to CXCR4 using T-cell tropic, syncytium-inducing (SI) isolates.How this shift occurs and how the shift can be controlled are still unclear.Since patients with rapid decline of T cell counts have constantly high levels of IFN-γ in the sera and lymphoid nodes, we investigated the influence of this cytokine on the expression of the HIV-1 coreceptors CCR5 and CXCR4 on the cell surfaces of human monocytic cell line U937 and promonocyte NB4.IFN-γ could intensively enhance the expression of both, while a low level of CCR5 expression was detected in two cell lines before stimulation.The results of semiquantitative RT-PCR also confirm the up-regulation.As the newly generated X4-strains have been demonstrated to be insensitive to chemokine in some reports, IFN-γ may play an important role in selecting CXCR4-used strains.

  9. The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation.

    Directory of Open Access Journals (Sweden)

    Raquel M Silva

    Full Text Available Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance.

  10. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

    Directory of Open Access Journals (Sweden)

    Joana T de Oliveira

    Full Text Available The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT, in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.

  11. PAX3-FOXO1 Induces Up-Regulation of Noxa Sensitizing Alveolar Rhabdomyosarcoma Cells to Apoptosis

    Directory of Open Access Journals (Sweden)

    Amy D. Marshall

    2013-07-01

    Full Text Available Alveolar rhabdomyosarcoma (ARMS has a much poorer prognosis than the more common embryonal subtype. Most ARMS tumors characteristically possess a specific genomic translocation between the genes of PAX3/7 and FOXO1 (FKHR, which forms fusion proteins possessing the DNA binding domains of PAX3/7 and the more transcriptionally potent transactivation domain of FOXO1. We have shown that the proapoptotic BH3-only family member Noxa is upregulated by the PAX3-FOXO1 fusion transcription factor in a p53-independent manner. The increased expression of Noxa renders PAX3-FOXO1-expressing cells more susceptible to apoptosis induced by a ă-secretase inhibitor (GSI1, Z-LLNle-CHO, the proteasome inhibitor bortezomib, and BH3 mimetic ABT-737. Apoptosis in response to bortezomib can be overcome by shRNA knockdown of Noxa. In vivo treatment with bortezomib reduced the growth of tumors derived from a PAX3-FOXO1-expressing primary myoblast tumor model and RH41 xenografts. We therefore demonstrate that PAX3-FOXO1 up-regulation of Noxa represents an unanticipated aspect of ARMS tumor biology that creates a therapeutic window to allow induction of apoptosis in ARMS cells.

  12. PAX3-FOXO1 induces up-regulation of Noxa sensitizing alveolar rhabdomyosarcoma cells to apoptosis.

    Science.gov (United States)

    Marshall, Amy D; Picchione, Fabrizio; Geltink, Ramon I Klein; Grosveld, Gerard C

    2013-07-01

    Alveolar rhabdomyosarcoma (ARMS) has a much poorer prognosis than the more common embryonal subtype. Most ARMS tumors characteristically possess a specific genomic translocation between the genes of PAX3/7 and FOXO1 (FKHR), which forms fusion proteins possessing the DNA binding domains of PAX3/7 and the more transcriptionally potent transactivation domain of FOXO1. We have shown that the proapoptotic BH3-only family member Noxa is upregulated by the PAX3-FOXO1 fusion transcription factor in a p53-independent manner. The increased expression of Noxa renders PAX3-FOXO1-expressing cells more susceptible to apoptosis induced by a γ-secretase inhibitor (GSI1, Z-LLNle-CHO), the proteasome inhibitor bortezomib, and BH3 mimetic ABT-737. Apoptosis in response to bortezomib can be overcome by shRNA knockdown of Noxa. In vivo treatment with bortezomib reduced the growth of tumors derived from a PAX3-FOXO1-expressing primary myoblast tumor model and RH41 xenografts. We therefore demonstrate that PAX3-FOXO1 up-regulation of Noxa represents an unanticipated aspect of ARMS tumor biology that creates a therapeutic window to allow induction of apoptosis in ARMS cells.

  13. Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration.

    Directory of Open Access Journals (Sweden)

    Yanli Ma

    Full Text Available Aflatoxin B1 (AFB1 is a potent carcinogen that can induce hepatocellular carcinoma. AFB1-8,9-exo-epoxide, one of AFB1 metabolites, acts as a mutagen to react with DNA and induce gene mutations, including the tumor suppressor p53. In addition, AFB1 reportedly stimulates IGF receptor activation. Aberrant activation of IGF-I receptor (IGF-IR signaling is tightly associated with various types of human tumors. In the current study, we investigated the effects of AFB1 on key elements in IGF-IR signaling pathway, and the effects of AFB1 on hepatoma cell migration. The results demonstrated that AFB1 induced IGF-IR, Akt, and Erk1/2 phosphorylation in hepatoma cell lines HepG2 and SMMC-7721, and an immortalized human liver cell line Chang liver. AFB1 also down-regulated insulin receptor substrate (IRS 1 but paradoxically up-regulated IRS2 through preventing proteasomal degradation. Treatment of hepatoma cells and Chang liver cells with IGF-IR inhibitor abrogated AFB1-induced Akt and Erk1/2 phosphorylation. In addition, IRS2 knockdown suppressed AFB1-induced Akt and Erk1/2 phosphorylation. Finally, AFB1 stimulated hepatoma cell migration. IGF-IR inhibitor or IRS2 knockdown suppressed AFB1-induced hepatoma cell migration. These data demonstrate that AFB1 stimulates hepatoma cell migration through IGF-IR/IRS2 axis.

  14. L-DOPA neurotoxicity is mediated by up-regulation of DMT1-IRE expression.

    Directory of Open Access Journals (Sweden)

    Fang Du

    Full Text Available BACKGROUND: The mechanisms underlying neurotoxicity caused by L-DOPA are not yet completely known. Based on recent findings, we speculated that the increased expression of divalent metal transporter 1 without iron-response element (DMT1-IRE induced by L-DOPA might play a critical role in the development of L-DOPA neurotoxicity. To test this hypothesis, we investigated the effects of astrocyte-conditioned medium (ACM and siRNA DMT-IRE on L-DOPA neurotoxicity in cortical neurons. METHODS AND FINDINGS: We demonstrated that neurons treated with L-DOPA have a significant dose-dependent decrease in neuronal viability (MTT Assay and increase in iron content (using a graphite furnace atomic absorption spectrophotometer, DMT1-IRE expression (Western blot analysis and ferrous iron (55Fe(II uptake. Neurons incubated in ACM with or without L-DOPA had no significant differences in their morphology, Hoechst-33342 staining or viability. Also, ACM significantly inhibited the effects of L-DOPA on neuronal iron content as well as DMT1-IRE expression. In addition, we demonstrated that infection of neurons with siRNA DMT-IRE led to a significant decrease in DMT1-IRE expression as well as L-DOPA neurotoxicity. CONCLUSION: The up-regulation of DMT1-IRE and the increase in DMT1-IRE-mediated iron influx play a key role in L-DOPA neurotoxicity in cortical neurons.

  15. Compassion-based emotion regulation up-regulates experienced positive affect and associated neural networks.

    Science.gov (United States)

    Engen, Haakon G; Singer, Tania

    2015-09-01

    Emotion regulation research has primarily focused on techniques that attenuate or modulate the impact of emotional stimuli. Recent evidence suggests that this mode regulation can be problematic in the context of regulation of emotion elicited by the suffering of others, resulting in reduced emotional connectedness. Here, we investigated the effects of an alternative emotion regulation technique based on the up-regulation of positive affect via Compassion-meditation on experiential and neural affective responses to depictions of individuals in distress, and compared these with the established emotion regulation strategy of Reappraisal. Using fMRI, we scanned 15 expert practitioners of Compassion-meditation either passively viewing, or using Compassion-meditation or Reappraisal to modulate their emotional reactions to film clips depicting people in distress. Both strategies effectively, but differentially regulated experienced affect, with Compassion primarily increasing positive and Reappraisal primarily decreasing negative affect. Imaging results showed that Compassion, relative to both passive-viewing and Reappraisal increased activation in regions involved in affiliation, positive affect and reward processing including ventral striatum and medial orbitfrontal cortex. This network was shown to be active prior to stimulus presentation, suggesting that the regulatory mechanism of Compassion is the stimulus-independent endogenous generation of positive affect.

  16. [Preliminary influence of 2015 cigarette excise tax up-regulation on cigarette retail price].

    Science.gov (United States)

    Feng, G Z; Wang, C X; Yang, J Q; Jiang, Y

    2016-10-10

    Objective: To evaluate the impact of cigarette excise tax up-regulation on the retail price of cigarettes in 2015. Methods: Nominal and real price of selected cigarette varieties were calculated with data from Tobacco Retail Price Monitoring Project, which was conducted in 10 cities of China from 2013 to 2015. The trend of the cigarette prices changing was analyzed with annual data. Results: A total of 352 varieties of cigarettes were surveyed during the three years. The nominal price of these cigarettes did not change significantly from 2013 to 2014. Compared with nominal price of 2014, the price of 286 varieties increased and the price of 10 most popular varieties increased from 0.6% to 7.4% after cigarette excise tax increased, but the actual prices had both rise and fall compared with 2013. Conclusions: Cigarette excise tax raise in 2015 had influence on the retail price of cigarettes. But the increase in retail price was very limited, if factors including inflation and purchasing power are taken into consideration. Therefore, the influence of 2015 cigarette excise tax raise on tobacco control needs further evaluation.

  17. Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

    Science.gov (United States)

    Zhang, Shuai; Li, Tao-Sheng; Soyama, Akihiko; Tanaka, Takayuki; Yan, Chen; Sakai, Yusuke; Hidaka, Masaaki; Kinoshita, Ayaka; Natsuda, Koji; Fujii, Mio; Kugiyama, Tota; Baimakhanov, Zhassulan; Kuroki, Tamotsu; Gu, Weili; Eguchi, Susumu

    2016-01-01

    Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the PH and sham groups 14 days after operation. However, compared with those in the sham group, the livers in mice in the PH+BDL group had a smaller size, a lower cell proliferative activity, and more fibrotic tissue 14 days after the operation, suggesting the insufficient regeneration of the cholestatic liver. Pathway-focused array analysis showed that many genes were up- or down-regulated over 1.5-fold in both PH+BDL and PH groups at 1, 3, 7, and 14 days after treatment. Interestingly, more genes that were functionally related to the extracellular matrix and inflammatory chemokines were found in the PH+BDL group than in the PH group at 7 and 14 days after treatment. Our data suggest that up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

  18. Underage drinkers' responses to negative-restrictive versus proactive-nonrestrictive slogans in humorous anti-alcohol abuse messages: are humorous responsible drinking campaign messages effective?

    Science.gov (United States)

    Lee, Moon J; Chen, Yi-Chun Yvonnes

    2013-01-01

    This study examined underage drinkers' responses to negative-restrictive versus proactive-nonrestrictive slogans in humorous anti-alcohol abuse advertisements. The authors conducted a posttest-only control group experiment with 91 teenagers and college-aged participants. For underage moderate drinkers, the negative-restrictive slogans (e.g., "Don't drink") increased participants' perceived risk of excessive drinking and increased a level of intention to change their drinking behavior. However, for underage binge drinkers, the negative-restrictive slogans lowered participants' risk perception of excessive drinking and intention to change their drinking behavior.

  19. Does the Interpersonal Model Generalize to Obesity Without Binge Eating?

    Science.gov (United States)

    Lo Coco, Gianluca; Sutton, Rachel; Tasca, Giorgio A; Salerno, Laura; Oieni, Veronica; Compare, Angelo

    2016-09-01

    The interpersonal model has been validated for binge eating disorder (BED), but it is not yet known if the model applies to individuals who are obese but who do not binge eat. The goal of this study was to compare the validity of the interpersonal model in those with BED versus those with obesity, and normal weight samples. Data from a sample of 93 treatment-seeking women diagnosed with BED, 186 women who were obese without BED, and 100 controls who were normal weight were examined for indirect effects of interpersonal problems on binge eating psychopathology mediated through negative affect. Findings demonstrated the mediating role of negative affect for those with BED and those who were obese without BED. Testing a reverse model suggested that the interpersonal model is specific for BED but that this model may not be specific for those without BED. This is the first study to find support for the interpersonal model in a sample of women with obesity but who do not binge. However, negative affect likely plays a more complex role in determining overeating in those with obesity but who do not binge. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  20. Exposure to cell phone radiation up-regulates apoptosis genes in primary cultures of neurons and astrocytes.

    Science.gov (United States)

    Zhao, Tian-Yong; Zou, Shi-Ping; Knapp, Pamela E

    2007-01-22

    The health effects of cell phone radiation exposure are a growing public concern. This study investigated whether expression of genes related to cell death pathways are dysregulated in primary cultured neurons and astrocytes by exposure to a working Global System for Mobile Communication (GSM) cell phone rated at a frequency of 1900MHz. Primary cultures were exposed to cell phone emissions for 2h. We used array analysis and real-time RT-PCR to show up-regulation of caspase-2, caspase-6 and Asc (apoptosis associated speck-like protein containing a card) gene expression in neurons and astrocytes. Up-regulation occurred in both "on" and "stand-by" modes in neurons, but only in "on" mode in astrocytes. Additionally, astrocytes showed up-regulation of the Bax gene. The effects are specific since up-regulation was not seen for other genes associated with apoptosis, such as caspase-9 in either neurons or astrocytes, or Bax in neurons. The results show that even relatively short-term exposure to cell phone radiofrequency emissions can up-regulate elements of apoptotic pathways in cells derived from the brain, and that neurons appear to be more sensitive to this effect than astrocytes.

  1. Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice

    Science.gov (United States)

    Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice spe...

  2. The Perspective Theory of Zong Bing in the 5th Century of China

    Institute of Scientific and Technical Information of China (English)

    LiuKeming; ZuoHongshan

    2003-01-01

    A brief historical introduction of researches on perspective in ancient China is presented,this paper studied and discussed the perspective theory or Zong Bing (宗炳) in the 5th century of China, including Zong Bing and this An introduction to Landscape Painting, and its mathematical basis, drawing ideas of Zong Bing as well.

  3. Energy drinks mixed with alcohol: what are the risks?

    Science.gov (United States)

    Marczinski, Cecile A; Fillmore, Mark T

    2014-10-01

    Energy drinks are popular beverages that typically include high levels of caffeine and other ingredients such as taurine, or caffeine-containing herbs, such as guarana. While energy drinks are often consumed alone, they are also frequently used as mixers for alcoholic beverages. This review summarizes what is known about the scope of use of alcohol mixed with energy drinks, the risks associated with such mixtures, and the objective laboratory data examining how the effects of their consumption differ from consuming alcohol alone. The weight of the evidence reveals that consuming alcohol mixed with energy drinks is riskier than consuming alcohol alone and constitutes a public health concern. Consumption of these mixed beverages is frequent, especially in young and underage drinkers, and compared with alcohol alone, their use is associated with elevated rates of binge drinking, impaired driving, risky sexual behavior, and risk of alcohol dependence. Laboratory research (human and animal) has demonstrated that consuming alcohol mixed with energy drinks leads to altered subjective states including decreased perceived intoxication, enhanced stimulation, and increased desire to drink/increased drinking compared to consuming alcohol alone. Possible underlying mechanisms explaining these observations are highlighted in this review.

  4. Can energy drinks increase the desire for more alcohol?

    Science.gov (United States)

    Marczinski, Cecile A

    2015-01-01

    Energy drinks, the fastest growing segment in the beverage market, have become popular mixers with alcohol. The emerging research examining the use of alcohol mixed with energy drinks (AmEDs) indicates that the combination of caffeine-containing energy drinks with alcohol may be riskier than the use of alcohol alone. The public health concerns arising from AmED use are documented in different research domains. Epidemiologic studies reveal that the consumption of AmEDs is frequent among young and underage drinkers, demographic groups that are more likely to experience the harms and hazards associated with alcohol use. In addition, for all consumers, elevated rates of binge drinking and risk of alcohol dependence have been associated with AmED use when compared to alcohol alone. Results from laboratory studies help explain why AmED use is associated with excessive intake of alcohol. When an energy drink (or caffeine) is combined with alcohol, the desire (or urge) to drink more alcohol is more pronounced in both humans and animals than with the same dose of alcohol alone. The experience of drinking alcohol appears to be more rewarding when combined with energy drinks. Given that caffeine in other foods and beverages increases preference for those products, further research on AmEDs may elucidate the underlying mechanisms that contribute to alcohol dependence.

  5. Up-regulation of sucrose synthase and UDP-glucose pyrophosphorylase impacts plant growth and metabolism.

    Science.gov (United States)

    Coleman, Heather D; Ellis, Dave D; Gilbert, Margarita; Mansfield, Shawn D

    2006-01-01

    The effects of the overexpression of sucrose synthase (SuSy) and UDP-glucose pyrophosphorylase (UGPase) on plant growth and metabolism were evaluated in tobacco (Nicotiana tabacum cv. Xanthi). T(1) transgenic plants expressing either gene under the control of a tandem repeat cauliflower mosaic virus 35S promoter (2x35S) or a xylem-localized 4CL promoter (4-coumarate:CoA ligase; 4CL) were generated, and reciprocally crossed to generate plants expressing both genes. Transcript levels, enzyme activity, growth parameters, fibre properties and carbohydrate content of stem tissue were quantified. The expression profiles of both genes confirmed the expression pattern of the promoters: 2x35S expressed more strongly in leaves, while 4CL expression was highest in stem tissue. In-depth plant characterization revealed that the single-transgene lines showed significant increases in the height growth compared with corresponding control lines. The double-transgene plants demonstrated an additive effect, proving to be even taller than the single-transgene parents. Several of these lines had associated increases in soluble sugar content. Although partitioning of storage carbohydrates into starch or cellulose was not observed, the increased height growth and increases in soluble carbohydrates suggest a role for SuSy as a marker in sink strength and lend credit to the function of UGPase in a similar role. The up-regulation of these two genes, although not increasing the percentage cellulose content, was effective in increasing the total biomass, and thus the overall cellulose yield, from a given plant.

  6. Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating Galectin-14.

    Science.gov (United States)

    Cho, Yuri; Lee, Yun Bin; Lee, Jeong-Hoon; Lee, Dong Hyeon; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Kim, Jong In; Im, Jong Hun; Lee, Jung Hwan; Oh, Eun Ju; Yoon, Jung-Hwan

    2016-01-01

    Aptamers are small synthetic oligonucleotides that bind to target proteins with high specificity and affinity. AS1411 is an aptamer that binds to nucleolin, which is overexpressed in the cytoplasm and occurs on the surface of cancer cells. We investigated the therapeutic potential of aptamers in hepatocellular carcinoma (HCC) by evaluating anti-tumor effects and confirming the affinity and specificity of AS1411- and modified AS1411-aptamers in HCC cells. Cell growth was assessed using the MTS assay, and cell death signaling was explored by immunoblot analysis. Fluorescence-activated cell sorting was performed to evaluate the affinity and specificity of AS1411-aptamers in SNU-761 HCC cells. We investigated the in vivo effects of the AS1411-aptamer using BALB/c nude mice in a subcutaneous xenograft model with SNU-761 cells. Treatment with a modified AS1411-aptamer significantly decreased in vitro (under normoxic [P = 0.035] and hypoxic [P = 0.018] conditions) and in vivo (under normoxic conditions, P = 0.041) HCC cell proliferation compared to control aptamers. AS1411- and control aptamers failed to control HCC cell proliferation. However, AS1411- and the modified AS1411-aptamer did not induce caspase activation. Decrease in cell growth by AS1411 or modified AS1411 was not prevented by caspase or necrosis inhibitors. In a microarray, AS1411 significantly enhanced galectin-14 expression. Suppression of HCC cell proliferation by the modified AS1411-aptamer was attenuated by galectin-14 siRNA transfection. Modified AS1411-aptamer suppressed HCC cell growth in vitro and in vivo by up-regulating galectin-14 expressions. Modified AS1411-aptamers may have therapeutic potential as a novel targeted therapy for HCC.

  7. Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.

    Science.gov (United States)

    Zambrano, Joelle N; Neely, Benjamin A; Yeh, Elizabeth S

    2017-02-09

    Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2(+)/ErbB2(+)) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2(+)/ErbB2(+) breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2(+)/ErbB2(+) breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer.

  8. Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Cheng, Jung-Chien [Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Huang, He-Feng, E-mail: huanghefg@hotmail.com [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Leung, Peter C.K., E-mail: peter.leung@ubc.ca [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada)

    2013-11-01

    Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.

  9. Up-regulation of Niacinamide in Intervertebral Disc Aggrecan in vitro

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The regulatory effects of niacinamide (Nia) on intervertebral disc (IVD) aggrecan in vitro was investigated. Chiba's 10 ng/mL interleukin-1 (IL-1)-induced rabbit IVD degeneration model in vitro was established. 0.5, 0.25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan (GS) content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed: (1) After treatment with 0.5 mg/mL Nia for one week, the GS content in nucleus pulposus (NP) was increased by 44.8 % as compared with control group (P<0.01); The GS content in IL-1 induction groups was increased with the increase of Nia concentrations: After treatment with 0.5 mg/mL for one week, the GS content in NP was increased by 68.3 % as compared with control group (P<0.01). After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period (P<0.01)and untreated group (P<0.01). (2) Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1β was alleviated. (3) RT-PCR showed that the expression of core protein gene in IL-1β-induced degenerated IVDS was increased with the increase of Nia concentrations.It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1β-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.

  10. Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells

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    Abir Mukherjee

    2015-09-01

    Full Text Available Lysophosphatidic acid (LPA, a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2 was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the human HK2 gene promoter identified the sterol regulatory element-binding protein as the primary mediator of LPA-induced HK2 transcription. The effects of LPA on HK2 and glycolysis rely on LPA2, an LPA receptor subtype overexpressed in ovarian cancer and many other malignancies. We further examined the general role of growth factor-induced glycolysis in cell proliferation. Like LPA, epidermal growth factor (EGF elicited robust glycolytic and proliferative responses in ovarian cancer cells. Insulin-like growth factor 1 (IGF-1 and insulin, however, potently stimulated cell proliferation but only modestly induced glycolysis. Consistent with their differential effects on glycolysis, LPA and EGF-dependent cell proliferation was highly sensitive to glycolytic inhibition while the growth-promoting effect of IGF-1 or insulin was more resistant. These results indicate that LPA- and EGF-induced cell proliferation selectively involves up-regulation of HK2 and glycolytic metabolism. The work is the first to implicate LPA signaling in promotion of glucose metabolism in cancer cells.

  11. Molecular characterization of Quercus suber MYB1, a transcription factor up-regulated in cork tissues.

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    Almeida, Tânia; Menéndez, Esther; Capote, Tiago; Ribeiro, Teresa; Santos, Conceição; Gonçalves, Sónia

    2013-01-15

    The molecular processes associated with cork development in Quercus suber L. are poorly understood. A previous molecular approach identified a list of genes potentially important for cork formation and differentiation, providing a new basis for further molecular studies. This report is the first molecular characterization of one of these candidate genes, QsMYB1, coding for an R2R3-MYB transcription factor. The R2R3-MYB gene sub-family has been described as being involved in the phenylpropanoid and lignin pathways, both involved in cork biosynthesis. The results showed that the expression of QsMYB1 is putatively mediated by an alternative splicing (AS) mechanism that originates two different transcripts (QsMYB1.1 and QsMYB1.2), differing only in the 5'-untranslated region, due to retention of the first intron in one of the variants. Moreover, within the retained intron, a simple sequence repeat (SSR) was identified. The upstream regulatory region of QsMYB1 was extended by a genome walking approach, which allowed the identification of the putative gene promoter region. The relative expression pattern of QsMYB1 transcripts determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) revealed that both transcripts were up-regulated in cork tissues; the detected expression was several times higher in newly formed cork harvested from trees producing virgin, second or reproduction cork when compared with wood. Moreover, the expression analysis of QsMYB1 in several Q. suber organs showed very low expression in young branches and roots, whereas in leaves, immature acorns or male flowers, no expression was detected. These preliminary results suggest that QsMYB1 may be related to secondary growth and, in particular, with the cork biosynthesis process with a possible alternative splicing mechanism associated with its regulatory function.

  12. Up-regulation of niacinamide in intervertebral disc aggrecan in vitro.

    Science.gov (United States)

    Xiong, Xiaoqian; Yang, Shuhua; Shao, Zengwu; Liu, Xin; Zhan, Zirui; Duan, Deyu

    2006-01-01

    The regulatory effects of niacinamide (Nia) on intervertebral disc (IVD) aggrecan in vitro was investigated. Chiba's 10 ng/mL interleukin-1 (IL-1)-induced rabbit IVD degeneration model in vitro was established. 0.5, 0.25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan (GS) content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed: (1) After treatment with 0.5 mg/mL Nia for one week, the GS content in nucleus pulposus (NP) was increased by 44.8% as compared with control group (P < 0 01); The GS content in IL-1 induction groups was increased with the increase of Nia concentrations: After treatment with 0.5 mg/mL for one week, the GS content in NP was increased by 68.3% as compared with control group (P < 0.01). After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period (P < 0.01) and untreated group (P < 0.01). (2) Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1beta was alleviated. (3) RT-PCR showed that the expression of core protein gene in IL-1beta-induced degenerated IVDS was increased with the increase of Nia concentrations. It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1beta-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.

  13. IL-1β up-regulates expression of IL-8 in endometrial stromal cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Zhang Guiyu; Ren Shuwen; Zhang Youzhong; Yang Xingsheng

    2005-01-01

    Objective:To investigate the effects of interleukin-1beta (IL-1β) on expression of IL-8 in endometrial stromal cells (ESC) and evaluate the relationship between IL1 β and IL-8 ,and the significance of IL-1β in the development of endometriosis. Methods:The endometrial stromal cells obtained from patient with and without endometriosis cultured within 3 ~5 passage were exposed to various concentrations of IL-1β. The amount of IL-8 protein was assessed by ELISA. The expression of IL-8 mRNA was determined by RT-PCR. Results: 1. IL-8 protein was detected in culture supernatant of which the cells were not treated with IL-1β. The amount of IL-8 protein secretion increased obviously after stimulation with IL-1β at 1.0ng/ml for 4h and the peak of secretion was at 12h. 2. Expression of IL-8 mRNA was positive in unstimulated endometrial stromal cells. However, after stromal cells were incubated with IL-1β, the intensity of expression of IL-8 mRNA was obviously increased and demonstrated a dose-and timedependent manner. Increase of IL-8 mRNA was observed following stimulation with IL-1β for 4h ,and the peak at 12h. Conclusions:IL-1β induces endometrial stromal cell of endometriosis to express IL-8 not only at transcription level but also at post-transcription level. This up-regulation is dose-and time-dependent. IL-1β may play an important role in the onset of endometriosis.

  14. PSG gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins.

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    Soledad A Camolotto

    Full Text Available BACKGROUND: Lysine acetylation is an important post-translational modification that plays a central role in eukaryotic transcriptional activation by modifying chromatin and transcription-related factors. Human pregnancy-specific glycoproteins (PSG are the major secreted placental proteins expressed by the syncytiotrophoblast at the end of pregnancy and represent early markers of cytotrophoblast differentiation. Low PSG levels are associated with complicated pregnancies, thus highlighting the importance of studying the mechanisms that control their expression. Despite several transcription factors having been implicated as key regulators of PSG gene family expression; the role of protein acetylation has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Here, we explored the role of acetylation on PSG gene expression in the human placental-derived JEG-3 cell line. Pharmacological inhibition of histone deacetylases (HDACs up-regulated PSG protein and mRNA expression levels, and augmented the amount of acetylated histone H3 associated with PSG 5'regulatory regions. Moreover, PSG5 promoter activation mediated by Sp1 and KLF6, via the core promoter element motif (CPE, -147/-140, was markedly enhanced in the presence of the HDAC inhibitor trichostatin A (TSA. This effect correlated with an increase in Sp1 acetylation and KLF6 nuclear localization as revealed by immunoprecipitation and subcellular fractionation assays. The co-activators PCAF, p300, and CBP enhanced Sp1-dependent PSG5 promoter activation through their histone acetylase (HAT function. Instead, p300 and CBP acetyltransferase domain was dispensable for sustaining co-activation of PSG5 promoter by KLF6. CONCLUSIONS/SIGNIFICANCE: Results are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6 following an augmented Sp1 acetylation and KLF6 nuclear localization.

  15. Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis

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    Uddman Rolf

    2005-09-01

    Full Text Available Abstract Background Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen. Methods 27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins. Results mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season. Conclusion The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.

  16. Orphan receptor GPR15/BOB is up-regulated in rheumatoid arthritis.

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    Cartwright, Alison; Schmutz, Caroline; Askari, Ayman; Kuiper, Jan-Herman; Middleton, Jim

    2014-06-01

    Chemokine receptors on leukocytes mediate the recruitment and accumulation of these cells within affected joints in chronic inflammatory diseases such as rheumatoid arthritis (RA). Identification of involved receptors offers potential for development of therapeutic interventions. The objective of this study was to investigate the expression of orphan receptor GPR15/BOB in the synovium of RA and non-RA patients and in peripheral blood of RA patients and healthy donors. GPR15/BOB protein and messenger RNA expression were examined in RA and non-RA synovium by immunofluorescence and reverse-transcription polymerase chain reaction (RT-PCR) respectively. GPR15/BOB expression on peripheral blood leukocytes was analysed by flow cytometry and GPR15/BOB messenger RNA was examined in peripheral blood monocytes by RT-PCR. GPR15/BOB protein was observed in CD68+ and CD14+ macrophages in synovia, with greater expression in RA synovia. GPR15/BOB protein was expressed in all patient synovia whereas in non-RA synovia expression was low or absent. Similarly GPR15/BOB messenger RNA was detected in all RA and a minority of non-RA synovia. GPR15/BOB protein was expressed on peripheral blood leukocytes from RA and healthy individuals with increased expression by monocytes and neutrophils in RA. GPR15/BOB messenger RNA expression was confirmed in peripheral blood monocytes. In conclusion GPR15/BOB is expressed by macrophages in synovial tissue and on monocytes and neutrophils in peripheral blood, and expression is up-regulated in RA patients compared to non-RA controls. This orphan receptor on monocytes/macrophages and neutrophils may play a role in RA pathophysiology.

  17. Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

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    Yu Qian

    2015-03-01

    Full Text Available Objective: Glioblastoma multiforme (GBM, an aggressive primary brain tumor, is radioresistant and recurs despite aggressive surgery, chemotherapy, and radiotherapy. Curcumin as a potential radiosensitizer has received extensive attention in cancer treatment. To explore an effectiveness of this radiosensitizer for GBM treatment, we evaluated the radiosensitizing effect of curcumin and investigated its potential molecular mechanisms in the human glioma cell line U87. Methods: The cytotoxic effects of curcumin on U87 cells were evaluated using the Cell Counting Kit-8 assay, and the radiosensitivity of U87 cells treated with curcumin was accessed by colony information assay. The effects of curcumin on cell proliferation and cell cycle regulation were determined using the 5-ethynyl-2-deoxyuridine incorporation assay and flow cytometry, respectively. Western blotting was applied to determine the effects of curcumin on protein expression of dual-specificity phosphatase-2 (DUSP-2, extracellular signal-regulated kinase (ERK, and c-Jun N-terminal kinase (JNK as well as phosphorylated ERK and JNK. Results: Curcumin significantly inhibited the proliferation of U87 cells in a dose-and time-dependent manner. Curcumin treatment at the concentrations of 5 µM and 10 M could significantly reduce the clonogenic activity and enhance the radiosensitivity of U87 cells with sensitive enhancement ratios (SERs of 1.71 and 4.65, respectively. Curcumin resulted in G2/M cell cycle arrest in U87 cells, which were radiosensitive. Pre-treatment of U87-MG cells with 5 µM curcumin enhanced radiation-induced cell proliferation inhibition and apoptosis. Furthermore, we observed that curcumin increased DUSP-2 protein expression and decreased the phosphorylation of ERK and JNK. Conclusion: Our results suggest that low-dose curcumin may enhance the radiosensitivity of human glioma U87 cells in vitro by inducing G2/M cell cycle arrest through up-regulation of DUSP-2 expression and

  18. Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.

    Science.gov (United States)

    Xuan, Xaioyan; Li, Shanshan; Lou, Xi; Zheng, Xianzhao; Li, Yunyun; Wang, Feng; Gao, Yuan; Zhang, Hongyan; He, Hongliu; Zeng, Qingru

    2015-05-01

    Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.02; and 31%, p = 0.001). Overexpression of Stat3 and p-Stat3 positively correlated with that of matrix metalloproteinase-2 (MMP2), a known regulator for cell migration, in 65% of ESCC while only 26% shown in benign esophageal mucosa. To further investigate the association of Stat3 with tumor metastasis in vitro, invasion of EC-1 cells (a human ESCC cell line) were investigated with Boyden chambers. The results showed that transfection of Stat3 not only promoted invasion of EC-1 cells but also significantly induced MMP2 expression in a dose-dependent manner. In contrast, suppressing expression of endogenous Stat3 mRNA and protein by Stat3 siRNA significantly reduced EC-1 cell invasion and MMP2 expression. A high-affinity Stat3-binding element was localized to the positions of 648-641 bp (TTCTCGAA) in the MMP2 promoter with electrophoretic mobility shift assay. Our results suggest that Stat3, p-Stat3, and MMP2 were overexpressed in ESCC and associated with invasion of ESCC; and Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter.

  19. Up-regulated manganese superoxide dismutase expression increases apoptosis resistance in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    HU Hai; WANG Ming-rong; LUO Man-li; DU Xiao-li; FENG Yan-bin; ZHANG Yu; SHEN Xiao-ming; XU Xin; CAI Yan; HAN Ya-ling

    2007-01-01

    Background Esophageal cancer is one of the most common malignancies in the world.In order to identify the proteins associated with esophageal squamous cell carcinomas(ESCC),we analyzed the protein profiles of ESCC cases with tumor and matched adjacent normal tissues.Methods Two-dimensional electrophoresis(2-DE)was carried out to analyze the protein profiles.Dysregulated protein spots were identified by Matrix-Assisted Laser Desorption Ionization Time-of-Flight(MALDI-TOF)and verified by liquid chromatography/electrospray ionization ion trap-mass spectrometry/mass spectrometry(LC-ESI-IT MS).RT-PCR and immunohistochemistry on tissue microarray were performed to confirm the gene dysregulation in esophageal cancerous tissues.RNA interference (RNAi)was used to knock down the gene expression in ESCC cell lines.Apoptosis assay with annexin V-FITC/PI staining was conducted and cells were analyzed by flow cytometry.Results 2-DE showed that two protein spots with approximate molecular weights and different pl were elevated in 12 out of 18 ESCCs as compared to the corresponding normal tissues.Both the two spots were identified as MnSOD by MALDI-TOF and were verified by LC-ESI-IT MS.MnSOD overexpression was detected in 14 tumors out of 24 cases by RT-PCR and 52 tumors out of 116 cases by immunohistochemistry comparing to normal epithelia.siRNA-mediated silencing of MnSOD in KYSE450 and KYSE150 cell lines revealed that MnSOD protected ESCC cells from apoptosis induced by ultraviolet(UV)and doxorubicin(DOX).Conclusions These findings suggest that there existed two isoforms of MnSOD protein in normal and tumor esophageal tissues.MnSOD was overexpressed in ESCC and its up-regulation in esophageal cancer cells was associated with apoptosis resistance.

  20. Restaurant eating in nonpurge binge-eating women.

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    Timmerman, Gayle M

    2006-11-01

    This study describes restaurant-eating behaviors for nonpurge binge-eating women in comparison to dieters. Restaurant-eating behaviors were determined from a content analysis of 14-day food diaries using a convenience sample of 71 women who reported binging without purging and 46 dieters without a recent binge history. Comparing bingers to dieters, there were no significant differences in frequency of eating out, dessert consumption at restaurants, or fast food eating. Bingers more often perceived restaurant eating to be uncontrolled and excessive. Both bingers and dieters consumed significantly more calories (226-253 kcal) and fat (10.4-16.0 gm) on restaurant days. Extra calories consumed on restaurant-eating days may contribute to weight gain over time, especially with frequent restaurant eating. Restaurants may present a high-risk food environment for bingers and dieters, contributing to loss of control and excess consumption.

  1. Radiation-induced cyclooxygenase 2 up-regulation is dependent on redox status in prostate cancer cells.

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    Li, Lingyun; Steinauer, Kirsten K; Dirks, Amie J; Husbeck, Bryan; Gibbs, Iris; Knox, Susan J

    2003-12-01

    Cyclooxygenase 2 (COX2) is the inducible isozyme of COX, a key enzyme in arachidonate metabolism and the conversion of arachidonic acid (AA) to prostaglandins (PGs) and other eicosanoids. Previous studies have demonstrated that the COX2 protein is up-regulated in prostate cancer cells after irradiation and that this results in elevated levels of PGE(2). In the present study, we further investigated whether radiation-induced COX2 up-regulation is dependent on the redox status of cells from the prostate cancer cell line PC-3. l-Buthionine sulfoximine (BSO), which inhibits gamma glutamyl cysteine synthetase (gammaGCS), and the antioxidants alpha-lipoic acid and N-acetyl-l-cysteine (NAC) were used to modulate the cellular redox status. BSO decreased the cellular GSH level and increased cellular reactive oxygen species (ROS) in PC-3 cells, whereas alpha-lipoic acid and NAC increased the GSH level and decreased cellular ROS. Both radiation and the oxidant H(2)O(2) had similar effects on COX2 up-regulation and PGE(2) production in PC-3 cells, suggesting that radiation-induced COX2 up-regulation is secondary to the production of ROS. The relative increases in COX2 expression and PGE(2) production induced by radiation and H(2)O(2) were even greater when PC-3 cells were pretreated with BSO. When the cells were pretreated with alpha-lipoic acid or NAC for 24 h, both radiation- and H(2)O(2)-induced COX2 up-regulation and PGE(2) production were markedly inhibited. These results demonstrate that radiation-induced COX2 up-regulation in prostate cancer cells is modulated by the cellular redox status. Radiation-induced increases in ROS levels contribute to the adaptive response of PC-3 cells, resulting in elevated levels of COX2.

  2. Drinking patterns of adolescents who develop alcohol use disorders: results from the Victorian Adolescent Health Cohort Study

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    Olsson, Craig A; Romaniuk, Helena; Salinger, Jodi; Staiger, Petra K; Bonomo, Yvonne; Hulbert, Carol; Patton, George C

    2016-01-01

    Objective We identify drinking styles that place teens at greatest risk of later alcohol use disorders (AUD). Design Population-based cohort study. Setting Victoria, Australia. Participants A representative sample of 1943 adolescents living in Victoria in 1992. Outcome measures Teen drinking was assessed at 6 monthly intervals (5 waves) between mean ages 14.9 and 17.4 years and summarised across waves as none, one, or two or more waves of: (1) frequent drinking (3+ days in the past week), (2) loss of control over drinking (difficulty stopping, amnesia), (3) binge drinking (5+ standard drinks in a day) and (4) heavy binge drinking (20+ and 11+ standard drinks in a day for males and females, respectively). Young Adult Alcohol Use Disorder (AUD) was assessed at 3 yearly intervals (3 waves) across the 20s (mean ages 20.7 through 29.1 years). Results We show that patterns of teen drinking characterised by loss of control increase risk for AUD across young adulthood: loss of control over drinking (one wave OR 1.4, 95% CI 1.1 to 1.8; two or more waves OR 1.9, CI 1.4 to 2.7); binge drinking (one wave OR 1.7, CI 1.3 to 2.3; two or more waves OR 2.0, CI 1.5 to 2.6), and heavy binge drinking (one wave OR 2.0, CI 1.4 to 2.8; two or more waves OR 2.3, CI 1.6 to 3.4). This is not so for frequent drinking, which was unrelated to later AUD. Although drinking was more common in males, there was no evidence of sex differences in risk relationships. Conclusions Our results extend previous work by showing that patterns of drinking that represent loss of control over alcohol consumption (however expressed) are important targets for intervention. In addition to current policies that may reduce overall consumption, emphasising prevention of more extreme teenage bouts of alcohol consumption appears warranted. PMID:26868948

  3. Genome-wide methylation and expression profiling identifies promoter characteristics affecting demethylation-induced gene up-regulation in melanoma

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    Halaban Ruth

    2010-02-01

    Full Text Available Abstract Background Abberant DNA methylation at CpG dinucleotides represents a common mechanism of transcriptional silencing in cancer. Since CpG methylation is a reversible event, tumor supressor genes that have undergone silencing through this mechanism represent promising targets for epigenetically active anti-cancer therapy. The cytosine analog 5-aza-2'-deoxycytidine (decitabine induces genomic hypomethylation by inhibiting DNA methyltransferase, and is an example of an epigenetic agent that is thought to act by up-regulating silenced genes. Methods It is unclear why decitabine causes some silenced loci to re-express, while others remain inactive. By applying data-mining techniques to large-scale datasets, we attempted to elucidate the qualities of promoter regions that define susceptibility to the drug's action. Our experimental data, derived from melanoma cell strains, consist of genome-wide gene expression data before and after treatment with decitabine, as well as genome-wide data on un-treated promoter methylation status, and validation of specific genes by bisulfite sequencing. Results We show that the combination of promoter CpG content and methylation level informs the ability of decitabine treatment to up-regulate gene expression. Promoters with high methylation levels and intermediate CpG content appear most susceptible to up-regulation by decitabine, whereas few of those highly methylated promoters with high CpG content are up-regulated. For promoters with low methylation levels, those with high CpG content are more likely to be up-regulated, whereas those with low CpG content are underrepresented among up-regulated genes. Conclusions Clinically, elucidating the patterns of action of decitabine could aid in predicting the likelihood of up-regulating epigenetically silenced tumor suppressor genes and others from pathways involved with tumor biology. As a first step toward an eventual translational application, we build a classifier

  4. Binge Eating Disorder and Body Uneasiness

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    Massimo Cuzzolaro

    2008-12-01

    Full Text Available Debate continues regarding the nosological status of binge eating disorder (BED and the specific diagnostic criteria, including whether, like anorexia nervosa and bulimia nervosa, it should be characterized by body image disturbances in addition to abnormal eating behaviour. The aims of this article are: a to concisely review the main points of the literature that has developed on diagnosis and treatment (especially pharmacological of BED and b to present the results of an original research on body image in obese patients with BED. The study was aimed to verify the following hypothesis: in persons with obesity, BED is associated with greater body uneasiness independently of some possible modulating factors. We studied a clinical sample of 159 (89 females and 70 males adult obese patients who fulfilled DSM-IV-TR diagnostic criteria for BED matched to 159 non-BED obese patients for gender, ethnicity, BMI class, age, weight, stature, onset age of obesity, education level, and marital status. We used the Body Uneasiness Test (BUT, a valuable multidimensional tool for the clinical assessment of body uneasiness in subjects suffering from eating disorders and/or obesity. Obese patients with BED reported higher scores than non-BED patients in the General Severity Index (BUT-A GSI and in every BUT-A subscale. All differences were statistically significant in both sexes. As expected women obtained higher scores than men. According to some other studies, our findings suggest that a negative body image should be included among diagnostic criteria for BED. Consequently, treatment should be focused not simply on eating behaviour and outcome studies should evaluate changes of body image as well.

  5. Underage drinking on saturday nights, sociodemographic and environmental risk factors: a cross-sectional study

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    Galasso Laura

    2011-07-01

    Full Text Available Abstract Background Excessive alcohol consumption in underage people is a rising phenomenon. A major proportion of the disease burden and deaths of young people in developed nations is attributable to alcohol abuse. The aim of this study was to investigate social, demographic and environmental factors that may raise the risk of Saturday night drinking and binge drinking among Italian school students. Methods The study was conducted on a sample of 845 Italian underage school students, by means of an anonymous, self-test questionnaire. Multivariate logistic regression was applied to identify independent risk factors for alcohol drinking and binge drinking. Ordered logistic regression was used to identify independent risk factors for harmful drinking patterns. Results The independent variables that confer a higher risk of drinking in underage students are older age classes, male sex, returning home after midnight, belonging to a group with little respect for the rules, or to a group where young people are not seen as leaders. The higher the perception of alcohol consumption by the group, the higher the risk. Spending time in bars or discos coincides with a two-fold or four-fold increase, respectively, in the risk of alcohol consumption. Conclusion Our findings show that certain environmental and social risk factors are associated with underage drinking. The most important role for preventing young people's exposure to these factors lies with the family, because only parents can exert the necessary control and provide a barrier against potentially harmful situations.

  6. Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation

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    Joshua B. Lewis

    2016-10-01

    Full Text Available It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6 is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung. Cldn6 transgenic (TG and control mice were continuously provided doxycycline from postnatal day (PN 30 until euthanasia date at PN90. A subset of Cldn6 TG and control mice were also subjected to daily secondhand tobacco smoke (SHS via a nose only inhalation system from PN30-90 and compared to room air (RA controls. Animals were euthanized on PN90 and lungs were harvested for histological and molecular characterization. Bronchoalveolar lavage fluid (BALF was procured for the assessment of inflammatory cells and molecules. Quantitative RT-PCR and immunoblotting revealed increased Cldn6 expression in TG vs. control animals and SHS decreased Cldn6 expression regardless of genetic up-regulation. Histological evaluations revealed no adverse pulmonary remodeling via Hematoxylin and Eosin (H&E staining or any qualitative alterations in the abundance of type II pneumocytes or proximal non-ciliated epithelial cells via staining for cell specific propeptide of Surfactant Protein-C (proSP-C or Club Cell Secretory Protein (CCSP, respectively. Immunoblotting and qRT-PCR confirmed the differential expression of Cldn6 and the pro-inflammatory cytokines TNF-α and IL-1β. As a general theme, inflammation induced by SHS exposure was influenced by the availability of Cldn6. These data reveal

  7. Up-regulation of Raf kinase inhibitor protein enhances chemosensitivity of cervical cancer cell

    Institute of Scientific and Technical Information of China (English)

    Xiao Chu; Xinqiang Ji; Mingcui Wang; Wenqing Zhang; Hui Ou; Chong Li

    2014-01-01

    Objective:The purpose of the study is to investigate the ef ects of up-regulation of Raf kinase inhibitor protein (RKlP) on the chemosensitivity of cervical cancer Hela cells. Methods:Eukaryotic expression plasmid pcDNA3.1(+)-ssRKIP containing human overal length RKIPcDNA was transfected into cervical cancer Hela cellby lipofectin assay, establishing a stable cellline containing a target gene by G418. Expression of RKIP in Hela cells was measured by Western blot analysis. After treatment with cisplatin of dif erent concentrations and intervals of time, the ef ect of RKIP on the proliferation of Hela cells was evaluated by MTT method. The flow cytometry was used to investigate whether the RKIP could inhibit apoptosis in Hela cells induced by cisplatin. Results:The expression of RKIP in Hela cells transfected with pcDNA3.1-ssRKIP was increased obviously. After dif erent concentrations of cisplatin treatment cells for 24, 48 and 72 h, the growth inhibition rate in Hela cells transfected with pcDNA3.1-ssRKIP was significantly higher than in control cells (P<0.05). With 5μg/mL cisplatin treatment for 24 h, pcDNA3.1-ssRKIP-transfected Hela cells had an obviously higher percentage of apoptosis (23.2 ± 0.24)%than non-transfected cells (12.4 ± 0.31)%and empty vector-transfected cells (13.4 ± 0.47)%. Without treatment of cisplatin, the percentage of apoptosis for Hela cells transfected with pcDNA3.1-ssRKIP was (5.7 ± 0.12)%, which was stil higher than those of the non-transfected cells (2.9 ± 0.21)%and empty vector-transfected cells (3 ± 0.08)%. Conclusion:Higher expres-sion of RKIP gene can improve chemosensitivitv of cervical cancer Hela cells to cisplatin.

  8. Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation

    Science.gov (United States)

    Lewis, Joshua B.; Milner, Dallin C.; Lewis, Adam L.; Dunaway, Todd M.; Egbert, Kaleb M.; Albright, Scott C.; Merrell, Brigham J.; Monson, Troy D.; Broberg, Dallin S.; Gassman, Jason R.; Thomas, Daniel B.; Arroyo, Juan A.; Reynolds, Paul R.

    2016-01-01

    It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung. Cldn6 transgenic (TG) and control mice were continuously provided doxycycline from postnatal day (PN) 30 until euthanasia date at PN90. A subset of Cldn6 TG and control mice were also subjected to daily secondhand tobacco smoke (SHS) via a nose only inhalation system from PN30-90 and compared to room air (RA) controls. Animals were euthanized on PN90 and lungs were harvested for histological and molecular characterization. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cells and molecules. Quantitative RT-PCR and immunoblotting revealed increased Cldn6 expression in TG vs. control animals and SHS decreased Cldn6 expression regardless of genetic up-regulation. Histological evaluations revealed no adverse pulmonary remodeling via Hematoxylin and Eosin (H&E) staining or any qualitative alterations in the abundance of type II pneumocytes or proximal non-ciliated epithelial cells via staining for cell specific propeptide of Surfactant Protein-C (proSP-C) or Club Cell Secretory Protein (CCSP), respectively. Immunoblotting and qRT-PCR confirmed the differential expression of Cldn6 and the pro-inflammatory cytokines TNF-α and IL-1β. As a general theme, inflammation induced by SHS exposure was influenced by the availability of Cldn6. These data reveal captivating

  9. The use of computer technology to reduce and prevent college drinking.

    Science.gov (United States)

    Wodarski, John S; Macmaster, Samuel; Miller, Nichole K

    2012-01-01

    Underage drinking, or binge drinking, has become a major concern in U.S. society. At The University of Tennessee (UT) a computer-based intervention was put into place for the past 3 years with funding from the Substance Abuse and Mental Health Services Administration (SAMHSA). The intervention was provided to all college students via UT's computer network system and was completed mostly online. Students were given a computerized, standardized assessment of alcohol use, and then a brief intervention was given based on the students' information. The intervention targeted students who were at highest risk for developing unsafe alcohol behaviors and/or increasing prior alcohol consumption habits in their first year of college. More than 54,000 graduate and undergraduate students completed the program. Since the launch of the program binge drinking has dropped 27% on campus, frequent binge drinking dropped 44%, and the number of liquor law violations to 18- to 20-year-olds decreased from 542 in 2004 to approximately 158 in 2007. The use of a computer-based intervention was comprehensive, low cost, and required low maintenance.

  10. Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation

    NARCIS (Netherlands)

    Pekcec, A.; Unkrüer, B.; Schlichtiger, J.; Soerensen, J.; Hartz, A.M.S.; Bauer, B.; van Vliet, E.A.; Gorter, J.A.; Potschka, H.

    2009-01-01

    Up-regulation of the blood-brain barrier efflux transporter P-glycoprotein in central nervous system disorders results in restricted brain access and limited efficacy of therapeutic drugs. In epilepsies, seizure activity strongly triggers expression of P-glycoprotein. Here, we identified the prostag

  11. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Kiso, Hironori [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Ohba, Takayoshi [Department of Cell Physiology, Akita University Graduate School of Medicine (Japan); Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Murakami, Manabu [Department of Pharmacology, Hirosaki University Graduate School of Medicine (Japan); Ono, Kyoichi [Department of Cell Physiology, Akita University Graduate School of Medicine (Japan); Watanabe, Hiroyuki, E-mail: hirow@doc.med.akita-u.ac.jp [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Ito, Hiroshi [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan)

    2013-07-05

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression.

  12. Cloning and functional analyses of a gene from sugar beet up-regulated upon cyst nematode infection

    NARCIS (Netherlands)

    Samuelian, S.; Kleine, M.; Spira, C.P.; Klein Lankhorst, R.M.; Jung, C.

    2004-01-01

    The cDNA-AFLP technique was used to isolate sugar beet genes up-regulated upon infection with the beet cyst nematode Heterodera schachtii. Hairy root cultures were obtained from resistant plants carrying a Beta procumbens translocation as well as from a non-resistant control. mRNA was isolated from

  13. Maternal obesity is associated with ovarian inflammation and up-regulation of early growth response factor 1

    Science.gov (United States)

    Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a pro-inflammatory gene signature and up-regulation of Egr-1 protein in ovaries from obese (OB, n=7) compared to lean (LN, n=10) ...

  14. Unintended consequences of cigarette price changes for alcohol drinking behaviors across age groups: evidence from pooled cross sections

    Directory of Open Access Journals (Sweden)

    McLellan Deborah L

    2012-07-01

    Full Text Available Abstract Background Raising prices through taxation on tobacco and alcohol products is a common strategy to raise revenues and reduce consumption. However, taxation policies are product specific, focusing either on alcohol or tobacco products. Several studies document interactions between the price of cigarettes and general alcohol use and it is important to know whether increased cigarette prices are associated with varying alcohol drinking patterns among different population groups. To inform policymaking, this study investigates the association of state cigarette prices with smoking, and current, binge, and heavy drinking by age group. Methods The 2001-2006 Behavioral Risk Factor Surveillance System surveys (n = 1,323,758 were pooled and analyzed using multiple regression equations to estimate changes in smoking and drinking pattern response to an increase in cigarette price, among adults aged 18 and older. For each outcome, a multiple linear probability model was estimated which incorporated terms interacting state cigarette price with age group. State and year fixed effects were included to control for potential unobserved state-level characteristics that might influence smoking and drinking. Results Increases in state cigarette prices were associated with increases in current drinking among persons aged 65 and older, and binge and heavy drinking among persons aged 21-29. Reductions in smoking were found among persons aged 30-64, drinking among those aged 18-20, and binge drinking among those aged 65 and older. Conclusions Increases in state cigarette prices may increase or decrease smoking and harmful drinking behaviors differentially by age. Adults aged 21-29 and 65 and older are more prone to increased drinking as a result of increased cigarette prices. Researchers, practitioners, advocates, and policymakers should work together to understand and prepare for these unintended consequences of tobacco taxation policy.

  15. Animal models of sugar and fat bingeing: relationship to food addiction and increased body weight.

    Science.gov (United States)

    Avena, Nicole M; Bocarsly, Miriam E; Hoebel, Bartley G

    2012-01-01

    Binge eating is a behavior that occurs in some eating disorders, as well as in obesity and in nonclinical populations. Both sugars and fats are readily consumed by human beings and are common components of binges. This chapter describes animal models of sugar and fat bingeing, which allow for a detailed analysis of these behaviors and their concomitant physiological effects. The model of sugar bingeing has been used successfully to elicit behavioral and neurochemical signs of dependence in rats; e.g., indices of opiate-like withdrawal, increased intake after abstinence, cross-sensitization with drugs of abuse, and the repeated release of dopamine in the nucleus accumbens following repeated bingeing. Studies using the model of fat bingeing suggest that it can produce some, but not all, of the signs of dependence that are seen with sugar binge eating, as well as increase body weight, potentially leading to obesity.

  16. Binge-Like Eating Attenuates Nisoxetine Feeding Suppression, Stress Activation, and Brain Norepinephrine Activity

    Science.gov (United States)

    Bello, Nicholas T.; Yeh, Chung-Yang; Verpeut, Jessica L.; Walters, Amy L.

    2014-01-01

    Stress is often associated with binge eating. A critical component of the control of stress is the central norepinephrine system. We investigated how dietary-induced binge eating alters central norepinephrine and related behaviors. Young male Sprague Dawley rats received calorie deprivation (24 h) and /or intermittent sweetened fat (vegetable shortening with sucrose; 30 min) twice a week for 10 weeks. The groups were Restrict Binge (calorie deprivation/sweetened fat), Binge (sweetened fat), Restrict (calorie deprivation), and Naive (no calorie deprivation/no sweetened fat). Dietary-induced binge eating was demonstrated by Restrict Binge and Binge, which showed an escalation in 30-min intake over time. Feeding suppression following nisoxetine (3 mg/kg; IP), a selective norepinephrine reuptake inhibitor, was not evident in Restrict Binge (Restrict Binge: 107±13, Binge: 52±9, Restrict: 80±8, Naive: 59±13% of saline injection at 1 h). In subsequent experiments with Restrict Binge and Naive, Restrict Binge had reduced corticosterone (Restrict Binge: 266±25; Naive: 494±36 ng/ml) and less feeding suppression (Restrict Binge: 81±12, Naive: 50±11% of non-restraint intake at 30 min) following restraint stress (1 h). Dietary-induced binge eating in Restrict Binge was not altered by a dorsal noradrenergic bundle lesion caused by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), but frontal cortex norepinephrine was positively correlated with the average 30-min intake post-lesion (0.69; p<0.01). In a separate set of animals, single-unit in vivo electrophysiological recording of locus coeruleus–norepinephrine neural activity demonstrated reduced sensory-evoked response as a consequence of the Restrict Binge schedule (Restrict Binge: 8.1±0.67, Naive: 11.9±1.09 Hz). These results, which suggest that a consequence of dietary-induced binge eating is to attenuate the responsiveness of the brain norepinephrine system, will further our understanding of how highly

  17. Binge-like eating attenuates nisoxetine feeding suppression, stress activation, and brain norepinephrine activity.

    Directory of Open Access Journals (Sweden)

    Nicholas T Bello

    Full Text Available Stress is often associated with binge eating. A critical component of the control of stress is the central norepinephrine system. We investigated how dietary-induced binge eating alters central norepinephrine and related behaviors. Young male Sprague Dawley rats received calorie deprivation (24 h and /or intermittent sweetened fat (vegetable shortening with sucrose; 30 min twice a week for 10 weeks. The groups were Restrict Binge (calorie deprivation/sweetened fat, Binge (sweetened fat, Restrict (calorie deprivation, and Naive (no calorie deprivation/no sweetened fat. Dietary-induced binge eating was demonstrated by Restrict Binge and Binge, which showed an escalation in 30-min intake over time. Feeding suppression following nisoxetine (3 mg/kg; IP, a selective norepinephrine reuptake inhibitor, was not evident in Restrict Binge (Restrict Binge: 107±13, Binge: 52±9, Restrict: 80±8, Naive: 59±13% of saline injection at 1 h. In subsequent experiments with Restrict Binge and Naive, Restrict Binge had reduced corticosterone (Restrict Binge: 266±25; Naive: 494±36 ng/ml and less feeding suppression (Restrict Binge: 81±12, Naive: 50±11% of non-restraint intake at 30 min following restraint stress (1 h. Dietary-induced binge eating in Restrict Binge was not altered by a dorsal noradrenergic bundle lesion caused by N-(2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4, but frontal cortex norepinephrine was positively correlated with the average 30-min intake post-lesion (0.69; p<0.01. In a separate set of animals, single-unit in vivo electrophysiological recording of locus coeruleus-norepinephrine neural activity demonstrated reduced sensory-evoked response as a consequence of the Restrict Binge schedule (Restrict Binge: 8.1±0.67, Naive: 11.9±1.09 Hz. These results, which suggest that a consequence of dietary-induced binge eating is to attenuate the responsiveness of the brain norepinephrine system, will further our understanding of how highly

  18. The overlap between binge eating disorder and substance use disorders

    DEFF Research Database (Denmark)

    Schreiber, Liana R N; Odlaug, Brian Lawrence; Grant, Jon E

    2013-01-01

    BACKGROUND AND AIMS: Binge eating disorder (BED) is a relatively common condition, especially in young adult females, and is characterized by chronic over-consumption of food resulting in embarrassment, distress, and potential health problems. It is formally included as a disorder in DSM-5...

  19. Effects of milnacipran on binge eating – a pilot study

    Directory of Open Access Journals (Sweden)

    Shun’ichi Noma

    2008-03-01

    Full Text Available Shun’ichi Noma1, Teruhisa Uwatoko1, Haruka Yamamoto2, Takuji Hayashi11Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Department of Psychiatry, Toyooka Hospital, Hyogo, JapanAbstract: Selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors are effective in the treatment of bulimia nervosa. There have been relatively few studies of the efficacy of specific serotonin and norepinephrine reuptake inhibitors in the treatment of eating disorders. Twenty-five outpatients with binge eating episodes, diagnosed as anorexia nervosa, binge-eating/purging type, bulimia nervosa/purging type, or bulimia nervosa/non-purging type, were treated with milnacipran and 20 patients completed the 8-week study. Symptom severity was evaluated using the Bulimic Investigatory Test, Edinburgh (BITE self-rating scale before administration of milnacipran and after 1, 4, and 8 weeks treatment. The scores improved after 8 weeks, especially drive to, and regret for, binge eating. Milnacipran was more effective in patients without purging and in younger patients, while there was no difference in the efficacy of milnacipran among subtypes of eating disorders.Keywords: milnacipran, specific serotonin and norepinephrine reuptake inhibitors, binge eating, vomiting, eating disorder, pharmacotherapy

  20. Overvaluation of Shape and Weight in Binge Eating Disorder

    Science.gov (United States)

    Hrabosky, Joshua I.; Masheb, Robin M.; White, Marney A.; Grilo, Carlos M.

    2007-01-01

    The excessive influence of shape or weight on self-evaluation--referred to as overvaluation--is considered by some a central feature across eating disorders but is not a diagnostic requirement for binge eating disorder (BED). This study examined shape/weight overvaluation in 399 consecutive patients with BED. Participants completed semistructured…

  1. Heterogeneity Moderates Treatment Response among Patients with Binge Eating Disorder

    Science.gov (United States)

    Sysko, Robyn; Hildebrandt, Tom; Wilson, G. Terence; Wilfley, Denise E.; Agras, W. Stewart

    2010-01-01

    Objective: The purpose of the study was to explore heterogeneity and differential treatment outcome among a sample of patients with binge eating disorder (BED). Method: A latent class analysis was conducted with 205 treatment-seeking, overweight or obese individuals with BED randomized to interpersonal psychotherapy (IPT), behavioral weight loss…

  2. Cognitive processes in alcohol binges : a review and research agenda

    NARCIS (Netherlands)

    Field, M.; Schoenmakers, T.; Wiers, R.W.H.J.

    2008-01-01

    Alcohol abuse is associated with a cluster of long-term changes in cognitive processes, as predicted by contemporary models of addiction. In this paper we review evidence which suggests that similar changes may occur during an alcohol binge, and as such they may play an important role in explaining

  3. Cognitive processes in alcohol binges: A review and research agenda

    NARCIS (Netherlands)

    Field, M.; Schoenmakers, T.; Wiers, R.W.

    2008-01-01

    Alcohol abuse is associated with a cluster of long-term changes in cognitive processes, as predicted by contemporary models of addiction. In this paper we review evidence which suggests that similar changes may occur during an alcohol binge, and as such they may play an important role in explaining

  4. Mesolimbic dopamine and its neuromodulators in obesity and binge eating.

    Science.gov (United States)

    Naef, Lindsay; Pitman, Kimberley A; Borgland, Stephanie L

    2015-12-01

    Obesity has reached epidemic prevalence, and much research has focused on homeostatic and nonhomeostatic mechanisms underlying overconsumption of food. Mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), is a key substrate for nonhomeostatic feeding. The goal of the present review is to compare changes in mesolimbic dopamine function in human obesity with diet-induced obesity in rodents. Additionally, we will review the literature to determine if dopamine signaling is altered with binge eating disorder in humans or binge eating modeled in rodents. Finally, we assess modulation of dopamine neurons by neuropeptides and peripheral peptidergic signals that occur with obesity or binge eating. We find that while decreased dopamine concentration is observed with obesity, there is inconsistency outside the human literature on the relationship between striatal D2 receptor expression and obesity. Finally, few studies have explored how orexigenic or anorexigenic peptides modulate dopamine neuronal activity or striatal dopamine in obese models. However, ghrelin modulation of dopamine neurons may be an important factor for driving binge feeding in rodents.

  5. Forskningsrapport: Samskabelsesparathed i Ringkøbing-Skjern Kommune, 2016

    DEFF Research Database (Denmark)

    Pedersen-Ulrich, Jens; Kjeldsen, Lena

    2016-01-01

    Forskningsrapporten præsenterer resultater af en spørgeskemaundersøgelse gennemført i Ringkøbing-Skjern Kommune i 2016. Undersøgelsen måler kommunens samskabelsesparathed i de enkelte fag- og stabsområder og er baseret på en samskabelsestypologi, der indeholder fire tilgange til samskabelse: styret...

  6. Binge Eating Disorder: A Review of a New "DSM" Diagnosis

    Science.gov (United States)

    Myers, Laura L.; Wiman, Allison M.

    2014-01-01

    In 1994, binge eating disorder (BED) was introduced as a disorder requiring further study in the "American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders", fourth edition ("DSM-IV"). It is now listed as a distinct eating disorder in the "DSM-5", along with bulimia nervosa and…

  7. Binge Eating Disorder: A Review of a New "DSM" Diagnosis

    Science.gov (United States)

    Myers, Laura L.; Wiman, Allison M.

    2014-01-01

    In 1994, binge eating disorder (BED) was introduced as a disorder requiring further study in the "American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders", fourth edition ("DSM-IV"). It is now listed as a distinct eating disorder in the "DSM-5", along with bulimia nervosa and anorexia…

  8. Localization of a filarial phosphate permease that is up-regulated in response to depletion of essential Wolbachia endobacteria.

    Science.gov (United States)

    Arumugam, Sridhar; Hoerauf, Achim; Pfarr, Kenneth M

    2014-03-01

    Wolbachia of filarial nematodes are essential, obligate endobacteria. When depleted by doxycycline worm embryogenesis, larval development and worm survival are inhibited. The molecular basis governing the endosymbiosis between Wolbachia and their filarial host is still being deciphered. In rodent filarial nematode Litomosoides sigmodontis, a nematode encoded phosphate permease gene (Ls-ppe-1) was up-regulated at the mRNA level in response to Wolbachia depletion and this gene promises to have an important role in Wolbachia-nematode endosymbiosis. To further characterize this gene, the regulation of phosphate permease during Wolbachia depletion was studied at the protein level in L. sigmodontis and in the human filaria Onchocerca volvulus. And the localization of phosphate permease (PPE) and Wolbachia in L. sigmodontis and O. volvulus was investigated in untreated and antibiotic treated worms. Depletion of Wolbachia by tetracycline (Tet) resulted in up-regulation of Ls-ppe-1 in L. sigmodontis. On day 36 of Tet treatment, compared to controls (Con), >98% of Wolbachia were depleted with a 3-fold increase in mRNA levels of Ls-ppe-1. Anti-Ls-PPE serum used in Western blots showed up-regulation of Ls-PPE at the protein level in Tet worms on day 15 and 36 of treatment. Immunohistology revealed the localization of Wolbachia and Ls-PPE in the embryos, microfilariae and hypodermis of L. sigmodontis female worms and up-regulation of Ls-PPE in response to Wolbachia depletion. Expression of O. volvulus phosphate permease (Ov-PPE) studied using anti-Ov-PPE serum, showed up-regulation of Ov-PPE at the protein level in doxycycline treated Wolbachia depleted O. volvulus worms and immunohistology revealed localization of Ov-PPE and Wolbachia and up-regulation of Ov-PPE in the hypodermis and embryos of doxycycline treated worms. Ls-PPE and Ov-PPE are upregulated upon Wolbachia depletion in same tissues and regions where Wolbachia are located in untreated worms, reinforcing a link

  9. Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol-Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats.

    Directory of Open Access Journals (Sweden)

    Ashfaq Ahmad

    Full Text Available Hydrogen sulphide (H2S is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C and caffeine in drinking water (62mg/L for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE mRNA was quantified using real time polymerase chain reaction (qPCR.There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05 in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05 in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05 plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II and noradrenaline (NA but attenuates oxidative stress and improves pulse wave velocity which helps to suppress

  10. Comparison of two self-report instruments for assessing binge eating in bariatric surgery candidates.

    Science.gov (United States)

    Elder, Katherine A; Grilo, Carlos M; Masheb, Robin M; Rothschild, Bruce S; Burke-Martindale, Carolyn H; Brody, Michelle L

    2006-04-01

    This study compared two self-report methods for assessing binge eating in severely obese bariatric surgery candidates. Participants were 249 gastric bypass candidates who completed the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R) and the Eating Disorder Examination-Questionnaire (EDE-Q) prior to surgery. Participants were classified by binge eating status (i.e., no or recurrent binge eating) with each of the measures. The degree of agreement was examined, as well as the relationship between binge eating and measures of convergent validity. The two measures identified a similar number of patients with recurrent binge eating (i.e., at least 1 binge/week); however, overlap was modest (kappa=.26). Agreement on twice weekly binge eating was poor (kappa=.05). The QEWP-R and EDE-Q both identified clinically meaningful groups of binge eaters. The EDE-Q appeared to differentiate between non/infrequent bingers and recurrent bingers better than the QEWP-R, based on measures of convergent validity. In addition, the EDE-Q demonstrated an advantage because it identified binge eaters with elevated weight and shape overconcern. Using the self-report measures concurrently did not improve identification of binge eating in this study. More work is needed to determine the construct validity and clinical utility of these measures with gastric bypass patients.

  11. Up-Regulation of microRNA-210 is Associated with Spermatogenesis by Targeting IGF2 in Male Infertility.

    Science.gov (United States)

    Tang, Dongdong; Huang, Yuanyuan; Liu, Weiqun; Zhang, Xiansheng

    2016-08-18

    BACKGROUND MicroRNAs (miRNAs) play pivotal roles in spermatogenesis. MicroRNA-210 (miR-210) expression was up-regulated in the testes of sterile men with non-obstructive azoospermia (NOA). However, the underlying mechanisms of miR-210 involved in the spermatogenesis in patients with NOA are unknown. MATERIAL AND METHODS Expression of miR-210 and insulin-like growth factor II (IGF2) in the testes of NOA cases (only including maturation arrest and hypospermatogenesis) were detected in this study. We carried out in vitro experiments to determine if IGF2 was directly targeted by miR-210 in NT2 cells. RESULTS Compared with obstructive azoospermia (OA) as normal control, our results suggest that miR-210 was significantly up-regulated in testis of patients with NOA (Pspermatogenesis by targeting IGF2 in male infertility.

  12. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    Institute of Scientific and Technical Information of China (English)

    Wang-sheng Duanmu; Liu Cao; Jing-yu Chen; Hong-fei Ge; Rong Hu; Hua Feng

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treat-ment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These ifndings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippo-campus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury.

  13. Up-regulation of thromboxane A2 receptor expression by lipid soluble smoking particles through post-transcriptional mechanisms

    DEFF Research Database (Denmark)

    Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

    2008-01-01

    . The present study was designed to test if lipid soluble smoking particles (DSP) enhance TxA(2) receptor (TP) expression in rat mesenteric arteries, and if intracellular mitogen-activated protein kinase (MAPK) pathways play a role. Organ culture of rat mesenteric arteries in the presence of DSP (0.2 microl...... actinomycin D, but was almost completely abolished by cycloheximide, a general translational inhibitor. Dexamethasone, a glucocorticoid, manifested a potent inhibitory effect as well. These results suggest that the up-regulation of TP receptor occurs via post-transcriptional events, and mainly translation...... are responsible for the up-regulation of TP receptor by DSP, in which enhanced translation is the major cause of the elevated protein expression and the enhanced contraction....

  14. Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

    Directory of Open Access Journals (Sweden)

    Sachiko Hirai

    Full Text Available Up-regulated sirtuin 1 (SIRT1, an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53. Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5. In the KatoIII cell line (TP53-null, DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.

  15. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Yolanda Stypula-Cyrus

    Full Text Available Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC. However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  16. Growth Arrest Specific 2 Is Up-Regulated in Chronic Myeloid Leukemia Cells and Required for Their Growth

    OpenAIRE

    Haixia Zhou; Yue Ge; Lili Sun; Wenjuan Ma; Jie Wu; Xiuyan Zhang; Xiaohui Hu; Eaves, Connie J; Depei Wu; Yun Zhao

    2014-01-01

    Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML), the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2) regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form o...

  17. Elevated glutathione levels confer cellular sensitization to cisplatin toxicity by up-regulation of copper transporter hCtr1.

    Science.gov (United States)

    Chen, Helen H W; Song, Im-Sook; Hossain, Anwar; Choi, Min-Koo; Yamane, Yoshiaki; Liang, Zheng D; Lu, Jia; Wu, Lily Y-H; Siddik, Zahid H; Klomp, Leo W J; Savaraj, Niramol; Kuo, Macus Tien

    2008-09-01

    Previous studies have demonstrated that treating cultured cells with cisplatin (CDDP) up-regulated the expression of glutathione (GSH) and its de novo rate-limiting enzyme glutamate-cysteine ligase (GCL), which consists of a catalytic (GCLC) and a modifier (GCLM) subunit. It has also been shown that many CDDP-resistant cell lines exhibit high levels of GCLC/GCLM and GSH. Because the GSH system is the major intracellular regulator of redox conditions that serve as an important detoxification cytoprotector, these results have been taken into consideration that elevated levels of GCL/GSH are responsible for the CDDP resistance. In contrast to this context, we demonstrated here that overexpression of GSH by transfection with an expression plasmid containing the GCLC cDNA conferred sensitization to CDDP through up-regulation of human copper transporter (hCtr) 1, which is also a transporter for CDDP. Depleting GSH levels in these transfected cells reversed CDDP sensitivity with concomitant reduction of hCtr1 expression. Although rates of copper transport were also up-regulated in the transfected cells, these cells exhibited biochemical signature of copper deficiency, suggesting that GSH functions as an intracellular copper-chelator and that overexpression of GSH can alter copper metabolism. More importantly, our results reveal a new role of GSH in the regulation of CDDP sensitivity. Overproduction of GSH depletes the bioavailable copper pool, leading to up-regulation of hCtr1 and sensitization of CDDP transport and cell killing. These findings also have important implications in that modulation of the intracellular copper pool may be a novel strategy for improving chemotherapeutic efficacy of platinum-based antitumor agents.

  18. Integrin-linked kinase mediates the hydrogen peroxide-dependent transforming growth factor-β1 up-regulation.

    Science.gov (United States)

    Gonzalez-Ramos, M; de Frutos, S; Griera, M; Luengo, A; Olmos, G; Rodriguez-Puyol, D; Calleros, L; Rodriguez-Puyol, M

    2013-08-01

    Transforming growth factor type-β1 (TGF-β1) has been recognized as a central mediator in many pathological events related to extracellular matrix (ECM) proteins accumulation, where their locally increased expression has been implicated in the fibrosis process of numerous organs, including glomerular fibrosis in the kidney. We and others have reported the TGF-β1 synthesis regulation by reactive oxygen species (ROS), and moreover we also described the implication of integrin-linked kinase (ILK) in the AP-1-dependent TGF-β1 up-regulation. Thus, we propose here that hydrogen peroxide (H2O2)-dependent TGF-β1 regulation may be mediated by ILK activation. First we confirmed the increase in TGF-β1 expression in human mesangial cells (HMC) after treatment with H2O2 or with an alternative H2O2-generating system such as the glucose-oxidase enzyme (GOX). By using immunoblotting, immunofluorescence, and ELISA techniques, we demonstrate that extracellular H2O2 up-regulates TGF-β1 transcription, as well as increases TGF-β1 promoter activity. Furthermore, catalase-decreased intracellular H2O2 abolished TGF-β1 up-regulation. The use of pharmacological inhibitors as well as knockdown of ILK with small interfering RNA (siRNA) demonstrated the implication of a PI3K/ILK/AKT/ERK MAPK signaling pathway axis in the H2O2-induced TGF-β1 overexpression. Finally, we explored the physiological relevance of these findings by treating HMC with angiotensin II, a known stimuli of H2O2 synthesis. Our results confirm the relevance of previous findings after a more physiological stimulus. In summary, our results provide evidence that ILK activity changes may act as a mechanism in response to different stimuli such as H2O2 in the induced TGF-β1 up-regulation in pathological or even physiological conditions.

  19. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Science.gov (United States)

    Stypula-Cyrus, Yolanda; Damania, Dhwanil; Kunte, Dhananjay P; Cruz, Mart Dela; Subramanian, Hariharan; Roy, Hemant K; Backman, Vadim

    2013-01-01

    Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC) family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC). However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs) interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA) targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS) to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  20. Classical macrophage activation up-regulates several matrix metalloproteinases through mitogen activated protein kinases and nuclear factor-κB.

    Directory of Open Access Journals (Sweden)

    Wei-Chun Huang

    Full Text Available Remodelling of the extracellular matrix (ECM and cell surface by matrix metalloproteinases (MMPs is an important function of monocytes and macrophages. Recent work has emphasised the diverse roles of classically and alternatively activated macrophages but the consequent regulation of MMPs and their inhibitors has not been studied comprehensively. Classical activation of macrophages derived in vitro from un-fractionated CD16(+/- or negatively-selected CD16(- macrophages up-regulated MMP-1, -3, -7, -10, -12, -14 and -25 and decreased TIMP-3 steady-state mRNA levels. Bacterial lipopolysaccharide, IL-1 and TNFα were more effective than interferonγ except for the effects on MMP-25, and TIMP-3. By contrast, alternative activation decreased MMP-2, -8 and -19 but increased MMP -11, -12, -25 and TIMP-3 steady-state mRNA levels. Up-regulation of MMPs during classical activation depended on mitogen activated protein kinases, phosphoinositide-3-kinase and inhibitor of κB kinase-2. Effects of interferonγ depended on janus kinase-2. Where investigated, similar effects were seen on protein concentrations and collagenase activity. Moreover, activity of MMP-1 and -10 co-localised with markers of classical activation in human atherosclerotic plaques in vivo. In conclusion, classical macrophage activation selectively up-regulates several MMPs in vitro and in vivo and down-regulates TIMP-3, whereas alternative activation up-regulates a distinct group of MMPs and TIMP-3. The signalling pathways defined here suggest targets for selective modulation of MMP activity.

  1. Respiratory virus infection up-regulates TRPV1, TRPA1 and ASICS3 receptors on airway cells

    Science.gov (United States)

    Omar, Shadia; Clarke, Rebecca; Abdullah, Haniah; Brady, Clare; Corry, John; Winter, Hanagh; Touzelet, Olivier; Power, Ultan F.; Lundy, Fionnuala; McGarvey, Lorcan P. A.

    2017-01-01

    Receptors implicated in cough hypersensitivity are transient receptor potential vanilloid 1 (TRPV1), transient receptor potential cation channel, Subfamily A, Member 1 (TRPA1) and acid sensing ion channel receptor 3 (ASIC3). Respiratory viruses, such as respiratory syncytial virus (RSV) and measles virus (MV) may interact directly and/or indirectly with these receptors on sensory nerves and epithelial cells in the airways. We used in vitro models of sensory neurones (SHSY5Y or differentiated IMR-32 cells) and human bronchial epithelium (BEAS-2B cells) as well as primary human bronchial epithelial cells (PBEC) to study the effect of MV and RSV infection on receptor expression. Receptor mRNA and protein levels were examined by qPCR and flow cytometry, respectively, following infection or treatment with UV inactivated virus, virus-induced soluble factors or pelleted virus. Concentrations of a range of cytokines in resultant BEAS-2B and PBEC supernatants were determined by ELISA. Up-regulation of TRPV1, TRPA1 and ASICS3 expression occurred by 12 hours post-infection in each cell type. This was independent of replicating virus, within the same cell, as virus-induced soluble factors alone were sufficient to increase channel expression. IL-8 and IL-6 increased in infected cell supernatants. Antibodies against these factors inhibited TRP receptor up-regulation. Capsazepine treatment inhibited virus induced up-regulation of TRPV1 indicating that these receptors are targets for treating virus-induced cough. PMID:28187208

  2. Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in the rat brain: an autoradiography study.

    Science.gov (United States)

    Ciudad-Roberts, Andrés; Camarasa, Jorge; Pubill, David; Escubedo, Elena

    2014-08-04

    Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce a heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated male Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and sacrificed them the day after to perform [(125)I]Epibatidine binding autoradiograms on serial coronal slices. MDMA induced significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory, motor, auditory and retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 34% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The heteromeric nAChR up-regulation in certain areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term consumption of MDMA.

  3. Berberine exerts anti-adipogenic activity through up-regulation of C/EBP inhibitors, CHOP and DEC2.

    Science.gov (United States)

    Pham, Truc P T; Kwon, Jeongho; Shin, Jaekyoon

    2011-09-23

    Berberine exerts an anti-adipogenic activity that is associated with the down-regulation of C/EBPα and PPARγ. Stimulation of AMP-activated kinase (AMPK) caused by inhibition of mitochondrial respiration has been suggested to underlie such molecular regulation. In the present study, we show that berberine up-regulated the expression of two different sets of C/EBP inhibitors, CHOP and DEC2, while down-modulating C/EBPα, PPARγ and other adipogenic markers and effectors in differentiating 3T3-L1 preadipocytes and mature adipocytes. Data also suggested that the berberine-induced up-regulation of CHOP and DEC2 was attributable to selective activation of an unfolded protein response (UPR) and modified extracellular environment, respectively. As a result, the anti-adipogenic activity of berberine was diminished remarkably by adjusting the differentiation culture media and limitedly but consistently by knockdown of CHOP expression. Together, up-regulation of C/EBP inhibitors appears to underlie the berberine-induced repression of C/EBPα and PPARγ and, so, the inhibition of adipogenesis.

  4. Proteolytic fragments of laminin promote excitotoxic neurodegeneration by up-regulation of the KA1 subunit of the kainate receptor.

    Science.gov (United States)

    Chen, Zu-Lin; Yu, Huaxu; Yu, Wei-Ming; Pawlak, Robert; Strickland, Sidney

    2008-12-29

    Degradation of the extracellular matrix (ECM) protein laminin contributes to excitotoxic cell death in the hippocampus, but the mechanism of this effect is unknown. To study this process, we disrupted laminin gamma1 (lamgamma1) expression in the hippocampus. Lamgamma1 knockout (KO) and control mice had similar basal expression of kainate (KA) receptors, but the lamgamma1 KO mice were resistant to KA-induced neuronal death. After KA injection, KA1 subunit levels increased in control mice but were unchanged in lamgamma1 KO mice. KA1 levels in tissue plasminogen activator (tPA)-KO mice were also unchanged after KA, indicating that both tPA and laminin were necessary for KA1 up-regulation after KA injection. Infusion of plasmin-digested laminin-1 into the hippocampus of lamgamma1 or tPA KO mice restored KA1 up-regulation and KA-induced neuronal degeneration. Interfering with KA1 function with a specific anti-KA1 antibody protected against KA-induced neuronal death both in vitro and in vivo. These results demonstrate a novel pathway for neurodegeneration involving proteolysis of the ECM and KA1 KA receptor subunit up-regulation.

  5. Deciding to quit drinking alcohol

    Science.gov (United States)

    ... quitting drinking; Quitting drinking; Quitting alcohol; Alcoholism - deciding to quit ... drinking problem when your body depends on alcohol to function and your drinking is causing problems with ...

  6. Is Alcohol Drinking Associated with Renal Impairment in the General Population of South Korea?

    Directory of Open Access Journals (Sweden)

    Ha-Na Kim

    2014-06-01

    Full Text Available Background/Aims: We examined relationships between the average amount of daily alcohol intake, drinking patterns, and renal dysfunction among South Korean adultsaged ≥ 20 years. Methods: The analysis used data from the Korean National Health and Nutrition Examination Survey (KNHANES, a cross-sectional survey of Korean civilians, conducted from January to December 2011. In this study, a sample of 5,251 participants was analysed. Results: Compared with abstinence, the odds ratio for a decrease in estimated glomerular filtration rate (eGFR was 0.14 (95% CI: 0.01-0.91 among heavy drinkers, and 0.42 (95% CI: 0.17-0.98 among binge drinkers and the association between the amount of mean daily alcohol intake, binge-drinking status and a likelihood of reduced eGFR value showed significant trends (p = 0.041 and p = 0.038, respectively, after adjusting for age, smoking status, amount of physical activity, morbid hypertension, diabetes, dyslipidaemia, anaemia and body mass index. There was no significant association between alcohol consumption and the urine albumin to creatinine ratio in men, or between alcohol consumption and renal dysfunction in women. Conclusions: Alcohol consumption was inversely associated with a reduction in eGFR in Korean men. However, these findings should be interpreted cautiously, given the other harmful effects related to alcohol consumption, especially heavy and binge drinking.

  7. Underage Drinking: A Review of Trends and Prevention Strategies.

    Science.gov (United States)

    Harding, Frances M; Hingson, Ralph W; Klitzner, Michael; Mosher, James F; Brown, Jorielle; Vincent, Robert M; Dahl, Elizabeth; Cannon, Carol L

    2016-10-01

    Underage drinking and its associated problems have profound negative consequences for underage drinkers themselves, their families, their communities, and society as a whole, and contribute to a wide range of costly health and social problems. There is increased risk of negative consequences with heavy episodic or binge drinking. Alcohol is a factor related to approximately 4,300 deaths among underage youths in the U.S. every year. Since the mid-1980s, the nation has launched aggressive underage drinking prevention efforts at the federal, state, and local levels, and national epidemiologic data suggest that these efforts are having positive effects. For example, since 1982, alcohol-related traffic deaths among youth aged 16-20 years have declined by 79%. Evidence-based or promising strategies for reducing underage drinking include those that limit the physical, social, and economic availability of alcohol to youth, make it illegal for drivers aged drinking, and provide mechanisms for early identification of problem drinkers. Strategies may be implemented through a comprehensive prevention approach including policies and their enforcement, public awareness and education, action by community coalitions, and early brief alcohol intervention and referral programs. This paper focuses on underage drinking laws and their enforcement because these constitute perhaps the most fundamental component of efforts to limit youth access to and use of alcohol.

  8. The role of anxiety in binge eating behavior: a critical examination of theory and empirical literature

    Directory of Open Access Journals (Sweden)

    Diane L. Rosenbaum

    2013-06-01

    Full Text Available The purpose of this manuscript is to expand the understanding of binge eating by reviewing the role of aspects of negative affect. Specifically, this paper will present evidence for further investigation of the bearing that anxiety may have in binge eating development and maintenance. A comprehensive review of the literature regarding the relation of binge eating and anxiety was performed. Valuable contributions have been made to the binge eating literature regarding some aspects of negative affect (i.e., depression; however, outside of bulimia nervosa studies, much of the theoretical and empirical binge eating research to date has not directly addressed the role of anxiety. Research supports expansion of investigations of negative emotionality and binge eating to include specific study of anxiety. Greater inclusivity and specificity in the unique contributions of various negative emotions may further the development of temporal models and intervention efforts.

  9. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chih-Yeu Fang

    2015-01-01

    Full Text Available (−-Epigallocatechin-3-gallate (EGCG, a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC, yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

  10. N-acetylcysteine (NAC) decreases binge eating in a rodent model

    OpenAIRE

    Hurley, Matthew M.; Resch, Jon M.; Maunze, Brian; Frenkel, Mogen M.; Baker, David A.; Choi, SuJean

    2016-01-01

    Binge eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetyl cysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically,...

  11. Examining the relationship between food thought suppression and binge eating disorder.

    Science.gov (United States)

    Barnes, Rachel D; Masheb, Robin M; White, Marney A; Grilo, Carlos M

    2013-10-01

    Food thought suppression, or purposely attempting to avoid thoughts of food, is related to a number of unwanted eating- and weight-related consequences, particularly in dieting and obese individuals. Little is known about the possible significance of food thought suppression in clinical samples, particularly obese patients who binge eat. This study examined food thought suppression in 150 obese patients seeking treatment for binge eating disorder (BED). Food thought suppression was not associated with binge eating frequency or body mass index but was significantly associated with higher current levels of eating disorder psychopathology and variables pertaining to obesity, dieting, and binge eating.

  12. The neurobiological basis of binge-eating disorder.

    Science.gov (United States)

    Kessler, Robert M; Hutson, Peter H; Herman, Barry K; Potenza, Marc N

    2016-04-01

    Relatively little is known about the neuropathophysiology of binge-eating disorder (BED). Here, the evidence from neuroimaging, neurocognitive, genetics, and animal studies are reviewed to synthesize our current understanding of the pathophysiology of BED. Binge-eating disorder may be conceptualized as an impulsive/compulsive disorder, with altered reward sensitivity and food-related attentional biases. Neuroimaging studies suggest there are corticostriatal circuitry alterations in BED similar to those observed in substance abuse, including altered function of prefrontal, insular, and orbitofrontal cortices and the striatum. Human genetics and animal studies suggest that there are changes in neurotransmitter networks, including dopaminergic and opioidergic systems, associated with binge-eating behaviors. Overall, the current evidence suggests that BED may be related to maladaptation of the corticostriatal circuitry regulating motivation and impulse control similar to that found in other impulsive/compulsive disorders. Further studies are needed to understand the genetics of BED and how neurotransmitter activity and neurocircuitry function are altered in BED and how pharmacotherapies may influence these systems to reduce BED symptoms.

  13. Increased Synaptic Excitation and Abnormal Dendritic Structure of Prefrontal Cortex Layer V Pyramidal Neurons following Prolonged Binge-Like Consumption of Ethanol

    Science.gov (United States)

    Klenowski, Paul M.; Fogarty, Matthew J.; Shariff, Masroor; Belmer, Arnauld

    2016-01-01

    Abstract Long-term alcohol use causes a multitude of neurochemical changes in cortical regions that facilitate the transition to dependence. Therefore, we used a model of long-term, binge-like ethanol consumption in rats to determine the effects on morphology and synaptic physiology of medial prefrontal cortex (mPFC) layer V pyramidal neurons. Following 10 weeks of ethanol consumption, we recorded synaptic currents from mPFC neurons and used neurobiotin filling to analyze their morphology. We then compared these data to measurements obtained from age-matched, water-drinking control rats. We found that long-term ethanol consumption caused a significant increase in total dendrite arbor length of mPFC layer V pyramidal neurons. Dendritic restructuring was primarily observed in basal dendrite arbors, with mPFC neurons from animals engaged in long-term ethanol drinking having significantly larger and more complex basal arbors compared with controls. These changes were accompanied by significantly increased total spine densities and spontaneous postsynaptic excitatory current frequency, suggesting that long-term binge-like ethanol consumption enhances basal excitatory synaptic transmission in mPFC layer V pyramidal neurons. Our results provide insights into the morphological and functional changes in mPFC layer V pyramidal neuronal physiology following prolonged exposure to ethanol and support changes in mPFC activity during the development of alcohol dependence. PMID:28032119

  14. Alcohol Energy Drinks

    Science.gov (United States)

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 24018 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  15. Change in binge eating and binge eating disorder associated with migration from Mexico to the U.S.

    Science.gov (United States)

    Swanson, Sonja A; Saito, Naomi; Borges, Guilherme; Benjet, Corina; Aguilar-Gaxiola, Sergio; Medina-Mora, Maria Elena; Breslau, Joshua

    2012-01-01

    Exposure to Western popular culture is hypothesized to increase risk for eating disorders. This study tests this hypothesis with respect to the proposed diagnosis of binge eating disorder (BED) in an epidemiological sample of people of Mexican origin in Mexico and the U.S. Data come from the Mexico National Comorbidity Survey, National Comorbidity Survey Replication, and National Latino and Asian American Survey (N = 2268). Diagnoses were assessed with the WMH-CIDI. Six groups were compared: Mexicans with no migrant family members, Mexicans with at least one migrant family member, Mexican return-migrants, Mexican-born migrants in the U.S., and two successive generations of Mexican-Americans in the U.S. The lifetime prevalence of BED was 1.6% in Mexico and 2.2% among Mexican-Americans. Compared with Mexicans in families with migrants, risk for BED was higher in US-born Mexican-Americans with two U.S.-born parents (aHR = 2.58, 95% CI 1.12-5.93). This effect was attenuated by 24% (aHR = 1.97, 95% CI 0.84-4.62) with adjustment for prior-onset depressive or anxiety disorder. Adjustment for prior-onset conduct disorder increased the magnitude of association (aHR = 2.75, 95% CI 1.22-6.20). A similar pattern was observed for binge eating. Among respondents reporting binge eating, onset in the U.S. (vs. Mexico) was not associated with prevalence of further eating disorder symptoms. Migration from Mexico to the U.S. is associated with an increased risk for BED that may be partially attributable to non-specific influences on internalizing disorders. Among respondents reporting binge eating in either country, similar levels of further symptoms were endorsed, suggesting some cross-cultural generalizability of criteria.

  16. Facets of negative affect prior to and following binge-only, purge-only, and binge/purge events in women with bulimia nervosa.

    Science.gov (United States)

    Berg, Kelly C; Crosby, Ross D; Cao, Li; Peterson, Carol B; Engel, Scott G; Mitchell, James E; Wonderlich, Stephen A

    2013-02-01

    Ecological momentary assessment (EMA) data suggest that global negative affect (NA) increases prior to and decreases following episodes of binge eating and purging, providing support for the affect regulation model of BN. The current study examined whether facets of NA are differentially related to bulimic behaviors. Women with bulimia nervosa (BN; n = 133) completed a 2-week EMA protocol. Momentary assessments of 4 facets of NA (Fear, Guilt, Hostility, and Sadness) were derived from the PANAS subscales. Trajectories of the NA facets were modeled prior to and following binge-only, purge-only, and binge/purge events. Fear, Guilt, Hostility, and Sadness increased prior to and decreased following binge-only and binge/purge events. The same results were found for purge-only events, with the exception that Hostility did not increase significantly prior to purging. Notably, ratings of Guilt were higher than those of Fear, Hostility, and Sadness at the time of binge-only and binge/purge events. Furthermore, post hoc analyses demonstrate that Guilt increased prior to and decreased following the 3 behavior types, even after controlling for Fear, Hostility, and Sadness. These results provide further support for the affect regulation model of BN and also suggest that guilt may be particularly important to the pathology of BN.

  17. Up-regulation of heme oxygenase-1 contributes to the amelioration of aluminum-induced oxidative stress in Medicago sativa.

    Science.gov (United States)

    Cui, Weiti; Zhang, Jing; Xuan, Wei; Xie, Yanjie

    2013-10-15

    In this report, pharmacological, histochemical and molecular approaches were used to investigate the effect of heme oxygenase-1 (HO-1) up-regulation on the alleviation of aluminum (Al)-induced oxidative stress in Medicago sativa. Exposure of alfalfa to AlCl3 (0-100 μM) resulted in a dose-dependent inhibition of root elongation as well as the enhancement of thiobarbituric acid reactive substances (TBARS) content. 1 and 10 μM (in particular) Al(3+) increased alfalfa HO-1 transcript or its protein level, and HO activity in comparison with the decreased changes in 100 μM Al-treated samples. After recuperation, however, TBARS levels in 1 and 10 μM Al-treated alfalfa roots returned to control values, which were accompanied with the higher levels of HO activity. Subsequently, exogenous CO, a byproduct of HO-1, could substitute for the cytoprotective effects of the up-regulation of HO-1 in alfalfa plants upon Al stress, which was confirmed by the alleviation of TBARS and Al accumulation, as well as the histochemical analysis of lipid peroxidation and loss of plasma membrane integrity. Theses results indicated that endogenous CO generated via heme degradation by HO-1 could contribute in a critical manner to its protective effects. Additionally, the pretreatments of butylated hydroxytoluene (BHT) and hemin, an inducer of HO-1, exhibited the similar cytoprotective roles in the alleviation of oxidative stress, both of which were impaired by the potent inhibitor of HO-1, zinc protoporphyrin IX (ZnPP). However, the Al-induced inhibition of root elongation was not influenced by CO, BHT and hemin, respectively. Together, the present results showed up-regulation of HO-1 expression could act as a mechanism of cell protection against oxidative stress induced by Al treatment.

  18. Tobacco carcinogen mediated up-regulation of AP-1 dependent pro-angiogenic cytokines in head and neck carcinogenesis.

    Science.gov (United States)

    Swenson, Wade G; Wuertz, Beverly R K; Ondrey, Frank G

    2011-09-01

    Tobacco is notably genotoxic and associated with head and neck carcinogenesis. Cigarette carcinogens have the capacity to alter early response gene expression in tobacco-related malignancies via genes such as nuclear factor kappa B (NFκB). A number of early response gene activation events are also facilitated by fos/jun activator protein 1 (AP-1) associated pathways. In the present study, we hypothesize that tobacco products may induce microenvironment alterations, promoting angiogenesis and providing a permissive environment for head and neck cancer progression. In an in vitro analysis, we employed immortalized oral keratinocyte (HOK-16B) and laryngeal squamous carcinoma (UM-SCC-11A) cells to investigate interleukin (IL)-8 and vascular endothelial growth factor (VEGF) induction by cigarette smoke condensate (CSC). IL-8 and VEGF expression is based on interactions between NFκB, AP-1, and NF-IL6. We identified at least 1.5-fold dose-dependent induction of AP-1, VEGF, and IL-8 promoter/reporter gene activity after 24 h exposure to CSC. Next, we stably transfected UM-SCC-11A cells with A-Fos, a dominant negative AP-1 protein. Treatment with CSC of the A-Fos cell lines compared to empty vector controls significantly down-regulated AP-1, VEGF, and IL-8 promoter/reporter gene expression. We also performed ELISAs and discovered significant up-regulation of IL-8 and VEGF secretion by UMSCC 11A after treatment with phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, and CSC, which was down-regulated by the A-Fos dominant negative protein. We conclude tobacco carcinogens up-regulate AP-1 activity and AP-1 dependent IL-8 and VEGF gene expression in head and neck cancer. This up-regulation may promote an angiogenic phenotype favoring invasion in both premalignant and squamous cancer cells of the head and neck.

  19. Proline accumulation in leaves of Periploca sepium via both biosynthesis up-regulation and transport during recovery from severe drought.

    Directory of Open Access Journals (Sweden)

    Yuyan An

    Full Text Available Drought resistance and recovery ability are two important requisites for plant adaptation to drought environments. Proline (Pro metabolism has been a major concern in plant drought tolerance. However, roles of Pro metabolism in plant recovery ability from severe drought stress are largely unexplored. Periploca sepium Bunge has gained increasing attention for its adaptation to dry environments. Here, we investigated Pro metabolism in different tissues of P. sepium seedlings in the course of drought stress and recovery. We found that leaf Pro metabolism response during post-drought recovery was dependant on drought severity. Pro biosynthesis was down-regulated during recovery from -0.4 MPa but increased continually and notably during recovery from -1.0 MPa. Significant correlation between Pro concentration and Δ1-pyrroline-5-carboxylate synthetase activity indicates that Glutamate pathway is the predominant synthesis route during both drought and re-watering periods. Ornithine δ-aminotransferase activity was up-regulated significantly only during recovery from -1.0 MPa, suggesting positive contribution of ornithine pathway to improving plant recovery capacity from severe drought. In addition to up-regulation of biosynthesis, Pro transport from stems and roots also contributed to high Pro accumulation in leaves and new buds during recovery from -1.0 MPa, as indicated by the combined analysis of Pro concentration and its biosynthesis in stems, roots and new buds. Except its known roles as energy, carbon and nitrogen sources for plant rapid recovery, significant positive correlation between Pro concentration and total antioxidant activity indicates that Pro accumulation can also promote plant damage repair ability by up-regulating antioxidant activity during recovery from severe drought stress.

  20. Does alcohol damage the adolescent brain? Neuroanatomical and neuropsychological consequences of adolescent drinking

    Directory of Open Access Journals (Sweden)

    Fleming RL

    2015-12-01

    Full Text Available Rebekah L Fleming1,2 1Durham VA Medical Center, 2Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA Abstract: Alcohol drinking is a significant risk factor for morbidity and mortality in adolescents worldwide. Adolescents frequently binge drink, and this pattern of use is associated with poor school performance, injuries, violence, drug use, and a variety of poor psychosocial outcomes in adulthood. These associations have raised concerns that alcohol drinking may damage the adolescent brain and lead to impaired cognition and behavior. Similar to the neurotoxicity seen in adult alcoholics, magnetic resonance imaging studies of brain anatomy in adolescent drinkers have shown that alcohol disrupts the development of temporal and frontal cortices and myelinated fiber tracts throughout the brain. Although adult brains show some recovery with abstinence, at present, no studies have examined brain recovery in adolescents. Studies of neuropsychological function have found deficits in attention and visuospatial ability that show dose-dependent correlations with alcohol exposure and withdrawal symptoms, but visuospatial performance recovers with short-term abstinence. Differences in executive function and decision-making have also been found, but the available evidence suggests that these are not primarily the result of alcohol exposure; instead, they reflect premorbid factors that increase risk-taking and substance use. Nevertheless, alcohol drinking by adolescents remains an important concern because of the potential for brain injury in addition to the many negative consequences associated with acute intoxication. Keywords: adolescence, binge drinking, alcohol, magnetic resonance imaging, neuropsychological function

  1. Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection.

    Directory of Open Access Journals (Sweden)

    Anthony Siau

    Full Text Available Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface

  2. Adenosine A(2A receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.

    Directory of Open Access Journals (Sweden)

    Pin-Chien Huang

    Full Text Available BACKGROUND: Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs and retinal ganglion cells (RGCs. The neuromodulator adenosine is essential for the generation of retinal waves. However, the cellular basis underlying adenosine's regulation of retinal waves remains elusive. Here, we investigated whether and how the adenosine A(2A receptor (A(2AR regulates retinal waves and whether A(2AR regulation of retinal waves acts via presynaptic SACs. METHODOLOGY/PRINCIPAL FINDINGS: We showed that A(2AR was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A(2AR decreased the frequency of spontaneous Ca²⁺ transients, suggesting that endogenous A(2AR may up-regulate wave frequency. To investigate whether A(2AR acts via presynaptic SACs, we targeted gene expression to SACs by the metabotropic glutamate receptor type II promoter. Ca²⁺ transient frequency was increased by expressing wild-type A(2AR (A2AR-WT in SACs, suggesting that A(2AR may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A(2AR-WT increased the frequency of wave-associated postsynaptic currents (PSCs or depolarizations compared to the control, without changing the RGC's excitability, membrane potentials, or PSC charge. These findings suggest that presynaptic A(2AR may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A(2AR mutant (A(2AR-ΔC in SACs, the wave frequency was reduced compared to the A(2AR-WT, but was similar to the control, suggesting that the full-length A(2AR in SACs is required for A(2AR up-regulation of retinal waves. CONCLUSIONS/SIGNIFICANCE: A(2AR up-regulates the frequency of retinal waves via

  3. Exposure to Cell Phone Radiation Up-Regulates Apoptosis Genes in Primary Cultures of Neurons and Astrocytes

    OpenAIRE

    Zhao, Tian-Yong; Zou, Shi-Ping; Pamela E Knapp

    2006-01-01

    The health effects of cell phone radiation exposure are a growing public concern. This study investigated whether expression of genes related to cell death pathways are dysregulated in primary cultured neurons and astrocytes by exposure to a working GSM (Global System for Mobile Communication) cell phone rated at a frequency of 1900 MHz. Primary cultures were exposed to cell phone emissions for 2 hrs. We used array analysis and real-time RT-PCR to show up-regulation of caspase-2, caspase-6 an...

  4. GS 455534 selectively suppresses binge eating of palatable food and attenuates dopamine release in the accumbens of sugar-bingeing rats.

    Science.gov (United States)

    Bocarsly, Miriam E; Hoebel, Bartley G; Paredes, Daniel; von Loga, Isabell; Murray, Susan M; Wang, Miaoyuan; Arolfo, Maria P; Yao, Lina; Diamond, Ivan; Avena, Nicole M

    2014-04-01

    Binge eating palatable foods has been shown to have behavioral and neurochemical similarities to drug addiction. GS 455534 is a highly selective reversible aldehyde dehydrogenase 2 inhibitor that has been shown to reduce alcohol and cocaine intake in rats. Given the overlaps between binge eating and drug abuse, we examined the effects of GS 455534 on binge eating and subsequent dopamine release. Sprague-Dawley rats were maintained on a sugar (experiment 1) or fat (experiment 2) binge eating diet. After 25 days, GS 455534 was administered at 7.5 and 15 mg/kg by an intraperitoneal injection, and food intake was monitored. In experiment 3, rats with cannulae aimed at the nucleus accumbens shell were maintained on the binge sugar diet for 25 days. Microdialysis was performed, during which GS 455534 15 mg/kg was administered, and sugar was available. Dialysate samples were analyzed to determine extracellular levels of dopamine. In experiment 1, GS 455534 selectively decreased sugar intake food was made available in the Binge Sugar group but not the Ad libitum Sugar group, with no effect on chow intake. In experiment 2, GS 455534 decreased fat intake in the Binge Fat group, but not the Ad libitum Fat group, however, it also reduced chow intake. In experiment 3, GS 455534 attenuated accumbens dopamine release by almost 50% in binge eating rats compared with the vehicle injection. The findings suggest that selective reversible aldehyde dehydrogenase 2 inhibitors may have the therapeutic potential to reduce binge eating of palatable foods in clinical populations.

  5. Melanocortin and Opioid Peptide Interactions in the Modulation of Binge Alcohol Drinking

    Science.gov (United States)

    2013-04-01

    antagonist, modulates the behavioral effects of morphine in mice. Psychopharmacology (Berl) 180(2):279-85. Fan AZ, Russell M, Stranges S, Dorn J...amygdala, hippocampus , and hypothala- mus (Bloch et al., 1979; Dube et al., 1978; Jacobowitz and O’Donohue, 1978; O’Donohue and Jacobowitz, 1980; O’Donohue...behavioral effects of morphine in mice. Psychopharmacology (Berl) 180:279–285. Fetissov SO, Bergstrom U, Johansen JE, Hokfelt T, Schalling M, Ranscht B

  6. Alcohol Marketing Receptivity, Marketing-Specific Cognitions, and Underage Binge Drinking

    NARCIS (Netherlands)

    McClure, A.C.; Stoolmiller, M.; Tanski, S.E.; Engels, R.C.M.E.; Sargent, J.D.

    2013-01-01

    Background Exposure to alcohol marketing is prevalent and is associated with both initiation and progression of alcohol use in underage youth. The mechanism of influence is not well understood, however. This study tests a model that proposes alcohol-specific cognitions as mediators of the relation b

  7. Habit, identity, and repetitive action: a prospective study of binge-drinking in UK students

    NARCIS (Netherlands)

    Gardner, B.; de Bruijn, G.-J.; Lally, P.

    2012-01-01

    Objectives. Repeated action can lead to the formation of habits and identification as ‘the kind of person’ that performs the behaviour. This has led to the suggestion that identity-relevance is a facet of habit. This study explores conceptual overlap between habit and identity, and examines where th

  8. Talking about alcohol consumption: health campaigns, conversational valence, and binge drinking intentions

    NARCIS (Netherlands)

    Hendriks, H.; de Bruijn, G.-J.; van den Putte, B.

    2012-01-01

    Objectives. Although research has shown that whether people talk about health issues influences health campaign effects, no evidence exists on whether conversational valence fulfils a mediating role within health campaign effects. In the context of alcohol consumption, this two-wave experimental res

  9. Binge Drinking and Internalised Sexual Stigma among Italian Lesbian, Gay and Bisexual Young Adults

    Directory of Open Access Journals (Sweden)

    Verrastro Valera

    2016-09-01

    Full Text Available BACKGROUND – Literature has studied the relation between youth alcohol consumption and sexual orientation, showing that lesbian, gay and bisexual (LGB young people are at increased risk to develop alcohol-related problems compared to heterosexuals.

  10. Average use of Alcohol and Binge Drinking in Pregnancy: Neuropsychological Effects at Age 5

    DEFF Research Database (Denmark)

    Kilburn, Tina R.

    were asked to undergo a neuropsychological development exam intended to assess both general measures of cognition, such as IQ, as well as investigating their IPT. The overall neuropsychological development data were obtained through administration of standardized tests for children, as well as parental...

  11. Differences in bingeing behavior and cocaine reward following intermittent access to sucrose, glucose or fructose solutions.

    Science.gov (United States)

    Rorabaugh, J M; Stratford, J M; Zahniser, N R

    2015-08-20

    Daily intermittent access to sugar solutions results in intense bouts of sugar intake (i.e. bingeing) in rats. Bingeing on sucrose, a disaccharide of glucose and fructose, has been associated with a "primed" mesolimbic dopamine (DA) pathway. Recent studies suggest glucose and fructose engage brain reward and energy-sensing mechanisms in opposing ways and may drive sucrose intake through unique neuronal circuits. Here, we examined in male Sprague-Dawley rats whether or not (1) intermittent access to isocaloric solutions of sucrose, glucose or fructose results in distinctive sugar-bingeing profiles and (2) previous sugar bingeing alters cocaine locomotor activation and/or reward, as determined by conditioned place preference (CPP). To encourage bingeing, rats were given 24-h access to water and 12-h-intermittent access to chow plus an intermittent bottle that contained water (control) or 8% solutions of sucrose, glucose or fructose for 9days, followed by ad libitum chow diet and a 10-day cocaine (15mg/kg; i.p.) CPP paradigm. By day 4 of the sugar-bingeing diet, sugar bingeing in the fructose group surpassed the glucose group, with the sucrose group being intermediate. All three sugar groups had similar chow and water intake throughout the diet. In contrast, controls exhibited chow bingeing by day 5 without altering water intake. Similar magnitudes of cocaine CPP were observed in rats with a history of sucrose, fructose or chow (control) bingeing. Notably, the glucose-bingeing rats did not demonstrate a significant cocaine CPP despite showing similar cocaine-induced locomotor activity as the other diet groups. Overall, these results show that fructose and glucose, the monosaccharide components of sucrose, produce divergent degrees of bingeing and cocaine reward.

  12. Drinking Coffee

    DEFF Research Database (Denmark)

    Strøbæk, Pernille Solveig

    2015-01-01

    The chapter explores how coffee is an integral part of our daily life. Focusing on coffee drinking at home, at work, and on the go I show that coffee consumption is a social practice. The chapter illustrates through everyday examples that coffee is more than a caffeine drug. Coffee, with or without...... caffeine, is a social lubricant. We talk to each other and share emotions with one another as we share a cup of coffee. Coffee makes conversation and we embrace coffee, to stay or to go, in the daily rhythm of our busy and global social existence. The practice and sociality of coffee consumption provide...... the coffee industry with the opportunity to make money on our coffee preferences – indeed, also for those of us who actually dislike the taste of coffee. Would you prefer coffee mixed and stirred with non-coffee products such as salt, caramel and licorice? Then you are one of us in the modern age of coffee...

  13. Carboxypeptidase E protects hippocampal neurons during stress in male mice by up-regulating prosurvival BCL2 protein expression.

    Science.gov (United States)

    Murthy, S R K; Thouennon, E; Li, W-S; Cheng, Y; Bhupatkar, J; Cawley, N X; Lane, M; Merchenthaler, I; Loh, Y P

    2013-09-01

    Prolonged chronic stress causing elevated plasma glucocorticoids leads to neurodegeneration. Adaptation to stress (allostasis) through neuroprotective mechanisms can delay this process. Studies on hippocampal neurons have identified carboxypeptidase E (CPE) as a novel neuroprotective protein that acts extracellularly, independent of its enzymatic activity, although the mechanism of action is unclear. Here, we aim to determine if CPE plays a neuroprotective role in allostasis in mouse hippocampus during chronic restraint stress (CRS), and the molecular mechanisms involved. Quantitative RT-PCR/in situ hybridization and Western blots were used to assay for mRNA and protein. After mild CRS (1 h/d for 7 d), CPE protein and mRNA were significantly elevated in the hippocampal CA3 region, compared to naïve littermates. In addition, luciferase reporter assays identified a functional glucocorticoid regulatory element within the cpe promoter that mediated the up-regulation of CPE expression in primary hippocampal neurons following dexamethasone treatment, suggesting that circulating plasma glucocorticoids could evoke a similar effect on CPE in the hippocampus in vivo. Overexpression of CPE in hippocampal neurons, or CRS in mice, resulted in elevated prosurvival BCL2 protein/mRNA and p-AKT levels in the hippocampus; however, CPE(-/-) mice showed a decrease. Thus, during mild CRS, CPE expression is up-regulated, possibly contributed by glucocorticoids, to mediate neuroprotection of the hippocampus by enhancing BCL2 expression through AKT signaling, and thereby maintaining allostasis.

  14. Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.

    Directory of Open Access Journals (Sweden)

    Kristine Porter

    Full Text Available Cells in the trabecular meshwork (TM, a tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic activity in TM cells is thought to play an important role in outflow pathway physiology. However, the molecular mechanisms triggered by phagocytosis in TM cells are unknown. Here we investigated the effects of chronic phagocytic stress on lysosomal function using different phagocytic ligands (E. coli, carboxylated beads, collagen I-coated beads, and pigment. Lysotracker red co-localization and electron micrographs showed the maturation of E. coli- and collagen I-coated beads-containing phagosomes into phagolysosomes. Maturation of phagosomes into phagolysosomes was not observed with carboxylated beads or pigment particles. In addition, phagocytosis of E. coli and collagen I-coated beads led to increased lysosomal mass, and the specific up-regulation and activity of cathepsin B (CTSB. Higher levels of membrane-bound and secreted CTSB were also detected. Moreover, in vivo zymography showed the intralysosomal degradation of ECM components associated with active CTSB, as well as an overall increased gelatinolytic activity in phagocytically challenged TM cells. This increased gelatinolytic activity with phagocytosis was partially blocked with an intracellular CTSB inhibitor. Altogether, these results suggest a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

  15. Transcutaneous electrical nerve stimulation (TENS) improves the diabetic cytopathy (DCP) via up-regulation of CGRP and cAMP.

    Science.gov (United States)

    Ding, Liucheng; Song, Tao; Yi, Chaoran; Huang, Yi; Yu, Wen; Ling, Lin; Dai, Yutian; Wei, Zhongqing

    2013-01-01

    The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS) on the diabetic cytopathy (DCP) in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM)/TENS group (n=15), DM group (n=15) and control group (n=15). The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min) for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP) was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG) in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.

  16. Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Zequn Jiang; Shasha Li; Yunyi Liu; Pengyi Deng; Jianguo Huang; Guangyuan He

    2011-01-01

    In this study,we confirmed that sesamin,an active lignan isolated from sesame seed and oil,is a novel skin-tanning compound.The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells.The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin.Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmiaassociated transcription factor (MITF).Sesamin could activate cAMP response element (CRE) binding protein (CREB),but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt.Moreover,sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway.Consistent with these results,sesamin-mediated increase of melanin synthesis was reduced significantly by H-89,a PKA inhibitor,but not by SB203580,a p38 MAPK inhibitor or by LY294002,a phosphatidylinositol-3-kinase (PI3K) inhibitor.Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89.These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase,which was,in turn,due to the activation of cAMP signaling.

  17. Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway.

    Science.gov (United States)

    Jiang, Zequn; Li, Shasha; Liu, Yunyi; Deng, Pengyi; Huang, Jianguo; He, Guangyuan

    2011-10-01

    In this study, we confirmed that sesamin, an active lignan isolated from sesame seed and oil, is a novel skin-tanning compound. The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin. Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmia-associated transcription factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor, but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89. These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase, which was, in turn, due to the activation of cAMP signaling.

  18. AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

    Directory of Open Access Journals (Sweden)

    Andreea Iren Serban

    2015-08-01

    Full Text Available Advanced glycation end products (AGEs can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by human embryonic kidney cells (HEK 293 upon exposure to 200 μg/mL bovine serum albumine (BSA or AGEs–BSA for 12, 24 and 48 h. The mRNA and protein expression levels of AGEs receptor (RAGE and heat shock proteins (HSPs 27, 60 and 70, the activity of antioxidant enzymes and the expression levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was evaluated by glutathione and malondialdehyde levels. The data revealed two different time scale responses. First, the up-regulation of interleukin-6 (IL-6, HSP 27 and high catalase activity were detected as early as 12 h after exposure to AGEs–BSA, while the second response, after 24 h, consisted of NF-κB p65, RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion, malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be important in the early ignition of inflammatory responses, while the cellular redox imbalance, RAGE activation and NF-κB p65 increased expression further enhance inflammatory signals in HEK 293 cells.

  19. EFFECT OF UP-REGULATION OF S-ADOMET SYNTHETASE ON TAXOL-INDUCED APOPTOSIS IN HUMAN BREAST CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    Chen Lirong; Zheng Shu; Fan Weimin; Zhang Suzhan

    1998-01-01

    Objective:To investigate the gene regulation of taxolinduced apoptosis. Methods: Northern blot hybridization,enzyme activity assay of S-AdoMet synthetase and flow cytometry were performed in the investigation of expression in the Mrna level and biological action of SAdoMet synthetase in taxol-induced apoptosis in human breast cancer cell line (Bcap 37). Results: Up-regulation of S-AdoMet synthetase expression was resulted by taxol treatment and the expression peaked at 48hours. Moreover,the up-regulation of S-AdoMet synthetase was associated with cytotoxicity of antimicrotubule agents including taxol and colchicine.Inhibition rate of S-AdoMet synthetase activity by 1%DMSO was 34% in taxol-treated cells and 14% in taxoluntreated cells compared to control groups, respectively.Posttreatment with 1% DMSO following pretreatment with individual antitumor agent for 3 hrs promoted apoptotic cell death of taxol-,colchicine-,and adriamycintreated Bcap37 cells. Conclusion : The induction of apoptosis enhanced by post-treatment with DMSO in taxol-treated cells is probably linked to its inhibition on enzyme activity of S-AdoMet synthetase ,suggesting that the increased expression of S-AdoMet synthetase possibly plays an important role in protecting cells from DNA fragmentation in taxol-induced apoptosis.

  20. Up-regulation of the Kv3.4 potassium channel subunit in early stages of Alzheimer's disease.

    Science.gov (United States)

    Angulo, Ester; Noé, Véronique; Casadó, Vicent; Mallol, Josefa; Gomez-Isla, Teresa; Lluis, Carmen; Ferrer, Isidre; Ciudad, Carlos J; Franco, Rafael

    2004-11-01

    Gene expression throughout the different stages of Alzheimer's disease was analysed in samples from cerebral cortex. The gene encoding the voltage-gated potassium channel Kv3.4 was already overexpressed in early stages of the disease, and in advanced stages Kv3.4 was present at high levels in neurodegenerative structures. This subunit regulates delayed-rectifier currents, which are primary determinants of spike repolarization in neurones. In unique samples from a patient with Alzheimer's disease whose amount of amyloid plaques was decreased by beta amyloid immunization, Kv3.4 was overexpressed. The channel subunit was expressed in the neuropil, in the remaining conventional plaques in the frontal cortex and in collapsed plaques in the orbitary cortex. Therefore, amyloid deposition in plaques does not seem to be responsible for the increase in Kv3.4 levels. Nevertheless, Kv3.4 up-regulation is related to amyloid pathology, given that transgenic mice with the Swedish mutation of amyloid precursor protein showed increased expression of Kv3.4. Up-regulation of voltage-gated potassium channel subunits alters potassium currents in neurones and leads to altered synaptic activity that may underlie the neurodegeneration observed in Alzheimer's disease. Thus, Kv3.4 likely represents a novel therapeutic target for the disease.

  1. Cloning and functional analyses of a gene from sugar beet up-regulated upon cyst nematode infection.

    Science.gov (United States)

    Samuelian, Suren; Kleine, Michael; Ruyter-Spira, Carolien P; Klein-Lankhorst, René M; Jung, Christian

    2004-01-01

    The cDNA-AFLP technique was used to isolate sugar beet genes up-regulated upon infection with the beet cyst nematode Heterodera schachtii. Hairy root cultures were obtained from resistant plants carrying a Beta procumbens translocation as well as from a non-resistant control. mRNA was isolated from hairy root clones and sugar beet plants infected or not with the beet cyst nematode and 8000 transcript-derived fragments (TDFs) were analysed. One TDF was found to be differentially expressed in both materials and was further investigated. Real-time PCR confirmed that this TDF is specifically up-regulated in resistant sugar beet upon nematode infection and its full-length cDNA was isolated. Sequence analysis suggests that the gene encodes a 317 amino acid polypeptide of unknown function. No homology to any sequence present in the public databases could be detected. To further elucidate its function in resistance to the beet cyst nematode, the cDNA was transformed into hairy roots of susceptible sugar beet under the control of the 35S promoter and hairy root clones were inoculated with nematodes. The number of developing females was significantly reduced in 12 out of 15 clones resulting from independent transgenic events suggesting that the gene can be used for inducing cyst nematode resistance in plants.

  2. Transcutaneous electrical nerve stimulation (TENS improves the diabetic cytopathy (DCP via up-regulation of CGRP and cAMP.

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    Liucheng Ding

    Full Text Available The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS on the diabetic cytopathy (DCP in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM/TENS group (n=15, DM group (n=15 and control group (n=15. The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.

  3. Up-regulation of heme oxygenase-1 by isoflurane preconditioning during tolerance against neuronal injury induced by oxygen glucose deprivation

    Institute of Scientific and Technical Information of China (English)

    Qifang Li; Yesen Zhu; Hong Jiang; Hui Xu; Heping Liu

    2008-01-01

    Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a variety of factors such as heat, heme, ischemia, and hydrogen peroxide. In recent years, mounting findings have suggested that HO-1 has a neuroprotective activity against ischemic injury. The neuroprotective role of isoflurane, a commonly used anesthetic, has been well documented, but little is known about the underlying mechanisms involved. Recently, isoflurane has been shown to up-regulate HO-1 in the liver. In this study,we show that isoflurane preconditioning promotes the survival of cultured ischemic hippocampal neurons by increasing the number of surviving neurons and their viability. Further study by reverse transcription-polymerase chain reaction and Western blot analysis showed that isoflurane preconditioning significantly increases HO-1 expression in oxygen glucose deprivation (OGD)-induced neuronal injury. Furthermore,inhibition of HO activity by tin protoporphyrin partially abolishes isoflurane preconditioning's protective effect as measured by lactate dehydrogenase release in OGD neurons.These findings indicated that the neuroprotective role of isoflurane preconditioning against OGD-induced injury might be associated with its role in up-regulating HO-1 in ischemic neurons.

  4. Up-regulation of heme oxygenase-1 by isoflurane preconditioning during tolerance against neuronal injury induced by oxygen glucose deprivation.

    Science.gov (United States)

    Li, Qifang; Zhu, Yesen; Jiang, Hong; Xu, Hui; Liu, Heping

    2008-09-01

    Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a variety of factors such as heat, heme, ischemia, and hydrogen peroxide. In recent years, mounting findings have suggested that HO-1 has a neuroprotective activity against ischemic injury. The neuroprotective role of isoflurane, a commonly used anesthetic, has been well documented, but little is known about the underlying mechanisms involved. Recently, isoflurane has been shown to up-regulate HO-1 in the liver. In this study, we show that isoflurane preconditioning promotes the survival of cultured ischemic hippocampal neurons by increasing the number of surviving neurons and their viability. Further study by reverse transcription-polymerase chain reaction and Western blot analysis showed that isoflurane preconditioning significantly increases HO-1 expression in oxygen glucose deprivation (OGD)-induced neuronal injury. Furthermore, inhibition of HO activity by tin protoporphyrin partially abolishes isoflurane preconditioning's protective effect as measured by lactate dehydrogenase release in OGD neurons. These findings indicated that the neuroprotective role of isoflurane preconditioning against OGD-induced injury might be associated with its role in up-regulating HO-1 in ischemic neurons.

  5. Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

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    Zhen-Yu He

    2017-02-01

    Full Text Available Triple-negative breast cancer (TNBC was regarded as the most aggressive and mortal subtype of breast cancer (BC since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3 significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.

  6. FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress.

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    Ponugoti, Bhaskar; Xu, Fanxing; Zhang, Chenying; Tian, Chen; Pacios, Sandra; Graves, Dana T

    2013-10-28

    Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor β1 (TGF-β1) and its downstream targets, integrin-α3 and -β6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-β1-independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-β1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis.

  7. Chronic up-regulation of the SHH pathway normalizes some developmental effects of trisomy in Ts65Dn mice.

    Science.gov (United States)

    Dutka, Tara; Hallberg, Dorothy; Reeves, Roger H

    2015-02-01

    Down Syndrome (DS) is a highly complex developmental genetic disorder caused by trisomy for human chromosome 21 (Hsa21). All individuals with DS exhibit some degree of brain structural changes and cognitive impairment; mouse models such as Ts65Dn have been instrumental in understanding the underlying mechanisms. Several phenotypes of DS might arise from a reduced response of trisomic cells to the Sonic Hedgehog (SHH) growth factor. If all trisomic cells show a similar reduced response to SHH, then up-regulation of the pathway in trisomic cells might ameliorate multiple DS phenotypes. We crossed Ptch1tm1Mps/+ mice, in which the canonical SHH pathway is expected to be up-regulated in every SHH-responsive cell due to the loss of function of one allele of the pathway suppressor, Ptch1, to the Ts65Dn DS model and assessed the progeny for possible rescue of multiple DS-related phenotypes. Down-regulation of Ptch produced several previously unreported effects on development by itself, complicating interpretation of some phenotypes, and a number of structural or behavioral effects of trisomy were not compensated by SHH signaling. However, a deficit in a nest-building task was partially restored in Ts;Ptch+/- mice, as were the structural anomalies of the cerebellum seen in Ts65Dn mice. These results extend the body of evidence indicating that reduced response to SHH in trisomic cells and tissues contributes to various aspects of the trisomic phenotype.

  8. Putative midkine family protein up-regulation in Patella caerulea (Mollusca, Gastropoda) exposed to sublethal concentrations of cadmium

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    Vanucci, Silvana [Department of Animal Biology and Marine Ecology, University of Messina, Salita Sperone 31, 98166 S Agata, Messina (Italy)]. E-mail: silvana.vanucci@unime.it; Minerdi, Daniela [Department of Animal Biology and Genetics, University of Florence, via Romana 19, 50125 Florence (Italy); Kadomatsu, Kenji [Department of Biochemistry, University of Nagoya Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Mengoni, Alessio [Department of Animal Biology and Genetics, University of Florence, via Romana 19, 50125 Florence (Italy); Bazzicalupo, Marco [Department of Animal Biology and Genetics, University of Florence, via Romana 19, 50125 Florence (Italy)

    2005-11-30

    A cDNA sequence of a putative midkine (MK) family protein was identified and characterised in the mollusc Patella caerulea. The midkine family consists of two members, midkine and pleiotrophin (PTN), and it is one of the recently discovered cytokines. Our results show that this putative midkine protein is up-regulated in specimens of P. caerulea exposed to sublethal cadmium concentrations (i.e. 0.5 and 1 mg l{sup -1} Cd) over a 10-day exposure period. Semiquantitative RT-PCR and quantitative Real time RT-PCR estimations indicate elevated expression of midkine mRNA in exposed specimens compared to controls. Moreover, RT-PCR Real time values were higher in the viscera (here defined as the part of the soft tissue including digestive gland plus gills) than in the foot (i.e. foot plus head plus heart) of the limpets. At present, information on the functional signalling significance of the midkine family proteins suggests that the up-regulation of P. caerulea putative midkine family protein is a distress signal likely with informative value on health status of the organism and with potential prognostic capability.

  9. TGEV infection up-regulates FcRn expression via activation of NF-κB signaling.

    Science.gov (United States)

    Guo, Jinyue; Li, Fei; Qian, Shaoju; Bi, Dingren; He, Qigai; Jin, Hui; Luo, Rui; Li, Shaowen; Meng, Xianrong; Li, Zili

    2016-08-24

    It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.

  10. UCP2 up-regulation within the course of autoimmune encephalomyelitis correlates with T-lymphocyte activation.

    Science.gov (United States)

    Smorodchenko, Alina; Schneider, Stephanie; Rupprecht, Anne; Hilse, Karoline; Sasgary, Soleman; Zeitz, Ute; Erben, Reinhold G; Pohl, Elena E

    2017-04-01

    Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) associated with severe neurological disability. Reactive oxygen species (ROS) and mitochondrial dysfunction play a pivotal role in the pathogenesis of this disease. Several members of the mitochondrial uncoupling protein subfamily (UCP2-UCP5) were suggested to regulate ROS by diminishing the mitochondrial membrane potential and constitute therefore a promising pharmacological target for MS. To evaluate the role of different uncoupling proteins in neuroinflammation, we have investigated their expression patterns in murine brain and spinal cord (SC) during different stages of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. At mRNA and protein levels we found that only UCP2 is up-regulated in the SC, but not in brain. The increase in UCP2 expression was antigen-independent, reached its maximum between 14 and 21days in both OVA and MOG immunized animals and correlated with an augmented number of CD3(+) T-lymphocytes in SC parenchyma. The decrease in abundance of UCP4 was due to neuronal injury and was only detected in CNS of MOG-induced EAE animals. The results provide evidence that the involvement of mitochondrial UCP2 in CNS inflammation during EAE may be mainly explained by the invasion of activated T-lymphocytes. This conclusion coincides with our previous observation that UCP2 is up-regulated in activated and rapidly proliferating T-cells and participates in fast metabolic re-programming of cells during proliferation.

  11. Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking

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    Meimei Chen

    2016-11-01

    Full Text Available In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

  12. Associated Factors for Self-Reported Binge Eating among Male and Female Adolescents.

    Science.gov (United States)

    Ledoux, Sylvie; And Others

    1993-01-01

    Adolescents (n=3,287) completed questionnaire concerning eating behaviors. Found that binge eaters had disorderly eating habits (skipping meals, snacking, eating sweets, unbalanced diets), concern with body shape (feeling too fat), and depressive symptoms more often than nonbinge eaters did. Relationship between binging episodes and eating habits,…

  13. Self-consciousness and binge eating in college women : an escape from rumination?

    NARCIS (Netherlands)

    Dalley, Simon; Donofrio, Stacey

    2014-01-01

    Background: Binge-eating is a highly distressing symptom that has been found to co-occur with other symptoms of eating disorders such as bulimia nervosa. One perspective of binge eating is that it is an attempt to escape high levels of aversive self-consciousness. A primary aim of this study is to e

  14. Metacognitions about desire thinking predict the severity of binge eating in a sample of Italian women.

    Science.gov (United States)

    Spada, Marcantonio M; Caselli, Gabriele; Fernie, Bruce A; Nikčević, Ana V; Ruggiero, Giovanni M; Boccaletti, Fabio; Dallari, Giulia; Sassaroli, Sandra

    2016-06-01

    In this study, our principal aim was to investigate whether metacognitions about desire thinking predict the severity of binge eating in women and, if so, whether this relationship is independent of age, self-reported body mass index (BMI), negative affect, irrational food beliefs and craving. One hundred and four women, consisting of 32 consecutive patients with binge eating disorder undergoing initial assessment for cognitive therapy for eating disorders, 39 moderate binge eaters, and 33 non-binge eaters (both from the general population), completed the following measures: Self-reported BMI, Hospital Anxiety and Depression Scale, Irrational Food Beliefs Scale, General Craving Scale, Metacognitions about Desire Thinking Questionnaire, and Binge Eating Scale. A series of Spearman's rho correlation analyses revealed that self-reported BMI, anxiety, depression, irrational food beliefs, craving, and all three factors of the metacognitions about desire thinking questionnaire were significantly associated with the severity of binge eating. A stepwise regression analysis identified self-reported BMI, craving, and negative metacognitions about desire thinking as significant predictors of the severity of binge eating. These results, taken together, highlight the possible role of metacognitions about desire thinking in predicting the severity of binge eating. The clinical implications of these findings are discussed.

  15. A Controlled Evaluation of the Distress Criterion for Binge Eating Disorder

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    Grilo, Carlos M.; White, Marney A.

    2011-01-01

    Objective: Research has examined various aspects of the validity of the research criteria for binge eating disorder (BED) but has yet to evaluate the utility of Criterion C, "marked distress about binge eating." This study examined the significance of the marked distress criterion for BED using 2 complementary comparison groups. Method:…

  16. Rapid Response Predicts Treatment Outcomes in Binge Eating Disorder: Implications for Stepped Care

    Science.gov (United States)

    Masheb, Robin M.; Grilo, Carlos M.

    2007-01-01

    The authors examined rapid response in 75 overweight patients with binge eating disorder (BED) who participated in a randomized clinical trial of guided self-help treatments (cognitive-behavioral therapy [CBTgsh] and behavioral weight loss [BWLgsh]). Rapid response, defined as a 65% or greater reduction in binge eating by the 4th treatment week,…

  17. A Controlled Evaluation of the Distress Criterion for Binge Eating Disorder

    Science.gov (United States)

    Grilo, Carlos M.; White, Marney A.

    2011-01-01

    Objective: Research has examined various aspects of the validity of the research criteria for binge eating disorder (BED) but has yet to evaluate the utility of Criterion C, "marked distress about binge eating." This study examined the significance of the marked distress criterion for BED using 2 complementary comparison groups. Method: A total of…

  18. Cost-Effectiveness of Guided Self-Help Treatment for Recurrent Binge Eating

    Science.gov (United States)

    Lynch, Frances L.; Striegel-Moore, Ruth H.; Dickerson, John F.; Perrin, Nancy; DeBar, Lynn; Wilson, G. Terence; Kraemer, Helena C.

    2010-01-01

    Objective: Adoption of effective treatments for recurrent binge-eating disorders depends on the balance of costs and benefits. Using data from a recent randomized controlled trial, we conducted an incremental cost-effectiveness analysis (CEA) of a cognitive-behavioral therapy guided self-help intervention (CBT-GSH) to treat recurrent binge eating…

  19. Mindfulness-Based Cognitive Therapy Applied to Binge Eating: A Case Study

    Science.gov (United States)

    Baer, Ruth A.; Fischer, Sarah; Huss, Debra B.

    2005-01-01

    Binge eating is a common problem associated with distress and dysfunction. Mindfulness-based interventions are attracting increasing attention, and the recent empirical literature suggests that they may be effective for a variety of disorders. Current theories about the etiology and maintenance of binge eating suggest that mindfulness training may…

  20. Young Adults' Food Selection Patterns: Relations with Binge Eating and Restraint

    Science.gov (United States)

    Lydecker, Janet A.; Palmberg, Allison A.; Hill, Katherine Vatalaro; Mazzeo, Suzanne E.

    2015-01-01

    Binge eating is increasingly prevalent in college students (White, Reynolds-Malear, & Cordero, 2011). Binge episodes involve eating an objectively large quantity of food in a discrete amount of time and a perceived lost control over eating (American Psychiatric Association [APA], 2013). Strong negative affect commonly precedes and follows each…

  1. Drinking pattern of wine and effects on human health: why should we drink moderately and with meals?

    Science.gov (United States)

    Boban, Mladen; Stockley, Creina; Teissedre, Pierre-Louis; Restani, Patrizia; Fradera, Ursula; Stein-Hammer, Claudia; Ruf, Jean-Claude

    2016-07-13

    Conclusions of epidemiological studies examining the effects of alcoholic beverages on human health may be unclear and limited if they do not take into account drinking pattern parameters such as beverage type, regular moderate versus binge drinking and drinking with or without meals. This review considers different aspects of drinking patterns and effects on human health with special attention to wine. We particularly discuss the potential underlying mechanisms for epidemiological evidence that the beneficial effects of wine are more evident if consumed with food. In this context, we address the effects of food on blood alcohol concentration and acetaldehyde production in the gastrointestinal tract, the role of wine components and uric acid in counteracting the detrimental effects of postprandial oxidative stress, as well as wine's antimicrobial properties and its potential to act as a digestive aid. In addition to its biological correlates, drinking patterns with regard to different socio-cultural circumstances in different populations are also considered. In order to avoid confusion and misconceptions in the general population because of the hormetic associations of wine with human health, it is important that all medical and scientific information concerning the effect of wine consumption on human health are evidence-based and communicated in a competent, credible and unbiased manner. In conclusion, we propose several practical recommendations concerning wine consumption and consumer information to minimize the risks of alcohol-related harm and to encourage individual responsibility and a healthy lifestyle.

  2. Attachment anxiety is associated with a fear of becoming fat, which is mediated by binge eating

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    Katherine E. Alexander

    2017-03-01

    Full Text Available Background Previous work demonstrated that individuals with higher levels of attachment anxiety are prone to increased binge eating (Alexander & Siegel, 2013. Given that our society rejects obese individuals and individuals with higher levels of attachment anxiety tend to be highly sensitive to rejection (Downey & Feldman, 1996, it follows that those with increased attachment anxiety may be especially fearful of becoming fat. Methods Undergraduate psychology students (n = 148 completed surveys measuring attachment, binge eating, and fear of becoming fat. Results The data demonstrate that attachment anxiety is positively associated with a fear of becoming fat (β = .30, p < .001 and binge eating mediates this relationship. In other words, binge eating underlies the fear of becoming fat. Discussion These findings contribute to a more refined understanding of binge eating which may create pathways for professionals to develop targeted interventions.

  3. Thinness and eating expectancies predict subsequent binge-eating and purging behavior among adolescent girls.

    Science.gov (United States)

    Smith, Gregory T; Simmons, Jean R; Flory, Kate; Annus, Agnes M; Hill, Kelly K

    2007-02-01

    One's expectancies for reinforcement from eating or from thinness are thought to represent summaries of one's eating-related learning history and to thus influence the development of binge-eating and purging behavior. In a 3-year longitudinal study, the authors tested this hypothesis and the hypothesis that binge eating also influences subsequent expectancy development. The authors used trajectory analysis to identify groups of middle school girls who followed different trajectories of binge eating, purging, eating expectancies, and thinness expectancies. Initial eating and thinness reinforcement expectancies identified girls whose binge eating and purging increased during middle school, and expectancies differentiated girls who began these problem behaviors from girls who did not. Initial binge-eating scores differentiated among eating expectancy developmental trajectories. The onset of most behaviors can be understood in terms of learned expectancies for reinforcement from these behaviors. The same model can be applied to the risk for eating disorders.

  4. Attachment anxiety is associated with a fear of becoming fat, which is mediated by binge eating

    Science.gov (United States)

    2017-01-01

    Background Previous work demonstrated that individuals with higher levels of attachment anxiety are prone to increased binge eating (Alexander & Siegel, 2013). Given that our society rejects obese individuals and individuals with higher levels of attachment anxiety tend to be highly sensitive to rejection (Downey & Feldman, 1996), it follows that those with increased attachment anxiety may be especially fearful of becoming fat. Methods Undergraduate psychology students (n = 148) completed surveys measuring attachment, binge eating, and fear of becoming fat. Results The data demonstrate that attachment anxiety is positively associated with a fear of becoming fat (β = .30, p < .001) and binge eating mediates this relationship. In other words, binge eating underlies the fear of becoming fat. Discussion These findings contribute to a more refined understanding of binge eating which may create pathways for professionals to develop targeted interventions. PMID:28286709

  5. Up-Regulated Expression of LAMP2 and Autophagy Activity during Neuroendocrine Differentiation of Prostate Cancer LNCaP Cells

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    Vara-Ciruelos, Diana; Ramos-Torres, Ágata; Altamirano-Dimas, Manuel; Díaz-Laviada, Inés; Rodríguez-Henche, Nieves

    2016-01-01

    Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells. Using cDNA microarrays, we compared gene expression profiles of NE cells and non-differentiated LNCaP cells. We identified up-regulation of 155 genes, among them LAMP2, a lysosomal membrane protein involved in lysosomal stability and autophagy. We then confirmed up-regulation of LAMP2 in NE cells by qRT-PCR, Western blot and confocal microscopy assays, showing that mRNA up-regulation correlated with increased levels of LAMP2 protein. Subsequently, we determined autophagy activity in NE cells by assessing the protein levels of SQSTM/p62 and LC3 by Western blot and LC3 and Atg5 mRNAs content by qRT-PCR. The decreased levels of SQSTM/p62 was accompanied by an enhanced expression of LC3 and ATG5, suggesting activation of autophagy in NE cells. Blockage of autophagy with 1μM AKT inhibitor IV, or by silencing Beclin 1 and Atg5, prevented NE cell differentiation, as revealed by decreased levels of the NE markers. In addition, AKT inhibitor IV as well as Beclin1 and Atg5 kwockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these results suggest that LAMP2 overexpression assists NE differentiation of LNCaP cells induced by serum deprivation and facilitates autophagy activity in order to attain the NE phenotype and cell survival. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer. PMID:27627761

  6. Growth arrest specific 2 is up-regulated in chronic myeloid leukemia cells and required for their growth.

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    Haixia Zhou

    Full Text Available Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML, the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2 regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form of GAS2 (GAS2DN to target GAS2, which resulted in calpain activity enhancement and growth inhibition of both K562 and MEG-01 cells. Targeting GAS2 also sensitized K562 cells to Imatinib mesylate (IM. GAS2DN suppressed the tumorigenic ability of MEG-01 cells and impaired the tumour growth as well. Moreover, the CD34+ cells from CML patients and healthy donors were transduced with control and GAS2DN lentiviral vectors, and the CD34+ transduced (YFP+ progeny cells (CD34+YFP+ were plated for colony-forming cell (CFC assay. The results showed that GAS2DN inhibited the CFC production of CML cells by 57±3% (n = 3, while affected those of normal hematopoietic cells by 31±1% (n = 2. Next, we found the inhibition of CML cells by GAS2DN was dependent on calpain activity but not the degradation of beta-catenin. Lastly, we generated microarray data to identify the differentially expressed genes upon GAS2DN and validated that the expression of HNRPDL, PTK7 and UCHL5 was suppressed by GAS2DN. These 3 genes were up-regulated in CML cells compared to normal control cells and the growth of K562 cells was inhibited upon HNRPDL silence. Taken together, we have demonstrated that GAS2 is up-regulated in CML cells and the inhibition of GAS2 impairs the growth of CML cells, which indicates GAS2 is a novel regulator of CML cells and a potential therapeutic target of this disease.

  7. Up-regulation of intestinal vascular endothelial growth factor by Afa/Dr diffusely adhering Escherichia coli.

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    Gaëlle Cane

    Full Text Available BACKGROUND: Angiogenesis has been recently described as a novel component of inflammatory bowel disease pathogenesis. The level of vascular endothelial growth factor (VEGF has been found increased in Crohn's disease and ulcerative colitis mucosa. To question whether a pro-inflammatory Escherichia coli could regulate the expression of VEGF in human intestinal epithelial cells, we examine the response of cultured human colonic T84 cells to infection by E. coli strain C1845 that belongs to the typical Afa/Dr diffusely adhering E. coli family (Afa/Dr DAEC. METHODOLOGY: VEGF mRNA expression was examined by Northern blotting and q-PCR. VEGF protein levels were assayed by ELISA and its bioactivity was analysed in endothelial cells. The bacterial factor involved in VEGF induction was identified using recombinant E. coli expressing Dr adhesin, purified Dr adhesin and lipopolysaccharide. The signaling pathway activated for the up-regulation of VEGF was identified using a blocking monoclonal anti-DAF antibody, Western blot analysis and specific pharmacological inhibitors. PRINCIPAL FINDINGS: C1845 bacteria induce the production of VEGF protein which is bioactive. VEGF is induced by adhering C1845 in both a time- and bacteria concentration-dependent manner. This phenomenon is not cell line dependent since we reproduced this observation in intestinal LS174, Caco2/TC7 and INT407 cells. Up-regulation of VEGF production requires: (1 the interaction of the bacterial F1845 adhesin with the brush border-associated decay accelerating factor (DAF, CD55 acting as a bacterial receptor, and (2 the activation of a Src protein kinase upstream of the activation of the Erk and Akt signaling pathways. CONCLUSIONS: Results demonstrate that a Afa/Dr DAEC strain induces an adhesin-dependent activation of DAF signaling that leads to the up-regulation of bioactive VEGF in cultured human intestinal cells. Thus, these results suggest a link between an entero-adherent, pro

  8. Genistein, isoflavonoids in soybeans, prevents the formation of excess radiation-induced centrosomes via p21 up-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Mikio; Kato, Akihiro [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-konoe, Sakyo, Kyoto 606-8501 (Japan); Habu, Toshiyuki [Department of Radiation System Biology, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan); Komatsu, Kenshi, E-mail: komatsu@house.rbc.kyoto-u.ac.jp [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-konoe, Sakyo, Kyoto 606-8501 (Japan)

    2011-11-01

    The centrosome is a cytoplasmic organelle which duplicates once during each cell cycle, and the presence of excess centrosomes promote chromosome instability through chromosome missegregation following cytokinesis. Ionizing radiation (IR) can induce extra centrosomes by permitting the continuation of CDK2/Cyclin-A/E-mediated centrosome duplication when cells are arrested in the cell cycle after irradiation. The work described here shows that, in addition to IR, extra centrosomes were induced in human U2OS and mouse NIH3T3 cells after treatment with agents which include DNA adduct-forming chemicals: benzopyrene (BP), 4-nitroquinoline 1-oxide (4NQO), a DNA cross linker: cis-diamminedichloro-platinum (cisplatin), topoisomerase inhibitors: camptothecin, etoposide, genistein, and ultra-violet light (UV). These agents were divided into two categories with respect to the regulation of p21, which is an inhibitor of CDK2/Cyclin-A/E: specifically, p21 was up-regulated by an IR exposure and treatment with topoisomerase inhibitors. However, UV, BP, 4NQO and cisplatin down-regulated p21 below basal levels. When cells were irradiated with IR in combination with all of these agents, except genistein, enhanced induction of extra centrosomes was observed, regardless of the nature of p21 expression. Genistein significantly suppressed the frequency of IR-induced extra centrosomes in a dose-dependent manner, and 20 {mu}g/ml of genistein reduced this frequency to 66%. Consistent with this, genistein substantially up-regulated p21 expression over the induction caused by IR alone, while other agents down-regulated or marginally affected this. This suggests the inhibitory effect of genistein on the induction of extra centrosomes occurs through the inactivation of CDK2/Cyclin-A/E via p21 up-regulation. This hypothesis is supported by the observation that p21 knockdown with siRNA reduced the activity of CDK2/Cyclin-A/E and restored the enhanced effect of a combined treatment with genistein

  9. Up-regulation of intestinal nuclear factor kappa B and intercellular adhesionmolecule-1 following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Chun-Hua Hang; Ji-Xin Shi; Jie-Shou Li; Wei-Qin Li; Hong-Xia Yin

    2005-01-01

    AIM: Nuclear factor kappa B (NF-κB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-κB is activated and intercellular adhesion molecule-1 (ICAM-1)expressed in the gut following traumatic brain injury (TBI).The aim of current study was to investigate the temporal pattern of intestinal NF-κB activation and ICAM-1expression following TBI.METHODS: Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-κB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples.RESULTS: There was a very low NF-κB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-κB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase)and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-κB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI.CONCLUSION: TBI could induce an immediate and persistent up-regulation of NF-κB activity and subsequent up-regulation of ICAM-1 expression in the intestine.Inflammatory response mediated by increased NF-κB activation and ICAM-1 expression may play an

  10. Alexithymia, depression, anxiety and binge eating in obese women

    Directory of Open Access Journals (Sweden)

    Agnieszka Źak-Gołąb

    2013-09-01

    Full Text Available Background and Objectives: Alexithymia is a personality trait that may affect the development and course of obesity and effectiveness of treatment. The aim of the study is to assess the prevalence of alexithymia in obese women beginning a weight reduction program and determine the relationships between alexithymia and anxiety, depression, and binge eating. Methods: Obese women (n = 100; age 45 ± 13 yr completed the following self-report inventories: Toronto Alexithymia Scale (TAS 26, Hospital Anxiety and Depression Scale (HADS, and Binge Eating Scale (BES. Results: Alexithymia was found in 46 patients and was more frequent among women who had attained only primary and vocational education than in those with a higher education level (39.1% vs. 10.9%; p = 0.002 and in those >45 years old than in younger women (30.4% vs. 69.6%; p = 0.03. The frequency of severe depression symptoms was higher in alexithymic women than in non-alexithymic women (19.6% vs. 5.6%; p = 0.03; however, the anxiety state was equally prevalent in both subgroups. The prevalence of alexithymia (52.6% vs. 44.4% and its level (73.2 ± 8.9 vs. 71.2 ± 11.3 points were similar in women with and without binge eating disorder. Multivariate mixed linear regression analysis revealed that higher body mass index was associated with primary and vocational education (odds ratio [OR] = 16.69 and severe depression symptoms (OR = 52.45, but not alexithymia. Conclusions: In addition to severe depression and low education level, obesity may predispose for the development of alexithymia. However, alexithymia does not affect the severity of obesity in women.

  11. A Typology of Violence against Self and Others and Its Associations with Drinking and Other Drug Use among High School Students in a U.S. General Population Survey

    Science.gov (United States)

    Harford, Thomas C.; Yi, Hsiao-Ye; Freeman, Robert C.

    2012-01-01

    This study examines associations between binge drinking and other substance use and perpetration of violence against self and others. Data were pooled from the 2003, 2005, and 2007 Youth Risk Behavior Surveys, yielding a sample of 43,172 U.S. high school students. A typology was constructed to reflect four categories of behaviors: other-directed…

  12. Characteristics of binge eating disorder in relation to diagnostic criteria

    Directory of Open Access Journals (Sweden)

    Wilfley DE

    2016-08-01

    Full Text Available Denise E Wilfley,1 Leslie Citrome,2 Barry K Herman3 1Department of Psychiatry, Washington University School of Medicine, St Louis, MO, 2Department of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, NY, 3Global Medical Affairs, Shire, Lexington, MA, USA Abstract: The objective of this review was to examine the evidentiary basis for binge eating disorder (BED with reference to the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5 diagnostic criteria for BED. A PubMed search restricted to titles and abstracts of English-language reviews, meta-analyses, clinical trials, randomized controlled trials, journal articles, and letters using human participants was conducted on August 7, 2015, using keywords that included “binge eating disorder,” DSM-5, DSM-IV, guilt, shame, embarrassment, quantity, psychological, behavior, and “shape and weight concerns.” Of the 257 retrieved publications, 60 publications were considered relevant to discussions related to DSM-5 diagnostic criteria and were included in the current review, and 20 additional references were also included on the basis of the authors’ knowledge and/or on a review of the reference lists from relevant articles obtained through the literature search. Evidence supports the duration/frequency criterion for BED and the primary importance of loss of control and marked distress in identifying individuals with BED. Although overvaluation of shape/weight is not a diagnostic criterion, its relationship to the severity of BED psychopathology may identify a unique subset of individuals with BED. Additionally, individuals with BED often exhibit a clinical profile consisting of psychiatric (eg, mood, obsessive–compulsive, and impulsive disorders and medical (eg, gastrointestinal symptoms, metabolic syndrome, and type 2 diabetes comorbidities and behavioral profiles (eg, overconsumption of calories outside of a binge eating episode and emotional

  13. HUMAN METHAMPHETAMINE PHARMACOKINETICS SIMULATED IN THE RAT: BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF A 72- HOUR BINGE

    Science.gov (United States)

    Kuczenski, Ronald; Segal, David S.; Melega, William P.; Lacan, Goran; McCunney, Stanley J.

    2009-01-01

    Bingeing is one pattern of high dose methamphetamine (METH) abuse which involves continuous drug taking over several days and can result in psychotic behaviors for which the brain pathology remains poorly-defined. A corresponding animal model of this type of METH exposure may provide novel insights into the neurochemical and behavioral sequelae associated with this condition. Accordingly, to simulate the pharmacokinetic profile of a human METH binge exposure in rats we used a computer-controlled, intravenous METH procedure (dynamic infusion) to overcome species differences in METH pharmacokinetics and to replicate the human 12-h plasma METH half-life. Animals were treated over 13 weeks with escalating METH doses, using dynamic infusion, and then exposed to a binge in which drug was administered every 3 h for 72h. Throughout the binge, behavioral effects included unabated intense oral stereotypies in the absence of locomotion and in the absence of sleep. Decrements in regional brain dopamine, norepinephrine and serotonin levels, measured at 1 and 10 h after the last injection of the binge, had, with the exception of caudate-putamen dopamine and frontal cortex serotonin, recovered by 48 h. At 10 h after the last injection of the binge, [3H]ligand binding to dopamine and vesicular monoamine transporters in caudate-putamen were reduced by 35% and 13%, respectively. In a separate METH binge treated cohort, post-binge behavioral alterations were apparent in an attenuated locomotor response to a METH challenge infusion at 24h after the last injection of the binge. Collectively, the changes we characterized during and following a METH binge suggest that for humans under similar exposure conditions, multiple time-dependent neurochemical deficits contribute to their behavioral profiles. PMID:19571794

  14. Human methamphetamine pharmacokinetics simulated in the rat: behavioral and neurochemical effects of a 72-h binge.

    Science.gov (United States)

    Kuczenski, Ronald; Segal, David S; Melega, William P; Lacan, Goran; McCunney, Stanley J

    2009-10-01

    Bingeing is one pattern of high-dose methamphetamine (METH) abuse, which involves continuous drug taking over several days and can result in psychotic behaviors for which the brain pathology remains poorly defined. A corresponding animal model of this type of METH exposure may provide novel insights into the neurochemical and behavioral sequelae associated with this condition. Accordingly, to simulate the pharmacokinetic profile of a human METH binge exposure in rats, we used a computer-controlled, intravenous METH procedure (dynamic infusion, DI) to overcome species differences in METH pharmacokinetics and to replicate the human 12-h plasma METH half-life. Animals were treated over 13 weeks with escalating METH doses, using DI, and then exposed to a binge in which drug was administered every 3 h for 72 h. Throughout the binge, behavioral effects included unabated intense oral stereotypies in the absence of locomotion and in the absence of sleep. Decrements in regional brain dopamine, norepinephrine, and serotonin levels, measured at 1 and 10 h after the last injection of the binge, had, with the exception of caudate-putamen dopamine and frontal cortex serotonin, recovered by 48 h. At 10 h after the last injection of the binge, [(3)H]ligand binding to dopamine and vesicular monoamine transporters in caudate-putamen were reduced by 35 and 13%, respectively. In a separate METH binge-treated cohort, post-binge behavioral alterations were apparent in an attenuated locomotor response to a METH challenge infusion at 24 h after the last injection of the binge. Collectively, the changes we characterized during and after a METH binge suggest that for human beings under similar exposure conditions, multiple time-dependent neurochemical deficits contribute to their behavioral profiles.

  15. Isoreserpine promotes {beta}-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Gwak, Jungsug; Song, Taeyun [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of); Song, Jie-Young; Yun, Yeon-Sook [Laboratory of Radiation Cancer Science, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Choi, Il-Whan [Department of Microbiology, Center for Viral Disease Research, Inje University College of Medicine, Busan 614-735 (Korea, Republic of); Jeong, Yongsu [Department of Genetic Engineering, and Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701 (Korea, Republic of); Shin, Jae-Gook [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of); Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan 614-735 (Korea, Republic of); Oh, Sangtaek, E-mail: ohsa@inje.ac.kr [PharmacoGenomics Research Center, Inje University, Busan 614-735 (Korea, Republic of)

    2009-09-25

    Aberrant accumulation of intracellular {beta}-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular {beta}-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, which was stimulated by Wnt3a-conditioned medium. We found that isoreserpine promoted the degradation of intracellular {beta}-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells. Moreover, isoreserpine repressed the expression of {beta}-catenin/T-cell factor (TCF)-dependent genes, such as cyclin D1 and c-myc, resulting in the suppression of HCT116 cell proliferation. Our findings suggest that isoreserpine can potentially be used as a chemotherapeutic agent against colon cancer.

  16. UP-REGULATION OF HEPATIC RECEPTOR FOR GROWTH HORMONE IN THE FLOUNDER (PARALICHTHYS OLIVACEUS) AFTER ORAL ADMINISTRATION WITH EXOGENOUS GH

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The iodination efficiency of salmon GH(Sgh) was 38.82%,using a modification of the chloramine-T method. The specific activity of the 125I-Sgh was about 40 μCi/μg protein. The results of binding assay showed a single class of high affinity and low-capacity binding site in flounder liver. Long-term administration with exogenous GH can induce the up-regulation of hepatic GH receptor in total binding capacity though there was no significant difference of association constant among any groups. Considering that there was no significant difference in capacity of free binding sites of livers from control and experimental fish, this result also indicated that the liver from experimental fish, compared to that from control fish, had more occupied binding sites.

  17. Berberine up-regulates the BDNF expression in hippocampus and attenuates corticosterone-induced depressive-like behavior in mice.

    Science.gov (United States)

    Shen, Ji-Duo; Ma, Li-Gang; Hu, Chun-Yue; Pei, Yang-Yi; Jin, Shuang-Li; Fang, Xiao-Yan; Li, Yu-Cheng

    2016-02-12

    Depression is increasingly become a global public healthy problem. This study was to investigate whether berberine could attenuate the depressive-like behavior induced by repeated corticosterone injection and explore the possible mechanisms. The present results showed that exogenous corticosterone injection caused depressive-like behaviors in mice, such as decreased sucrose intake in sucrose preference test (SPT) and increased immobility time in forced swimming test (FST). These behavioral alterations were accompanying with the decreased BDNF mRNA and protein levels in hippocampus and the elevated serum corticosterone levels. Treatment with berberine prevented these changes above. Our findings confirmed the antidepressant-like effect of berberine and suggested its mechanisms might be partially mediated by up-regulation of BDNF in hippocampus.

  18. Differential expression of Prx I and II in mouse testis and their up-regulation by radiation.

    Science.gov (United States)

    Lee, Keesook; Park, Ji-Sun; Kim, Yun-Jeong; Soo Lee, Yong Soo; Sook Hwang, Tae Sook; Kim, Dae-Joong; Park, Eun-Mi; Park, Young-Mee

    2002-08-16

    Testis is one of the most sensitive organs to ionizing radiation. The present study was designed to unravel the possible role of antioxidant proteins, peroxiredoxin I and II (Prx I and II) in the testis. Our results show that Prx I and II are constitutively expressed in the testis and their expression levels are decreased to some extent as the testis develops. Interestingly, immunohistochemical analysis revealed a preferential expression of Prx I and II in Leydig and Sertoli cells, respectively. Neither Prx I nor Prx II expression was obvious in the testicular germ cells including spermatogonia and spermatocytes. Ionizing radiation exerted oxidative stress on the testis and induced apoptosis primarily in the germ cells. When the irradiated testis was examined, the Prx system was found to be transiently up-regulated. Taken together, we suggest that the relative radiation-resistance of Leydig and Sertoli cells could be attributed in part to the antioxidant function of the Prx system in these cells.

  19. An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

  20. 16-Dehydropregnenolone lowers serum cholesterol by up-regulation of CYP7A1 in hyperlipidemic male hamsters.

    Science.gov (United States)

    Ramakrishna, Rachumallu; Kumar, Durgesh; Bhateria, Manisha; Gaikwad, Anil Nilkanth; Bhatta, Rabi Sankar

    2017-04-01

    16-Dehydropregnenolone (DHP) has been developed and patented as a promising antihyperlipidemic agent by CSIR-Central Drug Research Institute (CSIR-CDRI), India. Although DHP is implicated in controlling cholesterol homeostasis, the mechanism underlying its pharmacological effect in hyperlipidemic disease models is poorly understood. In the present study, we postulated that DHP lowers serum lipids through regulating the key hepatic genes accountable for cholesterol metabolism. The hypothesis was tested on golden Syrian hamsters fed with high-fat diet (HFD) following oral administration of DHP at a dose of 72mg/kg body weight for a period of one week. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total bile acids (TBA) in feces were measured. Real time comparative gene expression studies were performed for CYP7A1, LXRα and PPARα level in liver tissue of hamsters. The results revealed that the DHP profoundly decreased the levels of serum TC, TG, LDL-C and atherogenic index (AI), whilst elevated the HDL-C/TC ratio. Besides, DHP exhibited an anti-hyperlipidemic effect in the HFD induced hyperlipidemic hamsters by means of: (1) up-regulating the gene expression of CYP7A1 encoded cholesterol 7α-hydroxylase, that promotes the catabolism of cholesterol to bile acid; (2) inducing the gene expression of transcription factors LXRα and PPARα; (3) increasing the TBA excretion through feces. Collectively, the findings presented confer the hypolipidemic activity of DHP via up-regulation of hepatic CYP7A1 pathway that promotes cholesterol-to-bile acid conversion and bile acid excretion.

  1. LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gang-Shi Wang; Meng-Wei Wang; Ben-Yan Wu; Xin-Yan Yang; Wei-Hua Wang; Wei-Di You

    2008-01-01

    AIM:To analyze the expression profiles of a human gastric-cancer-related gene,GCRG123,in human gastric signet-ring cell carcinoma tissues,and to perform bioinformatics analysis on GCRG123.METHODS:In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues,including 15 cases of signet-ring cell carcinoma,15 of intestinal-type adenocarcinoma,and 15 of normal gastric mucosa.Northnem blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues.Online software,including BLAST,Multalin and BLAT,were applied for bioinformatics analysis.National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses.RESULTS:The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm.Ten out of 15 cases of gastric signet ring cell carcinoma,normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression.Low GCRG123 expressionv was observed in gastric intestinal-type adenocarcinoma and normal gastric glands.Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue.BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1,L1).BLAT analysis indicated that GCRG123 mapped to all chromosomes.GCRG123 was found to integrate in the intron-17 and -23 of Rb,5' flanking region of IL-2 and clotting factor IX genes.CONCLUSION:GCRG123,an active member of the L1family,was up-regulated in human gastric signet-ring cell carcinoma.

  2. Expression of iron-related proteins in the duodenum is up-regulated in patients with chronic inflammatory disorders

    Directory of Open Access Journals (Sweden)

    Molly Jacob

    2015-01-01

    Full Text Available Mechanisms responsible for derangements in iron homeostasis in chronic inflammatory conditions are not entirely clear. The aim of this study was to test the hypothesis that inflammation affects expression of iron-related proteins in the duodenum and monocytes in patients with chronic inflammatory disorders, thus contributing to dysregulated iron homeostasis. Duodenal mucosal samples and peripheral blood monocytes obtained from patients with chronic inflammatory disorders, viz. ulcerative colitis (UC, Crohn’s disease (CD and rheumatoid arthritis (RA, were used for gene and protein expression studies. Haemoglobin levels were significantly lower and serum C-reactive protein (CRP levels significantly higher in those in the disease groups. Gene expression of several iron-related proteins in the duodenum was significantly up-regulated in patients with UC and CD. In those with UC, it was found that protein expression of divalent metal transporter (DMT1 and ferroportin, which are involved in absorption of dietary non-heme iron, was also significantly higher in the duodenal mucosa. Gene expression of the duodenal proteins of interest correlated positively with one another and negatively with haemoglobin. Gene expression of iron-related proteins in monocytes was studied in patients with UC and found to be unaffected. In a separate group of patients with UC, serum hepcidin levels were found to be significantly lower than in control subjects. In conclusion, expression of iron related proteins was up-regulated in the duodenum of patients with chronic inflammatory conditions in this study. The effects appeared to be secondary to anemia and the consequent erythropoietic drive.

  3. Beta- lactam antibiotics stimulate biofilm formation in non-typeable haemophilus influenzae by up-regulating carbohydrate metabolism.

    Science.gov (United States)

    Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M; Webster, Paul

    2014-01-01

    Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

  4. Plant stanols induce intestinal tumor formation by up-regulating Wnt and EGFR signaling in Apc Min mice.

    Science.gov (United States)

    Marttinen, Maija; Päivärinta, Essi; Storvik, Markus; Huikko, Laura; Luoma-Halkola, Heli; Piironen, Vieno; Pajari, Anne-Maria; Mutanen, Marja

    2013-01-01

    The rate of APC mutations in the intestine increases in middle-age. At the same period of life, plant sterol and stanol enriched functional foods are introduced to diet to lower blood cholesterol. This study examined the effect of plant stanol enriched diet on intestinal adenoma formation in the Apc(Min) mouse. Apc(Min) mice were fed 0.8% plant stanol diet or control diet for nine weeks. Cholesterol, plant sterols and plant stanols were analyzed from the caecum content and the intestinal mucosa. Levels of β-catenin, cyclin D1, epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase 1/2 (ERK1/2) were measured from the intestinal mucosa by Western blotting. Gene expression was determined from the intestinal mucosa using Affymetrix and the data were analyzed for enriched categories and pathways. Plant stanols induced adenoma formation in the small intestine, however, the adenoma size was not affected. We saw increased levels of nuclear β-catenin, phosphorylated β-catenin (Ser675 and Ser552), nuclear cyclin D1, total and phosphorylated EGFR and phosphorylated ERK1/2 in the intestinal mucosa after plant stanol feeding. The Affymetrix data demonstrate that several enzymes of cholesterol synthesis pathway were up-regulated, although the cholesterol level in the intestinal mucosa was not altered. We show that plant stanols induce adenoma formation by activating Wnt and EGFR signaling. EGFR signaling seems to have promoted β-catenin phosphorylation and its translocation into the nucleus, where the expression of cyclin D1 was increased. Up-regulated cholesterol synthesis may partly explain the increased EGFR signaling in the plant stanol-fed mice.

  5. MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction.

    Science.gov (United States)

    Bostjancic, E; Zidar, N; Stajner, D; Glavac, D

    2010-01-01

    MicroRNAs are small regulatory RNA molecules that mediate regulation of gene expression, thus affecting a variety of physiological, developmental and pathological conditions. They are believed to be new promising therapeutic targets. In recent studies two muscle-specific microRNAs were discovered to contribute to heart diseases and development: miR-1 and miR-133, but there is little data on their expression patterns in human myocardial infarction. We performed simultaneous expression analysis of miR-1, miR-133a, miR-133b in samples of infarcted tissue and remote myocardium from twenty- four patients with acute myocardial infarction. MicroRNA expression was analysed using quantitative real-time PCR and compared to the expression patterns in myocardium of eight healthy adults who died in accidents. We found ~3.8-fold miR-1 up-regulation in remote myocardium when compared to infarcted tissue or healthy adult hearts. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. In addition, miR-133a/b down-regulation in infarcted tissue and remote myocardium was observed, indicating miR-133a/b involvement in the heart response to myocardial infarction. We conclude that miR-1 and miR-133 seem to be important regulators of heart adaptation after ischaemic stress.

  6. Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Arafa, El-Shaimaa A.; Zhu Qianzheng [Department of Radiology, Ohio State University, Columbus, OH 43210 (United States); Shah, Zubair I. [James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, OH 43210 (United States); Wani, Gulzar; Barakat, Bassant M.; Racoma, Ira [Department of Radiology, Ohio State University, Columbus, OH 43210 (United States); El-Mahdy, Mohamed A., E-mail: Mohamed.el-mahdy@osumc.edu [Department of Radiology, Ohio State University, Columbus, OH 43210 (United States); Wani, Altaf A., E-mail: wani.2@osu.edu [Department of Radiology, Ohio State University, Columbus, OH 43210 (United States); Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210 (United States); James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, OH 43210 (United States); DNA Research Chair, King Saud University, Riyadh (Saudi Arabia)

    2011-01-10

    The use of innocuous naturally occurring compounds to overcome drug resistance and cancer recalcitrance is now in the forefront of cancer research. Thymoquinone (TQ) is a bioactive constituent of the volatile oil derived from seeds of Nigella sativa Linn. TQ has shown promising anti-carcinogenic and anti-tumor activities through different mechanisms. However, the effect of TQ on cell signaling and survival pathways in resistant cancer cells has not been fully delineated. Here, we report that TQ greatly inhibits doxorubicin-resistant human breast cancer MCF-7/DOX cell proliferation. TQ treatment increased cellular levels of PTEN proteins, resulting in a substantial decrease of phosphorylated Akt, a known regulator of cell survival. The PTEN expression was accompanied with elevation of PTEN mRNA. TQ arrested MCF-7/DOX cells at G2/M phase and increased cellular levels of p53 and p21 proteins. Flow cytometric analysis and agarose gel electrophoresis revealed a significant increase in Sub-G1 cell population and appearance of DNA ladders following TQ treatment, indicating cellular apoptosis. TQ-induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of caspases and PARP cleavage in MCF-7/DOX cells. Moreover, TQ treatment increased Bax/Bcl2 ratio via up-regulating Bax and down-regulating Bcl2 proteins. More importantly, PTEN silencing by target specific siRNA enabled the suppression of TQ-induced apoptosis resulting in increased cell survival. Our results reveal that up-regulation of the key upstream signaling factor, PTEN, in MCF-7/DOX cells inhibited Akt phosphorylation, which ultimately causes increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ.

  7. Immunomodulatory drugs act as inhibitors of DNA methyltransferases and induce PU.1 up-regulation in myeloma cells.

    Science.gov (United States)

    Endo, Shinya; Amano, Masayuki; Nishimura, Nao; Ueno, Niina; Ueno, Shikiko; Yuki, Hiromichi; Fujiwara, Shiho; Wada, Naoko; Hirata, Shinya; Hata, Hiroyuki; Mitsuya, Hiroaki; Okuno, Yutaka

    2016-01-08

    Immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide are efficacious in the treatment of multiple myeloma and significantly prolong their survival. However, the mechanisms of such effects of IMiDs have not been fully elucidated. Recently, cereblon has been identified as a target binding protein of thalidomide. Lenalidomide-resistant myeloma cell lines often lose the expression of cereblon, suggesting that IMiDs act as an anti-myeloma agent through interacting with cereblon. Cereblon binds to damaged DNA-binding protein and functions as a ubiquitin ligase, inducing degradation of IKZF1 and IKZF3 that are essential transcription factors for B and T cell development. Degradation of both IKZF1 and IKZF3 reportedly suppresses myeloma cell growth. Here, we found that IMiDs act as inhibitors of DNA methyltransferases (DMNTs). We previously reported that PU.1, which is an ETS family transcription factor and essential for myeloid and lymphoid development, functions as a tumor suppressor in myeloma cells. PU.1 induces growth arrest and apoptosis of myeloma cell lines. In this study, we found that low-dose lenalidomide and pomalidomide up-regulate PU.1 expression through inducing demethylation of the PU.1 promoter. In addition, IMiDs inhibited DNMT1, DNMT3a, and DNMT3b activities in vitro. Furthermore, lenalidomide and pomalidomide decreased the methylation status of the whole genome in myeloma cells. Collectively, IMiDs exert demethylation activity through inhibiting DNMT1, 3a, and 3b, and up-regulating PU.1 expression, which may be one of the mechanisms of the anti-myeloma activity of IMiDs.

  8. Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes.

    Science.gov (United States)

    Newsome, Bradley J; Petriello, Michael C; Han, Sung Gu; Murphy, Margaret O; Eske, Katryn E; Sunkara, Manjula; Morris, Andrew J; Hennig, Bernhard

    2014-02-01

    Superfund chemicals such as polychlorinated biphenyls pose a serious human health risk due to their environmental persistence and link to multiple diseases. Selective bioactive food components such as flavonoids have been shown to ameliorate PCB toxicity, but primarily in an in vitro setting. Here, we show that mice fed a green tea-enriched diet and subsequently exposed to environmentally relevant doses of coplanar PCB exhibit decreased overall oxidative stress primarily due to the up-regulation of a battery of antioxidant enzymes. C57BL/6 mice were fed a low-fat diet supplemented with green tea extract (GTE) for 12 weeks and exposed to 5 μmol PCB 126/kg mouse weight (1.63 mg/kg-day) on weeks 10, 11 and 12 (total body burden: 4.9 mg/kg). F2-isoprostane and its metabolites, established markers of in vivo oxidative stress, measured in plasma via HPLC-MS/MS exhibited fivefold decreased levels in mice supplemented with GTE and subsequently exposed to PCB compared to animals on a control diet exposed to PCB. Livers were collected and harvested for both messenger RNA and protein analyses, and it was determined that many genes transcriptionally controlled by aryl hydrocarbon receptor and nuclear factor (erythroid-derived 2)-like 2 proteins were up-regulated in PCB-exposed mice fed the green tea-supplemented diet. An increased induction of genes such as SOD1, GSR, NQO1 and GST, key antioxidant enzymes, in these mice (green tea plus PCB) may explain the observed decrease in overall oxidative stress. A diet supplemented with green tea allows for an efficient antioxidant response in the presence of PCB 126, which supports the emerging paradigm that healthful nutrition may be able to bolster and buffer a physiological system against the toxicities of environmental pollutants.

  9. Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease

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    Cabeza Carolina

    2012-03-01

    Full Text Available Abstract Background Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF after axotomy and ii PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF. Results NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT, whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-γ signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A. Conclusions Our results suggest that the NPC cellular phenotype causes neuronal

  10. Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after TNBS induced colitis in rats

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    Price Donald D

    2006-01-01

    Full Text Available Abstract Background N-methyl-D-aspartic acid (NMDA spinal cord receptors play an important role in the development of hyperalgesia following inflammation. It is unclear, however, if changes in NMDA subunit receptor gene expression in the colonic myenteric plexus are associated with colonic inflammation. We investigated regulation of NMDA-NR1 receptor gene expression in TNBS induced colitis in rats. Male Sprague-Dawley rats (150 g–250 g were treated with 20 mg trinitrobenzene sulfonic acid (TNBS diluted in 50% ethanol. The agents were delivered with a 24 gauge catheter inserted into the lumen of the colon. The animals were sacrificed at 2, 7, 14, 21, and 28 days after induction of the colitis, their descending colon was retrieved for reverse transcription-polymerase chain reaction; a subset of animals' distal colon was used for two-dimensional (2-D western analysis and immunocytochemistry. Results NR1-exon 5 (N1 and NR1-exon 21 (C1 appeared 14, 21 and 28 days after TNBS treatment. NR1 pan mRNA was up-regulated at 14, 21, and 28 days. The NR1-exon 22 (C2 mRNA did not show significant changes. Using 2-D western analysis, untreated control rats were found to express only NR1001 whereas TNBS treated rats expressed NR1001, NR1011, and NR1111. Immunocytochemistry demonstrated NR1-N1 and NR1-C1 to be present in the myenteric plexus of TNBS treated rats. Conclusion These results suggest a role for colonic myenteric plexus NMDA receptors in the development of neuronal plasticity and visceral hypersensitivity in the colon. Up-regulation of NMDA receptor subunits may reflect part of the basis for chronic visceral hypersensitivity in conditions such as post-infectious irritable bowel syndrome.

  11. Beta- lactam antibiotics stimulate biofilm formation in non-typeable haemophilus influenzae by up-regulating carbohydrate metabolism.

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    Siva Wu

    Full Text Available Non-typeable Haemophilus influenzae (NTHi is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

  12. Do executive functioning deficits underpin binge eating disorder? A comparison of overweight women with and without binge eating pathology

    Science.gov (United States)

    Manasse, Stephanie M.; Forman, Evan M.; Ruocco, Anthony C.; Butryn, Meghan L.; Juarascio, Adrienne S.; Fitzpatrick, Kathleen Kara

    2015-01-01

    Objective Deficits in executive function (EF) --including inhibitory control, cognitive flexibility, decision-making, and working memory--may be risk or maintenance factors for binge eating disorder (BED). However, there is mixed evidence regarding EF deficits in individuals with BED. Significant methodological weaknesses (e.g., use of a single EF measure, omission of relevant covariates) in the current literature represent one reason for lack of consensus. Methods The current study compared EF in a sample of overweight women with (n=31) and without (n=43) full or sub-threshold BED, with the aim of conducting a multi-faceted investigation of the neurocognitive profile of BED. A neuropsychological battery of EF was administered to all participants. Results After controlling for IQ and age, individuals with binge eating displayed significantly poorer performance on tasks of problem-solving and inhibitory control, and displayed higher prioritization of immediate versus delayed rewards, but the two groups did not appear to differ on set-shifting, working memory, and risk taking. Differences in inhibitory control were no longer statistically significant when depressive symptomology was added as a covariate and correction for multiple comparisons was applied. Exploratory analyses indicated that full and sub-threshold BED groups did not differ in EF. Discussion Results partially support the hypothesis of relative EF deficits in individuals with BED, suggesting that binge eating may be maintained by cognitive factors distinct from those of obesity. Future research should aim to replicate with a larger sample, control for a wider range of psychiatric comorbidities, and examine whether EF deficits predict treatment outcome. PMID:25644028

  13. Communication About Problematic Drinking Between Young Adults and their Parents: An Application of Inconsistent Nurturing as Control Theory.

    Science.gov (United States)

    Glowacki, Elizabeth M

    2016-09-01

    Approximately 80% of college students drink, half of whom consume alcohol in the form of binge drinking. The current study applies Inconsistent Nurturing as Control Theory to examine the communication about excessive drinking that takes place between parents and their young adult children. Forty college students were asked to report on a moment or incident that led their parents to label their drinking as concerning and were then asked to report on how their parents acted towards the drinking before and after the moment of labeling. Interviews were transcribed and coded. The findings suggest that parents act with inconsistency when attempting to manage their children's drinking by enacting both reinforcing and punishing behaviors. Parents' reinforcing behaviors included drinking with their children and buying them alcohol, even after labeling the drinking as problematic. Parents' punishment behaviors included expressing concern about their children's sense of responsibility and making their children feel regretful about their drinking. Nearly 88% of the participants were able to recall the moment at which their parents labeled their drinking as problematic. Implications for using inconsistent messages in conversations about alcohol are discussed.

  14. Bing Zhi: pioneer of modern biology in China

    Institute of Scientific and Technical Information of China (English)

    Ming Li; Le Kang

    2010-01-01

    @@ Located in the lobby of the Institute of Zoology at Chinese Academy of Sciences,is a bronze statue of Dr.Bing Zhi.Many passers-by,especially the young ones,would ask who this person is and what he has accomplished.The short answer is,according to the plate of the statue,that he is a pioneer zoologist and educator and the founder of modern biology in China.The more detailed answer involves the word"first"for quite a few significances:As a biologist,Bing Zhi is the co-founder of the first non-governmental scientific society of China,the co-founder of the first Chinese scientific journal,the founder of the first biology department in China,the founder of the first biological research institute in China,and the founder of China Zoological Society; as an educator,he trained many young men who later became renowned specialists in their own areas.

  15. Cravings and food consumption in Binge Eating Disorder.

    Science.gov (United States)

    Ng, Longena; Davis, Caroline

    2013-12-01

    The purpose of this study was to extend existing work that examines the role of cravings in Binge Eating Disorder (BED). The current study uses a case-control design to establish a relationship between cravings and food exposure, and between cravings and food consumption in individuals diagnosed with BED. Twenty-nine females with BED, 40 obese controls, and 50 normal-weight controls were first presented with a neutral cue and completed a food-craving measure. They were then presented with their favourite snack food and completed the craving measure again, after which they were allowed to consume the food. The BED group had significantly higher scores for pre- and post-craving measures, and consumed more food compared to the controls. There was, however, no significant interaction between group and craving scores. Results also showed a positive correlation between food consumption and cravings scores both before and after food exposure for individuals with BED. The findings suggest that the level of cravings prior to food exposure may be sufficient to predict overeating in BED and that treatment may want to target this as a defining feature that differentiates individuals with BED from those who do not binge eat.

  16. Underage drinking in the UK: changing trends, impact and interventions. A rapid evidence synthesis.

    Science.gov (United States)

    Healey, Christine; Rahman, Atif; Faizal, Mohammad; Kinderman, Peter

    2014-01-01

    The UK is a high prevalence country for underage alcohol use. We conducted an evidence synthesis to examine (1) the changing trends in underage drinking in the UK compared to Europe and the USA, (2) the impact of underage drinking in terms of hospital admissions, (3) the association between underage drinking and violent youth offending, and (4) the evidence base for the effectiveness of alcohol harm reduction interventions aimed at children and adolescents under the age of 18 years. The following databases were searched from November 2002 until November 2012: Cochrane Database of Systematic Reviews, National Institute for Health and Clinical Excellence, The Evidence for Policy and Practice Information, DARE, Medline, The Campbell Collaboration, CINAHL, Criminal Justice Abstracts, Psych INFO and Social Care Online. Our findings revealed changes in the way children drink in the UK and how much they drink. Alcohol related harms are increasing in the UK despite overall population levels of consumption reducing in this age group. Girls aged 15-16 years report binge drinking and drunkenness more than boys. Girls are also more likely than boys to be admitted to hospital for alcohol related harm. The evidence suggests a strong association between heavy episodic binge drinking and violent youth offending. Only 7 out of 45 randomised controlled trials (RCTs) identified for this review included children and adolescents under the age of 18 years. Most were delivered in the emergency department (ED) and involved a brief intervention. All were characterised by a wide age range of participants, heterogeneous samples and high rates of refusal and attrition. The authors conclude that whilst the ED might be the best place to identify children and adolescents at risk of harm related to alcohol use it might not be the best place to deliver an intervention. Issues related to a lack of engagement with alcohol harm reduction interventions have been previously overlooked and warrant

  17. Motivation for Palatable Food Despite Consequences in an Animal Model of Binge-Eating

    Science.gov (United States)

    Oswald, Kimberly D.; Murdaugh, Donna L.; King, Vinetra L.; Boggiano, Mary M.

    2010-01-01

    Objective Binge-eating involves an abnormal motivation for highly palatable food in that these foods are repeatedly consumed despite their binge-triggering effects and life-affecting consequences associated with binge-eating. We determined if rats identified as binge-eating prone (BEP) similarly display abnormal motivation for palatable food. Method Food-sated BEP and binge-eating resistant (BER) rats were given voluntary access to palatable food paired with increasing intensity of footshock. Later, they were exposed to a period of cyclic caloric restriction-refeeding. Results BEPs consumed significantly more and tolerated higher levels of footshock for palatable food than BERs. Cyclic restriction-refeeding increased BERs' tolerance of shock for palatable food. Discussion Previously observed parallels of the rat BEP model to human binge-eating can now be extended to include an abnormal motivation for palatable food. This model should prove useful in identifying specific genes that interact with the nutritional environment to mediate binge-eating and may point to novel physiological targets to treat compulsive overeating. PMID:20186718

  18. The association of binge eating and neighbourhood fast-food restaurant availability on diet and weight status

    Science.gov (United States)

    Ledoux, Tracey; Adamus-Leach, Heather; O’Connor, Daniel P; Mama, Scherezade; Lee, Rebecca E

    2015-01-01

    Objective Fast-food restaurants (FFR) are prevalent. Binge eating is common among overweight and obese women. For women prone to binge eating, neighbourhood FFR availability (i.e. the neighbourhood around one’s home) may promote poor diet and overweight/obesity. The present study tested the effects of binge eating and neighbourhood FFR availability on diet (fat and total energy intake) and BMI among African American and Hispanic/Latino women. Design All measures represent baseline data from the Health is Power randomized clinical trial. The numbers of FFR in participants’ neighbourhoods were counted and dichotomized (0 or ≥1 neighbourhood FFR). Participants completed measures of binge eating status and diet. Weight and height were measured and BMI calculated. 2 (binge eating status) × 2 (neighbourhood FFR availability) ANCOVA tested effects on diet and BMI while controlling for demographics. Setting Houston and Austin, TX, USA. Subjects African American and Hispanic/Latino women aged 25–60 years. Results Of the total sample (n 162), 48% had 1–15 neighbourhood FFR and 29% were binge eaters. There was an interaction effect on BMI (P=0·05). Binge eaters with ≥1 neighbourhood FFR had higher BMI than non-binge eaters or binge eaters with no neighbourhood FFR. There were no significant interactions or neighbourhood FFR main effects on total energy or fat intake (P>0·05). A main effect of binge eating showed that binge eaters consumed more total energy (P=0·005) and fat (P=0·005) than non-binge eaters. Conclusions Binge eaters represented a substantial proportion of this predominantly overweight and obese sample of African American and Hispanic/ Latino women. The association between neighbourhood FFR availability and weight status is complicated by binge eating status, which is related to diet. PMID:24476972

  19. Ashamed and Fused with Body Image and Eating: Binge Eating as an Avoidance Strategy.

    Science.gov (United States)

    Duarte, Cristiana; Pinto-Gouveia, José; Ferreira, Cláudia

    2017-01-01

    Binge Eating Disorder (BED) is currently recognized as a severe disorder associated with relevant psychiatric and physical comorbidity, and marked emotional distress. Shame is a specific negative emotion that has been highlighted as central in eating disorders. However, the effect of shame and underlying mechanisms on binge eating symptomatology severity remained unclear. This study examines the role of shame, depressive symptoms, weight and shape concerns and eating concerns, and body image-related cognitive fusion, on binge eating symptomatology severity. Participated in this study 73 patients with the diagnosis of BED, established through a clinical interview-Eating Disorder Examination 17.0D-who completed measures of external shame, body-image related cognitive fusion, depressive symptoms and binge eating symptomatology. Results revealed positive associations between binge eating severity and depressive symptoms, shame, weight and shape concerns, eating concerns and body image-related cognitive fusion. A path analysis showed that, when controlling for the effect of depressive symptoms, external shame has a direct effect on binge eating severity, and an indirect effect mediated by increased eating concern and higher levels of body image-related cognitive fusion. Results confirmed the plausibility of the model, which explained 43% of the severity of binge eating symptoms. The proposed model suggests that, in BED patients, perceiving that others see the self negatively may be associated with an entanglement with body image-related thoughts and concerns about eating, which may, in turn, fuel binge eating symptoms. Findings have important clinical implications supporting the relevance of addressing shame and associated processes in binge eating. Copyright © 2015 John Wiley & Sons, Ltd.

  20. 125 INCOMPLETE COMPENSATORY UP-REGULATION OF X-LINKED GENES IN BOVINE GERMLINE, EARLY EMBRYOS, AND SOMATIC TISSUES.

    Science.gov (United States)

    Duan, J; Jue, N K; Jiang, Z; O'Neill, R; Wolf, E; Blomberg, L A; Dong, H; Zheng, X; Chen, J; Tian, X

    2016-01-01

    The maintenance of a proper gene dosage is essential in cellular networks. To resolve the dosage imbalance between eutherian females (XX) and male (XY), X chromosome inactivation (XCI) occurs in females, while X-chromosome dosage compensation up-regulates the active X to balance its expression with that of autosome pairs [Ohno's hypothesis; Ohno 1967 Sex Chromosomes and Sex-linked Genes (Springer-Verlag), p. 99]. These phenomena have been well studied in humans and mice, despite many controversies over the existence of such up-regulation. Using RNA sequencing data, we determined X chromosome dosage compensation in the bovine by analysing the global expression profiles of germ cells, embryos, and somatic tissues. Eight bovine RNA-seq data sets were obtained in from the Gene Expression Omnibus, covering bovine immature/mature oocytes (GSE59186 and GSE52415), pre-implantation conceptuses (GSE59186, GSE52415, and GSE56513), extra-embryonic tissues (PRJNA229443), and male/female somatic tissues (GSE74076, GSE63509, PRJEB6377, and GSE65125). The RNAseq data were trimmed and non-uniquely (paralogs included) mapped to the bovine reference genome assembly UMD3.1.1 using Hisat2 (version 2.0.5) aligner. The mRNA level of each gene, estimated by transformed transcripts per kilobase million was quantified by IsoEM (version 1.1.5). These RNA-seq data sets represented 4 chromosome scenarios in cells: XXXX:AAAA (diploid immature oocyte with DNA duplication), XX:AA (haploid mature oocyte with DNA duplication), XX:AA and X:AA (gradual changed X status in bovine pre-implantation conceptuses), and X:AA (extra-embryonic tissues and somatic cells in female with one active X or XY male) were analysed for dosage compensation. A total of 959 X-linked genes and 20,316 autosome genes were used to calculate the relative X to autosomal gene (A) expression (RXE): log2 (X expression) - log2 (A expression). The following dosage determinations were made: RXE values ≥ 0: complete dosage

  1. PTX3 is up-regulated in epithelial mammary cells during S. aureus intramammary infection in goat

    Directory of Open Access Journals (Sweden)

    Joel Fernando Soares Filipe

    2015-07-01

    Full Text Available Pentraxins are a superfamily of conserved molecules with immune functions such as complement activation and opsonization. PTX3 is the prototypic long pentraxin and is produced by different cell populations after pro-inflammatory stimuli. Different studies have demonstrated the up-regulation of PTX3 during ruminant mastitis, but its role is still unknown.The aim of this study was to elucidate the role of PTX3 in the immune response to S. aureus intra-mammary infection (IMI. Given that no data are available on PTX3 expression in goat tissues, we first studied its pattern of expression  in goat normal tissues. Then we investigated the role of PTX3 during mammary infection, comparing its expression in healthy and infected blood, milk and tissues.Six healthy goats were infused with PBS in the right udder and with S. aureus in the left udder. Mammary biopsies from udders were collected 30h post infection, formalin fixed and routinely processed for microscopic evaluation or immediately stored in RNAlater.Tissue samples were collected at the slaughterhouse from healthy goats and were immediately stored in RNAlater.Blood and milk were collected from healthy and infected goats; cells from blood and milk were isolated and processed for RNA extraction or for cytospins; milk fat globules were obtained through milk centrifugation and immediately processed for RNA extraction.Total RNA from different organs, blood or milk cells, milk fat globules and mammary tissues was extracted and used as template in qPCR for PTX3.PTX3 expression was investigated by immunohistochemistry on formalin fixed paraffin embedded mammary tissue samples and on cytospins of isolated goat blood and milk cells.PTX3 mRNA was expressed with very high levels in bone marrow, mammary gland, aorta, pancreas, skin and lung. Given the high expression in the mammary gland, we investigated which cell population expressed PTX3. PTX3 was mainly expressed in the apical cytoplasmic portion of

  2. Alcohol mixed with energy drinks: consumption patterns and motivations for use in U.S. college students.

    Science.gov (United States)

    Marczinski, Cecile A

    2011-08-01

    Binge drinking in college students is widespread and known to cause significant harms and health hazards for the drinker. One factor that may be exacerbating hazardous drinking in young people is the new popular trend of consuming alcohol mixed with energy drinks (AmED). However, rates of AmED use and motivations for AmED consumption in college students have not been well established. In this study, 706 undergraduate college students from a university in the United States participated in a web-based survey that queried self-reported alcohol, energy drink, and AmED use. In addition, motivations for using AmEDs were assessed. The results indicated that for all participants, 81% reported that they have tried at least one energy drink in the past and 36% reported consumption of at least one energy drink in the past 2 weeks. Alcohol consumption patterns were similar to findings from U.S. national surveys of college drinking, as 37% of respondents were classified as binge drinkers and 23% abstained from drinking. In the whole sample (including the alcohol abstainers), 44% reported trying AmED at least once and 9% reported AmED consumption at least once in the past 2 weeks. 78% of respondents agreed with the statement that AmEDs appeal to underage drinkers. When AmED users were asked about various motivations for consuming AmEDs, users reported that they consumed these beverages to get drunk and reduce sedation compared to alcohol alone. In conclusion, the consumption of AmEDs is common in U.S. college students. Motivations for using AmEDs include the reduction of the sedative effects of alcohol, an important interoceptive cue that one should stop drinking.

  3. Alcohol Mixed with Energy Drinks: Consumption Patterns and Motivations for Use in U.S. College Students

    Directory of Open Access Journals (Sweden)

    Cecile A. Marczinski

    2011-08-01

    Full Text Available Binge drinking in college students is widespread and known to cause significant harms and health hazards for the drinker. One factor that may be exacerbating hazardous drinking in young people is the new popular trend of consuming alcohol mixed with energy drinks (AmED. However, rates of AmED use and motivations for AmED consumption in college students have not been well established. In this study, 706 undergraduate college students from a university in the United States participated in a web-based survey that queried self-reported alcohol, energy drink, and AmED use. In addition, motivations for using AmEDs were assessed. The results indicated that for all participants, 81% reported that they have tried at least one energy drink in the past and 36% reported consumption of at least one energy drink in the past 2 weeks. Alcohol consumption patterns were similar to findings from U.S. national surveys of college drinking, as 37% of respondents were classified as binge drinkers and 23% abstained from drinking. In the whole sample (including the alcohol abstainers, 44% reported trying AmED at least once and 9% reported AmED consumption at least once in the past 2 weeks. 78% of respondents agreed with the statement that AmEDs appeal to underage drinkers. When AmED users were asked about various motivations for consuming AmEDs, users reported that they consumed these beverages to get drunk and reduce sedation compared to alcohol alone. In conclusion, the consumption of AmEDs is common in U.S. college students. Motivations for using AmEDs include the reduction of the sedative effects of alcohol, an important interoceptive cue that one should stop drinking.

  4. Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yue [Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou (China); Du, Chengli [Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China); Wang, Bo; Zhang, Yanling; Liu, Xiaoyan [Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou (China); Ren, Guoping, E-mail: renguoping12345@163.com [Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou (China)

    2014-07-18

    Highlights: • The expression of eEF1A2 is up-regulated in prostate cancer tissues. • Suppression of eEF1A2 inhibits the proliferation and promotes apoptosis. • Inhibition of eEF1A2 enhances the expression of apoptotic relevant proteins. • The expressions of eEF1A2 and cleavage-caspase3 are inversely correlated. - Abstract: Background: eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. Methods: We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Results: Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. Conclusion: Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer.

  5. Pro-Inflammatory Cytokine IL-1β Up-Regulates CXC Chemokine Receptor 4 via Notch and ERK Signaling Pathways in Tongue Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yi Sun

    Full Text Available Chronic inflammation contributes to tumor development through the induction of oncogenic mutations, genomic instability, early tumor promotion, and enhanced angiogenesis. Here, we report that IL-1 receptor 1 (IL-1R1 was expressed in 40 of 41 human tongue squamous cell carcinomas (TSCC. IL-1β up-regulated the expression of CXCR4, a CXC chemokine receptor that mediates cancer growth and metastasis, at both mRNA and protein levels in Tca8113 TSCC cells. IL-1β treatment of Tca8113 cells promoted migration in response to CXCR4 ligand stromal-derived factor α (SDF-1α. The inhibition of IL-1R1 by its antagonist IL-1Ra or RNA interference significantly reversed the up-regulation of CXCR4 induced by IL-1β. IL-1R1 activation also up-regulated the expression of IL-1β itself, suggesting a positive feedback regulation of CXCR4 expression. Furthermore, IL-1β induced the activation of Notch, which was originally considered a stem cell regulator. Pharmacological inhibition of Notch signaling reversed the up-regulation of CXCR4 induced by IL-1β, suggesting that Notch signaling may be involved in the growth and metastasis of cancers via up-regulation of CXCR4. In addition, IL-1β induced the activation of extracellular signal regulated kinase (ERK and ERK inhibition decreased the up-regulation of CXCR4 induced by IL-1β, suggesting the involvement of ERK signaling in cancer metastasis. Taken together these data suggest that IL-1β and IL-1R1 promote cancer growth and metastasis by up-regulating CXCR4 expression and that CXCR4 may be a link between inflammation and cancer.

  6. Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

    Science.gov (United States)

    Ahmad, Ashfaq; Sattar, Munavvar A.; Azam, Maleeha; Abdulla, Mohammed H.; Khan, Safia A.; Hashmi, Fayyaz; Abdullah, Nor A.; Johns, Edward J.

    2016-01-01

    The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development. PMID:27191852

  7. Facts on Underage Drinking

    Science.gov (United States)

    ... is involved in 95 percent of all violent crime on college campuses. ( 5) * * Underage Drinking by Gender and Ethnic Origin • Overall, males have higher rates of underage drinking than females. Among 12- to ...

  8. Drinking or Not Drinking in Pregnancy

    DEFF Research Database (Denmark)

    Niclasen, Janni

    2014-01-01

    Studies investigating associations between prenatal exposure to low-moderate doses of alcohol and mental health development in childhood are inconsistent. The aim of the present study was to compare women who drink and who do not drink alcohol in pregnancy on a number of potential confounding...

  9. Pharmacological approaches to the management of binge eating disorder.

    Science.gov (United States)

    Brownley, Kimberly A; Peat, Christine M; La Via, Maria; Bulik, Cynthia M

    2015-01-01

    In the USA, binge eating disorder (BED) is the most common eating disorder, with a lifetime prevalence of ~3.5 % in adult women, 2.0 % in adult men, and 1.6 % in adolescents. BED is characterized by frequent episodes of binge eating that are accompanied by a sense of loss of control over eating and result in marked psychological distress. BED is highly co-morbid with obesity and with depression and other psychiatric conditions, and it is associated with substantial role impairment. Currently, there are no US FDA-approved pharmacological treatments for BED. Animal and human studies implicate underlying dysregulation in dopamine, opioid, acetylcholine, and serotonin neurocircuitry within brain reward regions in the pathogenesis and maintenance of BED. To date, the efficacy of various agents that target these and other neurotransmitter systems involved in motivated feeding behavior, mood regulation, and impulse control have been investigated in the treatment of BED. Several antidepressant and anticonvulsant agents have demonstrated efficacy in reducing binge eating frequency, but only in limited cases have these effects resulted in patients achieving abstinence, which is the primary goal of treatment; they also range from less (fluvoxamine) to more (topiramate) effective in achieving weight loss that is both clinically meaningful and significantly greater than placebo. Collectively, the literature on pharmacological treatment approaches to BED is limited in that very few agents have been studied in multiple, confirmatory trials with adequate follow up, and almost none have been evaluated in large patient samples that are diverse with respect to age, sex, and ethnicity. In addition, prior trials have not adequately addressed, through study design, the high placebo response commonly observed in this patient population. Several novel agents are in various phases of testing, and recent animal studies focusing on glutamate-signaling circuits linking the amygdala to the

  10. Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila.

    Science.gov (United States)

    Muffat, Julien; Walker, David W; Benzer, Seymour

    2008-05-13

    Apolipoprotein D (ApoD) expression increases in several neurological disorders and in spinal cord injury. We provide a report of a physiological role for human ApoD (hApoD): Flies overexpressing hApoD are long-lived and protected against stress conditions associated with aging and neurodegeneration, including hyperoxia, dietary paraquat, and heat stress. We show that the fly ortholog, Glial Lazarillo, is strongly up-regulated in response to these extrinsic stresses and also can protect in vitro-cultured cells in situations modeling Alzheimer's disease (AD) and Parkinson's disease (PD). In adult flies, hApoD overexpression reduces age-associated lipid peroxide accumulation, suggesting a proximal mechanism of action. Similar data obtained in the mouse [Ganfornina, M.D., et al., (2008) Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 10.1111/j.1474-9726.2008.00395.] as well as in plants (Charron et al., personal communication) suggest that ApoD and its orthologs play an evolutionarily conserved role in response to stress, possibly managing or preventing lipid peroxidation.

  11. Osteoprotegerin is up-regulated in pancreatic cancers and correlates with cancer-associated new-onset diabetes.

    Science.gov (United States)

    Shi, Wanchun; Qiu, Wei; Wang, Wenhua; Zhou, Xiaohui; Zhong, Xiaojing; Tian, Gang; Deng, Anmei

    2014-12-01

    New-onset diabetes might help to yield biomarkers for the early diagnosis of pancreatic cancer (PaC). In this study, we computationally predicted and experimentally validated osteoprotegerin (OPG) being associated with pancreatic cancer related new-onset diabetes. We first performed a meta-analysis on microarray datasets to search for genes specifically highly expressed in PaC, and then filtered for cytokines involved in islet dysfunction. The expression of OPG in PaC and normal pancreas were validated by immunohistochemistry. Serum OPG levels in healthy controls, non-cancerous diabetes and PaC patients with or without diabetes were detected by enzyme-linked immunosorbent assay (ELISA). In silico assay found that OPG up-regulated in PaC tissues in comparison to normal pancreas. Immunohistochemical data further confirmed that OPG was overexpressed in PaC samples. Furthermore, increased expression of OPG in PaC tissues correlated to the occurrence of new-onset diabetes, and adversely affected the patients' overall survival in both univariate and multivariate analysis. In addition, the serum levels of OPG were significantly higher in pancreatic cancer patients with new-onset diabetes than other groups including pancreatic patients without diabetes, new-onset type 2 diabetes and healthy controls. In conclusion, there is a close association between OPG and pancreatic cancer related new-onset diabetes, and OPG might serve as a potential biomarker for the early diagnosis of pancreatic cancer from populations with new-onset diabetes.

  12. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Sugino, Haruhiko; Futamura, Takashi; Mitsumoto, Yasuhide; Maeda, Kenji; Marunaka, Yoshinori

    2009-03-17

    There is considerable evidence that schizophrenia is associated with immune system dysregulation. For example, blood and cerebrospinal fluid (CSF) levels of proinflammatory cytokines are significantly increased in schizophrenic patients, and their normalization correlates with improvement in psychotic symptoms. In fact, typical and atypical antipsychotics are reported to modulate immune function in in vitro and in vivo studies. In the present study, we examined the anti-inflammatory effect of antipsychotics, clozapine, olanzapine, risperidone and haloperidol, on serum cytokine levels in lipopolysaccharide (LPS)-treated mice. Atypical antipsychotics, such as clozapine, olanzapine and risperidone, but not haloperidol, suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and up-regulated IL-10. Moreover, only clozapine, robustly increased the serum levels of IL-10. Clozapine reproduced its anti-inflammatory feature in polyinsinic-polycytidylic acid sodium salt (Poly[I:C])-induced inflammation. Thus, the anti-inflammatory effect of clozapine would adapt to inflammation induced by some varieties of antigens. Several receptor ligands, such as 8-OH-DPAT, ketanserin, prazosin and scopolamine, were also examined as to their anti-inflammatory effects on serum cytokine levels in LPS-treated mice. Ketanserin and prazosin, but not 8-OH-DPAT nor scopolamine, behaved similarly to atypical antipsychotics. However, the remarkable increase of serum IL-10 level observed in clozapine was not detected in ketanserin and prazosin. These results suggest the unique efficacy of atypical antipsychotics in the suppression of proinflammatory cytokines, and the increase of anti-inflammatory cytokine, IL-10.

  13. ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Yuh-Pyng Sher

    Full Text Available Lung cancer is the leading cause of cancer death worldwide, and brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker of the epithelial-mesenchymal transition and ADAM9 (a type I transmembrane protein are related to lung cancer brain metastasis; however, it is unclear how they interact to mediate this metastasis. Because microRNAs regulate many biological functions and disease processes (e.g., cancer by down-regulating their target genes, microRNA microarrays were used to identify ADAM9-regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and western blot analysis showed that CDH2 is a target gene of miR-218. MiR-218 was generated from pri-mir-218-1, which is located in SLIT2, in non-invasive lung adenocarcinoma cells, whereas its expression was inhibited in aggressive lung adenocarcinoma. The down-regulation of ADAM9 up-regulated SLIT2 and miR-218, thus down-regulating CDH2 expression. This study revealed that ADAM9 activates CDH2 through the release of miR-218 inhibition on CDH2 in lung adenocarcinoma.

  14. Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1.

    Science.gov (United States)

    Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

    2015-11-05

    As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels.

  15. Up-regulation of expression of selected genes in human bone cells with specific capacitively coupled electric fields.

    Science.gov (United States)

    Clark, Charles C; Wang, Wei; Brighton, Carl T

    2014-07-01

    The objective of the described experiments was to determine the electrical parameters that lead to optimal expression of a number of bone-related genes in cultured human bone cells exposed to a capacitively coupled electric field. Human calvarial osteoblasts were grown in modified plastic Cooper dishes in which the cells could be exposed to various capacitively coupled electric fields. The optimal duration of stimulation and optimal duration of response to the electrical field, and the optimal amplitude, frequency and duty cycle were all determined for each of the genes analyzed. Results indicated that a capacitively coupled electric field of 60 kHz, 20 mV/cm, 50% duty cycle for 2 h duration per day significantly up-regulated mRNA expression of a number of transforming growth factor (TGF)-β family genes (bone morphogenetic proteins (BMP)-2 and -4, TGF-β1, - β2 and -β3) as well as fibroblast growth factor (FGF)-2, osteocalcin (BGP) and alkaline phosphatase (ALP). Protein levels of BMP-2 and -4, and TGF-β1 and - β2 were also elevated. The clinical relevance of these findings in the context of a noninvasive treatment modality for delayed union and nonunion fracture healing is discussed.

  16. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids.

    Science.gov (United States)

    Zhang, Kun; Liu, Yu; Liu, Xiaoqiang; Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-09-22

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions.

  17. Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis.

    Science.gov (United States)

    Barone, Rosario; Macaluso, Filippo; Catanese, Patrizia; Marino Gammazza, Antonella; Rizzuto, Luigi; Marozzi, Paola; Lo Giudice, Giuseppe; Stampone, Tomaso; Cappello, Francesco; Morici, Giuseppe; Zummo, Giovanni; Farina, Felicia; Di Felice, Valentina

    2013-01-01

    A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.

  18. Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin oxygenation induced by near-infrared laser.

    Science.gov (United States)

    Wang, Xinlong; Tian, Fenghua; Soni, Sagar S; Gonzalez-Lima, F; Liu, Hanli

    2016-08-03

    Photobiomodulation, also known as low-level laser/light therapy (LLLT), refers to the use of red-to-near-infrared light to stimulate cellular functions for physiological or clinical benefits. The mechanism of LLLT is assumed to rely on photon absorption by cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. In this study, we used broadband near-infrared spectroscopy (NIRS) to measure the LLLT-induced changes in CCO and hemoglobin concentrations in human forearms in vivo. Eleven healthy participants were administered with 1064-nm laser and placebo treatments on their right forearms. The spectroscopic data were analyzed and fitted with wavelength-dependent, modified Beer-Lambert Law. We found that LLLT induced significant increases of CCO concentration (Δ[CCO]) and oxygenated hemoglobin concentration (Δ[HbO]) on the treated site as the laser energy dose accumulated over time. A strong linear interplay between Δ[CCO] and Δ[HbO] was observed for the first time during LLLT, indicating a hemodynamic response of oxygen supply and blood volume closely coupled to the up-regulation of CCO induced by photobiomodulation. These results demonstrate the tremendous potential of broadband NIRS as a non-invasive, in vivo means to study mechanisms of photobiomodulation and perform treatment evaluations of LLLT.

  19. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Lu, Su [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Tang, Huamei, E-mail: tanghuamei@gmail.com [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Peng, Zhihai, E-mail: zhihai.peng@hotmail.com [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China)

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  20. Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C.

    Science.gov (United States)

    Wu, Li-Yuan; Liu, Shuhong; Liu, Yuan; Guo, Chaonan; Li, Hanwei; Li, Wenshu; Jin, Xueyuan; Zhang, Keming; Zhao, Ping; Wei, Lai; Zhao, Jingmin

    2015-05-01

    Interleukin-22 (IL-22) is known to play a critical role in liver immunity. However, the role of IL-22 in HCV-associated liver fibrosis is poorly understood. In this study, patients with HCV infection disclosed significant increases in peripheral numbers of IL-22-producing cells as well as in IL-22 plasma levels. In the liver, the increased intrahepatic IL-22(+) cells were positively correlated with fibrotic staging scores and clinical progression from CHC to cirrhosis. Moreover, the majority of IL-22(+) cells were located in fibrotic areas in the liver of patients with cirrhosis and co-localized with α-smooth muscle actin (α-SMA) positive hepatic stellate cells (HSCs). In vitro, administration of IL-22 was accompanied with inhibited LX-2 cell apoptosis, promoted LX-2 cell proliferation, increased expression of α-SMA, and up-regulated collagen production by LX-2 cells. Collectively, our data provide evidence that IL-22 may contribute to the fibrogenesis of HCV-associated liver fibrosis by activating HSCs.

  1. Endurance exercise and conjugated linoleic acid (CLA supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis.

    Directory of Open Access Journals (Sweden)

    Rosario Barone

    Full Text Available A new role for fat supplements, in particular conjugated linoleic acid (CLA, has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.

  2. Up-regulation of prostaglandin E receptor EP2 and EP4 subtypes in rat synovial tissues with adjuvant arthritis.

    Science.gov (United States)

    Kurihara, Y; Endo, H; Akahoshi, T; Kondo, H

    2001-02-01

    To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.

  3. Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up-regulation of lysyl oxidase-like 2.

    Science.gov (United States)

    de Jong, Olivier G; van Balkom, Bas W M; Gremmels, Hendrik; Verhaar, Marianne C

    2016-02-01

    Exosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix (ECM), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome-ECM interactions is limited. Here, we investigate whether the exosome-associated lysyl oxidase family member lysyl oxidase-like 2 (LOXL2) is involved in ECM remodelling. We found that LOXL2 is present on the exterior of endothelial cell (EC)-derived exosomes, placing it in direct vicinity of the ECM. It is up-regulated twofold in EC-derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL2 in exosome-producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC-derived exosomes is mediated by LOXL2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia-regulated focal ECM remodelling, a key process in both fibrosis and wound healing.

  4. Chronic adventitial inflammation, vasa vasorum expansion, and 5-lipoxygenase up-regulation in irradiated arteries from cancer survivors

    Science.gov (United States)

    Halle, Martin; Christersdottir, Tinna; Bäck, Magnus

    2016-01-01

    Radiation-induced cardiovascular disease is an emerging problem in a steadily increasing population of survivors of cancer. However, the underlying biology is poorly described, and the late onset, which occurs several years after exposure, precludes adequate investigations in animal and cell culture models. We investigated the role of the 5-lipoxygenase (5-LO)/leukotriene pathway in radiation-induced vascular changes. Use of paired samples of irradiated arteries and nonirradiated internal control arteries from the same patient that were harvested during surgery for cancer reconstruction ≤10 yr after radiotherapy provides a unique human model of chronic radiation–induced vascular changes. Immunohistochemical stainings and perioperative inspection revealed an adventitial inflammatory response, with vasa vasorum expansion and chronic infiltration of CD68+ macrophages. These macrophages stained positive for the leukotriene-forming enzyme 5-LO. Messenger RNA levels of 5-LO and leukotriene B4 receptor 1 were increased in irradiated arterial segments compared with control vessels. These results point to targeting the 5-LO/leukotriene pathway as a therapeutic adjunct to prevent late adverse vascular effects of radiotherapy.—Halle, M., Christersdottir, T., Bäck, M. Chronic adventitial inflammation, vasa vasorum expansion, and 5-lipoxygenase up-regulation in irradiated arteries from cancer survivors. PMID:27530979

  5. Up-regulated expression of AOS-LOXa and increased eicosanoid synthesis in response to coral wounding.

    Directory of Open Access Journals (Sweden)

    Helike Lõhelaid

    Full Text Available In octocorals, a catalase-like allene oxide synthase (AOS and an 8R-lipoxygenase (LOX gene are fused together encoding for a single AOS-LOX fusion protein. Although the AOS-LOX pathway is central to the arachidonate metabolism in corals, its biological function in coral homeostasis is unclear. Using an acute incision wound model in the soft coral Capnella imbricata, we here test whether LOX pathway, similar to its role in plants, can contribute to the coral damage response and regeneration. Analysis of metabolites formed from exogenous arachidonate before and after fixed time intervals following wounding indicated a significant increase in AOS-LOX activity in response to mechanical injury. Two AOS-LOX isoforms, AOS-LOXa and AOS-LOXb, were cloned and expressed in bacterial expression system as active fusion proteins. Transcription levels of corresponding genes were measured in normal and stressed coral by qPCR. After wounding, AOS-LOXa was markedly up-regulated in both, the tissue adjacent to the incision and distal parts of a coral colony (with the maximum reached at 1 h and 6 h post wounding, respectively, while AOS-LOXb was stable. According to mRNA expression analysis, combined with detection of eicosanoid product formation for the first time, the AOS-LOX was identified as an early stress response gene which is induced by mechanical injury in coral.

  6. Zirconium ions up-regulate the BMP/SMAD signaling pathway and promote the proliferation and differentiation of human osteoblasts.

    Directory of Open Access Journals (Sweden)

    Yongjuan Chen

    Full Text Available Zirconium (Zr is an element commonly used in dental and orthopedic implants either as zirconia (ZrO2 or in metal alloys. It can also be incorporated into calcium silicate-based ceramics. However, the effects of in vitro culture of human osteoblasts (HOBs with soluble ionic forms of Zr have not been determined. In this study, primary culture of human osteoblasts was conducted in the presence of medium containing either ZrCl4 or Zirconium (IV oxynitrate (ZrO(NO32 at concentrations of 0, 5, 50 and 500 µM, and osteoblast proliferation, differentiation and calcium deposition were assessed. Incubation of human osteoblast cultures with Zr ions increased the proliferation of human osteoblasts and also gene expression of genetic markers of osteoblast differentiation. In 21 and 28 day cultures, Zr ions at concentrations of 50 and 500 µM increased the deposition of calcium phosphate. In addition, the gene expression of BMP2 and BMP receptors was increased in response to culture with Zr ions and this was associated with increased phosphorylation of SMAD1/5. Moreover, Noggin suppressed osteogenic gene expression in HOBs co-treated with Zr ions. In conclusion, Zr ions appear able to induce both the proliferation and the differentiation of primary human osteoblasts. This is associated with up-regulation of BMP2 expression and activation of BMP signaling suggesting this action is, at least in part, mediated by BMP signaling.

  7. Zirconium ions up-regulate the BMP/SMAD signaling pathway and promote the proliferation and differentiation of human osteoblasts.

    Science.gov (United States)

    Chen, Yongjuan; Roohani-Esfahani, Seyed-Iman; Lu, ZuFu; Zreiqat, Hala; Dunstan, Colin R

    2015-01-01

    Zirconium (Zr) is an element commonly used in dental and orthopedic implants either as zirconia (ZrO2) or in metal alloys. It can also be incorporated into calcium silicate-based ceramics. However, the effects of in vitro culture of human osteoblasts (HOBs) with soluble ionic forms of Zr have not been determined. In this study, primary culture of human osteoblasts was conducted in the presence of medium containing either ZrCl4 or Zirconium (IV) oxynitrate (ZrO(NO3)2) at concentrations of 0, 5, 50 and 500 µM, and osteoblast proliferation, differentiation and calcium deposition were assessed. Incubation of human osteoblast cultures with Zr ions increased the proliferation of human osteoblasts and also gene expression of genetic markers of osteoblast differentiation. In 21 and 28 day cultures, Zr ions at concentrations of 50 and 500 µM increased the deposition of calcium phosphate. In addition, the gene expression of BMP2 and BMP receptors was increased in response to culture with Zr ions and this was associated with increased phosphorylation of SMAD1/5. Moreover, Noggin suppressed osteogenic gene expression in HOBs co-treated with Zr ions. In conclusion, Zr ions appear able to induce both the proliferation and the differentiation of primary human osteoblasts. This is associated with up-regulation of BMP2 expression and activation of BMP signaling suggesting this action is, at least in part, mediated by BMP signaling.

  8. Hemokinin-1(4-11-induced analgesia selectively up-regulates δ-opioid receptor expression in mice.

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    Cai-Yun Fu

    Full Text Available Our previous studies have shown that an active fragment of human tachykinins (hHK-1(4-11 produced an opioid-independent analgesia after intracerebroventricular (i.c.v. injection in mice, which has been markedly enhanced by a δ OR antagonist, naltrindole hydrochloride (NTI. In this study, we have further characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11 in mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK have not changed significantly. Furthermore, neither transcription nor expression of NK1 receptor, MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels of DOR have been up-regulated significantly, indicating that the enhanced expression of δ opioid receptor negatively modulates the analgesia induced by i.c.v. injection of hHK-1(4-11. Additionally, the combinatorial data from our previous and present experiments strongly suggest that the discriminable distribution sites in the central nervous system between hHK-1(4-11 and r/mHK-1 may be attributed to their discriminable analgesic effects. Altogether, our findings will not only contribute to the understanding of the complicated mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its active fragments at supraspinal level, but may also lead to novel pharmacological interventions.

  9. Hepatitis B Virus X Protein Up-regulates TNF-α and IL-1β Secretion of Macrophages

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To provide the experimental basis for further studying the molecular transformation mechanism of Hepatitis B virus (HBV) X protein (HBx) on hepatocellular carcinoma. Methods: Reconstructed plasmid pcDNA3.1(+)-HBx was transfected into THP-1 macrophages. Expression of HBx was assayed in macrophages lysate by Western-blotting, and TNF-α and IL-1β contents were detected respectively by ELISA. All the data were analyzed by SPSS13.0. Results: In THP-1 macrophages, the pcDNA3.1(+)-HBx plasmid expressed HBx with a molecular weight of about 17 KDa demonstrated by Western-blotting. The secreted TNF-α and IL-1β from macrophages were determined by ELISA, the results from analysis of all groups showed as following: control group was different from LPS group and pcDNA3.1(+) group (P<0.01), and so was pcDNA3.1(+)-HBx group; but there was no obvious difference between pcDNA3.1(+) group and LPS group (P>0.05), all of which indicated that transient overexpression of HBx enhanced LPS-induced production of TNF-α and IL-1β by macrophages.Conclusion: Transient overexpression of HBx up-regulates LPS-induced TNF-α and IL-1β secretion of macrophages.

  10. FRZB up-regulation is correlated with hepatic metastasis and poor prognosis in colon carcinoma patients with hepatic metastasis.

    Science.gov (United States)

    Shen, Yanping; Zhang, Fang; Lan, Huanrong; Chen, Ke; Zhang, Qi; Xie, Guoming; Teng, Lisong; Jin, Ketao

    2015-01-01

    Frizzled-related protein (FRZB) was up-regulated in hepatic metastasis samples compared with primary colon cancer samples in our previous work. However, the clinical relevance of FRZB in colon cancer hepatic metastasis remains uncertain. The aim of this study was to assess the prognostic value of FRZB in patients with colon carcinoma hepatic metastasis after hepatic resection. FRZB expression was evaluated by immunohistochemistry in formalin-fixed paraffin embedded (FFPE) primary colon carcinoma and paired hepatic metastasis tissues from 136 patients with liver metastasis from colon carcinoma that underwent hepatic resection. The relation between FRZB expression and clinicopathologic factors and long-term prognosis in these 136 patients was retrospectively examined. The prognostic significance of negative or positive FRZB expression in colon carcinoma hepatic metastasis was assessed using Kaplan-Meier survival analysis and log-rank tests. Positive expression of FRZB was correlated with liver metastasis of colon cancer. Univariate analysis indicated significantly worse overall survival (OS) for patients with a positive FRZB expression in colon carcinoma hepatic metastasis than for patients with a negative FRZB expression. Multivariate analysis showed positive-FRZB in colon carcinoma hepatic metastasis to be an independent prognostic factor for OS after hepatic resection (P = 0.001). Positive expression of FRZB was statistically significantly associated with poor prognosis of patients with colon carcinoma hepatic metastasis. FRZB could be a novel predictor for poor prognosis of patients with colon carcinoma hepatic metastasis after hepatic resection.

  11. Cinnamon and its Components Suppress Vascular Smooth Muscle Cell Proliferation by Up-Regulating Cyclin-Dependent Kinase Inhibitors.

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    Kwon, Hyeeun; Lee, Jung-Jin; Lee, Ji-Hye; Cho, Won-Kyung; Gu, Min Jung; Lee, Kwang Jin; Ma, Jin Yeul

    2015-01-01

    Cinnamomum cassia bark has been used in traditional herbal medicine to treat a variety of cardiovascular diseases. However, the antiproliferative effect of cinnamon extract on vascular smooth muscle cells (VSMCs) and the corresponding restenosis has not been explored. Hence, after examining the effect of cinnamon extract on VSMC proliferation, we investigated the possible involvement of signal transduction pathways associated with early signal and cell cycle analysis, including regulatory proteins. Besides, to identify the active components, we investigated the components of cinnamon extract on VSMC proliferation. Cinnamon extract inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation and suppressed the PDGF-stimulated early signal transduction. In addition, cinnamon extract arrested the cell cycle and inhibited positive regulatory proteins. Correspondingly, the protein levels of p21 and p27 not only were increased in the presence of cinnamon extract, also the expression of proliferating cell nuclear antigen (PCNA) was inhibited by cinnamon extract. Besides, among the components of cinnamon extract, cinnamic acid (CA), eugenol (EG) and cinnamyl alcohol significantly inhibited the VSMC proliferation. Overall, the present study demonstrates that cinnamon extract inhibited the PDGF-BB-induced proliferation of VSMCs through a G0/G1 arrest, which down-regulated the expression of cell cycle positive regulatory proteins by up-regulating p21 and p27 expression.

  12. The Vitamin E Analog Gamma-Tocotrienol (GT3 and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM

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    Rupak Pathak

    2016-11-01

    Full Text Available Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR and strongly induce endothelial thrombomodulin (TM; which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3 also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC generation assay. Expression of Kruppel-like factor 2 (KLF2, one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.

  13. CCR7 pathway induces epithelial-mesenchymal transition through up-regulation of Snail signaling in gastric cancer.

    Science.gov (United States)

    Zhang, Jianping; Zhou, Yunzhe; Yang, Yonggang

    2015-02-01

    The chemokine receptor 7 (CCR7) and Snail signaling have been linked to various types of cancers. The associations between these signalings and the epithelial-mesenchymal transition (EMT) are not clear in gastric cancer. Here, the expression of CCR7 and Snail was detected in gastric cancer by immunohistochemistry and Western blot. Meanwhile, gastric cancer cells were subjected to CCL19, si-control, and si-Snail treatment. Cell cycle, migration, and invasion were also analyzed. The expression patterns of CCR7 and Snail were similar in either gastric cancer tissues or cells. The increased expression of CCR7 was closely associated with the increased Snail expression, which both were closely correlated with metastasis, stage and differentiation, and poor prognosis. The increased p-ERK, p-AKT, Snail, and MMP9 expression and the decreased E-cadherin were confirmed in MGC803 cells in a dose-dependent manner in response to CCL19 treatment. However, the blockade of Snail abrogated the up-regulation of MMP9 and down-regulation of E-cadherin. CCR7-induced ERK and PI3K pathway regulated Snail signaling. Besides si-Snail treatment led to MGC803 cell cycle arrest and affected the migration and invasion. In conclusion, our study suggested that CCR7 promotes Snail expression to induce the EMT, resulting in cell cycle progression, migration, and invasion in gastric cancer. CCR7-Snail pathway provided more potential regimens for cancer therapy.

  14. Interleukin-6 enhances cancer stemness and promotes metastasis of hepatocellular carcinoma via up-regulating osteopontin expression

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    Wang, Chao-Qun; Sun, Hao-Ting; Gao, Xiao-Mei; Ren, Ning; Sheng, Yuan-Yuan; Wang, Zheng; Zheng, Yan; Wei, Jin-Wang; Zhang, Kai-Li; Yu, Xin-Xin; Zhu, Yin; Luo, Qin; Yang, Lu-Yu; Dong, Qiong-Zhu; Qin, Lun-Xiu

    2016-01-01

    Interleukin-6 (IL-6), one of the most important inflammatory cytokines, plays a pivotal role in metastasis and stemness of solid tumors. However, the underlying mechanisms of IL-6 in HCC metastasis remain unclear. In the present study, we demonstrated that stemness and metastatic potential of HCC cells were significantly enhanced after IL-6 stimulation. IL-6 could induce expression of osteopontin (OPN), along with other stemness-related genes, including HIF1α, BMI1, and HEY1. Block of OPN induction could significantly abrogate the effect of IL-6 on stemness and metastasis of HCC cells. Furthermore, IL-6 level was positively correlated with OPN in HCC. Patients with high plasma IL-6 or OPN level had poorer prognosis. In multivariate analysis, IL-6 and OPN were demonstrated to be independent prognostic indicators for HCC patients, and their combination had a better prognostic performance than IL-6 or OPN alone. Collectively, our findings indicate that IL-6 could enhance stemness and promote metastasis of HCC via up-regulating OPN expression, which can be a potential therapeutic target for combating HCC metastasis, and the combination of IL-6 and OPN serves as a promising prognostic predictor for HCC.

  15. Up-regulation of BRAF activated non-coding RNA is associated with radiation therapy for lung cancer.

    Science.gov (United States)

    Chen, Jian-xiang; Chen, Ming; Zheng, Yuan-da; Wang, Sheng-ye; Shen, Zhu-ping

    2015-04-01

    Radiation therapy has become more effective in treating primary tumors, such as lung cancer. Recent evidence suggested that BRAF activated non-coding RNAs (BANCR) play a critical role in cellular processes and are found to be dysregulated in a variety of cancers. The clinical significance of BANCR in radiation therapy, and its molecular mechanisms controlling tumor growth are unclear. In the present study, C57BL/6 mice were inoculated Lewis lung cancer cells and exposed to radiation therapy, then BANCR expression was analyzed using qPCR. Chromatin immunoprecipitation and western blot were performed to calculate the enrichment of histone acetylation and HDAC3 protein levels in Lewis lung cancer cells, respectively. MTT assay was used to evaluate the effects of BANCR on Lewis lung cancer cell viability. Finally, we found that BANCR expression was significantly increased in C57BL/6 mice receiving radiation therapy (Pcancer cells. Histone deacetylation was observed to involve in the regulation of BANCR in Lewis lung cancer cells. Moreover, over expression HDAC3 reversed the effect of rays on BANCR expression. MTT assay showed that knockdown of BANCR expression promoted cell viability surviving from radiation. In conclusion, these findings indicated that radiation therapy was an effective treatment for lung cancer, and it may exert function through up-regulation BANCR expression.

  16. Antioxidant pathways are up-regulated during biological nitrogen fixation to prevent ROS-induced nitrogenase inhibition in Gluconacetobacter diazotrophicus.

    Science.gov (United States)

    Alquéres, Sylvia M C; Oliveira, Jose Henrique M; Nogueira, Eduardo M; Guedes, Helma V; Oliveira, Pedro L; Câmara, Fernando; Baldani, Jose I; Martins, Orlando B

    2010-10-01

    Gluconacetobacter diazotrophicus, an endophyte isolated from sugarcane, is a strict aerobe that fixates N(2). This process is catalyzed by nitrogenase and requires copious amounts of ATP. Nitrogenase activity is extremely sensitive to inhibition by oxygen and reactive oxygen species (ROS). However, the elevated oxidative metabolic rates required to sustain biological nitrogen fixation (BNF) may favor an increased production of ROS. Here, we explored this paradox and observed that ROS levels are, in fact, decreased in nitrogen-fixing cells due to the up-regulation of transcript levels of six ROS-detoxifying genes. A cluster analyses based on common expression patterns revealed the existence of a stable cluster with 99.8% similarity made up of the genes encoding the α-subunit of nitrogenase Mo-Fe protein (nifD), superoxide dismutase (sodA) and catalase type E (katE). Finally, nitrogenase activity was inhibited in a dose-dependent manner by paraquat, a redox cycler that increases cellular ROS levels. Our data revealed that ROS can strongly inhibit nitrogenase activity, and G. diazotrophicus alters its redox metabolism during BNF by increasing antioxidant transcript levels resulting in a lower ROS generation. We suggest that careful controlled ROS production during this critical phase is an adaptive mechanism to allow nitrogen fixation.

  17. HSP70 increases extracellular matrix production by human vascular smooth muscle through TGF-β1 up-regulation.

    Science.gov (United States)

    González-Ramos, Marta; Calleros, Laura; López-Ongil, Susana; Raoch, Viviana; Griera, Mercedes; Rodríguez-Puyol, Manuel; de Frutos, Sergio; Rodríguez-Puyol, Diego

    2013-02-01

    The circulating levels of heat shock proteins (HSP) are increased in cardiovascular diseases; however, the implication of this for the fibrotic process typical of such diseases remains unclear. HSP70 can interact with the vascular smooth muscle cells (SMC), the major producer of extracellular matrix (ECM) proteins, through the Toll-like receptors 4 (TLR4). The transforming growth factor type-β1 (TGF-β1) is a well known vascular pro-fibrotic cytokine that is regulated in part by AP-1-dependent transcriptional mechanisms. We hypothesized that extracellular HSP70 could interact with SMCs, inducing TGF-β1 synthesis and subsequent changes in the vascular ECM. We demonstrate that extracellular HSP70 binds to human aorta SMC TLR4, which up-regulates the AP-1-dependent transcriptional activity of the TGF-β1 promoter. This is achieved through the mitogen activated protein kinases JNK and ERK, as demonstrated by the use of specific blockers and the knockdown of TLR4 with specific small interfering RNAs. The TGF-β1 upregulation increase the expression of the ECM proteins type I collagen and fibronectin. This novel observation may elucidate the mechanisms by which HSP70 contributes in the inflammation and fibrosis present in atherosclerosis and other fibrosis-related diseases.

  18. Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin oxygenation induced by near-infrared laser

    Science.gov (United States)

    Wang, Xinlong; Tian, Fenghua; Soni, Sagar S.; Gonzalez-Lima, F.; Liu, Hanli

    2016-08-01

    Photobiomodulation, also known as low-level laser/light therapy (LLLT), refers to the use of red-to-near-infrared light to stimulate cellular functions for physiological or clinical benefits. The mechanism of LLLT is assumed to rely on photon absorption by cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. In this study, we used broadband near-infrared spectroscopy (NIRS) to measure the LLLT-induced changes in CCO and hemoglobin concentrations in human forearms in vivo. Eleven healthy participants were administered with 1064-nm laser and placebo treatments on their right forearms. The spectroscopic data were analyzed and fitted with wavelength-dependent, modified Beer-Lambert Law. We found that LLLT induced significant increases of CCO concentration (Δ[CCO]) and oxygenated hemoglobin concentration (Δ[HbO]) on the treated site as the laser energy dose accumulated over time. A strong linear interplay between Δ[CCO] and Δ[HbO] was observed for the first time during LLLT, indicating a hemodynamic response of oxygen supply and blood volume closely coupled to the up-regulation of CCO induced by photobiomodulation. These results demonstrate the tremendous potential of broadband NIRS as a non-invasive, in vivo means to study mechanisms of photobiomodulation and perform treatment evaluations of LLLT.

  19. Azelastine hydrochloride (Azeptin) inhibits peplomycin (PLM)-induced pulmonary fibrosis by contradicting the up-regulation of signal transduction.

    Science.gov (United States)

    Yoneda, K; Yamamoto, T; Ueta, E; Osaki, T

    1997-10-01

    Inhibition of peplomycin (PLM)-induced pulmonary fibrosis by azelastine hydrochloride (Azeptin) was examined using ICR mice, and the effects of both drugs on signal transduction were investigated. Microscopically, Azeptin (a total of 56 mg/kg for 28 days) suppressed pulmonary fibrosis in mice which received an i.p. injection of a total of 60 or 75 mg/kg PLM. In parallel with the microscopic findings, smaller amounts of collagen were synthesized in the lungs of Azeptin-injected mice. PLM enhanced the expression of interleukin-1 beta- and transforming growth factor-beta-mRNA in lungs. In contrast, Azeptin suppressed the expression. Compatible with these in vivo results, Azeptin and PLM contradictively regulated protein tyrosine phosphorylation and c-myc mRNA expression in human gingival and mouse pulmonary fibroblasts. In addition, NF-kappa B was activated by fibroblast treatment with 5 micrograms/ml PLM for 1 h, but intranuclear NF-kappa B was decreased by cell treatment with 10(-5) M Azeptin. From these results, it is concluded that Azeptin inhibits PLM-induced pulmonary fibrosis by antagonizing the up-regulation of signal transduction.

  20. Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

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    Li Wang

    2014-04-01

    Full Text Available Objective: To investigate the effect of Astragaloside IV (AS-IV on the regulation of the Wnt/β-catenin signaling pathway in rats with unilateral ureteral obstruction (UUO. Methods: Rat renal interstitial fibrosis models were prepared using unilateral ureteral ligation. Rats were randomly divided into sham group, sham group with AS-IV (33mg/kg, unilateral ureteral obstruction group, and unilateral ureteral obstruction group receiving varied doses of AS-IV (3.3, 10, and 33 mg/kg. Immunohistochemical analysis, real-time fluorescence quantitative PCR (FQ-PCR, and western blot were used to detect the expression of genes and proteins associated with the Wnt/β-catenin signaling pathway in renal tissues. Results: Levels of Wnt3, Wnt4, and Frizzled gene expression increased significantly in the UUO model; AS-IV was associated with the downregulation of the expression of Wnt3, Wnt4, Frizzled4, p-LRP5, p-LRP6, disheveled, β-catenin, LEF-1, TCF-1, Snail, Jagged 1, Twist, MMP2, and MMP7 proteins in a concentration-dependent manner, while the expression of APC, CK1, and E-cadherin was increased. Conclusions: AS-IV effectively inhibits the up-regulation of proteins in the Wnt/β-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis.

  1. Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury.

    Science.gov (United States)

    Song, Xian-min; Xu, Xiao-hui; Zhu, Jiao; Guo, Zhili; Li, Jian; He, Cheng; Burnstock, Geoffrey; Yuan, Hongbin; Xiang, Zhenghua

    2015-06-01

    Peripheral nerve injury (PNI) is a common disease, which results in a partial or total loss of motor, sensory and autonomic functions, leading to a decrease in quality of life. Schwann cells play a vital role in maintaining the peripheral nervous system and in injury and repair. Using immunohistochemistry, Western blot, calcium assay and bromodeoxyuridine (BrdU) proliferation assay, the present study clearly demonstrated that P2X7 receptors (R) were expressed in myelinating and non-myelinating Schwann cells in longitudinal sections of sciatic nerves. After sciatic nerve injury (SNI), P2X7R expression in Schwann cells of injured sciatic nerves was significantly up-regulated during the early days of SNI. Double immunofluorescence of proliferating cell nuclear antigen (PCNA) and P2X7R implied that P2X7R may be involved in proliferation of Schwann cells. Further experiments on primary cultures of Schwann cells showed that P2X7R are functionally expressed in Schwann cells of rat sciatic nerves; ATP via P2X7R can promote Schwann cell proliferation, possibly via the MAPK/ERK intracellular signalling pathway. Other possible roles of P2X7R on Schwann cells are discussed.

  2. Laminar shear stress up-regulates peroxiredoxins (PRX) in endothelial cells: PRX 1 as a mechanosensitive antioxidant.

    Science.gov (United States)

    Mowbray, Amy L; Kang, Dong-Hoon; Rhee, Sue Goo; Kang, Sang Won; Jo, Hanjoong

    2008-01-18

    Shear stress plays a significant role in endothelial cell biology and atherosclerosis development. Previous work by our group has shown that fluid flow stimulates important functional changes in cells through protein expression regulation. Peroxiredoxins (PRX) are a family of antioxidant enzymes but have yet to be investigated in response to shear stress. Studies have shown that oscillatory shear stress (OS) increases reactive oxygen species (ROS) levels in endothelial cells, whereas laminar shear stress (LS) blocks this response. We hypothesized that PRX are responsible for the anti-oxidative effect of LS. To test this hypothesis, bovine aortic endothelial cells (BAEC) were subjected to LS (15 dyn/cm(2)), OS (+/-5 dyn/cm(2), 1 Hz), or static conditions for 24 h. Using Western blot and immunofluorescence staining, all six isoforms of PRX were identified in BAEC. When compared with OS and static, exposure to chronic LS up-regulated PRX 1 levels intracellularly. LS also increased expression of PRX 5 relative to static controls, but not OS. PRX exhibited broad subcellular localization, with distribution in the cytoplasm, Golgi, mitochondria, and intermediate filaments. In addition, PRX 1 knock down, using specific small interference RNA, attenuated LS-dependent reactive oxygen species reduction in BAEC. However, PRX 5 depletion did not. Together, these results suggest that PRX 1 is a novel mechanosensitive antioxidant, playing an important role in shear-dependent regulation of endothelial biology and atherosclerosis.

  3. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, Rebecca; Zeino, Maen [Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Frewert, Simon [Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, Saarbrücken (Germany); Efferth, Thomas, E-mail: efferth@uni-mainz.de [Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany)

    2014-11-15

    Treatment of glioblastoma multiforme (GBM), the most common and aggressive lethal brain tumor, represents a great challenge. Despite decades of research, the survival prognosis of GBM patients is unfavorable and more effective therapeutics are sorely required. Archazolid B, a potent vacuolar H{sup +}-ATPase inhibitor influencing cellular pH values, is a promising new compound exerting cytotoxicity in the nanomolar range on wild-type U87MG glioblastoma cells and U87MG.∆EGFR cells transfected with a mutant epidermal growth factor receptor (EGFR) gene. Gene expression profiling using microarray technology showed that archazolid B caused drastic disturbances in cholesterol homeostasis. Cholesterol, a main component of cellular membranes, is known to be essential for GBM growth and cells bearing EGFRvIII mutation are highly dependent on exogenous cholesterol. Archazolid B caused excessive accumulation of free cholesterol within intracellular compartments thus depleting cellular cholesterol and leading to up-regulation of SREBP targeted genes, including LDLR and HMGCR, the key enzyme of cholesterol biosynthesis. This cholesterol response is considered to be a novel resistance mechanism induced by archazolid B. We surmise that re-elevation of cholesterol levels in archazolid B treated cells may be mediated by newly synthesized cholesterol, since the drug leads to endosomal/lysosomal malfunction and cholesterol accumulation.

  4. Up-Regulation of the Excitatory Amino Acid Transporters EAAT1 and EAAT2 by Mammalian Target of Rapamycin

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    Abeer Abousaab

    2016-11-01

    Full Text Available Background: The excitatory amino-acid transporters EAAT1 and EAAT2 clear glutamate from the synaptic cleft and thus terminate neuronal excitation. The carriers are subject to regulation by various kinases. The EAAT3 isoform is regulated by mammalian target of rapamycin (mTOR. The present study thus explored whether mTOR influences transport by EAAT1 and/or EAAT2. Methods: cRNA encoding wild type EAAT1 (SLC1A3 or EAAT2 (SLC1A2 was injected into Xenopus oocytes without or with additional injection of cRNA encoding mTOR. Dual electrode voltage clamp was performed in order to determine electrogenic glutamate transport (IEAAT. EAAT2 protein abundance was determined utilizing chemiluminescence. Results: Appreciable IEAAT was observed in EAAT1 or EAAT2 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of mTOR. Coexpression of mTOR increased significantly the maximal IEAAT in EAAT1 or EAAT2 expressing oocytes, without significantly modifying affinity of the carriers. Moreover, coexpression of mTOR increased significantly EAAT2 protein abundance in the cell membrane. Conclusions: The kinase mTOR up-regulates the excitatory amino acid transporters EAAT1 and EAAT2.

  5. Up-regulation of Na + expression in the area postrema of total sleep deprived rats by TOF-SIMS analysis

    Science.gov (United States)

    Mai, Fu-Der; Chen, Bo-Jung; Ling, Yong-Chien; Wu, Un-In; Huang, Yi-Lun; Chang, Hung-Ming

    2008-12-01

    Area postrema (AP) is a circumventricular organ plays an important role in sodium homeostasis and cardiovascular regulation. Since sleep deficiency will cause cardiovascular dysfunction, the present study aims to determine whether sodium level would significantly alter in AP following total sleep deprivation (TSD). Sodium level was investigated in vivo by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Clinical manifestation of cardiovascular function was demonstrated by mean arterial pressure (MAP) values. Results indicated that in normal rats, TOF-SIMS spectrum revealed a major peak of sodium ion counting as 5.61 × 10 5 at m/ z 23. The sodium ions were homogeneous distributed in AP without specific localization. However, following TSD, the sodium intensity was relatively increased (6.73 × 10 5) and the signal for sodium image was strongly expressed throughout AP with definite spatial distribution. MAP of TSD rats is 138 ± 5 mmHg, which is significantly higher than that of normal ones (121 ± 3 mmHg). Regarding AP is an important area for sodium sensation and development of hypernatremic related sympatho-excitation; up-regulation of sodium expression following TSD suggests that high sodium level might over-activate AP, through complex neuronal networks involving in sympathetic regulation, which could lead to the formation of TSD relevant cardiovascular diseases.

  6. Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice.

    Science.gov (United States)

    Shiratori, H; Koshino, T; Uesugi, M; Nitto, H; Saito, T

    2001-09-20

    The effect of CD44-phenotypic expression on metastasis to the lung was studied using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20 C3H/HeJ mice and produced a visible mass in all mice in 5 weeks, and these transplanted tumors resulted in lung metastasis in all mice. The number of metastatic foci in the lungs was 12.0+/-2.1 (mean+/-SD) with LPS-stimulated cells, which was significantly higher than that of unstimulated cells (5.8+/-1.4; N=10 for each; P<0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of lung metastases in a dose-dependent manner (0.5% HA, 3.0+/-1.1; 0.005% HA, 5.1+/-1.5; without HA, 8.6+/-1.7; N=10 for each; P<0.05, each group with HA versus the group without HA). Adhesion assay by coculturing POS-1 cells and lung microvascular endothelial cells on culture plate showed that the adhesion was significantly lower in HA treated POS-1 than those without HA (1.18+/-0.12 and 2.74+/-0.17, respectively, P<0.05). These results suggest that lung metastasis was accelerated by up-regulation of CD44.

  7. Identification of up-regulated proteins potentially involved in the antagonism mechanism of Bacillus amyloliquefaciens G1.

    Science.gov (United States)

    Cao, Haipeng; Zheng, Weidong; He, Shan; Wang, Hao; Wang, Tu; Lu, Liqun

    2013-06-01

    The use of Bacillus probiotics has been demonstrated as a promising method in the biocontrol of bacterial diseases in aquaculture. However, the molecular antibacterial mechanism of Bacillus still remains unclear. In order to explore the antibacterial mechanism of the potential antagonistic Bacillus amyloliquefaciens strain G1, comparative proteomics between B. amyloliquefaciens strain G1 and its non-antagonistic mutant strain was investigated. The 2-dimensional electrophoresis gel maps of their total extracted proteins were described and 42 different proteins were found to be highly expressed in strain G1 in comparison with those in the mutant strain. 35 of these up-regulated proteins were successfully identified using MALDI-TOF-TOF MS and databank analysis, and their biological functions were analyzed through the KEGG database. The increased expression of these proteins suggested that high levels of energy metabolism, biosynthesis and stress resistance could play important roles in strain G1's antagonism. To our knowledge, this is the first report on the proteins involved in the antagonism mechanism of B. amyloliquefaciens using a proteomic approach and the proteomic data also contribute to a better understanding of the molecular basis for the antagonism of B. amyloliquefaciens.

  8. A telephone survey of parental attitudes and behaviours regarding teenage drinking

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    Barry Joe M

    2010-06-01

    Full Text Available Abstract Background Irish teenagers demonstrate high rates of drunkenness and there has been a progressive fall in age of first drinking in recent decades. International research indicates that parents exert substantial influence over their teenager's drinking. We sought to determine the attitudes and behaviours of Irish parents towards drinking by their adolescent children. Methods We conducted a telephone survey of a representative sample of of 234 parents who had a teenager aged between 13 and 17 years. Results Six per cent reported that they would be unconcerned if their son or daughter was to binge drink once per month. On the issue of introducing children to alcohol in the home, 27% viewed this as a good idea while 63% disagreed with this practice. Eleven per cent of parents reported that they had given a drink to their teenager at home. Parents who drank regularly themselves, who were from higher socio-demographic groups and who lived in the east of Ireland demonstrated more permissive attitudes to teenage drinking. Conclusions We found no evidence of widespread permissive attitudes and behaviours among Irish parents. Given that parental influences have been demonstrated to exert substantial impact on teenage drinking, it may be possible to harness the concerns of Irish parents more effectively to reverse the trends of escalating alcohol related harm in Ireland.

  9. Understanding and coping with binge eating disorder: the patient's perspective.

    Science.gov (United States)

    McElroy, Susan L; Guerdjikova, Anna I

    2015-08-01

    Binge eating disorder (BED) is the most common of the 6 feeding and eating disorders recognized by the DSM-5 and a significant public health problem that can be successfully managed with appropriate help. Many patients, however, are hesitant to discuss the symptoms of BED with their providers because of embarrassment or because they simply do not recognize the behavior as a problem behavior. Clinicians need to increase their awareness of BED, its warning signs, and how and why patients might try to hide it leading to increased BED recognition and timely diagnosis. Then, given the right tools, clinicians can help patients to not only accept the diagnosis and look into various treatment options but also to move beyond it to recognize if any comorbid disorders are present and in need of treatment.

  10. Binge eating disorder: from clinical research to clinical practice.

    Science.gov (United States)

    Goracci, Arianna; Casamassima, Francesco; Iovieno, Nadia; di Volo, Silvia; Benbow, Jim; Bolognesi, Simone; Fagiolini, Andrea

    2015-01-01

    This case report describes the clinical course of a young woman suffering from binge eating disorder (BED) associated with obesity. It illustrates the efficacy of different medications in the treatment of BED and related conditions and is followed by the comments and clinical observations of 2 practicing psychiatrists. The issues described in this paper have important clinical implications and are topical, given that BED is now recognized as a specific disorder in the new Diagnostic and Statistical Manual of Mental Disorders, fifth edition classification system, but neither the US Food and Drug Administration nor any other regulatory agency has yet approved a drug for treatment of this disease, despite its very prevalent and disabling nature. Growing evidence from the fields of psychopathology and neurobiology, including preclinical and clinical studies, converges to support the idea that "overeating" has much in common with other behavioral addictions, and substance abuse treatment agents may show promise for the treatment of BED.

  11. A primer on binge eating disorder diagnosis and management.

    Science.gov (United States)

    Citrome, Leslie

    2015-12-01

    Binge eating disorder (BED) is the most common eating disorder, with an estimated lifetime prevalence of 2.6% among U.S. adults, yet often goes unrecognized. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), BED is defined by recurrent episodes of binge eating (eating in a discrete period of time an amount of food larger than most people would eat in a similar amount of time under similar circumstances and a sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. It can affect both men and women, regardless if they are at normal weight, overweight, or obese, and regardless of their ethnic or racial group. Psychiatric comorbidities are very common, with 79% of adults with BED also experiencing anxiety disorders, mood disorders, impulse control disorders, or substance use disorders; almost 50% of persons with BED have ≥ 3 psychiatric comorbidities. Multiple neurobiological explanations have been proffered for BED, including dysregulation in reward center and impulse control circuitry, with potentially related disturbances in dopamine neurotransmission and endogenous μ-opioid signaling. Additionally, there is interplay between genetic influences and environmental stressors. Psychological treatments such as cognitive behavioral interventions have been recommended as first line and are supported by meta-analytic reviews. Unfortunately, routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED; however, at present, there is one approved agent for the treatment of moderate to severe BED-lisdexamfetamine, a stimulant that was originally approved for the treatment of attention deficit hyperactivity disorder.

  12. Diagnosing binge eating disorder in a primary care setting.

    Science.gov (United States)

    Montano, C Brendan; Rasgon, Natalie L; Herman, Barry K

    2016-01-01

    Binge eating disorder (BED), now recognized as a distinct eating disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is the most prevalent eating disorder. Although nearly half of individuals with BED are obese, BED also occurs in nonobese individuals. Despite the relatively high percentage of weight loss treatment-seeking individuals meeting BED criteria, primary care physicians may not be familiar with or have ever diagnosed BED. Many providers may also have difficulty distinguishing BED as a contributory factor in obesity. This review differentiates BED from other causes of obesity by describing how obese individuals with BED differ from obese individuals without BED and from nonobese individuals with BED in areas including psychopathology, behavior, genetics, physiology, quality of life and productivity. The ways in which health-care providers can identify individuals who may have BED are also highlighted so the proper course of treatment is pursued. Overall, obese individuals with BED demonstrate a number of key characteristics that differentiate them from obese individuals without eating disorders, including increased impulsivity in response to food stimuli with loss of control over eating, resulting in the consumption of more calories. They also experience significant guilt and other negative emotions following a meal. In addition, individuals with BED patients have more psychiatric comorbidity, display more psychopathology, exhibit longer binge durations, consume more meals as snacks during the day and have less dietary restraint compared with individuals with BED who are not obese. However, the differences between individuals with BED who are obese versus not obese are not as prominent. Taken together, the evidence appears to support the conclusion that BED is a unique and treatable neurobehavioral disorder associated with distinct behavioral and psychological profiles and distinct medical and functional outcomes, and that

  13. Group behavioral activation for patients with severe obesity and binge eating disorder: a randomized controlled trial.

    Science.gov (United States)

    Alfonsson, Sven; Parling, Thomas; Ghaderi, Ata

    2015-03-01

    The aim of the present study was to assess whether behavioral activation (BA) is an efficacious treatment for decreasing eating disorder symptoms in patients with obesity and binge eating disorder (BED). Ninety-six patients with severe obesity and BED were randomized to either 10 sessions of group BA or wait-list control. The study was conducted at an obesity clinic in a regular hospital setting. The treatment improved some aspects of disordered eating and had a positive effect on depressive symptoms but there was no significant difference between the groups regarding binge eating and most other symptoms. Improved mood but lack of effect on binge eating suggests that dysfunctional eating (including BED) is maintained by other mechanisms than low activation and negative mood. However, future studies need to investigate whether effects of BA on binge eating might emerge later than at post-assessment, as in interpersonal psychotherapy for bulimia nervosa.

  14. Evaluation of a functional treatment for binge eating associated with bulimia nervosa.

    Science.gov (United States)

    Giddings, T D; Miltenberger, R G

    2010-01-01

    Binge-eating disorders (BED) are a common problem affecting up to 5 percent of the American population in any given 6-month period. Currently, the most widely accepted treatment is some variation of Cognitive Behavior Therapy, although the abstinence rates following this type of treatment are only around 50%. A recent study by Bosch et al. explored the effects of extinction with four women who engaged in binge-eating behavior associated with BED and bulimia nervosa (BN). The treatment was successful, with three of the four participants obtaining abstinence. To date, this has been the only study examining this procedure. The purpose of the current study was to further evaluate extinction of binge eating with four young women who met diagnostic criteria for BN. The results showed that the treatment decreased binge eating to zero for all four women, although one dropped out of the study shortly after beginning the intervention.

  15. Adolescent binge-like ethanol exposure reduces basal α-MSH expression in the hypothalamus and the amygdala of adult rats

    Science.gov (United States)

    Lerma-Cabrera, Jose Manuel; Carvajal, Francisca; Alcaraz-Iborra, Manuel; de la Fuente, Leticia; Navarro, Montserrat; Thiele, Todd E.; Cubero, Inmaculada

    2013-01-01

    Melanocortins (MC) are central peptides that have been implicated in the modulation of ethanol consumption. There is experimental evidence that chronic ethanol exposure reduces α-MSH expression in limbic and hypothalamic brain regions and alters central pro-opiomelanocortin (POMC) mRNA activity in adult rats. Adolescence is a critical developmental period of high vulnerability in which ethanol exposure alters corticotropin releasing factor, neuropeptide Y, substance P and neurokinin neuropeptide activities, all of which have key roles in ethanol consumption. Given the involvement of MC and the endogenous inverse agonist AgRP in ethanol drinking, here we evaluate whether a binge-like pattern of ethanol treatment during adolescence has a relevant impact on basal and/or ethanol-stimulated α-MSH and AgRP activities during adulthood. To this end, adolescent Sprague-Dawley rats (beginning at PND25) were pre-treated with either saline (SP group) or binge-like ethanol exposure (BEP group; 3.0 g/kg given in intraperitoneal (i.p.) injections) of one injection per day over two consecutive days, followed by 2 days without injections, repeated for a total of 8 injections. Following 25 ethanol-free days, we evaluated α-MSH and AgRP immunoreactivity (IR) in the limbic and hypothalamic nuclei of adult rats (PND63) in response to ethanol (1.5 or 3.0 g/kg i.p.) and saline. We found that binge-like ethanol exposure during adolescence significantly reduced basal α-MSH IR in the central nucleus of the amygdala (CeA), the arcuate nucleus (Arc) and the paraventricular nucleus of the hypothalamus (PVN) during adulthood. Additionally, acute ethanol elicited AgRP IR in the Arc. Rats given the adolescent ethanol treatment required higher doses of ethanol than saline-treated rats to express AgRP. In light of previous evidence that endogenous MC and AgRP regulate ethanol intake through MC-receptor signaling, we speculate that the α-MSH and AgRP disturbances induced by binge-like ethanol

  16. Adolescent Girls and Their Mothers Talk About Experiences of Binge and Loss of Control Eating

    OpenAIRE

    Palmberg, Allison A.; Stern, Marilyn; Kelly, Nichole R.; Bulik, Cynthia; Belgrave, Faye Z.; Trapp, Stephen K.; Hofmeier, Sara M.; Mazzeo, Suzanne E.

    2014-01-01

    Evidence suggests that adolescents’ experience of binge eating (BE) might differ in important ways from that of adults. Moreover, although BE appears more common in African American women than other disordered eating behaviors, little is known about the influence of cultural factors on this behavior in adolescents. The current investigation used qualitative methodology to examine the perceptions of White and African American adolescent girls and their mothers regarding experiences of binge an...

  17. Binge eating disorder should be included in DSM-IV: a reply to Fairburn et al.'s "the classification of recurrent overeating: the binge eating disorder proposal".

    Science.gov (United States)

    Spitzer, R L; Stunkard, A; Yanovski, S; Marcus, M D; Wadden, T; Wing, R; Mitchell, J; Hasin, D

    1993-03-01

    Extensive recent research supports a proposal that a new eating disorder, binge eating disorder (BED), be included in DSM-IV. BED criteria define a relatively pure group of individuals who are distressed by recurrent binge eating who do not exhibit the compensatory features of bulimia nervosa. This large number of patients currently can only be diagnosed as eating disorder not otherwise specified (EDNOS). Recognizing this new disorder will help stimulate research and clinical programs for these patients. Fairburn et al.'s critique of BED fails to acknowledge the large body of knowledge that indicates that BED represents a distinct and definable subgroup of eating disordered patients and that the diagnosis provides useful information about psychopathology, prognosis, and outcome (Fairburn, Welch, & Hay [in press]. The classification of recurrent overeating: The "binge eating disorder" proposal. International Journal of Eating Disorders.) Against any reasonable standard for adding a new diagnosis to DSM-IV, BED meets the test.

  18. Stress hormone epinephrine enhances adipogenesis in murine embryonic stem cells by up-regulating the neuropeptide Y system.

    Directory of Open Access Journals (Sweden)

    Ruijun Han

    Full Text Available Prenatal stress, psychologically and metabolically, increases the risk of obesity and diabetes in the progeny. However, the mechanisms of the pathogenesis remain unknown. In adult mice, stress activates NPY and its Y2R in a glucocorticoid-dependent manner in the abdominal fat. This increased adipogenesis and angiogenesis, leading to abdominal obesity and metabolic syndrome which were inhibited by intra-fat Y2R inactivation. To determine whether stress elevates NPY system and accelerates adipogenic potential of embryo, here we "stressed" murine embryonic stem cells (mESCs in vitro with epinephrine (EPI during their adipogenic differentiation. EPI was added during the commitment stage together with insulin, and followed by dexamethasone in the standard adipogenic differentiation medium. Undifferentiated embryonic bodies (EBs showed no detectable expression of NPY. EPI markedly up-regulated the expression NPY and the Y1R at the commitment stage, followed by increased Y2R mRNA at the late of the commitment stage and the differentiation stage. EPI significantly increased EB cells proliferation and expression of the preadipocyte marker Pref-1 at the commitment stage. EPI also accelerated and amplified adipogenic differentiation detected by increasing the adipocyte markers FABP4 and PPARγ mRNAs and Oil-red O-staining at the end of the differentiation stage. EPI-induced adipogenesis was completely prevented by antagonists of the NPY receptors (Y1R+Y2R+Y5R, indicating that it was mediated by the NPY system in mESC's. Taken together, these data suggest that stress may play an important role in programming ESCs for accelerated adipogenesis by altering the stress induced hormonal regulation of the NPY system.

  19. Protective Role of Ca Against NaCl Toxicity in Jerusalem Artichoke by Up-Regulation of Antioxidant Enzymes

    Institute of Scientific and Technical Information of China (English)

    XUE Yan-Feng; LIU Ling; LIU Zhao-Pu; S. K.MEHTA; ZHAO Geng-Mao

    2008-01-01

    The ameliorative effect of external Ca2+ on Jerusalem artichoke (Helianthus tuberosus L.) under salt stress was studied through biochemical and physiological analyses of Jerusalem artichoke seedlings treated with or without 10 mol L-1 CaCl2, 150 mmol L-1 NaCl, and/or 5 mmol L-1 ethylene-bis(oxyethylenenitrilo)-tetraacetic acid (EGTA) for five days. Exposure to NaCl (150 mmol L-1) decreased growth, leaf chlorophyll content, and photosynthetic rate of Jerusalem artichoke seedlings. NaCl treatment showed 59% and 37% higher lipid peroxidation and electrolyte leakage, respectively, than the control. The activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were decreased by NaCl, indicating an impeded antioxidant defense mechanism of Jerusalem artichoke grown under salt stress. Addition of 10 mmol L-1 CaCl2 to the salt solutions significantly decreased the damaging effect of NaCl on growth and chlorophyll content and simultaneously restored the rate of photosynthesis almost to the level of the control. Ca2+ addition decreased the leaf malondialdehyde (MDA) content and electrolyte leakage from NaCl-treated seedlings by 47% and 24%, respectively, and significantly improved the activities of SOD, POD, and CAT in NaCl-treated plants. Addition of ECTA, a specific chelator of Ca2+, decreased the growth, chlorophyll content, and photosynthesis, and increased level of MDA and electrolyte leakage from NaCl-treated plants and from the control plants. ECTA addition to the growth medium also repressed the activities of SOD, POD, and CAT in NaCl-treated and control seedlings. External Ca2+ might protect Jerusalem artichoke against NaCl stress by up-regulating the activities of antioxidant enzymes and thereby decreasing the oxidative stress.

  20. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

    Science.gov (United States)

    Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

    2012-06-01

    Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol.