Science.gov

Sample records for alcohol-induced smoking urge

  1. Neural Substrates of Alcohol-Induced Smoking Urge in Heavy Drinking Nondaily Smokers

    PubMed Central

    King, Andrea; McNamara, Patrick; Angstadt, Michael; Phan, K Luan

    2010-01-01

    A strong link exists between cigarette smoking and alcohol use, which may be explained by the experimental observation that alcohol ingestion promotes cigarette craving and precipitates smoking. At the neuroanatomic level, it is unclear where and how alcohol exerts these effects, although the process likely involves the ventral striatum given its function in motivational salience and appetitive reinforcement. In a double-blinded, placebo-controlled, crossover study, heavy drinking nondaily social smokers (ie, light smokers or ‘chippers') were examined using functional magnetic resonance imaging after they ingested an acute dose of alcohol or placebo. We probed reactivity in the ventral striatum and other brain regions during exposure to visual smoking vs nonsmoking control cues. We found that alcohol enhanced self-reported ratings of desire to smoke, and in this context, significantly increased ventral striatum responses to smoking compared with control cues. In exploratory analyses, we observed that alcohol dampened orbitofrontal activity across both cue types, whereas dorsolateral prefrontal and anterior cingulate cortex activation to smoking cues was not affected by alcohol. This study bridges a pharmacological challenge approach to the study of brain reactivity to smoking cues, extends prior cigarette cue imaging studies to nondependent smokers, and elucidates a potential neurobiological mechanism to explain the co-consumption of alcohol and cigarettes in nondependent users. PMID:19907419

  2. Movie smoking and urge to smoke among adult smokers.

    PubMed

    Sargent, James D; Morgenstern, Matthis; Isensee, Barbara; Hanewinkel, Reiner

    2009-09-01

    Few studies have assessed the association between exposure to movie smoking and urge to smoke under real-world conditions. We conducted exit interviews with 4,073 movie patrons, of whom 2,817 were aged 18 years or older. Some 536 were smokers and had complete data. Subjects had exited 26 movies, of which 12 contained smoking. We used least squares regression to assess the association between exposure to movie smoking and urge to smoke (scale range 0-10), controlling for movie rating, age, sex, heaviness of smoking index (HSI, range 0-6), and time since last cigarette smoked. Median age was 27 years and 52% were female. Median urge to smoke level at movie exit was 7. The dose-response between higher categories of movie smoking and median urge to smoke was one point for two lower categories (1-11 and 11-54 s) and two for the highest category (>or=55 s), but these differences were not statistically significant. In the multivariate analysis, attendance of a movie with smoking was associated with a 0.81-point increase (95% CI = 0.46-1.16) in urge to smoke. For comparison, an HSI score of 3 (vs. 0) was associated with a 2-point increase in urge to smoke. In this sample of adult smokers, exposure to movie smoking was associated with higher urge to smoke after the movie, independent of movie rating. The effect size was consistent with responses seen in cue reactivity experiments. Exposure to movie smoking may affect urge to smoke among adult smokers.

  3. Movie smoking and urge to smoke among adult smokers

    PubMed Central

    Sargent, James D.; Morgenstern, Matthis; Isensee, Barbara

    2009-01-01

    Introduction Few studies have assessed the association between exposure to movie smoking and urge to smoke under real-world conditions. Methods We conducted exit interviews with 4,073 movie patrons, of whom 2,817 were aged 18 years or older. Some 536 were smokers and had complete data. Subjects had exited 26 movies, of which 12 contained smoking. We used least squares regression to assess the association between exposure to movie smoking and urge to smoke (scale range 0–10), controlling for movie rating, age, sex, heaviness of smoking index (HSI, range 0–6), and time since last cigarette smoked. Results Median age was 27 years and 52% were female. Median urge to smoke level at movie exit was 7. The dose–response between higher categories of movie smoking and median urge to smoke was one point for two lower categories (1–11 and 11–54 s) and two for the highest category (≥55 s), but these differences were not statistically significant. In the multivariate analysis, attendance of a movie with smoking was associated with a 0.81-point increase (95% CI = 0.46–1.16) in urge to smoke. For comparison, an HSI score of 3 (vs. 0) was associated with a 2-point increase in urge to smoke. Discussion In this sample of adult smokers, exposure to movie smoking was associated with higher urge to smoke after the movie, independent of movie rating. The effect size was consistent with responses seen in cue reactivity experiments. Exposure to movie smoking may affect urge to smoke among adult smokers. PMID:19542516

  4. Working Memory Moderates the Association Between Smoking Urge and Smoking Lapse Behavior After Alcohol Administration in a Laboratory Analogue Task

    PubMed Central

    Kahler, Christopher W.; Metrik, Jane; Spillane, Nichea S.; Tidey, Jennifer W.; Rohsenow, Damaris J.

    2015-01-01

    Introduction: Lapses after smoking cessation often occur in the context of alcohol use, possibly because alcohol increases urge to smoke. Poor working memory, or alcohol-induced decrements in working memory, may influence this relationship by making it more difficult for an individual to resist smoking in the face of smoking urges. Methods: Participants (n = 41) completed measures of working memory and urge to smoke before and after alcohol administration (placebo, 0.4g/kg, and 0.8g/kg, within subjects) and then participated in a laboratory analogue task in which smoking abstinence was monetarily incentivized. Results: Working memory moderated the relationship between smoking urge and latency to smoke: for those with relatively poorer working memory, urge to smoke was more strongly and negatively associated with latency to smoke (i.e., higher urges were associated with shorter latency). Conclusions: Those with weak working memory may need additional forms of treatment to help them withstand smoking urges. PMID:25481913

  5. Classifying smoking urges via machine learning.

    PubMed

    Dumortier, Antoine; Beckjord, Ellen; Shiffman, Saul; Sejdić, Ervin

    2016-12-01

    Smoking is the largest preventable cause of death and diseases in the developed world, and advances in modern electronics and machine learning can help us deliver real-time intervention to smokers in novel ways. In this paper, we examine different machine learning approaches to use situational features associated with having or not having urges to smoke during a quit attempt in order to accurately classify high-urge states. To test our machine learning approaches, specifically, Bayes, discriminant analysis and decision tree learning methods, we used a dataset collected from over 300 participants who had initiated a quit attempt. The three classification approaches are evaluated observing sensitivity, specificity, accuracy and precision. The outcome of the analysis showed that algorithms based on feature selection make it possible to obtain high classification rates with only a few features selected from the entire dataset. The classification tree method outperformed the naive Bayes and discriminant analysis methods, with an accuracy of the classifications up to 86%. These numbers suggest that machine learning may be a suitable approach to deal with smoking cessation matters, and to predict smoking urges, outlining a potential use for mobile health applications. In conclusion, machine learning classifiers can help identify smoking situations, and the search for the best features and classifier parameters significantly improves the algorithms' performance. In addition, this study also supports the usefulness of new technologies in improving the effect of smoking cessation interventions, the management of time and patients by therapists, and thus the optimization of available health care resources. Future studies should focus on providing more adaptive and personalized support to people who really need it, in a minimum amount of time by developing novel expert systems capable of delivering real-time interventions. Copyright © 2016 Elsevier Ireland Ltd. All rights

  6. Alcohol Consumption and Urges to Smoke among Women during a Smoking Cessation Attempt

    PubMed Central

    Businelle, Michael S.; Lam, Cho Y.; Kendzor, Darla E.; Cofta-Woerpel, Ludmila; McClure, Jennifer B.; Cinciripini, Paul M.; Wetter, David W.

    2013-01-01

    Laboratory and ad libitum smoking studies have indicated that alcohol consumption increases the frequency and intensity of smoking urges. However, few studies have examined the relation between smoking urges and alcohol use in natural settings during a quit attempt. The purpose of this study was to examine the relationships between smoking urge and alcohol use in women who reported drinking on at least one occasion during the first 7 days of a smoking quit attempt (N = 134). Participants were asked to use a palmtop computer to complete assessments that recorded smoking urges and recent alcohol use. Multilevel analyses examined the relation between smoking urge parameters and alcohol use. Smoking urges were higher during assessments where alcohol had been recently consumed compared to assessments where no alcohol had been consumed. Interestingly, the first urge rating of the day was higher and urges were more volatile on days where alcohol would eventually be consumed as compared to days where no alcohol was consumed. A closer examination of urge parameters on drinking days indicated that smoking urge trajectory was significantly flatter and urge volatility was significantly higher following alcohol consumption. However, smoking urge trajectory also flattened later in the day on nondrinking days. The findings suggest that there may be reciprocal relations between smoking urge and alcohol use (e.g., higher initial urges and more volatile urges may increase the likelihood of alcohol use; and, alcohol use may impact within day smoking urge parameters), and these relations could potentially impact smoking cessation and relapse. PMID:23379613

  7. Movie Smoking, Movie Horror, and Urge to Smoke

    PubMed Central

    SARGENT, James D.; MARUSKA, Karin; MORGENSTERN, Matthis; ISENSEE, Barbara; HANEWINKEL, Reiner

    2010-01-01

    It is known that exposure to smoking cues increases urge to smoke (UTS), but little is known about other media factors that might also increase UTS. We hypothesized that horror/thriller movies might also increase UTS by increasing negative affect. We surveyed 536 movie patrons who were smokers aged 18 years or older. Subjects had exited 26 movies, of which 12 contained smoking and two were horror films, one with and one without smoking. We used random effects regression to assess the association between exposure to movie smoking, movie horror, both and UTS, controlling for confounding factors. Median age was 26 years and 52% were female. Mean UTS was 5.9, 6.6, 6.6, and 8.7 for smokers exiting movies without smoking, with smoking, horror without smoking and horror with smoking respectively. Smoking in movies was associated with a significantly higher UTS (0.63 [95% CI 0.31–0.94]). Horror with smoking increased UTS by 2.8 points (95% C.I. 2.3, 3.5); the horror without smoking estimate was 0.88, but not statistically significant. This short report offers preliminary evidence that movie horror as one factor besides visual smoking cues that could increase UTS in a community setting. PMID:20301876

  8. Movie smoking, movie horror, and urge to smoke.

    PubMed

    Sargent, James D; Maruska, Karin; Morgenstern, Matthis; Isensee, Barbara; Hanewinkel, Reiner

    2009-01-01

    It is known that exposure to smoking cues increases urge to smoke (UTS), but little is known about other media factors that might also increase UTS. We hypothesized that horror/ thriller movies might also increase UTS by increasing negative affect. We surveyed 536 movie patrons who were smokers aged 18 years or older. Subjects had exited 26 movies, of which 12 contained smoking and two were horrorfilms, one with and one without smoking. We used random effects regression to assess the association between exposure to movie smoking, movie horror, both and UTS, controlling for confounding factors. Median age was 26 years and 52% were female. Mean UTS was 5.9, 6.6, 6.6, and 8.7 for smokers exiting movies without smoking, with smoking, horror without smoking and horror with smoking respectively. Smoking in movies was associated with a significantly higher UTS (0.63 [95% CI 0.31-0.94]). Horror with smoking increased UTS by 2.8 points (95% C.I. 2.3, 3.5); the horror without smoking estimate was 0.88, but not statistically significant. This short report offers preliminary evidence that movie horror as one factor besides visual smoking cues that could increase UTS in a community setting.

  9. Relations Among Caffeine Consumption, Smoking, Smoking Urge, and Subjective Smoking Reinforcement in Daily Life.

    PubMed

    Treloar, Hayley R; Piasecki, Thomas M; McCarthy, Danielle E; Baker, Timothy B

    2014-09-01

    Caffeine consumption and cigarette smoking tend to occur within the same individuals and at the same time. One potential explanation for this co-use is that caffeine consumption increases subjective smoking reinforcement. Electronic diaries were used to collect momentary reports of smoking, caffeine consumption, temptation/urge to smoke, and subjective smoking reinforcement in 74 prequit smokers. Momentary reports of caffeine consumption and smoking were associated, replicating previous findings. These results remained significant when contextual factors (time of day, weekday/weekend, presence of others, presence of others smoking, location, and past hour alcohol consumption) were covaried. Caffeine consumption was also associated with positive cigarette appraisals and reports of strong temptation/urge to smoke and urge reduction from the prior cigarette. Under the conditions of caffeine consumption versus at other times, smokers were significantly more likely to report their last cigarette as producing a rush/buzz, being pleasant, relaxing, and tasting good. The effects for temptation/urge to smoke and rush/buzz varied as a function of latency since smoking. Caffeine consumption increased reports of urge to smoke and rush/buzz only when smoking occurred more than 15 minutes prior to the diary entry. Findings suggest that caffeine consumption influences some aspects of smoking motivation or affects memorial processing of smoking reinforcement.

  10. Watching Others 'Vape' May Trigger Urge to Smoke

    MedlinePlus

    ... Vape' May Trigger Urge to Smoke Newer e-cigarettes boost same impulses as real cigarettes, researcher says To use the sharing features on ... 13, 2017 (HealthDay News) -- A type of e-cigarette called a vape pen can trigger the urge ...

  11. The effect of smoking cues in antismoking advertisements on smoking urge and psychophysiological reactions.

    PubMed

    Kang, Yahui; Cappella, Joseph N; Strasser, Andrew A; Lerman, Caryn

    2009-03-01

    Studies have found that smoking-related cues elicit smoking urges in addicted smokers. This work presents the first cue-reactivity study in the context of antismoking advertisements. Using a two (no cue vs. smoking cue) by two (high vs. low argument strength) mixed design, we tested the hypothesis that smoking cues presented in antismoking advertisements elicit smoking urges. The study tested 96 adult smokers using both self-reported and psychophysiological measures of smoking urge. It also explored gender differences during the urge elicitation. Smoking cues in antismoking advertisements elicited smoking urges in the weak argument condition. Antismoking advertisements with smoking cues and weak antismoking arguments could produce boomerang effects on smokers through urge elicitation.

  12. Revisiting the Factor Structure of the Questionnaire on Smoking Urges

    ERIC Educational Resources Information Center

    Toll, Benjamin A.; McKee, Sherry A.; Krishnan-Sarin, Suchitra; O'Malley, Stephanie S.

    2004-01-01

    This study assessed the factor structure of the Questionnaire on Smoking Urges (QSU), a commonly used assessment of cravings for cigarettes, with a sample of smokers presenting for treatment in a smoking cessation trial. On the basis of previous research, three confirmatory factor analytic models were tested. Model 1 hypothesized a 26-item,…

  13. Length of smoking deprivation moderates the effects of alcohol administration on urge to smoke

    PubMed Central

    Day, Anne M.; Kahler, Christopher W.; Spillane, Nichea S.; Metrik, Jane; Rohsenow, Damaris J.

    2014-01-01

    Although smoking deprivation is often used in laboratory studies to induce urges to smoke cigarettes, the optimal length of deprivation has not been established. Previous research showed that overnight abstinence from cigarettes led to high baseline urge to smoke that potentially masked alcohol’s acute effects on urge to smoke (Kahler et al., 2012). The current study examined whether alcohol’s effects on smoking urge were more pronounced when a shorter length of smoking deprivation was used (i.e., 3 hour instead of overnight abstinence). Using a balanced placebo design for alcohol administration, we found that participants experienced a significant increase in self-reported urge to smoke when administered alcohol after a 3-hour smoking deprivation (N=32), whereas this effect was smaller and nonsignificant when smokers were required to be abstinent overnight (N = 96). Research on factors that heighten smoking urges may find stronger effects if a 3-hour deprivation is used compared to using overnight abstinence. PMID:24556154

  14. Do individual differences in reinforcement smoking moderate the relationship between affect and urge to smoke?

    PubMed

    Leventhal, Adam M

    2010-01-01

    The elucidation of individual differences in tobacco use motivation is of considerable interest. Accordingly, the present study tested the hypothesis that between-person variation in reinforcement smoking (RS)--a tendency to smoke to regulate affect--moderates the relationship between poor mood and urge to smoke. In this cross-sectional, correlational study, smokers (N = 212; > or =5 cig/day) completed measures of RS, positive affect (PA), negative affect (NA), and smoking urge. RS significantly moderated the relation between PA and urge (betas > .11, ps < .04), such that the inverse correlation between PA and urge was stronger among smokers higher in RS. NA was positively correlated with urge in the overall sample (rs = .34, ps < .0001), but RS did not moderate this relationship. The overall results were consistent across 2 measures of mood and adjusted models that controlled for demographics and smoking characteristics. Continued investigation of these moderational pathways could identify which smokers may benefit most from treatments that target mood during smoking cessation.

  15. Individual and Combined Effects of Multiple High-Risk Triggers on Postcessation Smoking Urge and Lapse

    PubMed Central

    2014-01-01

    Introduction: Negative affect, alcohol consumption, and presence of others smoking have consistently been implicated as risk factors for smoking lapse and relapse. What is not known, however, is how these factors work together to affect smoking outcomes. This paper uses ecological momentary assessment (EMA) collected during the first 7 days of a smoking cessation attempt to test the individual and combined effects of high-risk triggers on smoking urge and lapse. Methods: Participants were 300 female smokers who enrolled in a study that tested an individually tailored smoking cessation treatment. Participants completed EMA, which recorded negative affect, alcohol consumption, presence of others smoking, smoking urge, and smoking lapse, for 7 days starting on their quit date. Results: Alcohol consumption, presence of others smoking, and negative affect were, independently and in combination, associated with increase in smoking urge and lapse. The results also found that the relationship between presence of others smoking and lapse and the relationship between negative affect and lapse were moderated by smoking urge. Conclusions: The current study found significant individual effects of alcohol consumption, presence of other smoking, and negative affect on smoking urge and lapse. Combing the triggers increased smoking urge and the risk for lapse to varying degrees, and the presence of all 3 triggers resulted in the highest urge and lapse risk. PMID:24323569

  16. Effects of Smoking Opportunity on Cue-Elicited Urge

    PubMed Central

    Sayette, Michael A.; Wertz, Joan M.; Martin, Christopher S.; Cohn, Jeffrey F.; Perrott, Michael A.; Hobel, Jill

    2009-01-01

    The authors analyzed smokers’ facial expressions using the Facial Action Coding System (P. Ekman & W. V. Friesen, 1978) under varying smoking opportunity conditions. In Experiment 1, smokers first were told that they either could (told-yes) or could not (told-no) smoke during the study. Told-yes smokers reported higher urges than did told-no smokers. Unexpectedly, told-yes smokers became increasingly likely to manifest expressions related to negative affect and less likely to evince expressions related to positive affect, compared with told-no smokers. In Experiment 2, smokers were more likely to show positive affect-related expressions if the delay was 15 s than if it was 60 s. Craving may be related to both a desire to use and an impatient desire to use immediately. PMID:12940501

  17. Craving, withdrawal, and smoking urges on days immediately prior to smoking relapse.

    PubMed

    Allen, Sharon S; Bade, Tracy; Hatsukami, Dorothy; Center, Bruce

    2008-01-01

    Rates of smoking relapse remain high, despite the wide availability of cessation aids. Presumably factors such as craving, withdrawal symptoms, and smoking urges are key contributors to relapse, but empirical support for this presumption is not conclusive and is complicated by the high variability in symptoms across individuals and time, as well as by the lack of an absolute symptom threshold for response. Data were analyzed from 137 female smokers, aged 18-40 years, who completed 30 days of a protocol for a longitudinal smoking cessation trial. Subjects were assigned a quit date and followed regardless of subsequent smoking status. At baseline, subjects completed written measures of nicotine craving, withdrawal symptoms, and smoking urges. They also completed these measures daily for 30 days, beginning on their quit date, Scores were standardized within subjects and graphed to identify temporal symptom patterns. A total of 26 women quit smoking and 111 relapsed (at least one cigarette puff). The intensity of subjects' craving, withdrawal, and smoking urges Factors 1 and 2 peaked on the day of relapse by an average of 1.4, 1.1, 1.2, and 1.1 standard deviations, respectively, with symptoms rising during the previous 2-5 days and dropping precipitously over the 2 days subsequent to relapse. Additionally, women who relapsed had higher absolute (unstandardized) symptom scores on their quit day than those who were abstinent for 30 days. These findings imply that escalation of withdrawal symptoms, craving, and smoking urges during a quit attempt may contribute to smoking relapse. Frequent symptom monitoring might be clinically important for relapse prevention.

  18. Positive and negative affect as predictors of urge to smoke: temporal factors and mediational pathways.

    PubMed

    Leventhal, Adam M; Greenberg, Jodie B; Trujillo, Michael A; Ameringer, Katherine J; Lisha, Nadra E; Pang, Raina D; Monterosso, John

    2013-03-01

    Elucidating interrelations between prior affective experience, current affective state, and acute urge to smoke could inform affective models of addiction motivation and smoking cessation treatment development. This study tested the hypothesis that prior levels of positive (PA) and negative (NA) affect predict current smoking urge via a mediational pathway involving current state affect. We also explored if tobacco deprivation moderated affect-urge relations and compared the effects of PA and NA on smoking urge to one another. At a baseline session, smokers reported affect experienced over the preceding few weeks. At a subsequent experimental session, participants were randomly assigned to 12-hr tobacco deprived (n = 51) or nondeprived (n = 69) conditions and reported state affect and current urge. Results revealed a mediational pathway whereby prior NA reported at baseline predicted state NA at the experimental session, which in turn predicted current urge. This mediational pathway was found primarily for an urge subtype indicative of urgent need to smoke and desire to smoke for NA relief, was stronger in the deprived (vs. nondeprived) condition, and remained significant after controlling for PA. Prior PA and current state PA were inversely associated with current urge; however, these associations were eliminated after controlling for NA. These results cohere with negative reinforcement models of addiction and with prior research and suggest that: (a) NA plays a stronger role in smoking motivation than PA; (b) state affect is an important mechanism linking prior affective experience to current urge; and (c) affect management interventions may attenuate smoking urge in individuals with a history of affective disturbance.

  19. Exposure to electronic nicotine delivery systems (ENDS) visual imagery increases smoking urge and desire.

    PubMed

    King, Andrea C; Smith, Lia J; Fridberg, Daniel J; Matthews, Alicia K; McNamara, Patrick J; Cao, Dingcai

    2016-02-01

    Use and awareness of electronic nicotine delivery systems (ENDS; also known as electronic cigarettes or e-cigarettes) has increased rapidly in recent years, particularly among young adults. As use of ENDS resembles traditional smoking in both hand-to-mouth movements and inhalation and exhalation behaviors, we determined whether exposure to e-cigarette use via video exposure would act as a cue to elicit urge and desire for a combustible cigarette. Young adult smokers (mean age of 26.3 ± 4.1 years) were randomized to view a brief video montage of advertisements depicting either e-cigarette vaping (n = 38) or bottled water drinking (n = 40). Pre- and postcue exposure assessments were conducted in a controlled laboratory setting without other smoking or vaping cues present or behaviors allowed. Primary outcomes included change from pre-exposure baseline in smoking urge (Brief Questionnaire of Smoking Urges) and desire for a combustible and e-cigarette (visual analogue scales). Results showed that relative to exposure to the bottled water video, exposure to the ENDS video significantly increased smoking urge (p < .001) as well as desire for a regular cigarette (p < .05) and an e-cigarette (p < .001). These findings provide preliminary evidence that passive exposure to video imagery of ENDS use may generalize as a condition cue and evoke urges for a combustible cigarette in young adult smokers. It remains to be determined whether such increases in urge and desire correspond to increases in actual smoking behavior.

  20. Distinct coping strategies differentially predict urge levels and lapses in a smoking cessation attempt.

    PubMed

    Brodbeck, Jeannette; Bachmann, Monica S; Znoj, Hansjörg

    2013-06-01

    This study analysed mechanisms through which stress-coping and temptation-coping strategies were associated with lapses. Furthermore, we explored whether distinct coping strategies differentially predicted reduced lapse risk, lower urge levels, or a weaker association between urge levels and lapses during the first week of an unassisted smoking cessation attempt. Participants were recruited via the internet and mass media in Switzerland. Ecological momentary assessment (EMA) with mobile devices was used to assess urge levels and lapses. Online questionnaires were used to measure smoking behaviours and coping variables at baseline, as well as smoking behaviour at the three-month follow-up. The sample consisted of 243 individuals, aged 20 to 40, who reported 4199 observations. Findings of multilevel regression analyses show that coping was mainly associated with a reduced lapse risk and not with lower urge levels or a weaker association between urge levels and lapses. 'Calming down' and 'commitment to change' predicted a lower lapse risk and also a weaker relation between urge levels and lapses. 'Stimulus control' predicted a lower lapse risk and lower urge levels. Conversely, 'task-orientation' and 'risk assessment' were related to higher lapse risk and 'risk assessment' also to higher urge levels. Disengagement coping i.e. 'eating or shopping', 'distraction', and 'mobilising social support' did not affect lapse risk. Promising coping strategies during the initial stage of smoking cessation attempt are targeted directly at reducing the lapse risk and are characterised by engagement with the stressor or one's reactions towards the stressor and a focus on positive consequences instead of health risks.

  1. Dopamine, urges to smoke, and the relative salience of drug versus non-drug reward

    PubMed Central

    Das, Ravi K.; Kamboj, Sunjeev K.; Curran, H. Valerie

    2015-01-01

    When addicted individuals are exposed to drug-related stimuli, dopamine release is thought to mediate incentive salience attribution, increasing attentional bias, craving and drug seeking. It is unclear whether dopamine acts specifically on drug cues versus other rewards, and if these effects correspond with craving and other forms of cognitive bias. Here, we administered the dopamine D2/D3 agonist pramipexole (0.5 mg) to 16 tobacco smokers in a double-blind placebo-controlled crossover design. Visual fixations on smoking and money images were recorded alongside smoking urges and fluency tasks. Pramipexole attenuated a marked bias in initial orienting towards smoking relative to money but did not alter a maintained attentional bias towards smoking. Pramipexole decreased urges to smoke retrospectively after the task but not on a state scale. Fewer smoking words were generated after pramipexole but phonological and semantic fluency were preserved. Although these treatment effects did not correlate with each other, changes in initial orienting towards smoking and money were inversely related to baseline scores. In conclusion, pramipexole can reduce the salience of an addictive drug compared with other rewards and elicit corresponding changes in smoking urges and cognitive bias. These reward-specific and baseline-dependent effects support an ‘inverted-U’ shaped profile of dopamine in addiction. PMID:24526184

  2. Peer Pressure, Psychological Distress and the Urge to Smoke

    PubMed Central

    Tsai, Yi-Wen; Wen, Yu-Wen; Tsai, Chia-Rung; Tsai, Tzu-I

    2009-01-01

    Background: Psychology and addiction research have found that cigarette smokers react with subjective and automatic responses to stimuli associated with smoking. This study examines the association between the number of cigarettes smokers consume per month and their response to cues derived from peer and psychological distress. Methods: We studied 1,220 adult past and current smokers drawn from a national face-to-face interview survey administered in 2004. We defined two types of cues possibly triggering a smoker to have a cigarette: peer cues and psychological cues. We used ordinary least square linear regressions to analyze smoking amount and response to peer and psychological distress cues. Results: We found a positive association between amount smoked and cue response: peer cues (1.06, 95%CI: 0.74–1.38) and psychological cues (0.44, 95%CI = 0.17–0.70). Response to psychological cues was lower among male smokers (−1.62, 95%CI = −2.26–−0.98), but response to psychological cues were higher among those who had senior high school level educations (0.96, 95%CI = 0.40–1.53) and who began smoking as a response to their moods (1.25, 95%CI = 0.68–1.82). Conclusions: These results suggest that both peer cues and psychological cues increase the possibility of contingent smoking, and should, therefore, be addressed by anti-smoking policies and anti-smoking programs. More specifically, special attention can be paid to help smokers avoid or counter social pressure to smoke and to help smokers resist the use of cigarettes to relieve distress. PMID:19578461

  3. Peer pressure, psychological distress and the urge to smoke.

    PubMed

    Tsai, Yi-Wen; Wen, Yu-Wen; Tsai, Chia-Rung; Tsai, Tzu-I

    2009-06-01

    Psychology and addiction research have found that cigarette smokers react with subjective and automatic responses to stimuli associated with smoking. This study examines the association between the number of cigarettes smokers consume per month and their response to cues derived from peer and psychological distress. We studied 1,220 adult past and current smokers drawn from a national face-to-face interview survey administered in 2004. We defined two types of cues possibly triggering a smoker to have a cigarette: peer cues and psychological cues. We used ordinary least square linear regressions to analyze smoking amount and response to peer and psychological distress cues. We found a positive association between amount smoked and cue response: peer cues (1.06, 95%CI: 0.74-1.38) and psychological cues (0.44, 95%CI = 0.17-0.70). Response to psychological cues was lower among male smokers (-1.62, 95%CI = -2.26-(-)0.98), but response to psychological cues were higher among those who had senior high school level education (0.96, 95%CI = 0.40-1.53) and who began smoking as a response to their moods (1.25, 95%CI = 0.68-1.82). These results suggest that both peer cues and psychological cues increase the possibility of contingent smoking, and should, therefore, be addressed by anti-smoking policies and anti-smoking programs. More specifically, special attention can be paid to help smokers avoid or counter social pressure to smoke and to help smokers resist the use of cigarettes to relieve distress.

  4. Effect of brief exercise on urges to smoke in men and women smokers.

    PubMed

    Allen, Alicia M; Abdelwahab, Nermine M; Carlson, Samantha; Bosch, Tyler A; Eberly, Lynn E; Okuyemi, Kola

    2017-09-20

    Although smoking urges have been demonstrated to vary by gender and also be influenced by exercise, it is unknown if exercise has a differential effect on smoking urges by gender. This study aimed to explore gender-specific effects of an acute bout of exercise on cessation-related symptoms in men and women smokers during acute abstinence. We enrolled smokers (≥5 cigarettes/day) who were 18-40years old for a study on exercise and smoking behavior. Participants abstained from smoking for at least 3h, prior to measurement of their maximal oxygen consumption tested, which was the acute bout of exercise. Prior to and after the exercise, participants completed the Questionnaire of Smoking Urges - Brief and the Minnesota Nicotine Withdrawal Scale. Participants (n=38; 61% women) were, on average, 30.0±0.9years old and smoked 13.0±0.8 cigarettes/day. All measured aspects of cessation-related symptoms significantly improved after the exercise in both men and women. In women there was a significant decline in anticipated relief from negative affect after the exercise (women: -0.45±0.20, p=0.0322; men: -0.41±0.26, p=0.1312). In men there was a significant decline in the intention to smoke after the exercise (men: -0.77±0.23, p=0.0053; women: -0.66±0.37, p=0.0909). An acute bout of exercise reduced smoking urges in both men and women smokers during an acute state of abstinence. Additional research is needed to replicate these observations in a larger, more diverse sample, and to explore the implication of these observations on cessation. Copyright © 2017. Published by Elsevier Ltd.

  5. Naltrexone Improves Quit Rates, Attenuates Smoking Urge, and Reduces Alcohol Use in Heavy Drinking Smokers Attempting to Quit Smoking

    PubMed Central

    Fridberg, Daniel J.; Cao, Dingcai; Grant, Jon E.; King, Andrea C.

    2015-01-01

    Background Heavy drinking smokers (HDS) have more difficulty quitting smoking than lighter drinkers or abstainers. The opioid antagonist naltrexone may improve smoking quit rates and reduce alcohol use in drinker–smokers, but its relative efficacy in smokers with a range of drinking patterns is unknown. The current study tested the hypothesis that HDS would show differential benefit of naltrexone versus placebo relative to moderate-to-light or nondrinking smokers in terms of improving smoking outcomes and reducing alcohol consumption. Methods Adult smokers (N = 315) enrolled in a 12-week, double-blinded, placebo-controlled trial of 50 mg naltrexone for smoking cessation were categorized into subgroups based upon past 6-month drinking patterns: HDS (n = 69; i.e., averaged ≥2 heavy drinking episodes per month), moderate-to-light drinking smokers (n = 204, i.e., consumed 1 drink up to a maximum of <2 heavy drinking episodes per month on average), or nondrinking smokers (n = 42, no alcohol consumed in the past 6 months). The groups were compared on the main study outcomes of biochemically verified prolonged abstinence quit rates (i.e., no smoking weeks 2 to 12), and smoking urge and alcohol use (drinks/wk) during treatment. Results Naltrexone significantly increased 12-week smoking abstinence rates and decreased smoking urge and alcohol use among HDS, but not moderate-to-light or nondrinking smokers. Mediation analyses in HDS revealed that naltrexone’s effect on smoking urge during the first 4 weeks of treatment mediated its effect on quit rates. Conclusions HDS appear to be particularly sensitive to naltrexone effects on smoking and drinking outcomes. This group may represent an important target for adjunctive treatment with naltrexone to optimize smoking cessation outcomes. PMID:25335648

  6. Long-term treatment with aripiprazole on the waking and postprandial urges to smoke in Chinese heavy smokers.

    PubMed

    Liu, Yu; Bao, Yan-ping; Sun, Hong-qiang; Beveridge, Thomas J R; Li, Su-xia; Di, Xiao-lan; Yang, Fu-de; Lu, Lin

    2010-08-01

    The central dopaminergic system plays a critical role in the reinforcing effects of nicotine, which are key determinants in the urge to smoke. Previous study has demonstrated that immediate administration of 10-mg aripiprazole significantly decreased various subjective responses to smoking. The present study investigated whether 2-week treatment with 10-mg aripiprazole could attenuate waking and postprandial urges to smoke in Chinese male and female heavy smokers. A randomized and placebo-controlled pilot clinical study was conducted to assess the effect of aripiprazole on various responses to smoking. The primary outcomes were subject's ratings on questionnaires of smoking urge, withdrawal syndromes, and cigarette evaluation. All participants were administered either placebo or 10-mg aripiprazole for 2 weeks. Throughout the experiment, participants were required to self-report (1) smoking urge and nicotine withdrawal symptoms before their first cigarette after awakening and after lunch and (2) subjective responses to the first cigarette smoked of the day and after lunch. Aripiprazole was associated with significantly decreased waking and postprandial urges to smoke. Aripiprazole failed to produce a significant effect on overall nicotine withdrawal symptoms after awakening and after lunch. However, waking, but not postprandial, withdrawal craving and syndromes were significantly reduced by aripiprazole. Aripiprazole had no effect on the overall subjective responses to the first cigarette of the day and after lunch. The attenuating effects of aripiprazole on waking and postprandial urges to smoke demonstrate the promising effect of aripiprazole in the treatment of nicotine dependence.

  7. Effects of nicotine mouth spray on urges to smoke, a randomised clinical trial.

    PubMed

    Hansson, Anna; Hajek, Peter; Perfekt, Roland; Kraiczi, Holger

    2012-01-01

    A new nicotine mouth spray was shown to be an effective stop-smoking treatment. This study was set up to examine the speed with which it relieves urges to smoke, and how it compares with nicotine lozenge in this respect. Randomised, cross-over trial that compared nicotine mouth spray 2 mg versus nicotine lozenge 2 or 4 mg. Clinical pharmacology research unit. 200 Volunteer smokers who smoked their first cigarette of the day within 30 min of waking. Subjects abstained from smoking the night before the morning they attended the laboratory. Treatment was administered following 5 h of witnessed abstinence. Urge to smoke was rated before and at 1, 3, 5, 10, 15, 25, 30, 45 min and 1, 1.5, and 2 h after treatment administration. The primary outcome concerned change during the first 1, 3 and 5 min after treatment administration. Nicotine mouth spray achieved greater reductions in craving than either lozenge during the first 1, 3 and 5 min postadministration. After using mouth spray, half of the users experienced 50% reduction in craving within 3.40 min, while the same treatment effect was achieved within 9.92 and 9.20 min for the 2 and 4 mg lozenge, respectively. Adverse events with both mouth spray and lozenge were mostly mild. Hiccups, local irritation, nausea and dyspepsia were more frequent with spray than lozenge. Nicotine mouth spray provides a faster relief of cravings than nicotine lozenge.

  8. A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.

    PubMed

    Jensen, K P; Smith, A H; Herman, A I; Farrer, L A; Kranzler, H R; Sofuoglu, M; Gelernter, J

    2017-02-01

    Nicotine withdrawal symptoms contribute to relapse in smokers, thereby prolonging the harm caused by smoking. To investigate the molecular basis for this phenomenon, we conducted a genome-wide association study of DSM-IV nicotine withdrawal in a sample of African American (AA) and European American (EA) smokers. A combined AA and EA meta-analysis (n=8021) identified three highly correlated single nucleotide polymorphisms (SNPs) in the protocadherin (PCDH)-α, -β and -γ gene cluster on chromosome 5 that were associated with nicotine withdrawal (P<5 × 10(-8)). We then studied one of the SNPs, rs31746, in an independent sample of smokers who participated in an intravenous nicotine infusion study that followed overnight smoking abstinence. After nicotine infusion, abstinent smokers with the withdrawal risk allele experienced greater alleviation of their urges to smoke, as assessed by the Brief Questionnaire on Smoking Urges (BQSU). Prior work has shown that the PCDH-α, -β and -γ genes are expressed in neurons in a highly organized manner. We found that rs31746 mapped to a long-range neuron-specific enhancer element shown previously to regulate PCDH-α, -β and -γ gene expression. Using Braincloud mRNA expression data, we identified a robust and specific association between rs31746 and PCDH-β8 mRNA expression in frontal cortex tissue (P<1 × 10(-5)). We conclude that PCDH-α, -β and -γ gene cluster regulatory variation influences the severity of nicotine withdrawal. Further studies on the PCDH-α, -β and -γ genes and their role in nicotine withdrawal may inform the development of novel smoking cessation treatments and reduce the harm caused by tobacco smoking.

  9. Effects of nicotine mouth spray on urges to smoke, a randomised clinical trial

    PubMed Central

    Hansson, Anna; Hajek, Peter; Perfekt, Roland; Kraiczi, Holger

    2012-01-01

    Objective A new nicotine mouth spray was shown to be an effective stop-smoking treatment. This study was set up to examine the speed with which it relieves urges to smoke, and how it compares with nicotine lozenge in this respect. Design Randomised, cross-over trial that compared nicotine mouth spray 2 mg versus nicotine lozenge 2 or 4 mg. Setting Clinical pharmacology research unit. Participants 200 Volunteer smokers who smoked their first cigarette of the day within 30 min of waking. Interventions Subjects abstained from smoking the night before the morning they attended the laboratory. Treatment was administered following 5 h of witnessed abstinence. Primary and secondary outcome measures Urge to smoke was rated before and at 1, 3, 5, 10, 15, 25, 30, 45 min and 1, 1.5, and 2 h after treatment administration. The primary outcome concerned change during the first 1, 3 and 5 min after treatment administration. Results Nicotine mouth spray achieved greater reductions in craving than either lozenge during the first 1, 3 and 5 min postadministration. After using mouth spray, half of the users experienced 50% reduction in craving within 3.40 min, while the same treatment effect was achieved within 9.92 and 9.20 min for the 2 and 4 mg lozenge, respectively. Adverse events with both mouth spray and lozenge were mostly mild. Hiccups, local irritation, nausea and dyspepsia were more frequent with spray than lozenge. Conclusions Nicotine mouth spray provides a faster relief of cravings than nicotine lozenge. PMID:23015605

  10. First- versus second-generation electronic cigarettes: predictors of choice and effects on urge to smoke and withdrawal symptoms.

    PubMed

    Dawkins, Lynne; Kimber, Catherine; Puwanesarasa, Yasothani; Soar, Kirstie

    2015-04-01

    To (1) estimate predictors of first- versus second-generation electronic cigarette (e-cigarette) choice; and (2) determine whether a second-generation device was (i) superior for reducing urge to smoke and withdrawal symptoms (WS) and (ii) associated with enhanced positive subjective effects. Mixed-effects experimental design. Phase 1: reason for e-cigarette choice was assessed via questionnaire. Phase 2: participants were allocated randomly to first- or second-generation e-cigarette condition. Urge to smoke and WS were measured before and 10 minutes after taking 10 e-cigarette puffs. University of East London, UK. A total of 97 smokers (mean age 26; standard deviation 8.7; 54% female). Single-item urge to smoke scale to assess craving and the Mood and Physical Symptoms Scale (MPSS) to assess WS. Subjective effects included: satisfaction, hit, 'felt like smoking' and 'would use to stop smoking' (yes versus no response). Equal numbers chose each device, but none of the predictor variables (gender, age, tobacco dependence, previous e-cigarette use) accounted for choice. Only baseline urge to smoke/WS predicted urge to smoke/WS 10 minutes after use (B =0.38; P <0.001 and B =0.53; P <0.001). E-cigarette device was not a significant predictor. Those using the second-generation device were more likely to report satisfaction and use in a quit attempt (χ(2)  = 12.10, P =0.001 and χ(2)  = 5.53, P =0.02). First- and second-generation electronic cigarettes appear to be similarly effective in reducing urges to smoke during abstinence, but second-generation devices appear to be more satisfying to users. © 2014 Society for the Study of Addiction.

  11. Does Vaping in E-Cigarette Advertisements Affect Tobacco Smoking Urge, Intentions, and Perceptions in Daily, Intermittent, and Former Smokers?

    PubMed

    Maloney, Erin K; Cappella, Joseph N

    2016-01-01

    Visual depictions of vaping in electronic cigarette advertisements may serve as smoking cues to smokers and former smokers, increasing urge to smoke and smoking behavior, and decreasing self-efficacy, attitudes, and intentions to quit or abstain. After assessing baseline urge to smoke, 301 daily smokers, 272 intermittent smokers, and 311 former smokers were randomly assigned to view three e-cigarette commercials with vaping visuals (the cue condition) or without vaping visuals (the no-cue condition), or to answer unrelated media use questions (the no-ad condition). Participants then answered a posttest questionnaire assessing the outcome variables of interest. Relative to other conditions, in the cue condition, daily smokers reported greater urge to smoke a tobacco cigarette and a marginally significantly greater incidence of actually smoking a tobacco cigarette during the experiment. Former smokers in the cue condition reported lower intentions to abstain from smoking than former smokers in other conditions. No significant differences emerged among intermittent smokers across conditions. These data suggest that visual depictions of vaping in e-cigarette commercials increase daily smokers' urge to smoke cigarettes and may lead to more actual smoking behavior. For former smokers, these cues in advertising may undermine abstinence efforts. Intermittent smokers did not appear to be reactive to these cues. A lack of significant differences between participants in the no-cue and no-ad conditions compared to the cue condition suggests that visual depictions of e-cigarettes and vaping function as smoking cues, and cue reactivity is the mechanism through which these effects were obtained.

  12. Differential effects of a body image exposure session on smoking urge between physically active and sedentary female smokers.

    PubMed

    Nair, Uma S; Collins, Bradley N; Napolitano, Melissa A

    2013-03-01

    Smoking is often used as a maladaptive weight control strategy among female smokers. Many of the perceived benefits accrued from smoking, including enhanced mood, reduced anxiety, and weight control, can also be achieved through physical activity. The purpose of this study was to examine the effects of a novel behavioral task (body-image exposure) that was designed to elicit body image and weight concerns on urge to smoke among 18-24 year old female smokers who vary in levels of physical activity. Using a cue-reactivity paradigm, 16 sedentary (SE) and 21 physically active (PA) female smokers (≥5 cigarettes/day for past 6 months) were exposed to a pilot tested body-image exposure session. Self-reported urge and latency to first puff were obtained before and after exposure session. Paired sample t tests showed significant increases in self-reported urge (p < .01) and quicker latency to first puff (p < .01) at posttest for the entire sample compared with pretest. Results of partial correlation (controlling for body mass index [BMI], nicotine dependence, withdrawal, and depressive symptoms) showed that increased time engaging in vigorous intensity physical activity was associated with lower self-reported urge to smoke at post (r = -0.44; p = .01) but not with latency to first puff (r = -.10; p = .62). These results suggest that among weight-concerned female smokers, physical activity may attenuate smoking urges in a context where weight concerns are increased. Future research should continue to explore effects of physical activity on reactivity to body image and smoking cues and variability in smoking cue-reactivity related to physical activity.

  13. Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers

    PubMed Central

    Ashare, Rebecca L; Tang, Kathy Z; Mesaros, A Clementina; Blair, Ian A; Leone, Frank; Strasser, Andrew A

    2012-01-01

    Varenicline promotes smoking cessation and reduces urges to smoke. However, the mechanisms associated with these effects and their time course are not well characterized. One mechanism may be extinction, but the duration of the current dosing protocol may not be sufficient. We examined the effect of extended pre-treatment with varenicline on smoking behavior among 17 non-treatment seeking adult smokers. Using a within-subjects, double-blind, placebo-controlled crossover design, participants received standard dosing of varenicline for 21 days, followed by a 14-day washout period and 21 days of placebo; order counterbalanced. Cigarettes per day (CPD), smoking topography, smoking urges (QSU), and side effects were assessed every three days. Biomarkers (e.g. nicotine metabolites) were collected on days 1, 7, and 21. There was a significant drug by time interaction indicating a reduction in CPD during varenicline phase (between days 10–21), but no reduction during placebo. Varenicline also led to reductions in nicotine metabolites and urges to smoke. Among this sample of non-treatment seeking smokers, varenicline significantly reduced smoking behavior. Results have important treatment implications because changes in CPD and craving did not occur until after the typical one-week run-up period. This suggests that a longer duration of pre-treatment may be beneficial for some smokers. PMID:22695488

  14. Impact of bupropion and cognitive–behavioral treatment for depression on positive affect, negative affect, and urges to smoke during cessation treatment

    PubMed Central

    Kahler, Christopher W.; Leventhal, Adam M.; Abrantes, Ana M.; Lloyd-Richardson, Elizabeth; Niaura, Raymond

    2009-01-01

    Introduction: Bupropion and cognitive–behavioral treatment (CBT) for depression have been used as components of treatments designed to alleviate affective disturbance during smoking cessation. Studies of treatment-related changes in precessation affect or urges to smoke are needed to evaluate the proposed mechanisms of these treatments. Methods: The present report examines affective trajectories and urges to smoke prior to, on quit day, and after quitting in a sample of 524 smokers randomized to receive bupropion versus placebo and CBT versus standard smoking cessation CBT. Results: Bupropion and/or CBT did not affect the observed decreases in positive affect and increases in negative affect prior to cessation. However, on quit day, observed levels of negative affect and urges to smoke were diminished significantly among individuals receiving bupropion. Decreases in positive affect prior to quitting, lower levels of positive affect, and increased levels of negative affect and urges to smoke on quit day were each related to higher risk of smoking lapse. Depression proneness was an independent predictor of lower positive affect and higher negative affect but did not moderate the effects of bupropion on outcomes. In mediational analyses, the effect of bupropion was accounted for in part by lower negative affect and urges to smoke on quit day. Discussion: Results support the efficacy of bupropion in reducing relapse risk associated with urges to smoke and negative affect and suggest the need to better understand the role of low positive affect as a risk factor for early lapse. PMID:19574407

  15. The Malay version of the brief questionnaire on smoking urge: translation and psychometric properties of the questionnaire.

    PubMed

    Blebil, Ali Qais; Sulaiman, Syed Azhar Syed; Hassali, Mohamed Azmi; Dujaili, Juman Abdulelah; Zin, Alfian Mohamed

    2015-03-01

    This study aimed to evaluate the psychometric properties of Malay translated version of the brief questionnaire of smoking urges (QSU-Brief). The translation procedure was done following the standard guidelines. The reliability and validity of the Malaysian version scale were evaluated based on the data collected from 133 Malaysian smokers. The internal consistency was calculated to assess the reliability. Factor analysis and construct validity were performed to validate psychometric properties of the scale. Total Cronbach's alpha of the scale was 0.806. The exploratory factor analysis revealed two factors that accounted for 66.15% of the explained total variance. The first component consisted of items 1, 3, 6, 7, and 10, while the second component included the rest. The QSU-Brief total score had a significant positive relationship with exhaled CO level (r=0.24; P=0.005), number of cigarettes smoked per day (r=0.30; P<0.001) and other clinical factors. Items 2 and 5 loaded strongly on factor 2, whereas both items loaded ambivalently on two factors in the previous studies. This discrepancy might be clarified by language differences. The Malaysian QSU-Brief is a good candidate for evaluating urge to smoke in both clinical practice and clinical trials.

  16. Advancing cessation research by integrating EMA and geospatial methodologies: associations between tobacco retail outlets and real-time smoking urges during a quit attempt.

    PubMed

    Watkins, Kellie L; Regan, Seann D; Nguyen, Nga; Businelle, Michael S; Kendzor, Darla E; Lam, Cho; Balis, David; Cuevas, Adolfo G; Cao, Yumei; Reitzel, Lorraine R

    2014-05-01

    Residential tobacco retail outlet (TRO) density and proximity have been associated with smoking behaviors. More research is needed to understand the mechanisms underlying these relations and their potential relevance outside of the residential setting. This study integrates ecological momentary assessment (EMA) and geo-location tracking to explore real-time associations between exposure to TROs and smoking urges among 47 economically disadvantaged smokers in a cessation trial (59.6% female; 36.2% White). EMA data were collected for 1 week postquit via smartphone, which recorded smoking urge strength ≤ 4 random times daily along with real-time participant location data. For each assessment, the participants' proximity to the closest TRO and the density of TROs surrounding the participant were calculated. Linear mixed model regressions examined associations between TRO variables and smoking urges and whether relations varied based on participants' distance from their home. Covariates included sociodemographics, prequit tobacco dependence, treatment group, and daily smoking status. Main effects were nonsignificant; however, the interaction between TRO proximity and distance from home was considered significant (p = .056). Specifically, closer proximity to TROs was associated with stronger smoking urges ≤ 1 mile of home (p = .001) but not >1 mile from home (p = .307). Significant associations were attributable to assessments completed at participants' home addresses. All density analyses were nonsignificant. Technological challenges encountered in this study resulted in a significant amount of missing data, highlighting the preliminary nature of these findings and limiting the inferences that can be drawn. However, results suggest that closer residential proximity to tobacco outlets may trigger stronger urges to smoke among economically disadvantaged smokers trying to quit, perhaps due to enhanced cigarette availability and accessibility. Therefore, limiting

  17. Advancing Cessation Research by Integrating EMA and Geospatial Methodologies: Associations Between Tobacco Retail Outlets and Real-time Smoking Urges During a Quit Attempt

    PubMed Central

    2014-01-01

    Introduction: Residential tobacco retail outlet (TRO) density and proximity have been associated with smoking behaviors. More research is needed to understand the mechanisms underlying these relations and their potential relevance outside of the residential setting. This study integrates ecological momentary assessment (EMA) and geo-location tracking to explore real-time associations between exposure to TROs and smoking urges among 47 economically disadvantaged smokers in a cessation trial (59.6% female; 36.2% White). Methods: EMA data were collected for 1 week postquit via smartphone, which recorded smoking urge strength ≤4 random times daily along with real-time participant location data. For each assessment, the participants’ proximity to the closest TRO and the density of TROs surrounding the participant were calculated. Linear mixed model regressions examined associations between TRO variables and smoking urges and whether relations varied based on participants’ distance from their home. Covariates included sociodemographics, prequit tobacco dependence, treatment group, and daily smoking status. Results: Main effects were nonsignificant; however, the interaction between TRO proximity and distance from home was considered significant (p = .056). Specifically, closer proximity to TROs was associated with stronger smoking urges ≤1 mile of home (p = .001) but not >1 mile from home (p = .307). Significant associations were attributable to assessments completed at participants’ home addresses. All density analyses were nonsignificant. Conclusions: Technological challenges encountered in this study resulted in a significant amount of missing data, highlighting the preliminary nature of these findings and limiting the inferences that can be drawn. However, results suggest that closer residential proximity to tobacco outlets may trigger stronger urges to smoke among economically disadvantaged smokers trying to quit, perhaps due to enhanced cigarette

  18. Evaluation of a Novel Nicotine Inhaler Device: Part 2—Effect on Craving and Smoking Urges

    PubMed Central

    Hearn, Alex; Redfern, Andrew

    2015-01-01

    Introduction: Many smokers find currently available nicotine replacement therapies unsatisfactory. The pharmacokinetics of nicotine delivered via a novel inhaler device, and its effect on craving satiation and smoking urges, were compared with the Nicorette® Inhalator (10mg). Methods: Results are reported for Parts B (N = 24) and D (N = 24) of a 4-part Phase I study. Participants (18–55 years, ≥10 cigarettes/day within 1hr of waking, expired carbon monoxide >10 ppm on screening) received single doses of nicotine on consecutive days (0.45 and 0.67mg [Part B] and 0.45mg [Part D] via the novel device; 10mg via Nicorette® [Parts B and D]). Venous pharmacokinetics, craving, and tolerability were assessed. Results: In Part B, the novel device 0.45 and 0.67mg produced significantly lower C max, AUClast, and AUCall than Nicorette® (all p ≤ .05), higher AUC0–10 and significantly shorter T max (18.7 and 19.2min vs. 38.0min, respectively, p ≤ .05). Craving score AUC was lower for the novel device 0.45mg than for Nicorette® in Part B (1356.3 vs. 1566.3, p = .029) and approached statistical significance in Part D (1208.5 vs. 1402.3 [p = .059]). Mean craving scores were lower for the novel device 0.45mg than Nicorette® at 7/8 postdose timepoints in Part B (p ≤ .05 at 180 and 240min) and at all timepoints in Part D (p ≤ .05 at 2, 4, and 10min). Conclusions: The novel device was at least as effective as the Nicorette® Inhalator (10mg) in relieving craving and smoking urges and was statistically superior at certain timepoints and in an overall craving AUC analysis, despite lower total nicotine exposure. PMID:25082830

  19. Early cessation success or failure among women attempting to quit smoking: trajectories and volatility of urge and negative mood during the first postcessation week.

    PubMed

    Cofta-Woerpel, Ludmila; McClure, Jennifer B; Li, Yisheng; Urbauer, Diana; Cinciripini, Paul M; Wetter, David W

    2011-08-01

    Aversive symptoms of abstinence from nicotine have been posited to lead to smoking relapse and research on temporal patterns of abstinence symptoms confirms this assumption. However, little is known about the association of symptom trajectories early after quitting with postcessation smoking or about the differential effects of tonic (background) versus phasic (temptation-related) symptom trajectories on smoking status. The current study examined trajectories of urge and negative mood among 300 women using the nicotine patch during the first postcessation week. Ecological momentary assessments collected randomly and during temptation episodes were analyzed using hierarchical linear modeling yielding four individual trajectory parameters: intercept (initial symptom level), linear slope (direction and rate of change), quadratic coefficient (curvature), and volatility (scatter). Early lapsers, who lapsed during the first postcessation week, exhibited more severe tonic urge and phasic negative mood immediately after quitting, and more volatile tonic and phasic urge compared to abstainers. Late lapsers, who were abstinent during the first week but lapsed by 1 month, exhibited more severe tonic urge immediately after quitting compared to abstainers. These results demonstrate the importance of early postcessation urge and negative affect and highlight the value of examining both tonic and phasic effects of abstinence from nicotine.

  20. Development and Alpha Testing of QuitIT: An Interactive Video Game to Enhance Skills for Coping With Smoking Urges

    PubMed Central

    Fiske, Jeff

    2013-01-01

    Background Despite many efforts at developing relapse prevention interventions, most smokers relapse to tobacco use within a few months after quitting. Interactive games offer a novel strategy for helping people develop the skills required for successful tobacco cessation. Objective The objective of our study was to develop a video game that enables smokers to practice strategies for coping with smoking urges and maintaining smoking abstinence. Our team of game designers and clinical psychologists are creating a video game that integrates the principles of smoking behavior change and relapse prevention. We have reported the results of expert and end-user feedback on an alpha version of the game. Methods The alpha version of the game consisted of a smoking cue scenario often encountered by smokers. We recruited 5 experts in tobacco cessation research and 20 current and former smokers, who each played through the scenario. Mixed methods were used to gather feedback on the relevance of cessation content and usability of the game modality. Results End-users rated the interface from 3.0 to 4.6/5 in terms of ease of use and from 2.9 to 4.1/5 in terms of helpfulness of cessation content. Qualitative themes showed several user suggestions for improving the user interface, pacing, and diversity of the game characters. In addition, the users confirmed a high degree of game immersion, identification with the characters and situations, and appreciation for the multiple opportunities to practice coping strategies. Conclusions This study highlights the procedures for translating behavioral principles into a game dynamic and shows that our prototype has a strong potential for engaging smokers. A video game modality exemplifies problem-based learning strategies for tobacco cessation and is an innovative step in behavioral management of tobacco use. PMID:24025236

  1. Nicotine delivery, tolerability and reduction of smoking urge in smokers following short-term use of one brand of electronic cigarettes.

    PubMed

    D'Ruiz, Carl D; Graff, Donald W; Yan, X Sherwin

    2015-09-30

    This randomized, partially single-blinded, 6-period crossover clinical study of adult smokers compared the nicotine pharmacokinetics, impacts on smoking urge and tolerability of various formulations of one brand of e-cigarettes with that of a tobacco cigarette. Five e-cigarettes with different e-liquid formulations containing 1.6 % and 2.4 % nicotine and a conventional tobacco cigarette were randomized among 24 subjects under two exposure sessions consisting of a 30-min controlled and a one-hour ad lib use period to assess plasma nicotine levels, impacts on smoking urge and adverse events. The 30-min controlled use session comprised an intensive use of the e-cigarettes with a total of 50 puffs taken every 30 s for comparison to a single conventional cigarette having a typical machine-measured nicotine yield (~0.8 mg). Ad lib product use conditions provided insight into more naturalistic product use behaviors and their accompanying smoking urge reductions. Adverse events (AEs) were assessed by the Principal Investigator. Significant (p < 0.05) increases in plasma nicotine concentrations occurred within 10 min of controlled e-cigarette use and significant (p < 0.001) reductions from baseline smoking urge were observed within 5 min. E-cigarette and cigarette nicotine plasma levels were comparable for up to one hour of use. After both sessions (90 min), nicotine exposure was the highest for the cigarette, with all e-cigarettes showing 23 % to 53 % lower plasma concentrations. During controlled use, peak reduction in smoking urge for e-cigs occurred later than for the cigarette. After completion of both sessions, significant smoking urge reduction persisted for most of the tested e-cigarettes, albeit at levels lower than that provided by the tobacco cigarette. Nicotine content, vehicle differences, and the presence of menthol did not significantly affect smoking urge reduction by the e-cigarettes. No subjects were discontinued due to AEs. The most frequently

  2. The brain activations for both cue-induced gaming urge and smoking craving among subjects comorbid with Internet gaming addiction and nicotine dependence.

    PubMed

    Ko, Chih-Hung; Liu, Gin-Chung; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Lin, Wei-Chen

    2013-04-01

    Internet gaming addiction (IGA) has been classified as an addictive disorder in the proposed DSM 5 draft. However, whether its underlying addiction mechanism is similar to other substance use disorders has not been confirmed. The present functional magnetic resonance images study is aimed at evaluating the brain correlates of cue-induced gaming urge or smoking craving in subjects with both IGA and nicotine dependence to make a simultaneous comparison of cue induced brain reactivity for gaming and smoking. For this purpose, 16 subjects with both IGA and nicotine dependence (comorbid group) and 16 controls were recruited from the community. All subjects were made to undergo 3-T fMRIs scans while viewing images associated with online games, smoking, and neutral images, which were arranged according to an event-related design. The resultant image data was analyzed with full factorial and conjunction analysis of SPM5. The results demonstrate that anterior cingulate, and parahippocampus activates higher for both cue-induced gaming urge and smoking craving among the comorbid group in comparison to the control group. The conjunction analysis demonstrates that bilateral parahippocampal gyrus activates to a greater degree for both gaming urge and smoking craving among the comorbid group in comparison to the control group. Accordingly, the study demonstrates that both IGA and nicotine dependence share similar mechanisms of cue-induced reactivity over the fronto-limbic network, particularly for the parahippocampus. The results support that the context representation provided by the parahippocampus is a key mechanism for not only cue-induced smoking craving, but also for cue-induced gaming urge.

  3. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  4. Smoking cessation medications

    MedlinePlus

    Smoking cessation - medications; Smokeless tobacco - medications; Medications for stopping tobacco ... Creating a plan to help you deal with smoking urges. Getting support from a doctor, counselor, or ...

  5. The Urge to Write

    ERIC Educational Resources Information Center

    LaFee, Scott

    2011-01-01

    It's said that buried in every journalist is a novel waiting to be written. Something similar seems to apply these days to school administrators, particularly superintendents. Not a novel, perhaps, but some kind of writing, from book to blog. The urge might be personal, but more and more, writing from a school executive's point of view has become…

  6. Mechanisms of alcohol-induced hepatocellular carcinoma

    PubMed Central

    Sidharthan, Sreetha

    2014-01-01

    Chronic alcohol abuse is a major risk factor for hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide. Alcohol can also function synergistically with other risk factors to cause HCC. Hence, alcohol consumption is a major factor affecting hepatic carcinogenesis in millions and the cause of a substantial public health burden. Chronic alcohol consumption interferes with several host anti-tumor mechanisms, thereby facilitating hepatocyte proliferation and tumorigenesis. This review summarizes the major mechanisms of alcohol-induced HCC. These include pathways of ethanol metabolism, alcohol-induced oxidative stress and hypomethylation of DNA, and interplay of alcohol with iron elevation, retinoid metabolism, the immune system, inflammatory pathways, and neoangiogenesis. The relevance of each pathway in affecting HCC transformation is a topic of intense investigation. Ongoing research will enhance our insight into the alcohol-induced occurrence of HCC and offer hope in developing better therapeutics. PMID:25383134

  7. Alcohol-Induced Disruption of Endocrine Signaling

    USDA-ARS?s Scientific Manuscript database

    This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and co-chaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effects of long term ethanol consumption on liver injury and repair, by Jack R. Wands; (2) Alcohol-induced...

  8. A standardized transcutaneous electric acupoint stimulation for relieving tobacco urges in dependent smokers.

    PubMed

    Lambert, Caroline; Berlin, Ivan; Lee, Tat-Leang; Hee, Siew Wan; Tan, Audrey S L; Picard, David; Han, Ji Sheng

    2011-01-01

    The efficacy of acupuncture in smoking cessation, and its effect on the urge to smoke are unclear. We evaluated the effect of a standardized protocol of transcutaneous electric acupoint stimulations (TEAS) on alleviating the urge to smoke. Ninety-eight smokers were recruited in two double-blind studies. Participants abstained from smoking for 26 h, and were randomized to receive TEAS alternating between 2 and 100 Hz at four acupoints (LI4 and PC8, PC6 and TE5) at four different intensities (10, 5, Intermittent 5 or 0 mA). The urge to smoke was assessed by the Questionnaire of Smoking Urges (QSU-Brief). In Experiment 1, the 10 mA group (n = 20) was compared with the 5 mA group (n = 20); the increase in smoking urges did not differ significantly. Considering the possibility that 5 mA may be an active intervention, in Experiment 2, a true placebo (0 mA), and a proxy of placebo [Intermittent 5 mA (i5 mA)] were compared with 10 mA TEAS. In this experiment, 10 mA (n = 20) TEAS showed a tendency to alleviate smoking urges compared with 0 mA (n = 16), and i5 mA (n = 19) TEAS. Only when the data of smokers with Fagerstöm Test for Nicotine Dependence score ≥5 were analyzed that the difference between the 10 mA group and the control group (0 and i5 mA) became significant. Based on these preliminary findings, we conclude that TEAS applied on the skin may antagonize the increase in urge to smoke in abstinent-dependent smokers. It seems warranted to assess the efficacy of TEAS in smoking cessation clinical trials involving a larger population of dependent smokers.

  9. A Standardized Transcutaneous Electric Acupoint Stimulation for Relieving Tobacco Urges in Dependent Smokers

    PubMed Central

    Lambert, Caroline; Berlin, Ivan; Lee, Tat-Leang; Hee, Siew Wan; Tan, Audrey S. L.; Picard, David; Han, Ji Sheng

    2011-01-01

    The efficacy of acupuncture in smoking cessation, and its effect on the urge to smoke are unclear. We evaluated the effect of a standardized protocol of transcutaneous electric acupoint stimulations (TEAS) on alleviating the urge to smoke. Ninety-eight smokers were recruited in two double-blind studies. Participants abstained from smoking for 26 h, and were randomized to receive TEAS alternating between 2 and 100 Hz at four acupoints (LI4 and PC8, PC6 and TE5) at four different intensities (10, 5, Intermittent 5 or 0 mA). The urge to smoke was assessed by the Questionnaire of Smoking Urges (QSU-Brief). In Experiment 1, the 10 mA group (n = 20) was compared with the 5 mA group (n = 20); the increase in smoking urges did not differ significantly. Considering the possibility that 5 mA may be an active intervention, in Experiment 2, a true placebo (0 mA), and a proxy of placebo [Intermittent 5 mA (i5 mA)] were compared with 10 mA TEAS. In this experiment, 10 mA (n = 20) TEAS showed a tendency to alleviate smoking urges compared with 0 mA (n = 16), and i5 mA (n = 19) TEAS. Only when the data of smokers with Fagerstöm Test for Nicotine Dependence score ≥5 were analyzed that the difference between the 10 mA group and the control group (0 and i5 mA) became significant. Based on these preliminary findings, we conclude that TEAS applied on the skin may antagonize the increase in urge to smoke in abstinent-dependent smokers. It seems warranted to assess the efficacy of TEAS in smoking cessation clinical trials involving a larger population of dependent smokers. PMID:19073777

  10. Lower risk for alcohol-induced cirrhosis in wine drinkers.

    PubMed

    Becker, Ulrik; Grønbaek, Morten; Johansen, Ditte; Sørensen, Thorkild I A

    2002-04-01

    Although there is a well-known relationship between total alcohol intake and future risk for cirrhosis, other factors such as the type of alcohol consumed are sparsely studied. The aim of this study was to assess the effects of wine compared with other types of alcoholic beverages on risk for alcohol-induced cirrhosis. In 3 prospective studies, 30,630 participants from the Copenhagen area were followed-up for a total observation time of 417,325 person-years. Information on weekly intake of beer, wine, and spirits, and sex, age, body mass index, smoking habits, and education was obtained from questionnaires. The primary outcome measures were first admission or death, with alcohol-induced cirrhosis obtained from death certificates and from the National Hospital Discharge Register. Data were analyzed by means of multiplicative Poisson regression models. We confirmed the increasing risk for cirrhosis with increasing alcohol intake. Individuals who drank more than 5 drinks per day had a relative risk of 14 to 20 for developing cirrhosis compared with non- or light drinkers. However, compared with individuals who drank no wine (relative risk set at 1.0), individuals drinking 16% to 30% wine of their total intake had a relative risk of 0.4 (95% confidence limits, 0.3-0.6) and those drinking 51% or more of wine had a relative risk of 0.3 (95% confidence limits, 0.2-0.5) for developing cirrhosis. In conclusion, the results suggest that a high intake of all 3 types of alcohol conveys an increased risk for cirrhosis, but wine drinkers are at a lower risk than beer and spirits drinkers.

  11. Smoking

    MedlinePlus

    ... Smoking harms nearly every organ of the body. Cigarette smoking causes 87 percent of lung cancer deaths. ... of the same problems as smokers do. E-cigarettes often look like cigarettes, but they work differently. ...

  12. Neuroimaging Craving: Urge Intensity Matters

    PubMed Central

    Wilson, Stephen J.; Sayette, Michael A.

    2015-01-01

    Functional neuroimaging has become an increasingly common tool for studying drug craving. Furthermore, functional neuroimaging studies, which have addressed an incredibly diverse array of questions regarding the nature and treatment of craving, have had a substantial impact on theoretical models of addiction. Here, we offer three points related to this sizeable and influential body of research. First, we assert that the craving most investigators seek to study represents not just a desire but a strong desire to use drugs, consistent with prominent theoretical and clinical descriptions of craving. Second, we highlight that, despite the clear conceptual and clinical emphasis on craving as an intense desire, brain imaging studies often have been explicitly designed in a way that reduces the ability to generate powerful cravings. We illustrate this point by reviewing the peak urge levels endorsed by participants in functional magnetic resonance imaging (fMRI) studies of cigarette craving in nicotine-deprived versus nondeprived smokers. Third, we suggest that brain responses measured during mild states of desire (such as following satiety) differ in fundamental ways from those measured during states of overpowering desire (i.e., craving) to use drugs. We support this position by way of a meta-analysis revealing that fMRI cue exposure studies using nicotine-deprived smokers have produced different patterns of brain activation than those using nondeprived smokers. Regarding brain imaging studies of craving, intensity of the urges matter, and more explicit attention to urge intensity in future work has the potential to yield valuable information about the nature of craving. PMID:25073979

  13. Neuroimaging craving: urge intensity matters.

    PubMed

    Wilson, Stephen J; Sayette, Michael A

    2015-02-01

    Functional neuroimaging has become an increasingly common tool for studying drug craving. Furthermore, functional neuroimaging studies, which have addressed an incredibly diverse array of questions regarding the nature and treatment of craving, have had a substantial impact on theoretical models of addiction. Here, we offer three points related to this sizeable and influential body of research. First, we assert that the craving most investigators seek to study represents not just a desire but a strong desire to use drugs, consistent with prominent theoretical and clinical descriptions of craving. Secondly, we highlight that, despite the clear conceptual and clinical emphasis on craving as an intense desire, brain imaging studies often have been designed explicitly in a way that reduces the ability to generate powerful cravings. We illustrate this point by reviewing the peak urge levels endorsed by participants in functional magnetic resonance imaging (fMRI) studies of cigarette craving in nicotine-deprived versus non-deprived smokers. Thirdly, we suggest that brain responses measured during mild states of desire (such as following satiety) differ in fundamental ways from those measured during states of overpowering desire (i.e. craving) to use drugs. We support this position by way of a meta-analysis revealing that fMRI cue exposure studies using nicotine-deprived smokers have produced different patterns of brain activation to those using non-deprived smokers. Regarding brain imaging studies of craving, intensity of the urges matter, and more explicit attention to urge intensity in future work has the potential to yield valuable information about the nature of craving. © 2014 Society for the Study of Addiction.

  14. Negative Urgency Is Associated With Heightened Negative Affect and Urge During Tobacco Abstinence in Regular Smokers

    PubMed Central

    Park, Annie D.; Farrahi, Layla N.; Pang, Raina D.; Guillot, Casey R.; Aguirre, Claudia G.; Leventhal, Adam M.

    2016-01-01

    Objective: Negative urgency—the tendency to act rashly during negative affective states—is a risk factor for regular cigarette smoking. This human laboratory study tested a novel theoretical model of the underlying mechanisms linking negative urgency and smoking motivation, which purports that smokers with high negative urgency are at increased susceptibility to abstinence-induced increases in negative affect, which, in turn, provokes the urge to smoke to suppress negative affect. Method: Smokers (N = 180, >10 cigarettes/day) attended a baseline session at which they completed self-report measures of negative urgency and other co-factors and subsequently attended two counterbalanced within-subject experimental sessions (i.e., 16 hours of smoking abstinence or smoking as usual). At both experimental sessions, self-reported tobacco withdrawal symptoms, affect, and smoking urge were assessed. Results: Negative urgency was associated with larger abstinence-induced increases in tobacco withdrawal symptoms, negative affect, and urge to smoke to alleviate negative affect, both with and without controlling for anxiety, depression, tobacco dependence, and sensation seeking (βs > .18, ps < .05). The association between negative urgency and abstinence-induced increases in urge to smoke to alleviate negative affect was mediated by greater abstinence-induced increases in negative affect (βs > .062, ps = .01). Conclusions: These results provide initial support of this model by providing evidence that smokers with higher (vs. lower) negative urgency may be more prone to greater negative affect during withdrawal, which in turn may promote urge to smoke to suppress negative emotion. Research extending this model to other settings, measures, and methodological approaches may be fruitful. PMID:27588535

  15. The effect of social anxiety on urge and craving among smokers with and without anxiety disorders.

    PubMed

    Kimbrel, Nathan A; Morissette, Sandra B; Gulliver, Suzy B; Langdon, Kirsten J; Zvolensky, Michael J

    2014-02-01

    Despite the often social nature of smoking, relatively little research has been conducted on the relationship between smoking and social anxiety disorder (SAD). Participants (N=99) included 34 smokers without current mental health disorders, 37 smokers with SAD, and 28 smokers who met criteria for other anxiety disorder diagnoses (e.g., panic disorder or generalized anxiety disorder, but not SAD). Nicotine and placebo patches were administered to participants in a counterbalanced manner across two assessment days. Urge and craving were assessed before and after a 5-h nicotine absorption/deprivation period. Compared to smokers without current mental health disorders, smokers with SAD did not report greater nicotine dependence, but did endorse greater motivation to use nicotine to avoid negative outcomes. In addition, after controlling for demographic variables, smoking characteristics, pre-deprivation urge and craving, and other anxiety/depression symptoms, social anxiety symptoms uniquely predicted urge and craving in the placebo patch condition; however, social anxiety had no influence on urge and craving in the nicotine patch condition. These findings suggest that one potential reason that smokers with SAD may have worse cessation outcomes is that they may experience higher levels of craving and urge to smoke during quit attempts. Thus, during a quit attempt, particularly in the absence of nicotine replacement therapy, smokers with SAD are likely to benefit from additional treatment aimed at managing or reducing their social anxiety symptoms. Published by Elsevier Ireland Ltd.

  16. The urge-to-cough and cough motor response modulation by the central effects of nicotine.

    PubMed

    Davenport, Paul W; Vovk, Andrea; Duke, Rita K; Bolser, Donald C; Robertson, Erin

    2009-04-01

    The urge-to-cough is a respiratory sensation that precedes the cough motor response. Since affective state modulates the perception of respiratory sensations such as dyspnoea, we wanted to test whether nicotine, an anxiolytic, would modulate the urge-to-cough and hence, the cough motor response. We hypothesized that withdrawal from and administration of nicotine in smoking subjects would modulate their anxiety levels, urge-to-cough and cough motor response to capsaicin stimulation. Twenty smoking (SM) adults (8F, 12M; 22+/-3 years; 2.9+/-2.0 pack years) and matched non-smoking (NS) controls (22+/-2 years) were presented with randomized concentrations of capsaicin (0-200 microM) before and after nicotine (SM only) gum and/or placebo (SM and NS) gum. Subjects rated their urge-to-cough using a Borg scale at the end of each capsaicin presentation. Cough number and cough motor pattern were determined from airflow tracings. Subjects completed State-Trait Anxiety Inventory (STAI) questionnaires before and after gum administration. SM subjects that withdrew from cigarette smoking for 12 h exhibited an increase in anxiety scores, a greater number of coughs and higher urge-to-cough ratings compared to NS subjects. Administration of nicotine gum reduced anxiety scores, cough number and urge-to-cough ratings to match the NS subjects. There was no effect of placebo gum on any of the measured parameters in the SM and NS groups. The results from this study suggest that modulation of the central neural state with nicotine withdrawal and administration in young smoking adults is associated with a change in anxiety levels which in turn modulates the perceptual and motor response to irritant cough stimulants.

  17. How does coping help people resist lapses during smoking cessation?

    PubMed

    O'Connell, Kathleen A; Hosein, Vanessa L; Schwartz, Joseph E; Leibowitz, Ruth Q

    2007-01-01

    To determine whether types of coping strategies have differential effects on preventing lapses and lowering urge levels and to investigate mechanisms by which coping strategies prevent lapses during smoking cessation. Sixty-one respondents performed ecological momentary assessment using palm-top computers and tape recorders to report their coping strategies and urge levels before and after temptations to smoke. Multilevel linear regression models were used to compare the effects of individual strategy types with the average strategy. Lapses versus resisted temptations and changes in urge levels. Number of strategies significantly predicted resisting smoking and change in urge levels. Compared with the effect of the average strategy, movement/exercise was marginally worse at preventing lapses, and food/drink was marginally related to higher postcoping urge levels. Although using multiple coping strategies helps people resist the urge to smoke, no particular coping strategy works better than any other. Coping strategies prevent lapses by reducing high urge levels during temptations.

  18. Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in Mice.

    PubMed

    Hamarneh, Sulaiman R; Kim, Byeong-Moo; Kaliannan, Kanakaraju; Morrison, Sara A; Tantillo, Tyler J; Tao, Qingsong; Mohamed, Mussa M Rafat; Ramirez, Juan M; Karas, Aaron; Liu, Wei; Hu, Dong; Teshager, Abeba; Gul, Sarah Shireen; Economopoulos, Konstantinos P; Bhan, Atul K; Malo, Madhu S; Choi, Michael Y; Hodin, Richard A

    2017-08-01

    Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease. Mice underwent acute binge or chronic ethanol exposure to induce alcoholic liver injury and steatosis ± IAP supplementation. Liver tissue was assessed for biochemical, inflammatory, and histopathological changes. An ex vivo co-culture system was used to examine the effects of alcohol and IAP treatment in regard to the activation of hepatic stellate cells and their role in the development of alcoholic liver disease. Pretreatment with IAP resulted in significantly lower serum alanine aminotransferase compared to the ethanol alone group in the acute binge model. IAP treatment attenuated the development of alcohol-induced fatty liver, lowered hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol-induced gut barrier dysfunction. Finally, IAP ameliorated the activation of hepatic stellate cells and prevented their lipogenic effect on hepatocytes. IAP treatment protected mice from alcohol-induced hepatotoxicity and steatosis. Oral IAP supplementation could represent a novel therapy to prevent alcoholic-related liver disease in humans.

  19. Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage.

    PubMed

    Tang, Yueming; Forsyth, Christopher B; Banan, Ali; Fields, Jeremy Z; Keshavarzian, Ali

    2009-06-01

    We reported previously that oats supplementation prevents gut leakiness and alcoholic steatohepatitis (ASH) in our rat model of alcoholic liver disease. Because oxidative stress is implicated in the pathogenesis of both alcohol-induced gut leakiness and ASH, and because oats have antioxidant properties, we tested the hypothesis that oats protect by preventing alcohol-induced oxidative damage to the intestine. Male Sprague-Dawley rats were gavaged for 12 weeks with alcohol (starting dose of 1 g/kg increasing to 6 g/kg/day over the first 2 weeks) or dextrose, with or without oats supplementation (10 g/kg/day). Oxidative stress and injury were assessed by measuring colonic mucosal inducible nitric-oxide synthase (iNOS) (by immunohistochemistry), nitric oxide (colorimetric assay), and protein carbonylation and nitrotyrosination (immunoblotting). Colonic barrier integrity was determined by assessing the integrity of the actin cytoskeleton (immunohistochemistry) and the integrity of tight junctions (electron microscopy). Oats supplementation prevented alcohol-induced up-regulation of iNOS, nitric oxide overproduction in the colonic mucosa, and increases in protein carbonyl and nitrotyrosine levels. This protection was associated with prevention of ethanol (EtOH)-induced disorganization of the actin cytoskeleton and disruption of tight junctions. We conclude that oats supplementation attenuates EtOH-induced disruption of intestinal barrier integrity, at least in part, by inhibiting EtOH-induced increases in oxidative stress and oxidative tissue damage. This inhibition prevents alcohol-induced disruption of the cytoskeleton and tight junctions. This study suggests that oats may be a useful therapeutic agent--a nutraceutical--for the prevention of alcohol-induced oxidative stress and organ dysfunction.

  20. In Brief: Action on climate change urged

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2008-06-01

    The science academies of the G8 countries-along with those in China, India, Brazil, Mexico, and South Africa-on 10 June issued a joint statement urging leaders at July's G8 Summit in Japan to take action on climate change. The statement indicates, ``Responding to climate change requires both mitigation and adaptation to achieve a transition to a low carbon society and our global sustainability objectives.'' In the statement, the academies urge all nations, and particularly those participating in the summit, to take a series of actions to deal with climate change. The statement is available at http://www.nationalacademies.org/includes/climatechangestatement.pdf.

  1. Alcohol-induced Cushing syndrome. Hypercortisolism caused by alcohol abuse.

    PubMed

    Besemer, F; Pereira, A M; Smit, J W A

    2011-01-01

    Cushing's syndrome (CS), a rare syndrome caused by overexposure to glucocorticoids, is difficult to diagnose. The underlying causes of CS include pituitary and ectopic adrenocorticotropic hormone (ACTH) producing tumours and adrenal adenomas or hyperplasia. Alcoholism, however, can cause similar symptoms, giving rise to a so-called pseudo-Cushing state, which aggravates the differential diagnostic dilemmas of CS. To document any specific clinical or biochemical features of alcohol-induced CS. A Medline computer-aided search was performed to identify studies that have attempted to differentiate between alcohol-induced pseudo-Cushing and CS. Only original articles, not reviews, written in English were included. A total of 62 articles were included. Clinical and biochemical abnormalities mimicking increased hypothalamus-pituitary-adrenal (HPA) axis activity were found in the majority of the patients, although the severity of the changes varied widely. The most frequently occurring abnormalities were: insufficient suppression after low-dose dexamethasone or increased 24-hour urinary free cortisol (UFC). After alcohol withdrawal, cortisol decreased and dexamethasone-induced suppression of cortisol increased. No differences were noted between alcoholic and control subjects after an ACTH stimulation test, insulin tolerance test or metyrapone test. Differences were found after a naloxone test and hexarelin test. Studies using corticotropin-releasing hormone stimulation and tests after ethanol ingestion revealed inconclusive results. There is no clear definition for the alcohol-induced pseudo-Cushing state, and hitherto studies fail to provide clues to differentiate between pseudo-Cushing and Cushing's syndrome. Only cessation of alcohol can normalise biochemical abnormalities and regress hypercortisolic symptoms.

  2. Ebselen prevents early alcohol-induced liver injury in rats.

    PubMed

    Kono, H; Arteel, G E; Rusyn, I; Sies, H; Thurman, R G

    2001-02-15

    Oxidants have been shown to be involved in alcohol-induced liver injury. Moreover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoselenium compound and glutathione peroxidase mimic, decreases oxidative stress and protects against stroke clinically. This study was designed to test the hypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/kg twice daily, intragastrically) or vehicle (1% tylose) was administered throughout the experiment. Mean urine ethanol concentrations were not significantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (37 +/- 5 IU/l) by enteral ethanol (112 +/- 7 IU/l); ebselen blunted this increase significantly (61 +/- 8 IU/l). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes were blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathione peroxidase activity in serum or liver tissue, ebselen blocked the increase in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increased the activity of NF-kappaB over 5-fold, the number of infiltrating neutrophils 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blunted all of these effects significantly. These results indicate that ebselen prevents early alcohol-induced liver injury, most likely by preventing oxidative stress, which decreases inflammation.

  3. New Treatment Strategies for Alcohol-Induced Heart Damage

    PubMed Central

    Fernández-Solà, Joaquim; Planavila Porta, Ana

    2016-01-01

    High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use. PMID:27690014

  4. Influence of extracellular calcium on allyl alcohol-induced hepatotoxicity.

    PubMed

    Strubelt, O; Younes, M; Pentz, R

    1986-07-01

    The role of calcium in allyl alcohol-induced hepatotoxicity was investigated in the isolated haemoglobin-free perfused rat liver. At a Ca++ concentration of 2.5 mmol/l in the perfusate, allyl alcohol (initial concentration 1.17 mmol/l) produced an enhanced release of GPT and SDH from the liver, an increase in the lactate/pyruvate ratio of the perfusate, a decrease in hepatic oxygen consumption and an increase of both hepatic calcium and malondialdehyde content. In the absence of Ca++ in the perfusate, no hepatic calcium accumulation occurred with allyl alcohol, but all other signs of hepatic damage were as severe as with 2.5 mmol/l Ca++. On the other hand, high extracellular Ca++ (5 mmol/l) alone led to a threefold increase of liver calcium but produced only marginal hepatotoxicity and only slightly enhanced the hepatotoxic effects of allyl alcohol. The concentrations of allyl alcohol in the perfusate were not altered at different Ca++ concentrations. In conclusion, the primary allyl alcohol-induced hepatotoxic injury does not appear to depend upon an influx of extracellular calcium.

  5. Alcohol-induced protein hyperacetylation: Mechanisms and consequences

    PubMed Central

    Shepard, Blythe D; Tuma, Pamela L

    2009-01-01

    Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylation. This reversible, post-translational modification on the epsilon-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol-induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function. PMID:19291822

  6. The nuclear receptor CAR modulates alcohol-induced liver injury.

    PubMed

    Chen, Xiaosong; Meng, Zhipeng; Wang, Xiaoqiong; Zeng, Samuel; Huang, Wendong

    2011-08-01

    The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily and a sensor and detoxifier of both xenobiotics and endobiotics. Recent studies also show that CAR participates in metabolism of glucose and lipid, and has an important role in fatty liver disease and diabetes. In this study, we investigate the roles of CAR in chronic and acute alcohol-induced liver injuries. The results showed that absence of CAR in rodents led to significantly increased susceptibility to chronic alcohol-induced liver injury, which was accompanied with elevated hepatocyte apoptosis and fat accumulation. However, pre-activation of CAR by a CAR agonist, TCPOBOP, strongly enhanced the hepatic toxicity by both chronic and acute alcohol infusion in wild-type, but not in CAR(-/-) mice. Gene expression analyses indicated that CAR pre-activation and alcohol infusion synergistically decreased the expression of enzymes that metabolize the alcohol in liver. These results support a role of CAR in modulating alcoholic liver injury and imply a risk of synergistic liver toxicity induced by alcohol and CAR activation.

  7. No untoward effects of smoking cues in anti-smoking public service announcements.

    PubMed

    Falcone, Mary; Lerman, Caryn; Cappella, Joseph N; Sanborn, Paul; Jepson, Christopher; Strasser, Andrew A

    2013-11-01

    Anti-smoking public service announcements (PSAs) often include smoking-related cues; however, visual drug cues can trigger acute cravings that may impede cognitive processing of the anti-smoking message. This experiment evaluated effects of smoking cues in PSAs on smoking urges, immediate smoking behavior, and persuasion measures in daily smokers. Three-hundred and eighteen non-treatment seeking smokers completed a single laboratory session during which they viewed sets of PSAs differentiated by presence of smoking cues (central to the PSA's argument, peripheral, or no cues) and argument strength (high versus low). After viewing the PSAs, participants completed self-report measures of smoking urges, attitudes toward quitting, self-efficacy, and intentions to quit smoking. Smoking behavior was recorded during a 1-h ad libitum smoking period immediately following PSA viewing and assessment. There was a significant positive effect of argument strength on attitudes toward quitting smoking (p=0.012). There were no main effects of smoking cues or smoking cue by argument strength interactions on any of the outcome measures. Visual smoking cues in PSAs do not increase urges to smoke, nor is there evidence that the inclusion of such cues impedes the recall or persuasive effects of anti-smoking arguments. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Otto Rank and man's urge to immortality.

    PubMed

    Goldwert, M

    1985-04-01

    Otto Rank, one of Sigmund Freud's original followers, posited the existence of an "urge to immortality" as man's deepest drive. In his Psychology and the Soul, Rank traced the desire for immortality through four historical eras, with particular emphasis on the creativity of the hero and the artist. By the end of his life, Rank had not only repudiated orthodox psychoanalysis and developed then abandoned a psychology of the will, he had moved "beyond psychology" to a religious view of history and the nature of man.

  9. Viewing alcohol warning advertising reduces urges to drink in young adults: an online experiment.

    PubMed

    Stautz, Kaidy; Marteau, Theresa M

    2016-07-08

    Tobacco counter-advertising is effective at promoting smoking cessation. Few studies have evaluated the impact of alcohol warning advertising on alcohol consumption and possible mechanisms of effect. This pilot study aimed to assess whether alcohol warning advertising is effective in reducing urges to drink alcohol, if emotional responses to advertising explain any such effect or perceived effectiveness, and whether effects differ among heavier drinkers. One hundred fifty-two young adult (aged 18-25) alcohol users completed an online experiment in which they were randomly assigned to view one of three sets of six advertisements: (i) alcohol warning; (ii) alcohol promoting; or (iii) advertisements for non-alcohol products. Urges to drink alcohol were self-reported post-exposure. Affective responses (pleasure and arousal) to each advertisement and perceived effectiveness of each advertisement were recorded. Typical level of alcohol consumption was measured as a potential effect modifier. Participants exposed to alcohol warning advertisements reported significantly lower urges to drink alcohol than those who viewed either alcohol promoting or non-alcohol advertisements. This effect was fully mediated by negative affective responses (displeasure) to the alcohol warning advertisements. Perceived effectiveness of alcohol warning advertisements was associated with high arousal responses. Impact of the advertisements was unaffected by typical level of alcohol consumption, although the study was not powered to detect anything other than large effects. In line with findings from the tobacco literature, alcohol warning advertisements that elicit negative affect reduce urges to drink alcohol. Their impact upon actual consumption awaits investigation.

  10. Alcohol-induced stress in painful alcoholic neuropathy.

    PubMed

    Dina, Olayinka A; Khasar, Sachia G; Alessandri-Haber, Nicole; Green, Paul G; Messing, Robert O; Levine, Jon D

    2008-01-01

    Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy, the severity of which increases during alcohol withdrawal. Chronic alcohol consumption also produces a sustained increase in stress hormones, epinephrine and corticosterone, that is exacerbated during alcohol withdrawal. We report that adrenal medullectomy and administration of a glucocorticoid receptor antagonist, mifepristone (RU 38486), both prevented and reversed a model of painful peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of stress levels of epinephrine to rats that had undergone adrenal medullectomy and were being fed the alcohol diet reconstituted this phenotype. Intrathecal administration of oligodeoxynucleotides antisense to the beta(2)-adrenergic- or glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects of ethanol. Our results suggest a convergence of the effects of mediators of the hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the induction and maintenance of alcohol-induced painful peripheral neuropathy.

  11. Dietary antioxidants prevent alcohol-induced ciliary dysfunction

    PubMed Central

    Simet, Samantha M.; Pavlik, Jacqueline A.; Sisson, Joseph H.

    2013-01-01

    Previously we have shown that chronic alcohol intake causes alcohol-induced ciliary dysfunction (AICD), leading to non-responsive airway cilia. AICD likely occurs through the downregulation of nitric oxide (NO) and cyclic nucleotide-dependent kinases, protein kinase G (PKG) and protein kinase A (PKA). Studies by others have shown that dietary supplementation with the antioxidants N-acetylcysteine (NAC) and procysteine prevent other alcohol-induced lung complications. This led us to hypothesize that dietary supplementation with NAC or procysteine prevents AICD. To test this hypothesis, C57BL/6 mice drank an alcohol/water solution (20% w/v) ad libitum for 6 weeks and were concurrently fed dietary supplements of either NAC or procysteine. Ciliary beat frequency (CBF) was measured in mice tracheas, and PKG/PKA responsiveness to β-agonists and NOx levels were measured from bronchoalveolar lavage (BAL) fluid. Long-term alcohol drinking reduced CBF, PKG and PKA responsiveness to β-agonists, and lung NOx levels in BAL fluid. In contrast, alcohol-drinking mice fed NAC or procysteine sustained ciliary function and PKG and PKA responsiveness to β-agonists. However, BAL NO levels remained low despite antioxidant supplementation. We also determined that removal of alcohol from the drinking water for as little as 1 week restored ciliary function, but not PKG and PKA responsiveness to β-agonists. We conclude that dietary supplementation with NAC or procysteine protects against AICD. In addition, alcohol removal for 1 week restores cilia function independent of PKG and PKA activity. Our findings provide a rationale for the use of antioxidants to prevent damage to airway mucociliary functions in chronic alcohol-drinking individuals. PMID:24169090

  12. Gender differences in alcohol-induced neurotoxicity and brain damage.

    PubMed

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse.

  13. Caffeine antagonism of alcohol-induced driving impairment.

    PubMed

    Liguori, A; Robinson, J H

    2001-07-01

    The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

  14. Microbiota protects mice against acute alcohol-induced liver injury

    PubMed Central

    Chen, Peng; Miyamoto, Yukiko; Mazagova, Magdalena; Lee, Kuei-Chuan; Eckmann, Lars; Schnabl, Bernd

    2015-01-01

    Background Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. Aim To investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. Methods We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. Results Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and upregulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute ethanol administration. The absence of microbiota was also associated with increased hepatic expression of ethanol metabolizing enzymes, which led to faster ethanol elimination from the blood and lower plasma ethanol concentrations. Intestinal levels of ethanol metabolizing genes showed regional expression differences, and were overall higher in germ-free relative to conventional mice. Conclusion Our findings indicate that absence of the intestinal microbiota increases hepatic ethanol metabolism and the susceptibility to binge-like alcohol drinking. PMID:26556636

  15. The Molecular Circadian Clock and Alcohol-Induced Liver Injury.

    PubMed

    Udoh, Uduak S; Valcin, Jennifer A; Gamble, Karen L; Bailey, Shannon M

    2015-10-14

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  16. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    PubMed Central

    Udoh, Uduak S.; Valcin, Jennifer A.; Gamble, Karen L.; Bailey, Shannon M.

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases. PMID:26473939

  17. Damage to the insula disrupts addiction to cigarette smoking.

    PubMed

    Naqvi, Nasir H; Rudrauf, David; Damasio, Hanna; Bechara, Antoine

    2007-01-26

    A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not involving the insula to undergo a disruption of smoking addiction, characterized by the ability to quit smoking easily, immediately, without relapse, and without persistence of the urge to smoke. This result suggests that the insula is a critical neural substrate in the addiction to smoking.

  18. Damage to the Insula Disrupts Addiction to Cigarette Smoking

    PubMed Central

    Naqvi, Nasir H.; Rudrauf, David; Damasio, Hanna; Bechara, Antoine

    2013-01-01

    A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not involving the insula to undergo a disruption of smoking addiction, characterized by the ability to quit smoking easily, immediately, without relapse, and without persistence of the urge to smoke. This result suggests that the insula is a critical neural substrate in the addiction to smoking. PMID:17255515

  19. Effects of transdermal nicotine during imaginal exposure to anxiety and smoking cues in college smokers.

    PubMed

    Morissette, Sandra Baker; Palfai, Tibor P; Gulliver, Suzy Bird; Spiegel, David A; Barlow, David H

    2005-06-01

    In a 2 (patch) x 2 (smoking) x 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch x Smoking x Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues. Copyright 2005 APA, all rights reserved.

  20. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation.

    PubMed

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

    2015-12-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation.

  1. Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

    PubMed Central

    Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

    2015-01-01

    Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provokingalcohol-induced proactive aggression was linked to higher levels of aggression under placebo, and (2) that pronounced alcohol-induced reactive aggression was related to increased amygdala and ventral striatum reactivity under alcohol, providing evidence for their role in human alcohol-induced reactive aggression. Our findings suggest that in healthy young adults a liability for alcohol-induced aggression in a non-provoking context might depend on overall high levels of aggression, but on alcohol-induced increased striatal and amygdala reactivity when triggered by provocation. PMID:25971590

  2. Alcohol-induced serotonergic modulation: the role of histone deacetylases.

    PubMed

    Agudelo, Marisela; Yoo, Changwon; Nair, Madhavan P

    2012-11-01

    Previous studies have demonstrated that alcohol use disorders (AUDs) are regulated by multiple mechanisms such as neurotransmitters and enzymes. The neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) may contribute to alcohol effects and serotonin receptors, including 5-HT3, play an important role in AUDs. Recent studies have also implicated histone deacetylases (HDACs) and acetyltransferases (HATS) in regulation of drug addiction, and HDAC inhibitors (HDACi) have been reported as transcriptional modulators of monoaminergic neurotransmission. Therefore, we hypothesize that HDACs may play a role in ethanol-induced serotonergic modulation. The effects of ethanol on serotonin and 5-HT3, and the role HDACs, HDAC activity and the HDACi, trichostatin A (TSA), play in alcohol-induced serotonergic effects were studied. Human SK-N-MC and neurons, were treated with ethanol (0.05, 0.1 and 0.2%), and/or TSA (50 nM), and 5-HT3 levels were assessed at 24-72 h. Gene expression was evaluated by qRT-PCR and protein by western blot and flow cytometry. Serotonin release was assessed by ELISA and HDAC activity by fluorometric assay. Our results show an increase in 5-HT3 gene after ethanol treatment. Further, ethanol significantly increased HDACs 1 and 3 genes accompanied by an increased in HDAC activity while TSA significantly inhibited HDACs. Studies with TSA show a significant upregulation of ethanol effects on 5-HT3, while surprisingly TSA inhibited ethanol-induced serotonin production. These results suggest that ethanol affects 5-HT3 and serotonin through mechanisms involving HDACs and HATs. In summary, our studies demonstrate some of the novel properties of HDAC inhibitors and contribute to the understanding of the mechanisms involve in alcohol-serotonergic modulation in the CNS.

  3. Cognitive functioning and the inhibition of alcohol-induced aggression.

    PubMed

    Hoaken, P N; Assaad, J M; Pihl, R O

    1998-09-01

    A highly replicable research finding is that alcohol intoxication tends to induce aggressive responding. Recent research investigating the role of cognitive function in this relationship has shown that individuals who perform poorly on certain cognitive tasks have difficulty responding to contingencies to inhibit aggression, while high performers do not. High performers, however, do show increased aggression while intoxicated. This study investigated whether subjects with above average cognitive functioning would, when intoxicated, inhibit aggression in order to attain monetary reward. Men (N = 43), aged 18-30, selected on the basis of high performance on a neuropsychological test putatively assessing function of dorsolateral prefrontal cortex, the spatial conditional associative learning task, participated in a modified version of the Taylor Aggression Task. Half the subjects were acutely alcohol intoxicated, the other half were sober. Furthermore, half the subjects in each of these groups received contingent monetary reward for choosing lower shocks. Aggression was defined as shock intensity delivered to a sham opponent. Contrary to the hypothesis, intoxicated subjects, even though significantly impaired cognitively relative to their nonintoxicated peers (F = 4.29, 1/41 df, p < .05), appeared to have no difficulty inhibiting their aggression in order to gain monetary reward. That is, there was no difference between intoxicated and nonintoxicated subjects on the dependent variable, shock intensity, when contingent money was available (F = .01, 1/20 df, p = .935). This finding provides further evidence that alcohol-induced aggression is not a uniform phenomenon, and it suggests a neuropsychological mechanism that may mediate the relationship. It may be that individuals with above average cognitive abilities retain sufficient residual functioning to inhibit aggressive responding, even when acutely alcohol intoxicated.

  4. Premonitory Urges and Sensorimotor Processing in Tourette Syndrome

    PubMed Central

    Rajagopal, Sangeerthana; Seri, Stefano; Cavanna, Andrea Eugenio

    2013-01-01

    Most patients with Tourette syndrome report characteristic sensory experiences (premonitory urges) associated with the expression of tic symptoms. Despite the central role of these experiences to the clinical phenomenology of Tourette syndrome, little is known about their underlying brain processes. In the present article we present the results of a systematic literature review of the published studies addressing the pathophysiological mechanisms of premonitory urges. We identified some preliminary evidence for specific alterations in sensorimotor processing at both cortical and subcortical levels. A better insight into the brain correlates of premonitory urges could lead to the identification of new targets to treat the sensory initiators of tics in patients with Tourette syndrome. PMID:23187151

  5. Cigarette smoking and chewing gum: response to a laboratory-induced stressor.

    PubMed

    Britt, D M; Cohen, L M; Collins, F L; Cohen, M L

    2001-09-01

    The current study examined the anxiolytic effects of cigarette smoking and chewing gum on urge to smoke, withdrawal, and anxiety in response to a public speaking task in 45 undergraduate smokers. Participants were asked to smoke, chew gum, or do nothing in response to the stressor. Participants completed measures of anxiety, withdrawal symptoms, and urge to smoke pre- and poststressor. The smoke group reported fewer urges to smoke pre- and poststressor than the other groups. The smoke and gum groups reported fewer withdrawal symptoms than did the control group poststressor. Chewing gum was helpful in managing levels of withdrawal symptoms compared with the control group. Groups did not differ on measures of anxiety. Results suggest that smoking in response to a stressor may not reduce levels of affective stress. Furthermore, chewing gum may be helpful in managing withdrawal symptoms in response to a stressor.

  6. Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

    PubMed Central

    Wang, Shaogui; Ni, Hong-Min; Huang, Heqing

    2014-01-01

    Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy. PMID:25140315

  7. Role of microRNAs in Alcohol-Induced Multi-Organ Injury

    PubMed Central

    Natarajan, Sathish Kumar; Pachunka, Joseph M.; Mott, Justin L.

    2015-01-01

    Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption. PMID:26610589

  8. Role of cytokines and chemokines in alcohol-induced tumor promotion

    PubMed Central

    Chen, Danlei; Zhang, Fengyun; Ren, Haifeng; Luo, Jia; Wang, Siying

    2017-01-01

    Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines and the oncogenic effect of alcohol. This review provides novel insight into the mechanisms of alcohol-induced tumor promotion. PMID:28360527

  9. [Medications in smoking cessation].

    PubMed

    Mansourati, J; Borel, M-L; Munier, S; Guevel-Jointret, A-L

    2005-10-22

    Physicians can aid their patients' smoking cessation by providing psychological support, advice, behavioral strategies, and drugs. Success depends on appropriate management, including selection of the right moment to begin treatment and an understanding of the development of the withdrawal syndrome, smoking urges, and the possibility of failure. The standard pharmacological treatment for nicotine dependence uses different forms of nicotine substitutes and bupropion, while we await data about other drugs currently under study. The score on the "simplified" Fagerström questionnaire usually determines the initial nicotine dose. Six forms of nicotine substitutes are available. They provide either prolonged nicotine release (transcutaneous patches) that prevents withdrawal symptoms, or rapid release through the buccal and nasal mucosa (chewing gum, suckers, inhalers and nasal sprays) to anticipate the positive effects represented by cigarettes and the urges occurring during withdrawal. The efficacy of these substitutes, widely studied, is approximately twice that of placebo. Their use is no longer contraindicated in patients with heart disease, when necessary. Bupropion should be used in treating nicotine dependence either as a first-line treatment, or if nicotine substitutes (150 mg/d the first week, 300 mg/d thereafter) fail. The combination of bupropion and nicotine substitutes can be considered, either from the outset for heavy or very heavy smokers, or afterwards, if withdrawal symptoms or urges to smoke persist in subjects treated by only one of these two drug classes. One of the new drugs under evaluation is rimonabant, the first representatives of a new class of drugs, selective CB1 endocannabinoid receptor antagonists. Promising results about its use in smoking cessation were released in 2004.

  10. Smoking and reproduction.

    PubMed

    Lincoln, R

    1986-01-01

    2 of the 5 health warnings that must now appear on American cigarette packs and cigarette advertising refer to some of the increased hazards smoking entails for the woman and her unborn child. Yet, the myriad reproductive risks associated with smoking are little known or considered by the general public--or even by physicians--when compared with the dangers of lung cancer, heart attacks and emphysema. In an attempt to remedy that deficit, 8 government agencies sponsored the 1st International Conference on Smoking and Reproductive Health, held October 15-17, 1985 in San Francisco. Speaker after expert speaker connected smoking during pregnancy with increased risks of low birth weight, miscarriage, infant mortality and morbidity--including poorer health of surviving children up to at least age 3--ectopic pregnancy, infertility, menstrual disorders, early menopause, osteoporosis, cervical cancer and dysplasia, cardiovascular disease and placental abnormalities. Similarly, the conference participants documented the association of smoking among men with lower sperm count and increased prevalence of abnormal sperm. The following measures were urged at the closing statements of the conference: 1) an increased effort to inform doctors and health professionals of these findings; 2) increasing the tax on cigarettes, so that smokers would pay for their own health costs; 3) decreasing or eliminating government subsidies for growing tobacco, while helping growers make the transition to nontobacco crops; 4) making smoking cessation programs more widely available; 5) prohibiting the sale of cigarettes through vending machines; and 6) banning all smoking in the workplace.

  11. [Effects of alcohol and smoking in pregnancy].

    PubMed

    Thäle, V; Schlitt, A

    2011-10-01

    Nicotine and alcohol are legal drugs, which damage not only the health of the consumer, but also the society due to health-economic costs. In pregnancy, the consequences of alcohol consumption and smoking for the unborn life in pregnancy are dramatic. The irreversibly damaging effect of alcohol is proven in each stage of the pregnancy, whereby the phase of the organogenesis is the most sensitive period. Beside a higher incidence for deformations of all organs, the damage of the central nervous system is leading, since mental-intellectual retardation of children after alcohol consumption in pregnancy is proven. Smoking in pregnancy leads likewise to harmful effects, with the intrauterine growth retardation of the fetus being the leading smoking-induced pathology. Smoking- and alcohol-induced damages for the unborn life are irreversible with no therapeutic options. The only therapy is prevention, which means complete cessation of alcohol and smoking in pregnancy.

  12. Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice.

    PubMed

    Du, Jian; He, Da; Sun, Lian-Na; Han, Ting; Zhang, Hong; Qin, Lu-Ping; Rahman, Khalid

    2010-08-01

    The protective effects of Semen Hoveniae extract (SHE) from Hovenia dulcis Thunb. (Rhamnaceae) on acute alcohol-induced liver injury were investigated in vivo using mice as test models. In the present study, SHE (150, 300, 600 mg/kg/day) was given to mice by intragastric administration for 4 days. Mice were gavaged with 60% ethanol 10 mL/kg after the last dose of extract. Six hours after alcohol administration, liver injury was evaluated by biochemical examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric methods. In mice, administration of SHE significantly decreased the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum. Administration of SHE also protected against alcohol-induced alcohol dehydrogenase (ADH) elevation in mice. Concurrently, there was an augmentation in the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione (GSH), and it also facilitated alcohol metabolism. Acute toxicity tests showed that a single dose of oral SHE up to 22 g/kg did not result in any death or toxic side effects in mice during 14 days' observation. These results demonstrate that SHE could protect against acute alcohol-induced liver injury without any toxic side effects. Therefore, Semen Hoveniae has potential for the development of a clinically useful agent which could protect the liver from alcohol-induced injury.

  13. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  14. Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice.

    PubMed

    Wang, Zhiguo; Su, Bo; Fan, Sumei; Fei, Haixia; Zhao, Wei

    2015-03-20

    The long-term consumption of alcohol has been associated with multiple pathologies at all levels, such as alcoholism, chronic pancreatitis, malnutrition, alcoholic liver disease (ALD) and cancer. In the current study, we investigated the protective effect of oligomeric proanthocyanidins (OPC) against alcohol-induced liver steatosis and injury and the possible mechanisms using ethanol-induced chronic liver damage mouse models. The results showed that OPC significantly improved alcohol-induced dyslipidemia and alleviated liver steatosis by reducing levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-c) and liver malondialdehyde (MDA), and increasing levels of serum high-density lipoprotein (HDL-c), liver superoxide dismutase (SOD). Further investigation indicated that OPC markedly decreased the expressions of lipid synthesis genes and inflammation genes such as sterol regulatory element-binding protein-1c (Srebp-1c), protein-2 (Srebp2), interleukin IL-1β, IL-6 and TNF-α. Furthermore, AML-12 cells line was used to investigate the possible mechanisms which indicated that OPC might alleviate liver steatosis and damage through AMP-activated protein kinase (AMPK) activation involving oxidative stress. In conclusion, our study demonstrated excellent protective effect of OPC against alcohol-induced liver steatosis and injury, which could a potential drug for the treatment of alcohol-induced liver injury in the future.

  15. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    PubMed Central

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice. PMID:23213269

  16. Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense.

    PubMed

    Jiang, Zhihui; Chen, Chen; Wang, Jian; Xie, Wenyan; Wang, Meng; Li, Xinsheng; Zhang, Xiaoying

    2016-01-01

    Alcoholic liver disease (ALD) is a serious and challenging health issue. In the past decade, natural components possessing hepatoprotective properties have gained more attention for ALD intervention. In this study, the phytochemical components of anthocyanins from purple potato were assessed using UPLC-MS/MS, and the hepatoprotective effects of purple potato anthocyanins (PPAs) were investigated in the ALD mouse model. Serum and liver biochemical parameters were determined, along with histopathological changes in liver tissue. In addition, the major contributors to alcohol-induced oxidative stress were assessed. The results indicated that the levels of aspartate transaminase and alanine transaminase were lower in the serum of the PPA-treated group than the alcohol-treated group. PPAs significantly inhibited the reduction of total cholesterol and triglycerides. Higher levels of superoxide dismutase and reduced glutathione enzymes as well as a reduction in the formation of malondialdehyde occurred in mice fed with PPAs. In addition, PPAs protected against increased alcohol-induced levels and activity of cytochrome P450 2E1 (CYP2E1), which demonstrates the effects of PPAs against alcohol-induced oxidative stress and liver injury. This study suggests that PPAs could be an effective therapeutic agent in alcohol-induced liver injuries by inhibiting CYP2E1 expression and thereby strengthening antioxidant defenses.

  17. Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation.

    PubMed

    Avila, Diana V; Myers, Scott A; Zhang, JingWen; Kharebava, Giorgi; McClain, Craig J; Kim, Hee-Yong; Whittemore, Scott R; Gobejishvili, Leila; Barve, Shirish

    2017-10-01

    It is increasingly evident that alcohol-induced, gut-mediated peripheral endotoxemia plays a significant role in glial cell activation and neuro-inflammation. Using a mouse model of chronic alcohol feeding, we examined the causal role of endotoxin- and cytokine-responsive Pde4 subfamily b (Pde4b) expression in alcohol-induced neuro-inflammation. Both pharmacologic and genetic approaches were used to determine the regulatory role of Pde4b. In C57Bl/6 wild type (WT) alcohol fed (WT-AF) animals, alcohol significantly induced peripheral endotoxemia and Pde4b expression in brain tissue, accompanied by a decrease in cAMP levels. Further, along with Pde4b, there was a robust activation of astrocytes and microglia accompanied by significant increases in the inflammatory cytokines (Tnfα, Il-1β, Mcp-1 and Il-17) and the generalized inflammatory marker Cox-2. At the cellular level, alcohol and inflammatory mediators, particularly LPS, Tnfα and Hmgb1 significantly activated microglial cells (Iba-1 expression) and selectively induced Pde4b expression with a minimal to no change in Pde4a and d isoforms. In comparison, the alcohol-induced decrease in brain cAMP levels was completely inhibited in WT mice treated with the Pde4 specific pharmacologic inhibitor rolipram and in Pde4b-/- mice. Moreover, all the observed markers of alcohol-induced brain inflammation were markedly attenuated. Importantly, glial cell activation induced by systemic endotoxemia (LPS administration) was also markedly decreased in Pde4b-/- mice. Taken together, these findings strongly support the notion that Pde4b plays a critical role in coordinating alcohol-induced, peripheral endotoxemia mediated neuro-inflammation and could serve as a significant therapeutic target. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila.

    PubMed

    De Nobrega, Aliza K; Lyons, Lisa C

    2016-04-01

    Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes makes Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibited rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the loss-of-righting reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrated circadian rhythms in the loss-of-righting reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced

  19. The impact of cyanoglycoside rich fraction isolated from Cassava (Manihot esculenta) on alcohol induced oxidative stress.

    PubMed

    Boby, R G; Indira, M

    2003-09-15

    The effects of feeding a cassava (Manihot esculenta) rich diet on alcohol induced peroxidative damages were investigated in male albino rats. Rats were divided into four groups and maintained for 60 days as follows. (1) CONTROL GROUP: cassava free diet, (2) alcohol group: cassava free diet+ethanol (4 g/kg body wt/day), (3) cassava group: cassava diet and (4) alcohol+cassava group: cassava diet+ethanol (4 g/kg body wt/day). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated in the liver. The activities of free radical scavenging enzymes such as superoxide dismutase (SOD), catalase and glutathione reductase were reduced and glutathione content was decreased in the liver. But the co-administration of a cassava rich diet increased the activity of free radical scavenging enzymes and glutathione content. The level of lipid peroxides in the liver was also decreased on co-administration of cassava. But the oxidative damage caused by cassava was potentiated by alcohol administration. These studies suggested that consumption of alcohol along with cassava offered some protection against the alcohol induced oxidative stress. So we isolated the cyanoglycoside rich fraction from cassava and its impact on rats administered alcohol was also investigated. The results revealed that alcohol induced oxidative stress was potentiated by the co-administration of cyanoglycoside rich fraction. These studies suggested that the fiber and antioxidant vitamins present in the cassava may be playing a protective role against the alcohol induced oxidative stress.

  20. ASMASE IS REQUIRED FOR CHRONIC ALCOHOL INDUCED HEPATIC ENDOPLASMIC RETICULUM STRESS AND MITOCHONDRIAL CHOLESTEROL LOADING

    PubMed Central

    Fernandez, Anna; Matias, Núria; Fucho, Raquel; Ribas, Vicente; Von Montfort, Claudia; Nuño, Natalia; Baulies, Anna; Martinez, Laura; Tarrats, Núria; Mari, Montserrat; Colell, Anna; Morales, Albert; Dubuquoy, Laurent; Mathurin, Philippe; Bataller, Ramón; Caballeria, Joan; Elena, Montserrat; Balsinde, Jesus; Kaplowitz, Neil; Garcia-Ruiz, Carmen; Fernandez-Checa, Jose C.

    2013-01-01

    Background & aims The pathogenesis of alcohol-induced liver disease (ALD) is poorly understood. Here, we examined the role of acid sphingomyelinase (ASMase) in alcohol induced hepatic endoplasmic reticulum (ER) stress, a key mechanism of ALD Methods We examined ER stress, lipogenesis, hyperhomocysteinemia, mitochondrial cholesterol (mChol) trafficking and susceptibility to LPS and concanavalin-A in ASMase−/− mice fed alcohol. Results Alcohol feeding increased SREBP-1c, DGAT-2 and FAS mRNA in ASMase+/+ but not in ASMase−/− mice. Compared to ASMase+/+ mice, ASMase−/− mice exhibited decreased expression of ER stress markers induced by alcohol, but the level of tunicamycin-mediated upregulation of ER stress markers and steatosis was similar in both types of mice. The increase in homocysteine levels induced by alcohol feeding was comparable in both ASMase+/+ mice and ASMase−/− mice. Exogenous ASMase, but not neutral SMase, induced ER stress by perturbing ER Ca2+ homeostasis. Moreover, alcohol-induced mChol loading and StARD1 overexpression were blunted in ASMase−/− mice. Tunicamycin upregulated StARD1 expression and this outcome was abrogated by tauroursodeoxycholic acid. Alcohol-induced liver injury and sensitization to LPS and concanavalin-A were prevented in ASMase−/− mice. These effects were reproduced in alcohol-fed TNFR1/R2−/− mice. Moreover, ASMase does not impair hepatic regeneration following partial hepatectomy. Of relevance, liver samples from patients with alcoholic hepatitis exhibited increased expression of ASMase, StARD1 and ER stress markers. Conclusion Our data indicate that ASMase is critical for alcohol-induced ER stress, and provide a rationale for further clinical investigation in ALD. PMID:23707365

  1. Circadian modulation of alcohol-induced sedation and recovery in male and female Drosophila

    PubMed Central

    De Nobrega, Aliza K.; Lyons, Lisa C.

    2016-01-01

    Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes make Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibit rhythms in alcohol-induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol-induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the Loss-of-Righting Reflex, alcohol-induced sedation, and recovery differently in males and females. We found that both sexes demonstrate circadian rhythms in the Loss-of-Righting Reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced

  2. Elderly people urged not to bath when home alone.

    PubMed

    1994-03-30

    Elderly people should only have a batch when someone else is in the house and should never lock the door, researchers have urged. The calls follow a survey which found one in seven older people have been trapped in the bath at least once.

  3. Quit Smoking

    MedlinePlus

    ... Quit Smoking Print This Topic En español Quit Smoking Browse Sections The Basics Overview Secondhand Smoke How ... to be active with your family and friends. Smoking hurts almost every part of the body. Smoking ...

  4. Testing the influence of external and internal cues on smoking motivation using a community sample.

    PubMed

    Litvin, Erika B; Brandon, Thomas H

    2010-02-01

    Exposing smokers to either external cues (e.g., pictures of cigarettes) or internal cues (e.g., negative affect induction) can induce urge to smoke and other behavioral and physiological responses. However, little is known about whether the two types of cues interact when presented in close proximity, as is likely the case in the real word. Additionally, potential moderators of cue reactivity have rarely been examined. Finally, few cue-reactivity studies have used representative samples of smokers. In a randomized 2 x 2 crossed factorial between-subjects design, the current study tested the effects of a negative affect cue intended to produce anxiety (speech preparation task) and an external smoking cue on urge and behavioral reactivity in a community sample of adult smokers (N = 175), and whether trait impulsivity moderated the effects. Both types of cues produced main effects on urges to smoke, despite the speech task failing to increase anxiety significantly. The speech task increased smoking urge related to anticipation of negative affect relief, whereas the external smoking cues increased urges related to anticipation of pleasure; however, the cues did not interact. Impulsivity measures predicted urge and other smoking-related variables, but did not moderate cue-reactivity. Results suggest independent rather than synergistic effects of these contributors to smoking motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  5. Treating Smoking Behavior by Discussion and Hypnosis: Destroying the Myths of Habit, Addiction, and Willpower.

    ERIC Educational Resources Information Center

    Moses, Ferris

    1987-01-01

    Describes an innovative procedure which uses discussion and hypnosis to help smokers lose their desire to smoke. The smoker is asked to reevaluate the validity of beliefs concerning smoking and urged to see destructive effects from poisonous tobacco smoke on mind and body. With hypnosuggestion the client is helped to implement abstinence from…

  6. Treating Smoking Behavior by Discussion and Hypnosis: Destroying the Myths of Habit, Addiction, and Willpower.

    ERIC Educational Resources Information Center

    Moses, Ferris

    1987-01-01

    Describes an innovative procedure which uses discussion and hypnosis to help smokers lose their desire to smoke. The smoker is asked to reevaluate the validity of beliefs concerning smoking and urged to see destructive effects from poisonous tobacco smoke on mind and body. With hypnosuggestion the client is helped to implement abstinence from…

  7. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    PubMed

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction.

  8. Tobacco Withdrawal Symptoms Mediate Motivation to Reinstate Smoking During Abstinence

    PubMed Central

    Aguirre, Claudia; Madrid, Jillian; Leventhal, Adam M.

    2015-01-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and three unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (10≥cig/day; N=286) attended two counterbalanced sessions at which abstinence duration was differentially manipulated (1-hour vs. 17-hours). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically-unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. PMID:25961814

  9. The Phenomenology of Hair Pulling Urges in Trichotillomania: A Comparative Approach

    PubMed Central

    Madjar, Shai; Sripada, Chandra S.

    2016-01-01

    Trichotillomania is a disorder characterized by recurrent urges to pull out one's hair, but the experiential characteristics of hair pulling urges are poorly understood. This study used a comparative approach to understand the subjective phenomenology of hair pulling: participants with trichotillomania symptoms were asked about their hair pulling urges as well as their urges to eat unhealthy foods. Participants who reported experiencing problematic unhealthy food urges were identified and asked to compare the phenomenological characteristics of their hair pulling and unhealthy food urges across a variety of dimensions. Results revealed significant differences for only some urge properties measured, and differences that existed were small to moderate in magnitude. Qualitative comparisons of the two urges revealed situational characteristics of hair pulling that could explain these small to moderate differences between the two urges. We conclude that hair pulling urges may be more comparable to ordinary urges such as unhealthy food urges than one might expect, but that hair pulling urges may nevertheless be rated as slightly more severe due to situational characteristics of these urges. This conception may improve clinician and lay understanding of the condition, assist with destigmatization efforts, and facilitate the development of treatment strategies. PMID:26925017

  10. Temporal relationship between premonitory urges and tics in Gilles de la Tourette syndrome.

    PubMed

    Brandt, Valerie C; Beck, Christian; Sajin, Valeria; Baaske, Magdalena K; Bäumer, Tobias; Beste, Christian; Anders, Silke; Münchau, Alexander

    2016-04-01

    Premonitory urges are a cardinal feature in Tourette syndrome and are commonly viewed as the driving force of tics, building up before and subsiding after the execution of tics. Although the urge-tic interplay is one of the most preeminent features in Tourette syndrome, the temporal relationship between tics and urges has never been examined experimentally, mainly due to the lack of an appropriate assessment tool. We investigated the temporal relationship between urge intensity and tics in 17 Tourette patients and between urge intensity and eye blinks in 16 healthy controls in a free ticcing/blinking condition and a tic/blink suppression condition. For this purpose, an urge assessment tool was developed that allows real-time monitoring and quantification of urge intensity. Compared to free ticcing/blinking, urge intensity was higher during the suppression condition in both Tourette patients and healthy controls, while tics and blinks occurred less frequently. The data show that urge intensity increases prior to tics and decreases after tics in a time window of approximately ±10 sec. Tic suppression had a significant effect on the shape of the urge distribution around tics and led to a decrease in the size of the correlation between urge intensity and tics, indicating that tic suppression led to a de-coupling of tics and urges. In healthy controls, urges to blink were highly associated with eye blink execution, albeit in a narrower time frame (∼±5 sec). Blink suppression had a similar effect on the urge distribution associated with eye blinks as tic suppression had on the urge to tic in Tourette patients. These results corroborate the negative reinforcement model, which proposes that tics are associated with a relief in urges, thereby perpetuating ticcing behaviour. This study also documents similarities and differences between urges to act in healthy controls and urges to tic in Tourette syndrome.

  11. The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury

    PubMed Central

    Zhang, Yu-Jie; Zhou, Tong; Wang, Fang; Zhou, Yue; Li, Ya; Zhang, Jiao-Jiao; Zheng, Jie; Xu, Dong-Ping; Li, Hua-Bin

    2016-01-01

    Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), triglyceride (TG), malondialdehyde (MDA), and decreased total protein (TP). Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage. PMID:27681723

  12. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats.

    PubMed

    Keshavarzian, A; Choudhary, S; Holmes, E W; Yong, S; Banan, A; Jakate, S; Fields, J Z

    2001-11-01

    Only 30% of alcoholics develop liver disease (ALD) suggesting that additional factors are needed. Endotoxin is one such factor, but its etiology is unclear. Since the gut is the main source of endotoxin, we sought to determine whether an increase in intestinal permeability (leaky gut) is required for alcohol-induced endotoxemia and liver injury and whether the gut leakiness is preventable. For 10 weeks, rats received by gavage increasing alcohol doses (to 8 g/kg/day) and either oats (10 g/kg) or chow b.i.d. Intestinal permeability was then assessed by urinary excretion of lactulose and mannitol. Liver injury was evaluated histologically, biochemically (liver fat content), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these changes. We conclude that chronic gavage of alcohol in rats is a simple experimental model that mimics key aspects of ALD, including endotoxemia and liver injury, and can be useful to study possible mechanisms of endotoxemia in ALD. Since preventing the gut leakiness by oats also prevented the endotoxemia and ameliorated liver damage in rat, our results suggest that alcohol-induced gut leakiness 1) may cause alcohol-induced endotoxemia and liver injury and 2) may be the critical cofactor in the 30% of alcoholics who develop ALD. Further studies are needed to determine whether ALD in humans can be prevented by preventing alcohol-induced gut leakiness, studies that should lead to the development of useful therapeutic agents for the prevention of ALD.

  13. Pharmacological ceramide reduction alleviates alcohol-induced steatosis and hepatomegaly in adiponectin knockout mice

    PubMed Central

    Correnti, Jason M.; Juskeviciute, Egle; Swarup, Aditi

    2014-01-01

    Hepatosteatosis, the ectopic accumulation of lipid in the liver, is one of the earliest clinical signs of alcoholic liver disease (ALD). Alcohol-dependent deregulation of liver ceramide levels as well as inhibition of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPAR-α) activity are thought to contribute to hepatosteatosis development. Adiponectin can regulate lipid handling in the liver and has been shown to reduce ceramide levels and activate AMPK and PPAR-α. However, the mechanisms by which adiponectin prevents alcoholic hepatosteatosis remain incompletely characterized. To address this question, we assessed ALD progression in wild-type (WT) and adiponectin knockout (KO) mice fed an ethanol-containing liquid diet or isocaloric control diet. Adiponectin KO mice relative to WT had increased alcohol-induced hepatosteatosis and hepatomegaly, similar modest increases in serum alanine aminotransferase, and reduced liver TNF. Restoring circulating adiponectin levels using recombinant adiponectin ameliorated alcohol-induced hepatosteatosis and hepatomegaly in adiponectin KO mice. Alcohol-fed WT and adiponectin KO animals had equivalent reductions in AMPK protein and PPAR-α DNA binding activity compared with control-fed animals. No difference in P-AMPK/AMPK ratio was detected, suggesting that alcohol-dependent deregulation of AMPK and PPAR-α in the absence of adiponectin are not primary causes of the observed increase in hepatosteatosis in these animals. By contrast, alcohol treatment increased liver ceramide levels in adiponectin KO but not WT mice. Importantly, pharmacological inhibition of de novo ceramide synthesis in adiponectin KO mice abrogated alcohol-mediated increases in liver ceramides, steatosis, and hepatomegaly. These data suggest that adiponectin reduces alcohol-induced steatosis and hepatomegaly through regulation of liver ceramides, but its absence does not exacerbate alcohol-induced liver damage. PMID

  14. The Pathogenesis of Alcohol-Induced Airflow Limitation in Acetaldehyde Dehydrogenase 2-Deficient Mice.

    PubMed

    Shimoda, Terufumi; Obase, Yasushi; Matsuse, Hiroto; Asai, Sadahiro; Iwanaga, Tomoaki

    2016-01-01

    In Japanese patients, alcohol-induced asthma is attributed to elevated plasma concentrations of acetaldehyde following alcohol consumption because of an acetaldehyde dehydrogenase 2 gene (ALDH2) polymorphism. The resulting increase in plasma histamine concentrations seems to trigger the onset of asthma symptoms. However, the specific pathogenic mechanism underlying this response remains unclear. ALDH2-deficient mice were therefore generated to investigate the pathogenesis of alcohol-induced asthma. ALDH2-deficient mice were generated using embryonic stem cells that were derived from C57BL/6 mice. The resulting mice were backcrossed into the BALB/c mice background. Exon 1 of ALDH2 was replaced with the Neo cassette. Pure ethanol was orally administered to ALDH2-deficient and wild-type mice, and the plasma concentrations of ethanol, acetaldehyde, and histamine, in addition to enhanced pause (Penh) values, were determined and compared between the 2 groups. We established an ALDH2-deficient mouse line to compare responses between wild-type and ALDH2-deficient mice receiving orally administered ethanol. The results showed that the plasma concentrations of acetaldehyde (p < 0.0001) and histamine (p < 0.005) were significantly higher, and the Penh values (p < 0.01) were significantly greater in the ALDH2-deficient mice, although plasma ethanol levels were not different. We studied the pathogenesis of alcohol-induced asthma using ALDH2-deficient mice. The results demonstrated that alcohol intake resulted in an increase in acetaldehyde levels, and a subsequent increase in histamine levels, which induced airway constriction. Alcohol consumption is known to be an important factor that exacerbates bronchial asthma, and studies investigating this factor are useful for the treatment of patients with alcohol-induced asthma. © 2017 S. Karger AG, Basel.

  15. [Smoking and smoking weaning].

    PubMed

    Gutzwiller, F; Bucher, H

    1994-10-01

    Stop-smoking counselling is a challenging task in primary health care, its efficacy being often underestimated by the physician. Health care physicians are not very inclined to advise their smoking patients to stop smoking and give specific counselling. This is in contradiction with the expectations of more than two thirds of the smoking patients, who expect their physicians to help them. The present article discusses the therapeutical methods for stop-smoking counselling in primary health care. In particular, the article illustrates the importance for this support (including the possibilities for nicotin substitution in the weaning stage).

  16. Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage.

    PubMed

    Saka, W A; Akhigbe, R E; Ishola, O S; Ashamu, E A; Olayemi, O T; Adeleke, G E

    2011-07-15

    There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague-Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract-treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p < 0.05) increased total serum bilirubin, alkaline phosphatase and aspartate transaminase activities. Alcohol-induced hepatic dysfunction was abrogated by Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction.

  17. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury

    PubMed Central

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  18. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping.

    PubMed

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2016-04-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for in vitro drug release in hydrochloric acid alone and with 40% v/v ethanol. The responses, dissolution at 120 min without alcohol (R1) and dissolution at 120 min with alcohol (R2), were statistically evaluated and regression equations are generated. PGA as a hydrophilic polymeric matrix was dumping the dose when dissolutions are carried in 0.1 N hydrochloric acid containing 40% v/v ethanol. ERS addition was giving structural support to the swelling and gelling property of PGA, and thus, was reducing the PGA erosion in dissolution media containing ethanol. Among the formulations, four formulations with diverse composition were meeting the target dissolution (30-40%) in both the conditions. The statistical validity of the mathematical equations was established, and the optimum concentration of the factors was established. Validation of the study with six confirmatory runs indicated high degree of prognostic ability of response surface methodology. Further coating with ReadiLycoat was providing an additional resistance to the alcohol-induced dose dumping. Optimized compositions showed resistance to dose dumping in the presence of alcohol.

  19. Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties.

    PubMed

    Reddy, Vaddi Damodara; Padmavathi, Pannuru; Kavitha, Godugu; Saradamma, Bulle; Varadacharyulu, Nallanchakravarthula

    2013-03-01

    Chronic alcohol consumption causes numerous biochemical and biophysical changes in the central nervous system, in which mitochondria is the primary organelle affected. In the present study, we hypothesized that alcohol alters the mitochondrial membrane properties and leads to mitochondrial dysfunction via mitochondrial reactive oxygen species (mROS) and reactive nitrogen species (RNS). Alcohol-induced hypoxia further enhances these effects. Administration of alcohol to rats significantly increased the mitochondrial lipid peroxidation and protein oxidation with decreased SOD2 mRNA and protein expression was decreased, while nitric oxide (NO) levels and expression of iNOS and nNOS in brain cortex were increased. In addition, alcohol augmented HIF-1α mRNA and protein expression in the brain cortex. Results from this study showed that alcohol administration to rats decreased mitochondrial complex I, III, IV activities, Na(+)/K(+)-ATPase activity and cardiolipin content with increased anisotropic value. Cardiolipin regulates numerous enzyme activities, especially those related to oxidative phosphorylation and coupled respiration. In the present study, decreased cardiolipin could be ascribed to ROS/RNS-induced damage. In conclusion, alcohol-induced ROS/RNS is responsible for the altered mitochondrial membrane properties, and alcohol-induced hypoxia further enhance these alterations, which ultimately leads to mitochondrial dysfunction.

  20. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

    PubMed Central

    Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao

    2017-01-01

    Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity. PMID:28567423

  1. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice.

    PubMed

    Zhou, Tong; Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao; Li, Hua-Bin

    2017-01-01

    Chronic excessive alcohol consumption (more than 40-80 g/day for males and more than 20-40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

  2. Can disulfiram use precipitate urges to drink alcohol?

    PubMed

    Nirenberg, T D; Sobell, L C; Ersner-Hershfield, S; Cellucci, A J

    1983-01-01

    Although pharmacological data suggest that patients taking disulfiram should have a reduced desire to drink alcohol, voluntary compliance with disulfiram treatment is quite poor. As a possible explanation for why so many patients discontinue taking disulfiram and return to excessive drinking, it was hypothesized that daily disulfiram administration might serve as a cognitive stimulus precipitating urges to drink alcohol and/or inadvertently exposing patients to additional drinking-related cues. If this is the case, then patients taking disulfiram should report more thoughts about or urges to drink alcohol. In an exploratory, uncontrolled clinical study, alcohol abusers who were taking disulfiram tended to self-record more cravings for alcohol over a two week period than did abstinent patients who were not taking disulfiram. Controlled research is needed to investigate whether disulfiram use may serve as a cue antecedent to relapse to drinking.

  3. Premonitory urge to tic in Tourette's is associated with interoceptive awareness.

    PubMed

    Ganos, Christos; Garrido, Alicia; Navalpotro-Gómez, Irene; Ricciardi, Lucia; Martino, Davide; Edwards, Mark J; Tsakiris, Manos; Haggard, Patrick; Bhatia, Kailash P

    2015-08-01

    A contribution of aberrant interoceptive awareness to the perception of premonitory urges in Gilles de la Tourette syndrome (GTS) has been hypothesized. We assessed interoceptive awareness in 19 adults with GTS and 25 age-matched healthy controls using the heartbeat counting task. We also used multiple regression to explore whether the severity of premonitory urges was predicted by interoceptive awareness or severity of tics and obsessive-compulsive symptoms. We observed lower interoceptive awareness in GTS compared with controls. Interoceptive awareness was the strongest predictor of premonitory urges in GTS, with greater interoceptive awareness being associated with more urges. Greater tic severity was also associated with higher rates of premonitory urges. The observed relationship between severity of premonitory urges and interoceptive awareness suggests that interoception might be involved in self-reported premonitory urges in GTS. High levels of interoceptive awareness might reflect a self-attentive capacity to perceive urges. © 2015 International Parkinson and Movement Disorder Society.

  4. Premonitory urges for tics in adult patients with Tourette syndrome.

    PubMed

    Crossley, Eleanor; Seri, Stefano; Stern, Jeremy S; Robertson, Mary M; Cavanna, Andrea E

    2014-01-01

    Patients with Tourette syndrome (TS) often report characteristic sensory experiences, also called premonitory urges (PUs), which precede tic expression and have high diagnostic relevance. This study investigated the usefulness of a scale developed and validated in children and adolescents-the Premonitory Urge for Tics Scale (PUTS, Woods et al., 2005 [13])-for the assessment of PUs in adult patients with TS. Standard statistical methods were applied to test the psychometric properties of the PUTS in 102 adult TS outpatients recruited from two specialist clinics in the United Kingdom. The PUTS showed good acceptability and endorsement rates, with evenly distributed scores and low floor and ceiling effects. Item-total correlations were moderate to strong; PUTS total scores were significantly correlated with quantitative measures of TS severity. The PUTS showed excellent internal consistency reliability (Cronbach's alpha=0.85) and Spearman's correlations demonstrated satisfactory convergent and discriminant validity. Although originally devised to assess urges to tic in young patients with TS, the PUTS demonstrated good psychometric properties in a large sample of adults recruited at specialist TS clinics. This instrument is therefore recommended for use across the life span as a valid and reliable self-report measure of sensory experiences accompanying tic expression. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Examining cognitive examining cognitive processes and drinking urge in PTSD.

    PubMed

    Read, Jennifer P; Bachrach, Rachel L; Wardell, Jeffrey D; Coffey, Scott F

    2017-03-01

    Despite their centrality to learning theories, strikingly little attention has been paid to the role of cognitions in efforts to understand associations between posttraumatic stress disorder (PTSD) and alcohol drinking. In the present study, we sought to examine information processing pathways for trauma and alcohol information, and the effects of posttraumatic stress and trauma cue exposure on these pathways. Participants were college students (N = 232; 49% female; Mage = 19.56,SD = 1.44) categorized into three diagnostic groups based on current PTSD status determined by structured clinical interview. These students then were exposed to a personalized trauma or neutral cue script, followed by a Stroop task modified to include trauma, alcohol, and contrast words. Indices of mood and urge to drink alcohol were administered throughout the task. Findings revealed that those with PTSD who were exposed to the personalized trauma cue showed a general response slowing across all stimuli types on the Stroop task. Intriguingly, this slowing effect was significantly associated with urge to drink alcohol for only those PTSD participants who were exposed to the trauma cues. In contrast, we did not find support for the hypothesis that trauma cues would lead to attention bias to trauma and alcohol specific Stroop stimuli among participants with PTSD, nor did slower RT for specific word types predict unique variance in urge to drink alcohol. Findings suggest that individual (PTSD) and environmental (cue) circumstances may work conjointly to precipitate changes in cognitive processing - changes that may have implications for drinking motivation. Given the importance of cognition in the etiology of both PTSD and drinking, this is a mechanism that warrants further investigation. Copyright © 2016. Published by Elsevier Ltd.

  6. Clinical pharmacokinetics of drugs used to treat urge incontinence.

    PubMed

    Guay, David R P

    2003-01-01

    Urge incontinence (also known as overactive bladder) is a common form of urinary incontinence, occurring alone or as a component of mixed urinary incontinence, frequently together with stress incontinence. Because of the pathophysiology of urge incontinence, anticholinergic/antispasmodic agents form the cornerstone of therapy. Unfortunately, the pharmacological activity of these agents is not limited to the urinary tract, leading to systemic adverse effects that often promote nonadherence. Although the pharmacokinetics of flavoxate, propantheline, scopolamine, imipramine/desipramine, trospium chloride and propiverine are also reviewed here, only for oxybutynin and tolterodine are there adequate efficacy/tolerability data to support their use in urge incontinence. Oxybutynin is poorly absorbed orally (2-11% for the immediate-release tablet formulation). Controlled-release oral formulations significantly prolong the time to peak plasma concentration and reduce the degree of fluctuation around the average concentration. Significant absorption occurs after intravesical (bladder) and transdermal administration, although concentrations of the active N-desethyl metabolite are lower after transdermal compared with oral administration, possibly improving tolerability. Food has been found to significantly affect the absorption of one of the controlled-release formulations of oxybutynin, enhancing the rate of drug release. Oxybutynin is extensively metabolised, principally via N-demethylation mediated by the cytochrome P450 (CYP) 3A isozyme. The pharmacokinetics of tolterodine are dependent in large part on the pharmacogenomics of the CYP2D6 and 3A4 isozymes. In an unselected population, oral bioavailability of tolterodine ranges from 10% to 74% (mean 33%) whereas in CYP2D6 extensive metabolisers and poor metabolisers mean bioavailabilities are 26% and 91%, respectively. Tolterodine is metabolised via CYP2D6 to the active metabolite 5-hydroxymethyl-tolterodine and via CYP3A

  7. Effects of Alcohol-Induced Working Memory Decline on Alcohol Consumption and Adverse Consequences of Use

    PubMed Central

    Lechner, William V.; Day, Anne M.; Metrik, Jane; Leventhal, Adam M.; Kahler, Christopher W.

    2015-01-01

    Rationale Alcohol use appears to decrease executive function acutely in a dose dependent manner, and lower baseline executive function appears to contribute to problematic alcohol use. However, no studies, to our knowledge, have examined the relationship between individual differences in working memory (a subcomponent of executive function) after alcohol consumption and drinking behaviors and consequences. Objectives The current study assessed the relationship between drinking behavior, alcohol-related consequences, and alcohol-induced changes in working memory (as assessed by Trails Making Test-B). Method Participants recruited from the community (n = 41), 57.3% male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. Working memory, past 30 day alcohol consumption, and consequences of alcohol use were measured at baseline; working memory was measured again after each beverage administration. Results Poorer working memory after alcohol administration (controlling for baseline working memory) was significantly associated with a greater number of drinks consumed per drinking day. Additionally, we observed a significant indirect relationship between the degree of alcohol-induced working memory decline and adverse consequences of alcohol use, which was mediated through greater average drinks per drinking day. Conclusions It is possible that greater individual susceptibility to alcohol-induced working memory decline may limit one’s ability to moderate alcohol consumption as evidenced by greater drinks per drinking day, and that this results in more adverse consequences of alcohol use. PMID:26407604

  8. The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head.

    PubMed

    Chen, Yi-Xuan; Zhu, Dao-Yu; Xu, Zheng-Liang; Yin, Jun-Hui; Yu, Xiao-Wei; Mei, Jiong; Gao, You-Shui; Zhang, Chang-Qing

    2017-08-21

    Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH), in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. Human bone mesenchymal stem cells (hBMSCs) were identified by multi-lineage differentiation. Alkaline phosphatase (ALP) activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E) staining and micro-computerized tomography (micro-CT) were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining was carried out to detect OCN and COL1. Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/β-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH. © 2017 The Author(s). Published by S. Karger AG, Basel.

  9. Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

    PubMed

    Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

    2016-10-01

    Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. Copyright © 2016 by the Research Society on Alcoholism.

  10. Effects of alcohol-induced working memory decline on alcohol consumption and adverse consequences of use.

    PubMed

    Lechner, William V; Day, Anne M; Metrik, Jane; Leventhal, Adam M; Kahler, Christopher W

    2016-01-01

    Alcohol use appears to decrease executive function acutely in a dose-dependent manner, and lower baseline executive function appears to contribute to problematic alcohol use. However, no studies, to our knowledge, have examined the relationship between individual differences in working memory (a subcomponent of executive function) after alcohol consumption and drinking behaviors and consequences. The current study assessed the relationship between drinking behavior, alcohol-related consequences, and alcohol-induced changes in working memory (as assessed by Trail Making Test-B). Participants recruited from the community (n = 41), 57.3 % male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. Working memory, past 30-day alcohol consumption, and consequences of alcohol use were measured at baseline; working memory was measured again after each beverage administration. Poorer working memory after alcohol administration (controlling for baseline working memory) was significantly associated with a greater number of drinks consumed per drinking day. Additionally, we observed a significant indirect relationship between the degree of alcohol-induced working memory decline and adverse consequences of alcohol use, which was mediated through greater average drinks per drinking day. It is possible that greater individual susceptibility to alcohol-induced working memory decline may limit one's ability to moderate alcohol consumption as evidenced by greater drinks per drinking day and that this results in more adverse consequences of alcohol use.

  11. Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats.

    PubMed

    Kaur, Maninder; Singh, Amarjeet; Kumar, Bimlesh; Singh, Sachin Kumar; Bhatia, Amit; Gulati, Monica; Prakash, T; Bawa, Palak; Malik, Adil Hussain

    2017-03-16

    Neuropathic pain associated with chronic alcohol consumption is a medico-socioeconomical problem that affects both central and peripheral nervous system and has no satisfactory treatment till date. The present study was designed to investigate the protective effect of co-administration of curcumin and sildenafil on alcohol induced neuropathic pain in rats. In order to carry out this, ethanol (35% v/v, 10g/kg, p.o.) was administered for 10 weeks to induce neuropathic pain. Curcumin (30 and 60mg/kg, i.p.) and sildenafil (5 and 10mg/kg, i.p.) were given alone and in combination at their lower doses (30mg/kg curcumin and 5mg/kg, sildenafil, i.p.) to investigate the changes in thermal and mechanical hyperalgesia, allodynia and histopathological parameters. Biochemical estimations of thiobarbituric acid reactive species, glutathione and protein was also carried out to evaluate oxidative stress. The results revealed that chronic alcohol consumption for 10 weeks caused significant thermal and mechanical hyperalgesia, allodynia and increased oxidative stress. Individual administration of both the drugs at their low as well as high doses were able to improve the symptoms of alcohol induced neuropathic pain. Whereas co-administration of curcumin and sildenafil at their lower doses itself were found to significantly improve nerve functions, biochemical and histopathological parameters as compared to their individual administration. It is therefore proposed that co-administration of curcumin and sildenafil may bring new dimension towards attenuation of alcohol induced neuropathic pain affecting central as well as peripheral nervous system.

  12. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Hashemi, Hajar; Gholami, Mina

    2017-03-01

    Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway

  13. Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

    PubMed

    Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; N Ch, Varadacharyulu

    2016-10-01

    Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity. In-vitro studies revealed that PSE possess strong DPPH (1,1-diphenyl-2-picryl hydrazyl) and nitric oxide radical scavenging activity. For in vivo studies male albino Wistar rats were treated with 20% alcohol (5g/kg b.wt/day) and PSE (250mg/kg b.wt/day) for 60days. Results showed that alcohol administration significantly altered plasma lipid profile with marked increase in the levels of plasma transaminases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (γGT). Moreover, lipid peroxides, nitric oxide (NOx) levels in plasma and liver were increased with increased iNOS protein expression in liver was noticed in alcohol administered rats and these levels were significantly brought back close to normal level by PSE administration except iNOS protein expression. Alcohol administration also decreased the content of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-s transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in liver, which were significantly enhanced by administration of PSE. The active compounds pterostilbene, lignan and lupeols present in PSE might have shown protection against alcohol-induced hepatic damage by possibly reducing the rate of lipid peroxidation, NOx levels and increasing the antioxidant defence mechanism in alcohol administered rats. Both biochemical and histopathological results in the alcohol-induced liver damage model emphasize beneficial action of PSE as a hepatoprotective agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain.

    PubMed

    Rump, Travis J; Abdul Muneer, P M; Szlachetka, Adam M; Lamb, Allyson; Haorei, Catherine; Alikunju, Saleena; Xiong, Huangui; Keblesh, James; Liu, Jianuo; Zimmerman, Matthew C; Jones, Jocelyn; Donohue, Terrence M; Persidsky, Yuri; Haorah, James

    2010-11-30

    The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders. Published by Elsevier Inc.

  15. Smoking Through a Topography Device Diminishes Some of the Acute Rewarding Effects of Smoking.

    PubMed

    Ross, Kathryn C; Juliano, Laura M

    2016-05-01

    Smoking topography (ST) devices are an important methodological tool for quantifying puffing behavior (eg, puff volume, puff velocity) as well as identifying puffing differences across individuals and situations. Available ST devices are designed such that the smoker's mouth and hands have direct contact with the device rather than the cigarette itself. Given the importance of the sensorimotor aspects of cigarette smoking in smoking reward, it is possible that ST devices may interfere with the acute rewarding effects of smoking. Despite the methodological importance of this issue, few studies have directly compared subjective reactions to smoking through a topography device to naturalistic smoking. Smokers (N = 58; 38% female) smoked their preferred brand of cigarettes one time through a portable topography device and one time naturalistically, in counterbalanced order across two laboratory sessions. Smoking behavior (eg, number of puffs) and subjective effects (eg, urge reduction, affect, smoking satisfaction) were assessed. Negative affect reduction was greater in the natural smoking condition relative to the topography condition, but differences were not significant on measures of urge, withdrawal, or positive affect. Self-reported smoking satisfaction, enjoyment of respiratory tract sensations, psychological reward, craving reduction, and other rewarding effects of smoking were also significantly greater in the naturalistic smoking condition. The effects of using a ST device on the smoking experience should be considered when it is used in research as it may diminish some of the rewarding effects of smoking. When considering the inclusion of a smoking topography device in one's research, it is important to know if use of that device will alter the smoker's experience. This study assessed affective and subjective reactions to smoking through a topography device compared to naturalistic smoking. We found that smoking satisfaction, psychological reward, enjoyment

  16. Bacteriuria is associated with urge urinary incontinence in older women

    PubMed Central

    Rodhe, Nils; Englund, Lars; Mölstad, Sigvard; Samuelsson, Eva

    2008-01-01

    Objective To investigate the association between bacteriuria and frequency and type of urinary incontinence in elderly people living in the community. Bacteriuria and urinary incontinence are common conditions and often coexisting in this population; the authors have previously reported the prevalence of bacteriuria to be 22.4% in women and 9.4% in men. Design Cross-sectional study. Setting The catchment area of a primary healthcare centre in a Swedish middle-sized town. Subjects Residents, except for those in nursing homes, aged 80 and over. Participation rate: 80.3% (431/537). Main outcome measures Urinary cultures and questionnaire data on urinary incontinence. Results In women the OR for having bacteriuria increased with increasing frequency of urinary incontinence; the OR was 2.83 (95% CI 1.35–5.94) for women who were incontinent daily as compared with continent women. Reporting urge urinary incontinence increased the risk of having bacteriuria: 3.36 (95% CI 1.49–7.58) in comparison with continent women while there was no significant association between stress urinary incontinence and bacteriuria. The prevalence of bacteriuria among men was too low to make any meaningful calculations about the association between bacteriuria and frequency and type of incontinence. Conclusion Bacteriuria is associated with more frequent leakage and predominantly with urge urinary incontinence. The causes of this association and their clinical implications remain unclear. There might be some individuals who would benefit from antibiotic treatment, but further studies are warranted. PMID:18297561

  17. Polydatin alleviates alcohol-induced acute liver injury in mice: Relevance of matrix metalloproteinases (MMPs) and hepatic antioxidants.

    PubMed

    Koneru, Meghana; Sahu, Bidya Dhar; Gudem, Sagarika; Kuncha, Madhusudana; Ravuri, Halley Gora; Kumar, Jerald Mahesh; Kilari, Eswar Kumar; Sistla, Ramakrishna

    2017-04-15

    Alcohol, a most commonly consumed beverage, is the foremost cause of liver injury throughout the world. Polydatin, a stilbenoid glucoside, was known to possess antioxidant and anti-inflammatory properties and is being investigated for use in various disorders. The present study was intended at investigating the hepatoprotective efficacy of polydatin against acute-alcohol induced liver injury model in mice. C57BL/6 mice were fed with five doses of 50% ethyl alcohol (10ml/kg body weight) to induce acute liver injury. Effect of polydatin against alcohol induced hepatic injury was investigated by giving 50 or 100mg/kg polydatin, orally, for 8 days. Serum markers of liver injury, morphology, histology and fibrosis of liver tissue, levels of enzymatic and non-enzymatic antioxidants and the mitochondrial respiratory enzyme activities in liver tissue were investigated. The activities and the protein expression of matrix metalloproteinases (MMP-2 and -9), the expression of NF-κB in the liver tissue were also studied. Polydatin pre-treatment significantly alleviated the alcohol induced hepatic injury by reducing the serum liver injury markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), attenuating oxidative stress and restoring antioxidant balance in the hepatic tissue. Simultaneously, polydatin pre-treatment also prevented alcohol induced mitochondrial damage and refurbished the matrix metalloproteinases levels of the hepatic tissue. The findings of the present study suggest that polydatin may have a potential benefit in preventing alcohol-induced acute hepatic injury. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Development of a Virtual Reality Coping Skills Game to Prevent Post-Hospitalization Smoking Relapse in Tobacco Dependent Cancer Patients.

    PubMed

    Krebs, Paul; Burkhalter, Jack; Lewis, Shireen; Hendrickson, Tinesha; Chiu, Ophelia; Fearn, Paul; Perchick, Wendy; Ostroff, Jamie

    2009-08-01

    Many hospitalized smokers return to smoking after hospital discharge even though continued smoking can compromise treatment effectiveness, reduce survival, increase risk of disease recurrence, and impair quality of life. After leaving a smoke-free hospital, patients encounter smoking cues at home, such as family members who smoke or emotional triggers such as stress, which can elicit powerful urges to smoke and lead to smoking relapse. Enabling smokers to experience such urges in a controlled setting while providing the ability to practice coping skills may be a useful strategy for building quitting self-efficacy. We are developing a virtual reality coping skills (VRCS) game to help hospitalized smokers practice coping strategies to manage these triggers in preparation for returning home after hospitalization. Our multidisciplinary team developed a prototype VRCS game using Second Life, a platform that allowed rapid construction of a virtual reality environment. The prototype contains virtual home spaces (e.g., living room, kitchen) populated with common triggers to smoke and a "toolkit" with scripted actions that enable the avatar to rehearse various coping strategies. Since eliciting and managing urges to smoke is essential to the game's utility as an intervention, we assessed the ability of the prototype virtual environment to engage former smokers in these scenarios. We recruited eight former smokers with a recent history of hospitalization and guided each through a VRCS scenario during which we asked the patient to evaluate the strength of smoking urges and usefulness of coping strategies. Initial data indicate that patients report high urges to smoke (mean = 8.8 on a 10 point scale) when their avatar confronted virtual triggers such as drinking coffee. Patients rated virtual practice of coping strategies, such as drinking water or watching TV, as very helpful (mean = 8.4 on a 10 point scale) in reducing these urges. With further development, this VRCS game

  19. Protective role of CYP2E1 inhibitor diallyl disulfide (DADS) on alcohol-induced malondialdehyde-deoxyguanosine (M1dG) adduct formation.

    PubMed

    Sapkota, Muna; Hottor, Tete K; DeVasure, Jane M; Wyatt, Todd A; McCaskill, Michael L

    2014-06-01

    Alcohol use disorders are often associated with lung disease. Alcohol exposure leads to the production of reactive oxygen species, lipid peroxidation, and formation of malondialdehyde (MDA) as well as to induce the expression of cytochrome p450 2E1 (CYP2E1). Likewise, cigarette smoking can lead to lung lipid peroxidation and formation of MDA. MDA can bind to DNA forming MDA-deoxyguanosine (M1dG) adducts, which have been implicated in alcohol-related cancers and cardiovascular disease. Because CYP2E1 regulates MDA production, and our previous studies have shown that alcohol and cigarette smoke can lead to MDA formation, we hypothesized that CYP2E1 would modulate M1dG adduct formation and single-strand DNA damage in alcohol- and cigarette smoke-exposed lung cells and tissue. Normal human bronchial epithelial cells (HBECs) were pretreated with 10 μM diallyl disulfide (DADS) for 1 hour and treated with 80 mM ethanol (EtOH) ± 5% cigarette smoke extract (CSE) for 3 hours for comet assay and 6 hours for CYP2E1, MDA, and M1dG adduct assays. C57BL/6 mice were administered 20% EtOH ad libitum in drinking water for 8 weeks and exposed to whole-body cigarette smoke for 5 weeks. Mice were also fed a CYP2E1 inhibitor, DADS, at 1 μM/g of feed in their daily diet for 7 weeks. Whole lung tissue homogenate was used for CYP2E1, MDA, and M1dG adduct assays. EtOH exposure significantly increased HBEC olive tail moment. DADS pretreatment of HBECs attenuated this EtOH effect. EtOH also induced MDA and M1dG adduct formation, which was also significantly reduced by DADS treatment. CSE ± EtOH did not enhance these effects. In lung tissue homogenate of 8-week alcohol-fed mice, MDA and M1dG adduct levels were significantly elevated in comparison with control mice and mice fed DADS while consuming alcohol. No increase in MDA and M1dG adduct formation was observed in 5-week cigarette smoke-exposed mice. These findings suggest that CYP2E1 plays a pivotal role in alcohol-induced M1dG adducts

  20. Protective Role of CYP2E1 Inhibitor Diallyl Disulfide (DADS) on Alcohol Induced Malondialdehyde-Deoxyguanosine (M1dG) Adduct Formation

    PubMed Central

    Sapkota, M.; Hottor, T. K.; DeVasure, J. M.; Wyatt, T. A.; McCaskill, M. L.

    2014-01-01

    alcohol-induced M1dG adducts, and the use of DADS as dietary supplement can reverse the effects of alcohol on M1dG formation. PMID:24891074

  1. Plastic Surgeons Urge Giving Up E-Cigs Before Procedure

    MedlinePlus

    ... HealthDay News) -- Plastic surgery patients should avoid smoking e-cigarettes for at least four weeks before their procedures, ... reasonable to advise plastic surgery candidates to cease e-cigarette use," said Dr. Peter Taub,, of Mount Sinai ...

  2. Role of the right dorsal anterior insula in the urge to tic in Tourette syndrome.

    PubMed

    Tinaz, Sule; Malone, Patrick; Hallett, Mark; Horovitz, Silvina G

    2015-08-01

    The mid-posterior part of the insula is involved in processing bodily sensations and urges and is activated during tic generation in Tourette syndrome. The dorsal anterior part of the insula, however, integrates sensory and emotional information with cognitive valuation and is implicated in interoception. The right dorsal anterior insula also participates in urge suppression in healthy subjects. This study examined the role of the right dorsal anterior insula in the urge to tic in Tourette syndrome. Resting-state functional magnetic resonance imaging was performed in 13 adult Tourette patients and 13 matched controls. The role of the right dorsal anterior insula within the urge-tic network was investigated using graph theory-based neural network analysis. The functional connectivity of the right dorsal anterior insula was also correlated with urge and tic severity. Even though the patients did not exhibit any overt tics, the right dorsal anterior insula demonstrated higher connectivity, especially with the frontostriatal nodes of the urge-tic network in patients compared with controls. The functional connectivity between the right dorsal anterior insula and bilateral supplementary motor area also correlated positively with urge severity in patients. These results suggest that the right dorsal anterior insula is part of the urge-tic network and could influence the urge- and tic-related cortico-striato-thalamic regions even during rest in Tourette syndrome. It might be responsible for heightened awareness of bodily sensations generating premonitory urges in Tourette syndrome. © 2015 International Parkinson and Movement Disorder Society.

  3. Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

    PubMed Central

    Ji, Cheng

    2015-01-01

    Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries. PMID:26047032

  4. Effect of indomethacin on alcohol-induced morphological anomalies in mice

    SciTech Connect

    Randall, C.L.; Anton, R.F.; Becker, H.C.

    1987-07-20

    The purpose of the present study was 1) to examine the effect of indomethacin (INDO), a prostaglandin synthesis inhibitor, on alcohol-induced growth and morphological impairment in C57BL/6J mice (Study 1) and 2) to determine if INDO crosses the placenta (Study 2). On day 10 of gestation, mice were injected (s.c.) acutely with either 0, 5, 10, or 20 mg/kg INDO, followed one hour later by alcohol (5.8 g/kg orally) or isocaloric sucrose. Fetuses were removed on day 19 of pregnancy, weighed, and examined for anomalous development. As expected, Study 1 demonstrated that maternal alcohol treatment decreased fetal weight and increased the number of fetuses with birth defects. INDO alone decreased fetal weight but did not affect morphologic development. More importantly, INDO antagonized alcohol-induced birth defects, but only at the highest dose. The results of Study 2 suggest that the relative ineffectiveness of INDO may be related to its inability to readily cross the placenta. Since high doses of INDO also caused maternal toxicity, the usefulness of this compound in future studies of this type was questioned. 22 references, 4 tables.

  5. Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury.

    PubMed

    Wang, Yuping; Mukhopadhyay, Partha; Cao, Zongxian; Wang, Hua; Feng, Dechun; Haskó, György; Mechoulam, Raphael; Gao, Bin; Pacher, Pal

    2017-09-21

    Cannabidiol (CBD) is a non-psychoactive component of marijuana, which has anti-inflammatory effects. It has also been approved by FDA for various orphan diseases for exploratory trials. Herein, we investigated the effects of CBD on liver injury induced by chronic plus binge alcohol feeding in mice. CBD or vehicle was administered daily throughout the alcohol feeding study. At the conclusion of the feeding protocol, serums samples, livers or isolated neutrophils were utilized for molecular biology, biochemistry and pathology analysis. CBD significantly attenuated the alcohol feeding-induced serum transaminase elevations, hepatic inflammation (mRNA expressions of TNFα, MCP1, IL1β, MIP2 and E-Selectin, and neutrophil accumulation), oxidative/nitrative stress (lipid peroxidation, 3-nitrotyrosine formation, and expression of reactive oxygen species generating enzyme NOX2). CBD treatment also attenuated the respiratory burst of neutrophils isolated from chronic plus binge alcohol fed mice or from human blood, and decreased the alcohol-induced increased liver triglyceride and fat droplet accumulation. Furthermore, CBD improved alcohol-induced hepatic metabolic dysregulation and steatosis by restoring changes in hepatic mRNA or protein expression of ACC-1, FASN, PPARα, MCAD, ADIPOR-1, and mCPT-1. Thus, CBD may have therapeutic potential in the treatment of alcoholic liver diseases associated with inflammation, oxidative stress and steatosis, which deserves exploration in human trials.

  6. Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

    PubMed

    Ghezzi, Alfredo; Krishnan, Harish R; Lew, Linda; Prado, Francisco J; Ong, Darryl S; Atkinson, Nigel S

    2013-01-01

    Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

  7. Alcohol-Induced Histone Acetylation Reveals a Gene Network Involved in Alcohol Tolerance

    PubMed Central

    Ghezzi, Alfredo; Krishnan, Harish R.; Lew, Linda; Prado, Francisco J.; Ong, Darryl S.; Atkinson, Nigel S.

    2013-01-01

    Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. PMID:24348266

  8. Histone modifications and alcohol-induced liver disease: are altered nutrients the missing link?

    PubMed

    Moghe, Akshata; Joshi-Barve, Swati; Ghare, Smita; Gobejishvili, Leila; Kirpich, Irina; McClain, Craig J; Barve, Shirish

    2011-05-28

    Alcoholism is a major health problem in the United States and worldwide, and alcohol remains the single most significant cause of liver-related diseases and deaths. Alcohol is known to influence nutritional status at many levels including nutrient intake, absorption, utilization, and excretion, and can lead to many nutritional disturbances and deficiencies. Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease (ALD). There is growing interest regarding epigenetic changes, including histone modifications that regulate gene expression during disease pathogenesis. Notably, modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation, and control gene transcription. This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD. The review is focused on four critical metabolites, namely, acetate, S-adenosylmethionine, nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

  9. Hepatoprotective effect of aged black garlic on chronic alcohol-induced liver injury in rats.

    PubMed

    Kim, Min Hee; Kim, Min Ji; Lee, Jeung Hee; Han, Jang Il; Kim, Jin Hee; Sok, Dai-Eun; Kim, Mee Ree

    2011-01-01

    The hepatoprotective effect of aged black garlic (ABG) against ethanol-induced oxidative liver damage was investigated in adult male Sprague-Dawley rats for 4 weeks. Rats were divided into three groups: a saline (WT) group, an ethanol (ET) group (15 mL/kg of body weight 20% [wt/vol] ethanol), and an ethanol + ABG (ET+ABG) group (ethanol + 100 mg/kg of body weight ABG). ABG administration led to decreased epididymal and total fat pad (P<.05) and liver weights, ameliorated prominent fatty changes around the portal triad, and reduced fat accumulation in liver. ABG caused a significant decrease of the alcohol-induced increases in hepatic activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. Cytochrome P450 2E1 activity was reduced by 55%, whereas the activities of glutathione S-transferase and quinine reductase were increased by 1.5-fold (P<.05) and fourfold (P<.05), respectively, in the ET+ABG group compared with the ET group. ABG treatment significantly decreased the thiobarbituric acid-reactive substances level in liver, heart, and plasma. Glutathione content and the activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase in liver were significantly enhanced. Furthermore, the oxidative damage to blood lymphocyte DNA caused by chronic alcohol ingestion was significantly decreased in the ET+ABG group. In conclusion, ABG has strong antioxidative properties and may be a promising agent for protecting against chronic alcohol-induced liver damage.

  10. Exacerbation of Alcohol-Induced Oxidative Stress in Rats by Polyunsaturated Fatty Acids and Iron Load

    PubMed Central

    Patere, S. N.; Majumdar, A. S.; Saraf, M. N.

    2011-01-01

    The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron. PMID:22303057

  11. A novel small molecule, LAS-0811, inhibits alcohol-induced apoptosis in VL-17A cells.

    PubMed

    Kim, Tae-Hun; Venugopal, Senthil K; Zhu, Ming; Wang, Si-Si; Lau, Derick; Lam, Kit S; Clemens, Dahn L; Zern, Mark A

    2009-02-20

    One of the pathways by which alcohol induces hepatocyte apoptosis is via oxidative stress. We screened several chemically-synthesized small molecules and found LAS-0811, which inhibits oxidative stress. In this study, we elucidated its role in inhibiting alcohol-induced apoptosis in hepatocyte-like VL-17A cells. VL-17A cells were pre-incubated with LAS-0811, followed by ethanol incubation. Ethanol-induced reactive oxygen species and apoptosis were significantly inhibited in LAS-0811 pre-treated cells. VL-17A cells were transfected with a reporter (ARE/TK-GFP) plasmid containing green fluorescent protein (GFP) as a reporter gene and the anti-oxidant response element as the promoter. LAS-0811 pre-treatment significantly induced the GFP expression compared to the cells treated with ethanol alone. LAS-0811 induced the activation of nrf2 and enhanced the expression and activity of glutathione peroxidase, one of the downstream targets of nrf2. The results indicate that LAS-0811 protects VL-17A cells against ethanol-induced oxidative stress and apoptosis at least in part via nrf2 activation.

  12. Thymoquinone Inhibition of Acquisition and Expression of Alcohol-Induced Behavioral Sensitization.

    PubMed

    Khan, Muhammad Sona; Gohar, Aneela; Abbas, Ghulam; Mahmood, Wajahat; Rauf, Khalid; Sewell, Robert D E

    2015-10-01

    Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol-induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose-dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization.

  13. Hepatoprotective potential of Aloe vera polysaccharides against chronic alcohol-induced hepatotoxicity in mice.

    PubMed

    Cui, Yan; Ye, Qing; Wang, Heya; Li, Yingchao; Yao, Weirong; Qian, He

    2014-07-01

    Aloe vera polysaccharides are reported to exhibit multiple biological effects, including anti-oxidation, anti-inflammation and immune enhancement. However, their influence on alcoholic liver disease (ALD) remains unclear. This study was designed to determine the protective effect of extracted A. vera polysaccharides (AVGP) against ALD in a chronic alcohol-feeding mouse model and investigate the possible underlying mechanisms. Supplementation of AVGP significantly attenuated the levels of serum aminotransferases, lipids and hepatic TG and ameliorated histopathological alterations in the model of ALD. Interestingly, AVGP markedly up-regulated hepatic expression of lipolytic genes (AMPK-α2 and PPAR-α) but had no effect on lipogenic gene expression. AVGP diminished alcohol-dependent oxidative stress partly through a decrease in MDA and increase in GSH and SOD. Alcohol-induced inflammation was also mitigated by AVGP treatment via significant reduction in LPS and TNF-α, down-regulation of TLR-4 and MyD88 and up-regulation of IκB-α. This study clearly showed that AVGP exerts a potent protective effect against chronic alcohol-induced liver injury. Its hepatoprotective effect appears to be associated with its antioxidant capacity and its ability to accelerate lipolysis and inhibit inflammatory response. The results indicate that AVGP could be considered as a potent food supplement in the prevention of ALD. © 2013 Society of Chemical Industry.

  14. Soyasaponin Bb Protects Rat Hepatocytes from Alcohol-Induced Oxidative Stress by Inducing Heme Oxygenase-1

    PubMed Central

    Lijie, Zhu; Ranran, Fu; Xiuying, Liu; Yutang, He; Bo, Wang; Tao, Ma

    2016-01-01

    Background: It has been known that oxidative stress induced by alcohol played a crucial role in the formation of alcoholic liver disease. Although the formation mechanisms underlying liver injury induced by alcohol still remained largely unknown, it has been considered that oxidative stress played a core role in the pathogenesis of hepatocyte damage. Objective: The aim of this study was to investigate the effects of soyasaponin Bb (Ss-Bb) on oxidative stress in alcohol-induced rat hepatocyte injury. Results: It has been shown that the administration of Ss-Bb could significantly restore antioxidant activity in BRL 3A cells. Moreover, the impaired liver function and morphology changes resulting from ethanol exposure were improved by Ss-Bb treatment. Treatment with a pharmacological inhibitor of haem oxygenase-1 (HO-1) indicated a critical role of HO-1 in mediating the protective role. Finally, we found that pretreatment with Ss-Bb to ethanol exposure cells increased the expression level of HO-1. Conclusion: It was suggested that Ss-Bb may protect against alcohol-induced hepatocyte injury through ameliorating oxidative stress, and the induction of HO-1 was an important protective mechanism. SUMMARY Effects of soyasaponin Bb was investigated on oxidative stress in rat hepatocytesCell viability and antioxidant capacities were evaluated to determine the effectsThe expression level of HO-1 was measured to reveal the proptective mechanisms PMID:27867273

  15. Alcohol-Induced Disinhibition Expectancies and Impaired Control as Prospective Predictors of Problem Drinking in Undergraduates

    PubMed Central

    Leeman, Robert F.; Toll, Benjamin A.; Taylor, Laura A.; Volpicelli, Joseph R.

    2009-01-01

    Trait disinhibition is associated with problem drinking and alcohol drinking itself can bring about a state of disinhibition. It is unclear however, if expectancies of alcohol-induced disinhibition are unique predictors of problem drinking. Impaired control (i.e., difficulty in limiting alcohol consumption) may be related to disinhibition expectancies in that both involve issues of control related to alcohol use. Data from a prospective survey of undergraduates assessed during freshman (N = 337) and senior year (N = 201) were analyzed to determine whether subscales of the Drinking-Induced Disinhibition Scale and the Impaired Control Scale predicted unique variance in heavy episodic drinking and alcohol-related problems. In Time 1 cross-sectional models, dysphoric disinhibition expectancies predicted alcohol-related problems and impaired control predicted both alcohol-related problems and heavy episodic drinking. In prospective models, Time 1 impaired control predicted Time 2 alcohol-related problems and Time 1 euphoric/social disinhibition expectancies predicted Time 2 heavy episodic drinking. These findings suggest that expectancies of alcohol-induced disinhibition and impaired control predict unique variance in problem drinking cross-sectionally and prospectively and that these phenomena should be targeted in early intervention efforts. PMID:20025361

  16. Alcohol-induced disinhibition expectancies and impaired control as prospective predictors of problem drinking in undergraduates.

    PubMed

    Leeman, Robert F; Toll, Benjamin A; Taylor, Laura A; Volpicelli, Joseph R

    2009-12-01

    Trait disinhibition is associated with problem drinking and alcohol drinking can bring about a state of disinhibition. It is unclear however, if expectancies of alcohol-induced disinhibition are unique predictors of problem drinking. Impaired control (i.e., difficulty in limiting alcohol consumption) may be related to disinhibition expectancies in that both involve issues of control related to alcohol use. Data from a prospective survey of undergraduates assessed during freshman (N = 337) and senior year (N = 201) were analyzed to determine whether subscales of the Drinking-Induced Disinhibition Scale (Leeman, Toll, & Volpicelli, 2007) and the Impaired Control Scale (Heather et al., 1993) predicted unique variance in heavy episodic drinking and alcohol-related problems. In Time 1 cross-sectional models, Dysphoric disinhibition expectancies predicted alcohol-related problems and impaired control predicted both alcohol-related problems and heavy episodic drinking. In prospective models, Time 1 impaired control predicted Time 2 alcohol-related problems and Time 1 Euphoric/social Disinhibition expectancies predicted Time 2 heavy episodic drinking. These findings suggest that expectancies of alcohol-induced disinhibition and impaired control predict unique variance in problem drinking cross-sectionally and prospectively, and that these phenomena should be targeted in early intervention efforts. Copyright 2009 APA

  17. Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats.

    PubMed

    Pari, Leelavinothan; Suresh, Arumugam

    2008-05-01

    Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.

  18. Does caffeine counteract alcohol-induced impairment? The ironic effects of expectancy.

    PubMed

    Fillmore, Mark T; Roach, Emily L; Rice, Julietta T

    2002-11-01

    Studies have shown that expectations of alcohol-induced impairment can produce adaptive responses to alcohol that reduce the degree of behavioral impairment displayed. The present study tested psychomotor performance following combined caffeine and alcohol administration in 42 social drinkers (23 men). Subjects were led to expect either that caffeine would antagonize alcohol-induced impairment or that it would have no effect. The study tested the hypothesis that drinkers who expected an antagonist effect of caffeine would display greater alcohol impairment than those who expected no antagonist effect. Groups practiced a pursuit rotor task and received a moderate dose of alcohol (0.65 g/kg) combined with either 4.0 mg/kg caffeine or placebo caffeine. Some groups were led to expect that caffeine would counteract the impairing effect of alcohol and others were led to expect no counteracting effect. Psychomotor performance was then tested over a 3-hour period. In accord with the hypothesis, groups led to expect counteracting effects of caffeine displayed greater impairment than those led to expect no counteraction. Caffeine had no significant antagonist effect on alcohol impairment. The findings suggest that compensation for alcohol impairment occurs when drinkers hold clear expectations that the drug will disrupt performance. When no such clear expectation exists, no compensatory response occurs and the impairing effects of alcohol are observed.

  19. Ginger-derived nanoparticles protect against alcohol-induced liver damage

    PubMed Central

    Zhuang, Xiaoying; Deng, Zhong-Bin; Mu, Jingyao; Zhang, Lifeng; Yan, Jun; Miller, Donald; Feng, Wenke; McClain, Craig J.; Zhang, Huang-Ge

    2015-01-01

    Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)–mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant–derived nanoparticles. PMID:26610593

  20. Enhancement of alcohol-induced hypoglycaemia by H2-receptor antagonists.

    PubMed

    Czyzyk, A; Lao, B; Szutowski, M; Szczepanik, Z; Muszyński, J

    1997-06-01

    The oral ethanol loading test (0.5 g/kg body mass) was carried out in 3 groups with 10 healthy male volunteers each before and after 7 days of administration of either cimetidine (CAS 51481-61-9), ranitidine (CAS 66357-59-3), or famotidine (CAS 76824-35-6). The parameters determined during 6 h comprised the blood levels of ethanol, acetaldehyde, glucose, lactate, pyruvate and bicarbonates, as well as blood pH, PCO2 and PO2. Only ranitidine significantly increased the mean blood ethanol concentration and none of the drugs modified the blood acetaldehyde concentration. Hypoglycaemia following alcohol ingestion was significantly enhanced by all H2-receptor antagonists, but was most pronounced after famotidine. The alcohol-induced rise in blood pyruvate and lactate rather had a tendency to decrease during the second test. The presented results suggest that the evident enhancement of alcohol-induced hypoglycaemia by H2-receptor antagonists is not dependent on the increase of ethanol absorption from the gastrointestinal tract, but represents rather a specific effect of these drugs on glucose metabolism.

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

    PubMed

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

    2014-03-01

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

  2. Puerarin improves metabolic function leading to hepatoprotective effects in chronic alcohol-induced liver injury in rats.

    PubMed

    Chen, Xu; Li, Rong; Liang, Tao; Zhang, Kefeng; Gao, Ya; Xu, Lingyuan

    2013-07-15

    Puerarin (PR), an active component extracted from the kudzu root, has been widely used as an ethno-medicine to treat hepatopathy in China. Therefore, the aim of the present study was to investigate the hepatoprotective action of PR in chronic alcohol-induced liver injury in rats. Data showed that the serum levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were elevated following PR administration. In addition, the levels of endogenous CYP2E1, CYP1A2, and CYP3A proteins in liver tissue were also gradually decreased following PR treatment. Histopathological examinations suggested that alcohol-induced hepatocellular lesions were mitigated by PR treatment. Collectively, these data indicate that PR contributes to cytoprotection against alcohol-induced liver lesions through improving metabolic function. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Secondhand Smoke

    MedlinePlus

    Secondhand smoke is a mixture of the smoke that comes from the burning end of a cigarette, cigar, ... about 70 can cause cancer. Health effects of secondhand smoke include Ear infections in children More frequent and ...

  4. Cytochrome P4502E1, oxidative stress, JNK, and autophagy in acute alcohol-induced fatty liver.

    PubMed

    Yang, Lili; Wu, Defeng; Wang, Xiaodong; Cederbaum, Arthur I

    2012-09-01

    Binge alcohol drinking induces hepatic steatosis. Recent studies showed that chronic ethanol-induced fatty liver was, at least in part, CYP2E1 dependent. The mechanism of acute alcohol-induced steatosis and whether CYP2E1 plays any role are still unclear. Increasing oxidative stress by alcohol can activate the JNK MAP kinase signaling pathway, suggesting that JNK might be a target for prevention of alcohol-induced steatosis. We used CYP2E1 knockout (KO) mice, a JNK inhibitor, and JNK1 or JNK2 knockout mice to test the role of CYP2E1, JNK, and the individual role of JNK1 and JNK2 in acute alcohol-induced steatosis. In wild-type (WT) mice, acute alcohol activates CYP2E1 and increases oxidative stress, which reciprocally increases activation of the JNK signaling pathway. Acute alcohol-induced fatty liver and oxidative stress were blunted in CYP2E1 KO mice and by the JNK inhibitor in WT mice. The antioxidant N-acetylcysteine decreased the acute alcohol-induced oxidative stress, the activation of JNK, and the steatosis but not the activation of CYP2E1. Acute alcohol decreased autophagy and increased expression of SREBP, effects blocked by the JNK inhibitor. Acute alcohol-induced fatty liver was the same in JNK1 and JNK2 KO mice as in WT mice; thus either JNK1 or JNK2 per se is sufficient for induction of steatosis by acute alcohol. The results show that acute alcohol elevation of CYP2E1, oxidative stress, and activation of JNK interact to lower autophagy and increase lipogenic SREBP resulting in fatty liver.

  5. Perceived smoking availability differentially affects mood and reaction time

    PubMed Central

    Ross, Kathryn C.; Juliano, Laura M.

    2015-01-01

    Introduction This between subjects study explored the relationship between smoking availability and smoking motivation and is the first study to include three smoking availability time points. This allowed for an examination of an extended period of smoking unavailability, and a test of the linearity of the relationships between smoking availability and smoking motivation measures. Methods Ninety 3-hour abstinent smokers (mean ∼15 cigarettes per day) were randomly assigned to one of three availability manipulations while being exposed to smoking stimuli (i.e., pack of cigarettes): smoke in 20 min, smoke in 3 h, or smoke in 24 h. Participants completed pre- and post-manipulation measures of urge, positive affect and negative affect, and simple reaction time. Results The belief that smoking would next be available in 24 h resulted in a significant decrease in positive affect and increase in negative affect relative to the 3 h and 20 min conditions. A Lack of Fit test suggested a linear relationship between smoking availability and affect. A quadratic model appeared to be a better fit for the relationship between smoking availability and simple reaction time with participants in the 24 h and 20 min conditions showing a greater slowing of reaction time relative to the 3 h condition. There were no effects of the manipulations on self-reported urge, but baseline ceiling effects were noted. Conclusions Future investigations that manipulate three or more periods of time before smoking is available will help to better elucidate the nature of the relationship between smoking availability and smoking motivation. PMID:25727393

  6. Perceived smoking availability differentially affects mood and reaction time.

    PubMed

    Ross, Kathryn C; Juliano, Laura M

    2015-06-01

    This between subjects study explored the relationship between smoking availability and smoking motivation and is the first study to include three smoking availability time points. This allowed for an examination of an extended period of smoking unavailability, and a test of the linearity of the relationships between smoking availability and smoking motivation measures. Ninety 3-hour abstinent smokers (mean ~15 cigarettes per day) were randomly assigned to one of three availability manipulations while being exposed to smoking stimuli (i.e., pack of cigarettes): smoke in 20 min, smoke in 3 h, or smoke in 24 h. Participants completed pre- and post-manipulation measures of urge, positive affect and negative affect, and simple reaction time. The belief that smoking would next be available in 24 h resulted in a significant decrease in positive affect and increase in negative affect relative to the 3 h and 20 min conditions. A Lack of Fit test suggested a linear relationship between smoking availability and affect. A quadratic model appeared to be a better fit for the relationship between smoking availability and simple reaction time with participants in the 24 h and 20 min conditions showing a greater slowing of reaction time relative to the 3 h condition. There were no effects of the manipulations on self-reported urge, but baseline ceiling effects were noted. Future investigations that manipulate three or more periods of time before smoking is available will help to better elucidate the nature of the relationship between smoking availability and smoking motivation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Ginger Treatment Ameliorates Alcohol-induced Myocardial Damage by Suppression of Hyperlipidemia and Cardiac Biomarkers in Rats.

    PubMed

    Subbaiah, Ganjikunta Venkata; Mallikarjuna, Korivi; Shanmugam, Bhasha; Ravi, Sahukari; Taj, Patan Usnan; Reddy, Kesireddy Sathyavelu

    2017-01-01

    Alcohol-induced hyperlipidemia is positively correlated with cardiovascular diseases. Several herbal extracts have been reported to protect the cardiac injury and suppress the hyperlipidemia. However, the effect of ginger extracts on alcohol-induced hyperlipidemia and associated myocardial damage remains unclear. This study investigated the cardio-protective properties of ginger ethanolic extract (Gt) against alcohol-induced myocardial damage, and further distinguished the association between hyperlipidemia and occurrence of myocardial damage in rats. Twenty four Wistar male albino rats (250 ± 20 g) were divided into four groups including, Normal control (NC) (0.9% NaCl), Ginger treated (Gt) (200 mg/Kg b.w.), Alcohol treated (At) (20% of 6g/kg b.w. alcohol), and Alcohol along with Ginger treatment (At+Gt). In this study, lipid profiles such as fatty acids, triglycerides, total cholesterol, phospholipids, low density lipoprotein and high density lipoproteins, and cardiac biomarkers, including LDH, AST, CK-MB, cTn-T and cTn-I were examined in rats. Furthermore, histopathological studies were also conducted. We found that alcohol-induced myocardial damage was associated with increased lipid profile except high density lipoprotein in alcohol treated (20%, 6g/kg b.w.) rats compared with control. Ginger treatment significantly reduced the alcohol-induced lipid profiles except high density lipoproteins. Furthermore, elevated cardiac biomarkers activity with alcohol intoxication was substantially suppressed by ginger treatment. In addition, ginger treatment for 7-weeks significantly minimized the alcohol-induced myocardial damage. Our results concluded that ginger could protect alcohol-induced myocardial damage by suppression of hyperlipidemia and cardiac biomarkers. Ginger extract could alleviate the myocardial injury partially due to the suppression of circulating FFAs and TG levels.Increased circulating cholesterol, LDL and phospholipids with alcohol intake were

  8. Ginger Treatment Ameliorates Alcohol-induced Myocardial Damage by Suppression of Hyperlipidemia and Cardiac Biomarkers in Rats

    PubMed Central

    Subbaiah, Ganjikunta Venkata; Mallikarjuna, Korivi; Shanmugam, Bhasha; Ravi, Sahukari; Taj, Patan Usnan; Reddy, Kesireddy Sathyavelu

    2017-01-01

    Background: Alcohol-induced hyperlipidemia is positively correlated with cardiovascular diseases. Several herbal extracts have been reported to protect the cardiac injury and suppress the hyperlipidemia. However, the effect of ginger extracts on alcohol-induced hyperlipidemia and associated myocardial damage remains unclear. Objective: This study investigated the cardio-protective properties of ginger ethanolic extract (Gt) against alcohol-induced myocardial damage, and further distinguished the association between hyperlipidemia and occurrence of myocardial damage in rats. Materials and Methods: Twenty four Wistar male albino rats (250 ± 20 g) were divided into four groups including, Normal control (NC) (0.9% NaCl), Ginger treated (Gt) (200 mg/Kg b.w.), Alcohol treated (At) (20% of 6g/kg b.w. alcohol), and Alcohol along with Ginger treatment (At+Gt). In this study, lipid profiles such as fatty acids, triglycerides, total cholesterol, phospholipids, low density lipoprotein and high density lipoproteins, and cardiac biomarkers, including LDH, AST, CK-MB, cTn-T and cTn-I were examined in rats. Furthermore, histopathological studies were also conducted. Results: We found that alcohol-induced myocardial damage was associated with increased lipid profile except high density lipoprotein in alcohol treated (20%, 6g/kg b.w.) rats compared with control. Ginger treatment significantly reduced the alcohol-induced lipid profiles except high density lipoproteins. Furthermore, elevated cardiac biomarkers activity with alcohol intoxication was substantially suppressed by ginger treatment. In addition, ginger treatment for 7-weeks significantly minimized the alcohol-induced myocardial damage. Conclusion: Our results concluded that ginger could protect alcohol-induced myocardial damage by suppression of hyperlipidemia and cardiac biomarkers. SUMMARY Ginger extract could alleviate the myocardial injury partially due to the suppression of circulating FFAs and TG levels

  9. Urge to cough and its application to the behavioural treatment of cough.

    PubMed

    Vertigan, A E; Gibson, P G

    2011-01-01

    The Urge-To-Cough has recently been recognised as a significant factor in understanding the pathophysiology of cough. The principles in the urge to cough model are relevant to the behavioural management of laryngeal conditions including chronic non-specific cough, cough due to paradoxical vocal fold movement, aspiration and reflux. This paper analyses the pathophysiology and behavioural management of these conditions according to the urge to cough model (Tab. 3, Ref. 28).

  10. Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial

    PubMed Central

    Pittler, Max H.; White, Adrian R.; Stevinson, Clare; Ernst, Edzard

    2003-01-01

    Background Extract of globe artichoke (Cynara scolymus) is promoted as a possible preventive or cure for alcohol-induced hangover symptoms. However, few rigorous clinical trials have assessed the effects of artichoke extract, and none has examined the effects in relation to hangovers. We undertook this study to test whether artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover. Methods We recruited healthy adult volunteers between 18 and 65 years of age to participate in a randomized double-blind crossover trial. Participants received either 3 capsules of commercially available standardized artichoke extract or indistinguishable, inert placebo capsules immediately before and after alcohol exposure. After a 1-week washout period the volunteers received the opposite treatment. Participants predefined the type and amount of alcoholic beverage that would give them a hangover and ate the same meal before commencing alcohol consumption on the 2 study days. The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions. Secondary outcome measures were differences between the interventions in scores using a mood profile questionnaire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure. Results Fifteen volunteers participated in the study. The mean number (and standard deviation) of alcohol units (each unit being 7.9 g, or 10 mL, of ethanol) consumed during treatment with artichoke extract and placebo was 10.7 (3.1) and 10.5 (2.4) respectively, equivalent to 1.2 (0.3) and 1.2 (0.2) g of alcohol per kilogram body weight. The volume of nonalcoholic drink consumed and the duration of sleep were similar during the artichoke extract and placebo interventions. None of the outcome measures differed significantly between interventions. Adverse events were rare and were mild and transient. Interpretation Our results suggest that

  11. Negative Reinforcement and Premonitory Urges in Youth With Tourette Syndrome: An Experimental Evaluation.

    PubMed

    Capriotti, Matthew R; Brandt, Bryan C; Turkel, Jennifer E; Lee, Han-Joo; Woods, Douglas W

    2014-03-01

    Tourette syndrome (TS) is marked by the chronic presence of motor and vocal tics that are usually accompanied by aversive sensory experiences called "premonitory urges." Phenomenological accounts suggest that these urges occur before tics and diminish following their occurrence. This has led some to suggest that tics are negatively reinforced by removal of premonitory urges. This hypothesis has proven difficult to test experimentally, however, due in part to challenges in measuring premonitory urge strength. We tested predictions of the negative reinforcement conceptualization of premonitory urges using novel experimental tactics within the context of the "tic detector" paradigm. We compared tic rates and ratings of premonitory urge strength exhibited by youth with TS or chronic tic disorder under free-to-tic baseline (BL), reinforced tic suppression (RTS), and reinforced tic suppression with escape (RTS + E) conditions. Results were consistent with previous research and hypotheses of the present study. Participants rated the strength of their premonitory urges as higher during RTS conditions than during BL conditions. Within RTS + E conditions, tic rates were higher during escape portions when the contingency supporting tic suppression was inactive than during components where the contingency was active, and ratings of urge strength were higher at the onset of break periods than at the offset. All participants engaged in some level of escape from reinforced suppression during the course of the experiment. Results of this study support the notion that tics may be negatively reinforced by removal of aversive premonitory urges. Future directions for basic and clinical research are discussed.

  12. Prospective Analysis of Early Lapse to Drinking and Smoking Among Individuals in Concurrent Alcohol and Tobacco Treatment

    PubMed Central

    Holt, Laura J.; Litt, Mark D.; Cooney, Ned L.

    2012-01-01

    The aims of the current study were to examine, prospectively, 1) dynamic changes in affective state, self-efficacy, and urge in the hours before initial smoking and drinking lapses among individuals in concurrent alcohol and smoking treatment, and 2) the extent to which self-efficacy, urge to use, and/or the use of one substance predicted lapse to the other substance. Ninety-six men and women recruited for a clinical trial of concurrent alcohol and tobacco treatment were eligible for inclusion. Only data from those who experienced an initial lapse to drinking (n=29), or smoking (n=32) were included. Two outpatient substance abuse clinics provided concurrent alcohol and smoking treatment on a weekly basis for three months. Ecological Momentary Assessment (EMA) methods were employed over a 28-day monitoring period to assess antecedents to first drink and a 14-day monitoring period was examined for initial smoking lapses. Baseline and EMA measures of positive and negative affect, alcohol/smoking urge, alcohol/smoking abstinence self-efficacy, nicotine withdrawal, and quantity/frequency of alcohol and tobacco use were examined as lapse predictors. Analyses of EMA ratings controlled for the corresponding baseline measure. Smoking lapse among individuals in concurrent alcohol and tobacco treatment was foreshadowed by higher urges to smoke, lower positive mood, and lower confidence to resist smoking. Drinking lapse was preceded by lower confidence to resist smoking, but only among individuals who reported recent smoking. Concurrent alcohol and smoking treatment should focus on the enhancement of abstinence self-efficacy, positive mood, and the curbing of urges in order to offset lapse risk. PMID:22023022

  13. Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

    PubMed

    Truitt, E B; Gaynor, C R; Mehl, D L

    1987-01-01

    Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

  14. Alcohol induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation

    PubMed Central

    Veazey, Kylee J.; Carnahan, Mindy N.; Muller, Daria; Miranda, Rajesh C.; Golding, Michael C.

    2013-01-01

    Background From studies using a diverse range of model organisms, we now acknowledge that epigenetic changes to chromatin structure provide a plausible link between environmental teratogens and alterations in gene expression leading to disease. Observations from a number of independent laboratories indicate ethanol has the capacity to act as a powerful epigenetic disruptor and potentially derail the coordinated processes of cellular differentiation. In this study, we sought to examine whether primary neurospheres cultured under conditions maintaining stemness were susceptible to alcohol-induced alterations of the histone code. We focused our studies on trimethylated histone 3 lysine 4 and trimethylated histone 3 lysine 27, as these are two of the most prominent post-translational histone modifications regulating stem cell maintenance and neural differentiation. Methods Primary neurosphere cultures were maintained under conditions promoting the stem cell state and treated with ethanol for five days. Control and ethanol treated cellular extracts were examined using a combination of quantitative RT-PCR and chromatin immunoprecipitation techniques. Results We find that the regulatory regions of genes controlling both neural precursor cell identity and processes of differentiation exhibited significant declines in the enrichment of the chromatin marks examined. Despite these widespread changes in chromatin structure, only a small subset of genes including Dlx2, Fabp7, Nestin, Olig2, and Pax6 displayed ethanol induced alterations in transcription. Unexpectedly, the majority of chromatin modifying enzymes examined including members of the Polycomb Repressive Complex displayed minimal changes in expression and localization. Only transcripts encoding Dnmt1, Uhrf1, Ehmt1, Ash2l, Wdr5, and Kdm1b exhibited significant differences. Conclusions Our results indicate primary neurospheres maintained as stem cells in vitro are susceptible to alcohol-induced perturbation of the

  15. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction.

    PubMed

    Chang, Jennifer; Fedinec, Alexander L; Kuntamallappanavar, Guruprasad; Leffler, Charles W; Bukiya, Anna N; Dopico, Alex M

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from "energy drinks") continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40-70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS(-/-)) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  16. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction

    PubMed Central

    Chang, Jennifer; Fedinec, Alexander L.; Kuntamallappanavar, Guruprasad; Leffler, Charles W.; Bukiya, Anna N.

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from “energy drinks”) continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40–70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS−/−) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  17. Role of MCP-1 in Alcohol-induced Aggressiveness of Colorectal Cancer Cells

    PubMed Central

    Xu, Mei; Wang, Siying; Qi, Yuanlin; Chen, Li; Frank, Jacqueline A.; Yang, Xiuwei H.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2015-01-01

    Epidemiological studies demonstrate that alcohol consumption is associated with an increased risk of colorectal cancer (CRC). In addition to promoting carcinogenesis, alcohol may also accelerate the progression of existing CRC. We hypothesized that alcohol may enhance the aggressiveness of CRC. In this study, we investigated the effect of alcohol on the migration/invasion and metastasis of CRC. Alcohol increased the migration/invasion of colorectal cancer cells (DLD1, HCT116, HT29 and SW480) in a concentration-dependent manner. Among these colon cancer cell lines, HCT116 cells were most responsive while HT29 cells were the least responsive to ethanol-stimulated cell migration/invasion. These in vitro results were supported by animal studies which demonstrated that ethanol enhanced the metastasis of colorectal cancer cells to the liver and lung. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays an important role in regulating tumor microenvironment and metastasis. Alcohol increased the expression of MCP-1 and its receptor CCR2 at both protein and mRNA levels. The pattern of alcohol-induced alterations in MCP-1 expression was consistent with its effect on migration/invasion; HCT116 cells displayed the highest up-regulation of MCP-1/CCR2 in response to alcohol exposure. An antagonist of CCR2 blocked alcohol-stimulated migration. Alcohol caused an initial cytosolic accumulation of β-catenin and its subsequent nuclear translocation by inhibiting GSK3β activity. Alcohol stimulated the activity of MCP-1 gene promoter in a β-catenin-dependent manner. Furthermore, knock-down of MCP-1/CCR2 or β-catenin was sufficient to inhibit alcohol-induced cell migration/invasion. Together, these results suggested that alcohol may promote the metastasis of CRC through modulating GSK3β/β-catenin/MCP-1 pathway. PMID:26014148

  18. Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells

    PubMed Central

    2014-01-01

    Background The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear. Methods The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay. Results ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (p < 0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared to adjacent normal tissues (p < 0.05) and its expression was decreased in the alcohol consumption group (p < 0.05). ADHFE1 was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells. Conclusion These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells. PMID:24886599

  19. Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells.

    PubMed

    Xu, Mei; Wang, Siying; Qi, Yuanlin; Chen, Li; Frank, Jacqueline A; Yang, Xiuwei H; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-05-01

    Epidemiological studies demonstrate that alcohol consumption is associated with an increased risk of colorectal cancer (CRC). In addition to promoting carcinogenesis, alcohol may also accelerate the progression of existing CRC. We hypothesized that alcohol may enhance the aggressiveness of CRC. In this study, we investigated the effect of alcohol on the migration/invasion and metastasis of CRC. Alcohol increased the migration/invasion of colorectal cancer cells (DLD1, HCT116, HT29, and SW480) in a concentration-dependent manner. Among these colon cancer cell lines, HCT116 cells were most responsive while HT29 cells were the least responsive to ethanol-stimulated cell migration/invasion. These in vitro results were supported by animal studies which demonstrated that ethanol enhanced the metastasis of colorectal cancer cells to the liver and lung. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays an important role in regulating tumor microenvironment and metastasis. Alcohol increased the expression of MCP-1 and its receptor CCR2 at both protein and mRNA levels. The pattern of alcohol-induced alterations in MCP-1 expression was consistent with its effect on migration/invasion; HCT116 cells displayed the highest up-regulation of MCP-1/CCR2 in response to alcohol exposure. An antagonist of CCR2 blocked alcohol-stimulated migration. Alcohol caused an initial cytosolic accumulation of β-catenin and its subsequent nuclear translocation by inhibiting GSK3β activity. Alcohol stimulated the activity of MCP-1 gene promoter in a β-catenin-dependent manner. Furthermore, knock-down of MCP-1/CCR2 or β-catenin was sufficient to inhibit alcohol-induced cell migration/invasion. Together, these results suggested that alcohol may promote the metastasis of CRC through modulating GSK3β/β-catenin/MCP-1 pathway. © 2015 Wiley Periodicals, Inc.

  20. Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells.

    PubMed

    Moon, Ji Wook; Lee, Soo Kyung; Lee, Yong Woo; Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Seo, Jung Seon; Kim, Jin; Kim, Hyeon Soo; Park, Sun-Hwa

    2014-05-28

    The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear. The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay. ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (p<0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared to adjacent normal tissues (p<0.05) and its expression was decreased in the alcohol consumption group (p<0.05). ADHFE1 was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells. These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells.

  1. Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors.

    PubMed

    Powell, Christine L; Bradford, Blair U; Craig, Christopher Patrick; Tsuchiya, Masato; Uehara, Takeki; O'Connell, Thomas M; Pogribny, Igor P; Melnyk, Stepan; Koop, Dennis R; Bleyle, Lisa; Threadgill, David W; Rusyn, Ivan

    2010-05-01

    Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors is mediated by an effect on the oxidative metabolism of alcohol in the liver. Male C57BL/6J mice were administered a control high-fat diet or diet enriched in methyl donors with or without alcohol for 4 weeks using the enteral alcohol feeding model. As expected, attenuation of ALI and an increase in reduced glutathione:oxidized glutathione ratio were achieved with methyl donor supplementation. Interestingly, methyl donors led to a 35% increase in blood alcohol elimination rate, and while there was no effect on alcohol metabolism in the stomach, a profound effect on liver alcohol metabolism was observed. The catalase-dependent pathway of alcohol metabolism was induced, yet the increase in CYP2E1 activity by alcohol was blunted, which may be mitigating production of oxidants. Additional factors contributing to the protective effects of methyl donors in ALI were increased activity of low- and high-K(m) aldehyde dehydrogenases leading to lower hepatic acetaldehyde, maintenance of the efficient mitochondrial energy metabolism, and promotion of peroxisomal beta-oxidation. Profound changes in alcohol metabolism represent additional important mechanism of the protective effect of methyl donors in ALI.

  2. Quitting Smoking

    MedlinePlus

    ... half of the people who don't quit smoking will die of smoking-related problems. Quitting smoking is important for your health. Soon after you ... they succeed. There are many ways to quit smoking. Some people stop "cold turkey." Others benefit from ...

  3. Secondhand Smoke

    MedlinePlus

    ... Can I Help Someone Who's Being Bullied? Volunteering Secondhand Smoke KidsHealth > For Teens > Secondhand Smoke Print A A ... español El humo secundario del cigarrillo What Is Secondhand Smoke? Everyone knows that smoking is a bad idea. ...

  4. Patterned changes in urge ratings with tic suppression in youth with chronic tic disorders.

    PubMed

    Brabson, Laurel A; Brown, Jessica L; Capriotti, Matthew R; Ramanujam, Krishnapriya; Himle, Michael B; Nicotra, Cassandra M; Ostrander, Rick; Kelly, Laura M; Grados, Marco A; Walkup, John T; Perry-Parrish, Carisa; Reynolds, Elizabeth K; Hankinson, Jessica C; Specht, Matt W

    2016-03-01

    Premonitory urges are central to emerging behavioral models of chronic tic disorders (CTD). Urge reduction has been proposed as a behavioral explanation for tic maintenance and exacerbation as well as the efficacy of behavioral treatments. Prior investigations have produced inconsistent findings despite common methodologies. The current study evaluated the possibility that data aggregation obscures distinct and meaningful patterns of change in urge ratings when tics are freely expressed versus suppressed. Participants (n = 12) included children with moderate-to-marked tic severity and noticeable premonitory urges. Tic frequencies and urge ratings were obtained at 15 s and 10-s intervals, respectively, across an alternating sequence of 10-min tic freely and 40-min tic suppression conditions. Patterns were established using a two step approach. Five distinct patterns of urge rating change emerged, suggesting data aggregation may obscure meaningful patterns in the urge-tic relationship when tics are completed versus suppressed. Eligibility criteria may have unintentionally excluded younger affected children and included older participants with more severe tic disorders than commonly seen. Additional research with less stringent eligibility criteria and a larger sample size will help validate the results. The relationship between urges and tics is much more complex than previously theorized. Investigations that rely on global assessments of urge and tic severity and/or assume uniformity when aggregating participant data may obscure meaningful differences in the urge-tic relationship. Future investigations should examine the possibility that individual differences and/or developmental considerations modulate the functional urge-tic relationship. Copyright © 2015. Published by Elsevier Ltd.

  5. Undernutrition Enhances Alcohol-Induced Hepatocyte Proliferation in the Liver of Rats Fed Via Total Enteral Nutrition

    USDA-ARS?s Scientific Manuscript database

    To assess the relative contributions of undernutrition and ethanol (EtOH) exposure to alcohol-induced hepatotoxicity, female Sprague-Dawley rats were intragastrically infused liquid diets containing 187 kcal/kg3/4/day or 154 kcal/kg3/4/day, with or without 11 g/kg/day EtOH. EtOH clearance was impai...

  6. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway.

    PubMed

    Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

    2014-09-26

    Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

  7. Effects of triterpenoid from Schisandra chinensis on oxidative stress in alcohol-induced liver injury in rats.

    PubMed

    Li, Bin; Zhu, Lijie; Wu, Ting; Zhang, Jiachen; Jiao, Xinyao; Liu, Xiuying; Wang, Yanqun; Meng, Xianjun

    2015-03-01

    Alcohol-induced oxidative stress plays a crucial role in the pathological development of alcoholic liver disease. The aim of this study was to investigate the effects of triterpenoid from Schisandra chinensis on oxidative stress in alcohol-induced liver injury in rats. We found that the administration of triterpenoid attenuated alcohol-induced oxidative stress in multiple organs including liver. Moreover, the impaired liver function and histological changes resulted from alcohol consumption was improved by triterpenoid treatment. Finally, we found that pretreatment with triterpenoid from Schisandra chinensis to alcohol-fed rats increased the expression level of haem oxygenase-1 (HO-1) while inhibited the induction of cytochrome P-450 2E1 (CYP2E1) in liver microsomes. Further assays revealed that the microsomal activity of HO-1 was accordingly induced whereas CYP2E1 was suppressed in rats received triterpenoid intervention. Our findings suggest that triterpenoid from Schisandra chinensis may protect against alcohol-induced liver injury through ameliorating oxidative stress in rats.

  8. LaURGE: Louisiana Undergraduate Recruitment and Geoscience Education

    NASA Astrophysics Data System (ADS)

    Nunn, J. A.; Agnew, J.

    2009-12-01

    NSF and the Shell Foundation sponsor a program called Louisiana Undergraduate Recruitment and Geoscience Education (LaURGE). Goals of LaURGE are: 1) Interweave geoscience education into the existing curriculum; 2) Provide teachers with lesson plans that promote interest in geoscience, critical thinking by students, and are consistent with current knowledge in geoscience; and 3) Provide teachers with supplies that make these lessons the highlights of the course. Biology workshops were held at LSU in Baton Rouge and Centenary College in Shreveport in July 2009. 25 teachers including 5 African-Americans attended the workshops. Teachers were from public and private schools in seven different parishes. Teacher experience ranged from 3 years to 40 years. Courses impacted are Biology, Honors Biology, AP Biology, and Environmental Science. The workshops began with a field trip to Mississippi to collect fossil shark teeth and create a virtual field trip. After the field trip, teachers do a series of activities on fossil shark teeth to illustrate evolution and introduce basic concepts such as geologic time, superposition, and faunal succession. Teachers were also given a $200 budget from which to select fossils for use in their classrooms. One of our exercises explores the evolution of the megatoothed shark lineage leading to Carcharocles megalodon, the largest predatory shark in history with teeth up to 17 cm long. Megatoothed shark teeth have an excellent fossil record and show continuous transitions in morphology from the Eocene to Pliocene. We take advantage of the curiosity of sharks shared by most people, and allow teachers to explore the variations among different shark teeth and to explain the causes of those variations. Objectives are to have teachers (and their students): 1) sort fossil shark teeth into biologically reasonable species; 2) form hypotheses about evolutionary relationships; and 3) describe and interpret evolutionary trends in the fossil Megatoothed

  9. Attentional shifts to smoking cues in smokers.

    PubMed

    Waters, Andrew J; Shiffman, Saul; Bradley, Brendan P; Mogg, Karin

    2003-10-01

    Many theories of addiction assume that responses to drug cues maintain drug use and precipitate relapse. There is evidence that measures derived from experimental cognitive psychology yield important information about cue reactivity. We used a pictorial version of the visual probe task to evaluate: (i) whether minimally deprived smokers attend differentially to smoking cues (attentional bias); (ii) whether this bias is related to self-reported craving and dependence; and (iii) whether it predicted outcome in a subsequent cessation attempt. Participants took part in a structured smoking cessation program. Each participant completed the visual probe task roughly 2 weeks before quitting while non-deprived. A research smoking cessation clinic. 141 heavy smokers seeking treatment for smoking cessation. The computerized attentional bias measure and self-reported urge were taken in a laboratory session. Participants also monitored their smoking and craving on electronic diaries both when smoking ad libitum and for up to 6 weeks post-cessation. Participants were faster and more accurate in responding to a visual probe that replaced a smoking picture than to a neutral picture, indicating that they showed attentional bias towards the smoking cues. Attentional bias on the first half of the task correlated with pre-task craving, indicating that the bias may tap motivational processes, but it did not predict outcome in smoking cessation. The visual probe task can add useful information about attentional responses to drug cues. Further work is required to uncover the theoretical significance and utility of this measure.

  10. The effect of acute increase in urge to void on cognitive function in healthy adults.

    PubMed

    Lewis, M S; Snyder, P J; Pietrzak, R H; Darby, D; Feldman, R A; Maruff, P

    2011-01-01

    In healthy adults, voluntary inhibition of micturition is associated with an increasing sensation in the urge to void and pain, and acute pain has been associated with transient deterioration in aspects of cognitive function. Eight healthy young adults consumed 250 ml of water every 15 min until they could no longer inhibit voiding. Performance on standardized measures of cognitive function was measured at hourly intervals which were classified as baseline, when individuals reported an increase in the urge to void, a strong increase in the urge to void, an extreme increase in the urge to void and postmicturition. Sensations of the urge to void and pain increased with time of inhibition of urge to void and with amount of water consumed. Having an extreme urge to void exerted a large negative effect on attentional and working memory functions (d>0.8). These cognitive functions returned to normal levels after micturition. The magnitude of decline in cognitive function associated with an extreme urge to void was as large and equivalent or greater than the cognitive deterioration observed for conditions known to be associated with increased accident risk. Copyright © 2010 Wiley-Liss, Inc.

  11. Effect of an antismoking advertisement on cinema patrons' perception of smoking and intention to smoke: a quasi-experimental study.

    PubMed

    Hanewinkel, Reiner; Isensee, Barbara; Sargent, James D; Morgenstern, Matthis

    2010-07-01

    To assess the effect of an antismoking advertisement under real-world conditions. Design Quasi-experimental study. Multiplex cinema in Kiel, Germany; 4073 patrons were surveyed after having viewed a movie. Some 4005 patrons were > or = 10 years old (28.7% between 10 and 17 years). A total of 654 subjects (16.3%) were smokers. In the intervention condition (weeks 1 and 3), a 30-second antismoking advertisement-accentuating long-term health consequences of smoking and promoting cessation-was shown prior to all movies; in the control condition (weeks 2 and 4) no such spot was shown. (i) Awareness of smoking in the movie, (ii) approval of smoking in the movie, (iii) attitude towards smoking, (iv) intention to smoke in the future and (v) desire to smoke among smokers. Findings Patrons who were exposed to the antismoking advertisement were more likely to be female, but did not differ with respect to smoking status. After controlling for gender differences, patrons exposed to the antismoking advertisement had (i) higher awareness of smoking in the movies, (ii) lower levels of approval of smoking in the movies, and (iii) a more negative attitude towards smoking in general compared with those not exposed. Among smokers, smoking in the movies increased urge to smoke, but there was no interaction between smoking in the movies and experimental condition. Study results suggest that placing an antismoking advertisement before movies can affect attitudes towards smoking, bolstering evidence in support of such policies.

  12. Optimisation of the Schizosaccharomyces pombe urg1 expression system.

    PubMed

    Watson, Adam T; Daigaku, Yasukazu; Mohebi, Saed; Etheridge, Thomas J; Chahwan, Charly; Murray, Johanne M; Carr, Antony M

    2013-01-01

    The ability to study protein function in vivo often relies on systems that regulate the presence and absence of the protein of interest. Two limitations for previously described transcriptional control systems that are used to regulate protein expression in fission yeast are: the time taken for inducing conditions to initiate transcription and the ability to achieve very low basal transcription in the "OFF-state". In previous work, we described a Cre recombination-mediated system that allows the rapid and efficient regulation of any gene of interest by the urg1 promoter, which has a dynamic range of approximately 75-fold and which is induced within 30-60 minutes of uracil addition. In this report we describe easy-to-use and versatile modules that can be exploited to significantly tune down Purg1 "OFF-levels" while maintaining an equivalent dynamic range. We also provide plasmids and tools for combining Purg1 transcriptional control with the auxin degron tag to help maintain a null-like phenotype. We demonstrate the utility of this system by improved regulation of HO-dependent site-specific DSB formation, by the regulation Rtf1-dependent replication fork arrest and by controlling Rhp18(Rad18)-dependent post replication repair.

  13. Join the "Club of the Sterilized" Hanoi urges.

    PubMed

    1996-01-01

    In Viet Nam, the government has mounted a program of encouraging sterilization to control population growth. Peasants who have been sterilized are being urged to form and join special motivational clubs to give momentum to the initiative, and financial incentives are provided to those who accept sterilization after having two children. The government action follows concerns that rapid population growth will strain the country's newly achieved economic gains and ability to produce enough food. Until recently, large families were eligible for greater amounts of land being allocated, and the government's new initiative faces challenges in districts that are prosperous or are predominantly Roman Catholic. With domestic funds in short supply, Viet Nam has depended upon the UN Population Fund for training, equipment supply, and development of an assembly line at a condom factory. The government plans to screen pregnant women for fetal anomalies to insure that only healthy fetuses are carried to term. For several decades, Viet Nam will be suffering from the effects of the spraying of herbicides undertaken by the US during the war. Miscarriages, stillbirths, and fetal deformities are among those effects.

  14. Smoking cue reactivity across massed extinction trials: negative affect and gender effects.

    PubMed

    Collins, Bradley N; Nair, Uma S; Komaroff, Eugene

    2011-04-01

    Designing and implementing cue exposure procedures to treat nicotine dependence remains a challenge. This study tested the hypothesis that gender and negative affect (NA) influence changes in smoking urge over time using data from a pilot project testing the feasibility of massed extinction procedures. Forty-three smokers and ex-smokers completed the behavioral laboratory procedures. All participants were over 17 years old, smoked at least 10 cigarettes daily over the last year (or the year prior to quitting) and had expired CO below 10 ppm at the beginning of the ~4-hour session. After informed consent, participants completed 45 min of baseline assessments, and then completed a series of 12 identical, 5-minute exposure trials with inter-trial breaks. Smoking cues included visual, tactile, and olfactory cues with a lit cigarette, in addition to smoking-related motor behaviors without smoking. After each trial, participants reported urge and negative affect (NA). Logistic growth curve models supported the hypothesis that across trials, participants would demonstrate an initial linear increase followed by a decrease in smoking urge (quadratic effect). Data supported hypothesized gender, NA, and gender×NA effects. Significant linear increases in urge were observed among high and low NA males, but not among females in either NA subgroup. A differential quadratic effect showed a significant decrease in urge for the low NA subgroup, but a non-significant decrease in urge in the high NA group. This is the first study to demonstrate gender differences and the effects of NA on the extinction process using a smoking cue exposure paradigm. Results could guide future cue reactivity research and exposure interventions for nicotine dependence.

  15. An urge to jump affirms the urge to live: an empirical examination of the high place phenomenon.

    PubMed

    Hames, Jennifer L; Ribeiro, Jessica D; Smith, April R; Joiner, Thomas E

    2012-02-01

    The experience of a sudden urge to jump when in a high place has been speculated to be associated with suicidal ideation; however, scant data has informed this speculation. We termed this experience the high place phenomenon (HPP) and proposed that it stems from a misinterpreted safety signal (i.e., survival instinct). The present study aimed to assess the prevalence of the HPP, to provide evidence that the phenomenon is not exclusive to suicide ideators, and to explore the role of anxiety sensitivity in the phenomenon. 431 undergraduate college students completed online measures of lifetime frequency of experiencing the HPP, suicidal ideation, anxiety sensitivity, depressive symptoms, and history of mood episodes. The HPP was commonly reported in the general population, even among participants with no history of suicidal ideation. There was a significant correlation between anxiety sensitivity and the HPP, and this relationship was moderated by level of current suicidal ideation. Particularly, the relationship between anxiety sensitivity and the HPP was potentiated among participants with low levels of suicidal ideation. The cross-sectional design of the study limits the strength of the conclusions that can be drawn. The HPP is commonly experienced among suicide ideators and non-ideators alike. Thus, individuals who report experiencing the phenomenon are not necessarily suicidal; rather, the experience of HPP may reflect their sensitivity to internal cues and actually affirm their will to live. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Smoking cessation.

    PubMed

    Marlow, Scott P; Stoller, James K

    2003-12-01

    Cigarette smoking is the primary cause of chronic obstructive pulmonary disease, and smoking cessation is the most effective means of stopping the progression of chronic obstructive pulmonary disease. Worldwide, approximately a billion people smoke cigarettes and 80% reside in low-income and middle-income countries. Though in the United States there has been a substantial decline in cigarette smoking since 1964, when the Surgeon General's report first reviewed smoking, smoking remains widespread in the United States today (about 23% of the population in 2001). Nicotine is addictive, but there are now effective drugs and behavioral interventions to assist people to overcome the addiction. Available evidence shows that smoking cessation can be helped with counseling, nicotine replacement, and bupropion. Less-studied interventions, including hypnosis, acupuncture, aversive therapy, exercise, lobeline, anxiolytics, mecamylamine, opioid agonists, and silver acetate, have assisted some people in smoking cessation, but none of those interventions has strong research evidence of efficacy. To promote smoking cessation, physicians should discuss with their smoking patients "relevance, risk, rewards, roadblocks, and repetition," and with patients who are willing to attempt to quit, physicians should use the 5-step system of "ask, advise, assess, assist, and arrange." An ideal smoking cessation program is individualized, accounting for the reasons the person smokes, the environment in which smoking occurs, available resources to quit, and individual preferences about how to quit. The clinician should bear in mind that quitting smoking can be very difficult, so it is important to be patient and persistent in developing, implementing, and adjusting each patient's smoking-cessation program. One of the most effective behavioral interventions is advice from a health care professional; it seems not to matter whether the advice is from a doctor, respiratory therapist, nurse, or other

  17. Alcohol-induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation.

    PubMed

    Veazey, Kylee J; Carnahan, Mindy N; Muller, Daria; Miranda, Rajesh C; Golding, Michael C

    2013-07-01

    From studies using a diverse range of model organisms, we now acknowledge that epigenetic changes to chromatin structure provide a plausible link between environmental teratogens and alterations in gene expression leading to disease. Observations from a number of independent laboratories indicate that ethanol (EtOH) has the capacity to act as a powerful epigenetic disruptor and potentially derail the coordinated processes of cellular differentiation. In this study, we sought to examine whether primary neurospheres cultured under conditions maintaining stemness were susceptible to alcohol-induced alterations in the histone code. We focused our studies on trimethylated histone 3 lysine 4 and trimethylated histone 3 lysine 27, as these are 2 of the most prominent posttranslational histone modifications regulating stem cell maintenance and neural differentiation. Primary neurosphere cultures were maintained under conditions promoting the stem cell state and treated with EtOH for 5 days. Control and EtOH-treated cellular extracts were examined using a combination of quantitative RT-PCR and chromatin immunoprecipitation techniques. We find that the regulatory regions of genes controlling both neural precursor cell identity and processes of differentiation exhibited significant declines in the enrichment of the chromatin marks examined. Despite these widespread changes in chromatin structure, only a small subset of genes including Dlx2, Fabp7, Nestin, Olig2, and Pax6 displayed EtOH-induced alterations in transcription. Unexpectedly, the majority of chromatin-modifying enzymes examined including members of the Polycomb Repressive Complex displayed minimal changes in expression and localization. Only transcripts encoding Dnmt1, Uhrf1, Ehmt1, Ash2 l, Wdr5, and Kdm1b exhibited significant differences. Our results indicate that primary neurospheres maintained as stem cells in vitro are susceptible to alcohol-induced perturbation of the histone code and errors in the epigenetic

  18. Alcohol-induced suppression of gluconeogenesis is greater in ethanol fed female rat hepatocytes than males.

    PubMed

    Sumida, Ken D; Cogger, Alma A; Matveyenko, Aleksey V

    2007-03-01

    The impact of alcohol-induced suppression on hepatic gluconeogenesis (HGN) after chronic ethanol consumption between males and females is unknown. To determine the effects of chronic alcohol consumption (8 weeks) on HGN, the isolated hepatocyte technique was used on 24 h fasted male and female Wistar rats. Livers were initially perfused with collagenase and the hepatocytes were isolated. Aliquots of the cell suspension were placed in Krebs-Henseleit buffer and incubated for 30 min with lactate, [U -14C]lactate, and nine different concentrations of ethanol (EtOH). Dose-effect curves were generated for the determination of maximal and half-maximal alcohol-induced inhibition on HGN. There was no significant difference in HGN (lactate only and no EtOH) between males and females fed the control diet (88.5 +/- 5.1 nmol/mg protein/30 min). Similarly, the HGN (lactate only and no EtOH) in males fed the ethanol diet (ME) were not significantly different (82.8 +/- 3.5 nmol/mg protein/30 min) compared to controls. In contrast, the females chronically fed the ethanol diet (FE) had significantly (P < .05) lower HGN (67.8 +/- 4.6 nmol/mg protein/30 min) compared to both ME and controls. With alcohol in the incubation medium, the HGN significantly (P<.05) declined in all groups. While alcohol suppressed HGN to a larger (P < .05) extent in ME (45.8 +/- 3.7 nmol/mg protein/30 min) compared to controls (64.0 +/- 3.8 nmol/mg protein/30 min), the inhibition was even greater (P < .05) in FE (32.7 +/- 3.2 nmol/mg protein/30 min). The more pronounced effect of chronic alcohol consumption on HGN in the presence of ethanol in female hepatocytes was supported by the concomitant decreases (P < .05) in 14C-lactate incorporation into 14C-glucose, lactate uptake, and 14C-lactate uptake. The results suggest that chronic alcohol consumption elicits a greater reduction on HGN in the presence of ethanol in the hepatocytes of females compared to males.

  19. Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains.

    PubMed

    Getachew, Bruk; Hauser, Sheketha R; Taylor, Robert E; Tizabi, Yousef

    2008-11-01

    Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive- and anxiety-like behaviors

  20. Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation.

    PubMed

    Lippai, Dora; Bala, Shashi; Petrasek, Jan; Csak, Timea; Levin, Ivan; Kurt-Jones, Evelyn A; Szabo, Gyongyi

    2013-07-01

    Alcohol-induced neuroinflammation is mediated by proinflammatory cytokines, including IL-1β. IL-1β production requires caspase-1 activation by inflammasomes-multiprotein complexes that are assembled in response to danger signals. We hypothesized that alcohol-induced inflammasome activation contributes to increased IL-1β in the brain. WT and TLR4-, NLRP3-, and ASC-deficient (KO) mice received an ethanol-containing or isocaloric control diet for 5 weeks, and some received the rIL-1ra, anakinra, or saline treatment. Inflammasome activation, proinflammatory cytokines, endotoxin, and HMGB1 were measured in the cerebellum. Expression of inflammasome components (NLRP1, NLRP3, ASC) and proinflammatory cytokines (TNF-α, MCP-1) was increased in brains of alcohol-fed compared with control mice. Increased caspase-1 activity and IL-1β protein in ethanol-fed mice indicated inflammasome activation. TLR4 deficiency protected from TNF-α, MCP-1, and attenuated alcohol-induced IL-1β increases. The TLR4 ligand, LPS, was not increased in the cerebellum. However, we found up-regulation of acetylated and phosphorylated HMGB1 and increased expression of the HMGB1 receptors (TLR2, TLR4, TLR9, RAGE) in alcohol-fed mice. NLRP3- or ASC-deficient mice were protected from caspase-1 activation and alcohol-induced IL-1β increase in the brain. Furthermore, in vivo treatment with rIL-1ra prevented alcohol-induced inflammasome activation and IL-1β, TNF-α, and acetylated HMGB1 increases in the cerebellum. Conversely, intracranial IL-1β administration induced TNF-α and MCP-1 in the cerebellum. In conclusion, alcohol up-regulates and activates the NLRP3/ASC inflammasome, leading to caspase-1 activation and IL-1β increase in the cerebellum. IL-1β amplifies neuroinflammation, and disruption of IL-1/IL-1R signaling prevents alcohol-induced inflammasome activation and neuroinflammation. Increased levels of acetylated and phosphorylated HMGB1 may contribute to alcoholic neuroinflammation.

  1. Wood Smoke

    EPA Pesticide Factsheets

    Smoke is made up of a complex mixture of gases and fine, microscopic particles produced when wood and other organic matter burn. The biggest health threat from wood smoke comes from fine particles (also called particulate matter).

  2. Asia Smoke

    Atmospheric Science Data Center

    2013-04-16

    ... title:  Smoke from Asian Fires Traverses the Pacific     View Larger Image ... moved eastwards over the northern portion of the Pacific Ocean, the thickness of the smoke passing over an area south of the Aleutian ...

  3. Smoking Cessation

    MedlinePlus

    ... National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014 [accessed 2017 ... National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010 [accessed 2017 ...

  4. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults.

    PubMed

    Reese, Hannah E; Scahill, Lawrence; Peterson, Alan L; Crowe, Katherine; Woods, Douglas W; Piacentini, John; Walkup, John T; Wilhelm, Sabine

    2014-03-01

    In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive-compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD.

  5. Relationships between Premonitory Urge and Anxiety in Youth with Chronic Tic Disorders.

    PubMed

    Rozenman, Michelle; Johnson, Olivia E; Chang, Susanna W; Woods, Douglas W; Walkup, John T; Wilhelm, Sabine; Peterson, Alan; Scahill, Lawrence; Piacentini, John

    2015-07-01

    Tourette's Disorder and other chronic tic disorders are common neurodevelopmental conditions. One characteristic of tic disorders is the premonitory urge, an aversive or unpleasant sensory phenomenon that may precede tics. Initial examination of premonitory urge in pediatric tic disorders suggests that awareness and experience of sensations preceding tics may be related to anxiety and OCD. However, it may be possible that specific anxiety-related symptoms, such as anxious physiologic arousal, are particularly relevant to the experience of premonitory urge. The current study examines relationships between tic-related premonitory urge and anxiety-related symptom clusters in treatment-seeking youths with a primary diagnoses of Tourette's or other chronic tic disorder. The sample consisted of 124 youth, ages 9 to 17, who participated in the multi-site Comprehensive Behavioral Intervention for Tics randomized controlled trial (CBIT; Piacentini et al., 2010). Specific anxiety-related subtypes, including generalized worry, separation, social, and panic/somatic symptoms, as well as severity of obsessions and compulsions, were assessed as potential correlates of premonitory urge. Findings indicated that age, global tic-related impairment, and specific panic/somatic symptoms accounted for a substantial proportion of variance in youth report of premonitory urge. These findings provide information about the characteristics of premonitory urge in pediatric tic disorders, and have implications for the treatment of pediatric tic syndromes.

  6. Green tea extract (Camellia sinensis) fermented by Lactobacillus fermentum attenuates alcohol-induced liver damage.

    PubMed

    Park, Jong Ho; Kim, Younghoon; Kim, Sae Hun

    2012-01-01

    Here, the impact of an extract derived from green tea (Camellia sinensis) and fermentation with Lactobacilli fermentum strain OCS19 was explored with acute alcohol-induced liver damage. The study employed the HepG2 hepatic cell line and an in vivo murine model of liver damage. L. fermentum-fermented green tea extract (FGTE) was found to possess pronounced alcohol metabolizing enzyme activity. It significantly enhanced the cell viability of HepG2 cells following of them exposure, to ethanol (p<0.05) as compared with an extract derived from Hovenia dulcis, a positive control that is known for its action as an alcohol antagonist. Our in vivo studies indicated that prior administration of FGTE to alcohol-exposed mice significantly prevented subsequent increases in blood alcohol concentration (p<0.05), in addition to the induction of serum alanine aminotransferase (ALT) and triglycerides (p<0.05). Furthermore, the activity of hepatic alcohol dehydrogenase (ADH) and its mRNA expression level both increased in the livers of mice treated with FGTE, similarly to the H. dulcis-treated group. Taken together, these results may suggest that green tea extract coupled with L. fermentum fermentation attenuates the risk of ethanol-induced liver damage.

  7. Betulinic acid prevents alcohol-induced liver damage by improving the antioxidant system in mice

    PubMed Central

    Xia, Wei; Wu, Jianping; Yuan, Liyun; Wu, Jing; Tu, Di; Fang, Jun

    2014-01-01

    Betulinic acid (BA), a pentacyclic lupane-type triterpene, has a wide range of bioactivities. The main objective of this work was to evaluate the hepatoprotective activity of BA and the potential mechanism underlying the ability of this compound to prevent liver damage induced by alcohol in vivo. Mice were given oral doses of BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and induced liver injury by feeding 50% alcohol orally at the dosage of 10 ml/kg after 1 h last administration of BA. BA pretreatment significantly reduced the serum levels of alanine transaminase, aspartate transaminase, total cholesterol, and triacylglycerides in a dose-dependent manner in the mice administered alcohol. Hepatic levels of glutathione, superoxide dismutase, glutathione peroxidase, and catalase were remarkably increased, while malondialdehyde contents and microvesicular steatosis in the liver were decreased by BA in a dose-dependent manner after alcohol-induced liver injury. These findings suggest that the mechanism underlying the hepatoprotective effects of BA might be due to increased antioxidant capacity, mainly through improvement of the tissue redox system, maintenance of the antioxidant system, and decreased lipid peroxidation in the liver. PMID:24378582

  8. Effect of resveratrol on alcohol-induced mortality and liver lesions in mice.

    PubMed

    Bujanda, Luis; García-Barcina, María; Gutiérrez-de Juan, Virginia; Bidaurrazaga, Joseba; de Luco, Marian Fernández; Gutiérrez-Stampa, Marian; Larzabal, Mikel; Hijona, Elisabeth; Sarasqueta, Cristina; Echenique-Elizondo, Miguel; Arenas, Juan I

    2006-11-14

    Resveratrol is a polyphenol with important antiinflammatory and antioxidant properties. We investigated the effect of resveratrol on alcohol-induced mortality and liver lesions in mice. Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol). Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. The animals had free access to standard diet. Blood levels were determined for transaminases, IL-1 and TNF-alpha. A histological evaluation was made of liver damage, and survival among the animals was recorded. Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p < 0.05). IL-1 levels were significantly reduced in the alcohol plus resveratrol group compared with the alcohol group (p < 0.05). TNF-alpha was not detected in any group. Histologically, the liver lesions were more severe in the alcohol group, though no significant differences between groups were observed. Mortality in the alcohol group was 78% in the seventh week, versus 22% in the alcohol plus resveratrol group (p < 0.001). All mice in the alcohol group died before the ninth week. The results obtained suggest that resveratrol reduces mortality and liver damage in mice.

  9. Restraint stress exacerbates alcohol-induced reproductive toxicity in male rats.

    PubMed

    Priya, P Hari; Girish, B P; Reddy, P Sreenivasula

    2014-12-01

    Cumulative exposure to multiple stresses may lead to aggravating the toxicity of each stress, qualitatively or quantitatively altering biological responses because of toxicological interaction. In this study, we intended to determine the possible effects of restraint stress on reproductive toxicity due to ethanol usage in male rats. Early pubertal male Wistar rats were subjected to either restraint stress (5 h/day) or alcohol intoxication (2 mg/kg body weight) or both for 60 days. Body weights of control and experimental rats were similar during the 60 days of this study. Testes were harvested, weighed, and prepared for enzyme assays, and cauda epididymides were isolated for the determination of density, motility, and viability of stored spermatozoa. Restraint stress or alcohol treatment significantly reduced testis weight and caused significant reductions in steroidogenesis and spermatogenesis. Mean density, motility, and viability of stored spermatozoa were reduced in experimental rats. Plasma testosterone concentrations in rats subjected to restraint stress or alcohol were decreased compared with those of controls, concomitant with increased concentrations of LH and FSH in experimental rats. These data suggest that sub-chronic exposure to restraint stress or alcohol contribute to reduce testicular and epididymal function in exposed rats. The study also suggests that restraint stress exacerbates alcohol-induced reproductive toxicity in rats.

  10. Protective effect of Cratoxylum formosum extract against acid/alcohol-induced gastric mucosal damage in rats.

    PubMed

    Sripanidkulchai, Kittisak; Teepsawang, Somsuda; Sripanidkulchai, Bungorn

    2010-10-01

    Cratoxylum formosum is an edible plant that is commonly consumed among the people in Northeast Thailand. This study aimed to investigate the gastroprotective effect of the ethanolic extract of C. formosum leaves (C. formosum ethanolic extract [CFE]). Gastric ulceration was induced in Wistar male rats by oral administration of acid/alcohol. Oral dosing with CFE at 250 and 500 mg/kg of body weight after the acid/alcohol induction significantly decreased the number of bleeding spots, area of bleeding, ulcer score, and ulcer index. Pretreatment with 500 mg/kg CFE significantly prevented the gastric damage. Histological studies of the acid/alcohol-induced animals indicated the gastric inflammation with lesion depth through the mucosal layer. Whereas the gastric lesion of the CFE-treated animals at both 250 and 500 mg/kg doses was decreased to be one-fourth of the mucosal layers, pretreatment with 500 mg/kg CFE prior to acid/alcohol induction completely protected against the mucosal damage. Biochemical analysis of gastric mucosa revealed a significant decrease of malondialdehyde in the CFE-treated group in a dose-response manner. These findings suggest that the gastroprotective activity of CFE could be mediated possibly through its antioxidant effect.

  11. Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis

    PubMed Central

    Andican, Gülnur; Gelisgen, Remisa; Unal, Ethem; Tortum, Osman Baran; Dervisoglu, Sergülen; Karahasanoglu, Tayfun; Burçak, Gülden

    2005-01-01

    AIM: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP). Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation. METHODS: AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done. RESULTS: Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO. CONCLUSION: NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress. PMID:15818750

  12. Synthesis, micellization behavior and alcohol induced amphipathic cellulose film of cellulose-based amphiphilic surfactant

    NASA Astrophysics Data System (ADS)

    Yang, Fang; Liu, Ya-nan; Yu, Jian-ling; Li, Hai-peng; Li, Gang

    2015-08-01

    This paper presented a novel preparation method of the cellulose-based amphiphilic surfactant, and the surfactant was used to prepare amphipathic cellulose membrane. The native cotton cellulose was tailored to cellulose segments in ionic liquid 1-butyl-3-methylimidazolium chloride. Then, the hydrophobic and hydrophilic modification of cellulose segments were carried out by esterification and graft polymerization of the ɛ-caprolactone (ɛ-CL) monomer onto the hydroxyl group of cellulose as well as sulphonation with sulfamic acid. The amphipathic cellulose membrane was made by cellulose-based amphiphilic surfactant cross-linking with glutaraldehyde. The molecular structure of amphipathic cellulose surfactant was confirmed by FT-IR, and its surface active properties were investigated by Wilhelmy plate method and Steady-state fluorescence probe method, respectively. Experimental results showed that cellulose-based amphiphilic surfactant caused low interfacial tension of 48.62 mN/m and its critical micelle concentration (cmc) value was 0.65 wt% when the grafting ratio of cellulose-g-PCL (poly-caprolactone) was 25.40%. The contact angle between a droplet of water and the surface of membrane was 90.84o, and the surface free energy of the alcohol induced cellulose membrane was 15.7 mJ/m2. This study may help increase using natural and biodegradable surface-activity materials with improved properties as surfactants.

  13. Development, Prevention, and Treatment of Alcohol-Induced Organ Injury: The Role of Nutrition

    PubMed Central

    Barve, Shirish; Chen, Shao-Yu; Kirpich, Irina; Watson, Walter H.; McClain, Craig

    2017-01-01

    Alcohol and nutrition have the potential to interact at multiple levels. For example, heavy alcohol consumption can interfere with normal nutrition, resulting in overall malnutrition or in deficiencies of important micronutrients, such as zinc, by reducing their absorption or increasing their loss. Interactions between alcohol consumption and nutrition also can affect epigenetic regulation of gene expression by influencing multiple regulatory mechanisms, including methylation and acetylation of histone proteins and DNA. These effects may contribute to alcohol-related organ or tissue injury. The impact of alcohol–nutrition interactions has been assessed for several organs and tissues, including the intestine, where heavy alcohol use can increase intestinal permeability, and the liver, where the degree of malnutrition can be associated with the severity of liver injury and liver disease. Alcohol–nutrition interactions also play a role in alcohol-related lung injury, brain injury, and immune dysfunction. Therefore, treatment involving nutrient supplementation (e.g., with zinc or S-adenosylmethionine) may help prevent or attenuate some types of alcohol-induced organ damage.

  14. Reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing.

    PubMed

    Stock, Ann-Kathrin; Mückschel, Moritz; Beste, Christian

    2017-01-01

    Recent research has drawn interest to the effects of binge drinking on response selection. However, choosing an appropriate response is a complex endeavor that usually requires us to process and integrate several streams of information. One of them is proprioceptive information about the position of limbs. As to now, it has however remained elusive how binge drinking affects the processing of proprioceptive information during response selection and control in healthy individuals. We investigated this question using neurophysiological (EEG) techniques in a response selection task, where we manipulated proprioceptive information. The results show a reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing. The most likely explanation for this finding is that proprioceptive information does not seem to be properly integrated in response selection processes during acute alcohol intoxication as found in binge drinking. The neurophysiological data suggest that processes related to the preparation and execution of the motor response, but not upstream processes related to conflict monitoring and spatial attentional orienting, underlie these binge drinking-dependent modulations. Taken together, the results show that even high doses of alcohol have very specific effects within the cascade of neurophysiological processes underlying response control and the integration of proprioceptive information during this process. © 2015 Society for the Study of Addiction.

  15. Were James Bond’s drinks shaken because of alcohol induced tremor?

    PubMed Central

    Johnson, Graham; Guha, Indra Neil

    2013-01-01

    Objective To quantify James Bond’s consumption of alcohol as detailed in the series of novels by Ian Fleming. Design Retrospective literature review. Setting The study authors’ homes, in a comfy chair. Participants Commander James Bond, 007; Mr Ian Lancaster Fleming. Main outcome measures Weekly alcohol consumption by Commander Bond. Methods All 14 James Bond books were read by two of the authors. Contemporaneous notes were taken detailing every alcoholic drink taken. Predefined alcohol unit levels were used to calculate consumption. Days when Bond was unable to consume alcohol (such as through incarceration) were noted. Results After exclusion of days when Bond was unable to drink, his weekly alcohol consumption was 92 units a week, over four times the recommended amount. His maximum daily consumption was 49.8 units. He had only 12.5 alcohol free days out of 87.5 days on which he was able to drink. Conclusions James Bond’s level of alcohol intake puts him at high risk of multiple alcohol related diseases and an early death. The level of functioning as displayed in the books is inconsistent with the physical, mental, and indeed sexual functioning expected from someone drinking this much alcohol. We advise an immediate referral for further assessment and treatment, a reduction in alcohol consumption to safe levels, and suspect that the famous catchphrase “shaken, not stirred” could be because of alcohol induced tremor affecting his hands. PMID:24336307

  16. Amelioration of alcohol-induced hepatotoxicity and oxidative stress in rats by Acorus calamus.

    PubMed

    Ilaiyaraja, N; Khanum, Farhath

    2011-12-01

    The protective effect of a methanolic extract (ME) of Acorus calamus against alcohol-induced hepatotoxicity and oxidative stress was studied in rats. The in vitro assays using DPPH and ABTS showed a strong antioxidant activity of the extract with the total polyphenolic content of 156 mg/g. Chronic ethanol administration causes an increase in oxidative stress and tissue injury with decreased antioxidant status. In this study, continuous administration of ethanol (7.9 g/kg body weight/day) for a period of 6 weeks resulted in a significant (p < .001) increase in the levels of serum aspartate aminotransferase, serum alanine aminotransferase, alkaline phospahatase, and bilirubin with the decreased level of total antioxidant status. Moreover, the levels of lipid peroxidation markers (malondialdehyde and hydroperoxides) as well as protein carbonyl content were also increased (p < .001), whereas the levels of non-enzymic antioxidants (glutathione, vitamin C, and vitamin E) decreased significantly in the liver tissues of ethanol-administered control rats. Pretreatment of rats with ME at doses of 300 and 600 g/kg body weight before alcohol administration significantly reduced the hepatic marker enzymes, level of lipid peroxidation, and protein oxidation, and increased the enzymatic and non-enzymatic antioxidant levels in liver. These observations were supplemented by histopathological examination of liver sections. Overall, the present study shows that the administration of ME ameliorates the antioxidant status as well as protects against the toxic effects of ethanol in rats, thereby suggesting its use as an effective botanical supplement for hepatoprotection.

  17. Amelioration of alcohol-induced hepatotoxicity by the administration of ethanolic extract of Sida cordifolia Linn.

    PubMed

    Rejitha, S; Prathibha, P; Indira, M

    2012-10-01

    Sida cordifolia Linn. (Malvaceae) is a plant used in folk medicine for the treatment of the inflammation of oral mucosa, asthmatic bronchitis, nasal congestion and rheumatism. We studied the hepatoprotective activity of 50 % ethanolic extract of S. cordifolia Linn. against alcohol intoxication. The duration of the experiment was 90 d. The substantially elevated levels of toxicity markers such as alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase due to the alcohol treatment were significantly lowered in the extract-treated groups. The activity of antioxidant enzymes and glutathione content, which was lowered due to alcohol toxicity, was increased to a near-normal level in the co-administered group. Lipid peroxidation products, protein carbonyls, total collagen and hydroxyproline, which were increased in the alcohol-treated group, were reduced in the co-administered group. The mRNA levels of cytochrome P450 2E1, NF-κB, TNF-α and transforming growth factor-β1 were found to be increased in the alcohol-treated rats, and their expressions were found to be decreased in the co-administered group. These observations were reinforced by histopathological analysis. Thus, the present study clearly indicates that 50 % ethanolic extract of the roots of S. cordifolia Linn. has a potent hepatoprotective action against alcohol-induced toxicity, which was mediated by lowering oxidative stress and by down-regulating the transcription factors.

  18. Exposure to secondhand smoke in Finnish workplaces and compliance with national smoke-free workplace legislation.

    PubMed

    Heloma, Antero; Helakorpi, Satu; Honkonen, Jarkko; Danielsson, Petri; Uutela, Antti

    2011-11-01

    The present study examined time trends and associations in exposure to secondhand smoke (SHS) at work in Finland in 1985-2008 and compliance with national smoke-free workplace legislation that has been enforced since 1995. The study population comprised respondents of nationally representative annual postal surveys from 1985 to 2008. The differences in the prevalence of SHS-exposed respondents were measured with particular reference to workplace size and workplace smoking arrangements. From 1985 to 2008 daily exposure to SHS at work decreased in all workplaces. The annual decrease was largest in 1994-95 when the smoke-free workplace legislation was enacted. The proportion of exposed employees in workplaces with designated smoking rooms was two-fold compared to employees in workplaces where no one smoked, and this ratio remained unchanged between 1995 and 2008. Employees in small workplaces were exposed most and exposure to SHS was lowest in the largest workplaces. Totally smoke-free workplaces give better protection against the exposure to SHS than workplaces with designated smoking areas. We urge a law reform that does not allow any designated smoking rooms indoors. In the prevention of SHS exposure, special attention should be directed to small workplaces.

  19. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

    SciTech Connect

    Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

    2014-09-26

    Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

  20. Second Generation Electronic Nicotine Delivery System Vape Pen Exposure Generalizes as a Smoking Cue.

    PubMed

    King, Andrea C; Smith, Lia J; McNamara, Patrick J; Cao, Dingcai

    2017-01-12

    Second generation electronic nicotine delivery systems (ENDS; also known as e-cigarettes, vaporizers or vape pens) are designed for a customized nicotine delivery experience and have less resemblance to regular cigarettes than first generation "cigalikes." The present study examined whether they generalize as a conditioned cue and evoke smoking urges or behavior in persons exposed to their use. Data were analyzed in N = 108 young adult smokers (≥5 cigarettes per week) randomized to either a traditional combustible cigarette smoking cue or a second generation ENDS vaping cue in a controlled laboratory setting. Cigarette and e-cigarette urge and desire were assessed pre- and post-cue exposure. Smoking behavior was also explored in a subsample undergoing a smoking latency phase after cue exposure (N = 26). The ENDS vape pen cue evoked both urge and desire for a regular cigarette to a similar extent as that produced by the combustible cigarette cue. Both cues produced similar time to initiate smoking during the smoking latency phase. The ENDS vape pen cue elicited smoking urge and desire regardless of ENDS use history, that is, across ENDS naїve, lifetime or current users. Inclusion of past ENDS or cigarette use as covariates did not significantly alter the results. These findings demonstrate that observation of vape pen ENDS use generalizes as a conditioned cue to produce smoking urge, desire, and behavior in young adult smokers. As the popularity of these devices may eventually overtake those of first generation ENDS cigalikes, exposure effects will be of increasing importance. This study shows that passive exposure to a second generation ENDS vape pen cue evoked smoking urge, desire, and behavior across a range of daily and non-daily young adult smokers. Smoking urge and desire increases after vape pen exposure were similar to those produced by exposure to a first generation ENDS cigalike and a combustible cigarette, a known potent cue. Given the increasing

  1. Antioxidants prevent ethanol-induced contractions of canine cerebral vascular smooth muscle: relation to alcohol-induced brain injury.

    PubMed

    Li, W; Zheng, T; Altura, B T; Altura, B M

    2001-03-30

    The present study was designed to test the hypothesis that alpha-tocopherol (Vit. E) and pyrrolidine dithiocarbamate (PDTC) might exert direct effects on alcohol-induced contractions of canine basilar cerebral arteries. After precontraction of arterial ring segments with ethanol, PDTC (10(-8)-10(-6) M) and Vit. E (10(-6)-10(-4) M) induced concentration-dependent relaxations of cerebral arteries, compared to untreated controls. The effective concentrations producing approximately 50% of the maximal relaxation responses (EC(50) values) were about 2.48+/-0.09 x 10(-7) M for PDTC, and 1.87+/-0.10 x 10(-5) mM for Vit. E, respectively. Preincubation of these arterial rings with EC(50)'s of PDTC or Vit. E for 40 min attenuate markedly the contractions produced by alcohol, at concentrations of 1-400 mM. However, both PDTC and Vit.E do not relax equi-potent precontractions induced by either KCl or prostaglandin F(2alpha) (PGF(2alpha)) or inhibit their contractions. These data suggest that alcohol-induced contractions of cerebral arteries are mediated via excitation-contraction coupling pathways different from those used by KCl or receptor-mediated agonists such as PGF(2alpha). The present results, when viewed in light of other recently published data, suggest that antioxidants may prove useful in the amelioration and treatment of alcohol-induced brain damage and strokes.

  2. Protective effects of recombinant human cytoglobin against chronic alcohol-induced liver disease in vivo and in vitro

    PubMed Central

    Wen, Jian; Wu, Yongbin; Wei, Wei; Li, Zhen; Wang, Ping; Zhu, Shiwei

    2017-01-01

    Alcoholic liver disease (ALD) is an important worldwide public health issue with no satisfying treatment available since now. Here we explore the effects of recombinant human cytoglobin (rhCygb) on chronic alcohol-induced liver injury and the underlying mechanisms. In vivo studies showed that rhCygb was able to ameliorate alcohol-induced liver injury, significantly reversed increased serum index (ALT, AST, TG, TC and LDL-C) and decreased serum HDL-C. Histopathology observation of the liver of rats treated with rhCygb confirmed the biochemical data. Furthermore, rhCygb significantly inhibited Kupffer cells (KCs) proliferation and TNF-α expression in LPS-induced KCs. rhCygb also inhibited LPS-induced NADPH oxidase activity and ROS, NO and O2•− generation. These results collectively indicate that rhCygb exert the protective effect on chronic alcohol-induced liver injury through suppression of KC activation and oxidative stress. In view of its anti-oxidative stress and anti-inflammatory features, rhCygb might be a promising candidate for development as a therapeutic agent against ALD. PMID:28128325

  3. Nephro-protective action of P. santalinus against alcohol-induced biochemical alterations and oxidative damage in rats.

    PubMed

    Bulle, Saradamma; Reddy, Vaddi Damodara; Hebbani, Ananda Vardhan; Padmavathi, Pannuru; Challa, Chandrasekhar; Puvvada, Pavan Kumar; Repalle, Elisha; Nayakanti, Devanna; Aluganti Narasimhulu, Chandrakala; Nallanchakravarthula, Varadacharyulu

    2016-12-01

    The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na(+)/K(+)-ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. New Guidelines Urge Early Intro to Peanut in High-Risk Infants

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162898.html New Guidelines Urge Early Intro to Peanut in High- ... diets as early as 4 months of age, new U.S. guidelines suggest. The recommendation comes from the ...

  5. Ecological momentary assessment of antecedents and consequences of smoking in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Mitchell, John T; Dennis, Michelle F; English, Joseph S; Dennis, Paul A; Brightwood, Amy; Beckham, Jean C; Kollins, Scott H

    2014-09-01

    The current study assessed antecedents and consequences of ad lib cigarette smoking in smokers diagnosed with attention-deficit/hyperactivity disorder (ADHD) using ecological momentary assessment (EMA). Adult smokers with ADHD (n = 17) completed 870 smoking and 622 nonsmoking electronic diary entries over a 7-day observation period of their naturalistic smoking behavior. Data collection occurred from 2011 to 2012. Generalized estimating equations indicated that ADHD smokers were more likely to smoke when urge to smoke, negative affect, boredom, stress, worry, and restlessness were elevated. In addition, participants were more likely to smoke in situations that elicited higher levels of nervousness and frustration. ADHD symptoms, in general, did not differ between smoking and nonsmoking contexts, though hyperactive-impulsive ADHD symptoms were elevated prior to smoking in frustrating situations. Additional situational antecedent variables were associated with smoking, including being in the presence of others smoking, being in a bar or restaurant, while outside, and while consuming caffeinated or alcoholic beverages. Participants also reported a significant improvement in urge to smoke, negative affect, stress, hunger, and ADHD symptoms after smoking a cigarette. Findings suggest certain contextual factors that may maintain ad lib cigarette smoking in smokers with ADHD and identify potential treatment targets in smoking cessation interventions for this at-risk group. Clinical implications and future research directions are discussed. Funding for this study was provided by the National Institute on Drug Abuse.

  6. Smoking and Tobacco Use

    MedlinePlus

    ... Smoking & Tobacco Use Subscribe Translate Text Size Print Smoking & Tobacco Use HIV and Smoking Tobacco use is the leading cause of preventable ... Provider Smoking Cessation Resources . /* ** // ** */ The Benefits of Quitting Smoking Quitting smoking has major and immediate health benefits ...

  7. Stop smoking support programs

    MedlinePlus

    Smokeless tobacco - stop smoking programs; Stop smoking techniques; Smoking cessation programs; Smoking cessation techniques ... It is hard to quit smoking if you are acting alone. Smokers may have a ... of quitting with a support program. Stop smoking programs ...

  8. p53 pathway determines the cellular response to alcohol-induced DNA damage in MCF-7 breast cancer cells

    PubMed Central

    Zhao, Ming; Howard, Erin W.; Guo, Zhiying; Parris, Amanda B.; Yang, Xiaohe

    2017-01-01

    Alcohol consumption is associated with increased breast cancer risk; however, the underlying mechanisms that contribute to mammary tumor initiation and progression are unclear. Alcohol is known to induce oxidative stress and DNA damage; likewise, p53 is a critical modulator of the DNA repair pathway and ensures genomic integrity. p53 mutations are frequently detected in breast and other tumors. The impact of alcohol on p53 is recognized, yet the role of p53 in alcohol-induced mammary carcinogenesis remains poorly defined. In our study, we measured alcohol-mediated oxidative DNA damage in MCF-7 cells using 8-OHdG and p-H2AX foci formation assays. p53 activity and target gene expression after alcohol exposure were determined using p53 luciferase reporter assay, qPCR, and Western blotting. A mechanistic study delineating the role of p53 in DNA damage response and cell cycle arrest was based on isogenic MCF-7 cells stably transfected with control (MCF-7/Con) or p53-targeting siRNA (MCF-7/sip53), and MCF-7 cells that were pretreated with Nutlin-3 (Mdm2 inhibitor) to stabilize p53. Alcohol treatment resulted in significant DNA damage in MCF-7 cells, as indicated by increased levels of 8-OHdG and p-H2AX foci number. A p53-dependent signaling cascade was stimulated by alcohol-induced DNA damage. Moderate to high concentrations of alcohol (0.1–0.8% v/v) induced p53 activation, as indicated by increased p53 phosphorylation, reporter gene activity, and p21/Bax gene expression, which led to G0/G1 cell cycle arrest. Importantly, compared to MCF-7/Con cells, alcohol-induced DNA damage was significantly enhanced, while alcohol-induced p21/Bax expression and cell cycle arrest were attenuated in MCF-7/sip53 cells. In contrast, inhibition of p53 degradation via Nutlin-3 reinforced G0/G1 cell cycle arrest in MCF-7 control cells. Our study suggests that functional p53 plays a critical role in cellular responses to alcohol-induced DNA damage, which protects the cells from DNA damage

  9. miR-519 suppresses nasopharyngeal carcinoma cell proliferation by targeting oncogene URG4/URGCP.

    PubMed

    Yu, Guodong; Zhang, Tian; Jing, Ying; Bao, Qingmin; Tang, Qiang; Zhang, Yu

    2017-03-15

    Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumor in Southeast Asia, its regulatory mechanism is still to be understood. miR-519 inhibits the progression of several tumors, including cervical cancer, ovarian cancer and gastric cancer. But its role in NPC hasn't been studied. In present study, we found miR-519 was downregulated in NPC cells, its overexpression inhibited NPC cell proliferation and arrested cell cycle at G0/G1 phase, while its knockdown promoted NPC cell proliferation and cell cycle progression. An oncogene URG4/URGCP (upregulated gene-4/upregulator of cell proliferation) was the target of miR-519, URG4 was upregulated in NPC cells, miR-519 inhibited URG4 expression by directly binding to the 3'UTR of URG4. miR-519 inhibited Cyclin D1 expression and the phosphorylation level of Rb, and increased p21 and p27 expression, confirming miR-519 blocked G1/S transition. Moreover, miR-519 level was negative correlated with URG4 level in NPC tissues. In summary, we found miR-519 NPC cell proliferation by inhibiting URG4.

  10. Acute effects of low and high dose alcohol on smoking lapse behavior in a laboratory analogue task

    PubMed Central

    Kahler, Christopher W.; Metrik, Jane; Spillane, Nichea S.; Day, Anne; Leventhal, Adam M.; McKee, Sherry A.; Tidey, Jennifer W.; McGeary, John E.; Knopik, Valerie S.; Rohsenow, Damaris J.

    2014-01-01

    Rationale Smoking lapses (i.e., returns to smoking after quitting) often occur following alcohol consumption with observational data suggesting greater quantities of alcohol lead to greater risk. However, a causal dose-dependent effect of alcohol consumption on smoking lapse behavior has not been established, and the mechanisms that might account for such an effect have not been tested. Objectives In a within-subjects design, we examined effects of low (0.4 g/kg) and high (0.8 g/kg) dose alcohol, relative to placebo, on smokers’ ability to resist initiating smoking after acute smoking abstinence. Methods Participants were 100 heavy alcohol drinkers, smoking 10–30 cigarettes per day. Across three separate days, participants consumed placebo, low, or high dose alcohol following 3 h of smoking abstinence, and 35 min later were offered the opportunity to smoke while resisting smoking was monetarily reinforced proportional to the amount of time delayed. Results Consistent with a dose-response effect, participants smoked 3.35 min (95% CI [−7.09, 0.40], p=.08) earlier following low dose alcohol and 6.36 min (95% CI [−9.99, −2.73], p=.0006) earlier following high dose alcohol compared to drinking a placebo beverage. Effects of dose on smoking behavior were partially mediated by increases in urge to smoke. There was no evidence that alcohol’s effects on urge to smoke or ability to resist smoking were mediated through its stimulating or sedating effects. Conclusions Alcohol can reduce the ability to resist smoking in a dose-dependent fashion, in part, due to its effect on increasing the intensity of smoking urges. PMID:24858377

  11. Nrf2 Knockdown Disrupts the Protective Effect of Curcumin on Alcohol-Induced Hepatocyte Necroptosis.

    PubMed

    Lu, Chunfeng; Xu, Wenxuan; Zhang, Feng; Shao, Jiangjuan; Zheng, Shizhong

    2016-12-05

    It has emerged that hepatocyte necroptosis plays a critical role in chronic alcoholic liver disease (ALD). Our previous study has identified that the beneficial therapeutic effect of curcumin on alcohol-caused liver injury might be attributed to activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), whereas the role of curcumin in regulating necroptosis and the underlying mechanism remain to be determined. We first found that chronic alcohol consumption triggered obvious hepatocyte necroptosis, leading to increased expression of receptor-interacting protein 1, receptor-interacting protein 3, high-mobility group box 1, and phosphorylated mixed lineage kinase domain-like in murine livers. Curcumin dose-dependently ameliorated hepatocyte necroptosis and alleviated alcohol-caused decrease in hepatic Nrf2 expression in alcoholic mice. Then Nrf2 shRNA lentivirus was introduced to generate Nrf2-knockdown mice. Our results indicated that Nrf2 knockdown aggravated the effects of alcohol on liver injury and necroptosis and even abrogated the inhibitory effect of curcumin on necroptosis. Further, activated Nrf2 by curcumin inhibited p53 expression in both livers and cultured hepatocytes under alcohol stimulation. The next in vitro experiments, similar to in vivo ones, revealed that although Nrf2 knockdown abolished the suppression of curcumin on necroptosis of hepatocytes exposed to ethanol, p53 siRNA could clearly rescued the relative effect of curcumin. In summary, for the first time, we concluded that curcumin attenuated alcohol-induced hepatocyte necroptosis in a Nrf2/p53-dependent mechanism. These findings make curcumin an excellent candidate for ALD treatment and advance the understanding of ALD mechanisms associated with hepatocyte necroptosis.

  12. Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking.

    PubMed

    Swanson, Garth R; Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Kaminsky, Thomas; Van Den Berg, Jolice; Murphy, Terrence; Raeisi, Shohreh; Fogg, Louis; Vitaterna, Martha Hotz; Forsyth, Christopher; Turek, Fred; Burgess, Helen J; Keshavarzian, Ali

    2016-07-01

    Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.

  13. Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function

    PubMed Central

    Groebner, Jennifer L.; Fernandez, David J.; Tuma, Dean J.; Tuma, Pamela L.

    2016-01-01

    Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to micro-tubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease. PMID:25148871

  14. Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells.

    PubMed

    Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

    Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol's effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event

  15. Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union.

    PubMed

    Rehm, Jürgen; Anderson, Peter; Prieto, Jose Angel Arbesu; Armstrong, Iain; Aubin, Henri-Jean; Bachmann, Michael; Bastus, Nuria Bastida; Brotons, Carlos; Burton, Robyn; Cardoso, Manuel; Colom, Joan; Duprez, Daniel; Gmel, Gerrit; Gual, Antoni; Kraus, Ludwig; Kreutz, Reinhold; Liira, Helena; Manthey, Jakob; Møller, Lars; Okruhlica, Ľubomír; Roerecke, Michael; Scafato, Emanuele; Schulte, Bernd; Segura-Garcia, Lidia; Shield, Kevin David; Sierra, Cristina; Vyshinskiy, Konstantin; Wojnar, Marcin; Zarco, José

    2017-09-28

    Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded. Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries

  16. Alcohol-induced autophagy contributes to loss in skeletal muscle mass

    PubMed Central

    Thapaliya, Samjhana; Runkana, Ashok; McMullen, Megan R; Nagy, Laura E; McDonald, Christine; Prasad, Sathyamangla V Naga; Dasarathy, Srinivasan

    2014-01-01

    Patients with alcoholic cirrhosis and hepatitis have severe muscle loss. Since ethanol impairs skeletal muscle protein synthesis but does not increase ubiquitin proteasome-mediated proteolysis, we investigated whether alcohol-induced autophagy contributes to muscle loss. Autophagy induction was studied in: A) Human skeletal muscle biopsies from alcoholic cirrhotics and controls, B) Gastrocnemius muscle from ethanol and pair-fed mice, and C) Ethanol-exposed murine C2C12 myotubes, by examining the expression of autophagy markers assessed by immunoblotting and real-time PCR. Expression of autophagy genes and markers were increased in skeletal muscle from humans and ethanol-fed mice, and in myotubes following ethanol exposure. Importantly, pulse-chase experiments showed suppression of myotube proteolysis upon ethanol-treatment with the autophagy inhibitor, 3-methyladenine (3MA) and not by MG132, a proteasome inhibitor. Correspondingly, ethanol-treated C2C12 myotubes stably expressing GFP-LC3B showed increased autophagy flux as measured by accumulation of GFP-LC3B vesicles with confocal microscopy. The ethanol-induced increase in LC3B lipidation was reversed upon knockdown of Atg7, a critical autophagy gene and was associated with reversal of the ethanol-induced decrease in myotube diameter. Consistently, CT image analysis of muscle area in alcoholic cirrhotics was significantly reduced compared with control subjects. In order to determine whether ethanol per se or its metabolic product, acetaldehyde, stimulates autophagy, C2C12 myotubes were treated with ethanol in the presence of the alcohol dehydrogenase inhibitor (4-methylpyrazole) or the acetaldehyde dehydrogenase inhibitor (cyanamide). LC3B lipidation increased with acetaldehyde treatment and increased further with the addition of cyanamide. We conclude that muscle autophagy is increased by ethanol exposure and contributes to sarcopenia. PMID:24492484

  17. Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking

    PubMed Central

    Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Kaminsky, Thomas; Van Den Berg, Jolice; Murphy, Terrence; Raeisi, Shohreh; Fogg, Louis; Vitaterna, Martha Hotz; Forsyth, Christopher; Turek, Fred; Burgess, Helen J.; Keshavarzian, Ali

    2016-01-01

    Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20–30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption. PMID:27198191

  18. Lipopolysaccharide downregulates macrophage-derived IL-22 to modulate alcohol-induced hepatocyte cell death.

    PubMed

    Liu, Yaming; Verma, Vikas K; Malhi, Harmeet; Gores, Greg J; Kamath, Patrick S; Sanyal, Arun; Chalasani, Naga; Gao, Bin; Shah, Vijay H

    2017-09-01

    Interleukin-22 (IL-22) is a Th17 cell hepatoprotective cytokine that is undergoing clinical trials to treat patients with alcoholic hepatitis (AH). Lipopolysaccharide (LPS) activation of macrophage is implicated in hepatocyte cell death and pathogenesis of AH. The role of IL-22 production from macrophage, its regulation by LPS, and effects on alcohol-induced hepatocyte cell death are unexplored and were examined in this study. Low levels of IL-22 mRNA/protein were detected in macrophage but were significantly upregulated by 6.5-fold in response to the tissue reparative cytokine IL-10. Conversely, LPS significantly decreased IL-22 mRNA levels in a temporal and concentration-dependent manner with a maximum reduction of 5-fold. LPS downregulation of IL-22 mRNA levels was rescued in the presence of a pharmacological inhibitor of c-Jun NH2-terminal kinase (JNK) and by JNK knockdown. Next, we explored whether macrophage-derived IL-22 regulated ethanol-induced hepatocyte death. Conditioned media from IL-10-stimulated macrophages attenuated ethanol-induced hepatocyte caspase-3/7 activity, and apoptosis as assessed by fluorometric assay and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. This effect was diminished in conditioned media from macrophages with IL-22 knockdown. Cytokine analysis in sera samples of patients with AH revealed that IL-22 levels were significantly elevated compared with healthy controls and heavy-drinking controls, implying a state of IL-22 resistance in human AH. Macrophage-derived IL-22 protects hepatocytes from ethanol-induced cell death. IL-22 downregulation is a new regulatory target of LPS in the pathogenesis of AH.

  19. Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells

    PubMed Central

    Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

    2016-01-01

    Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol’s effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event

  20. Absence of cytochrome P450 2A5 enhances alcohol-induced liver injury in mice.

    PubMed

    Hong, Feng; Liu, Xiyu; Ward, Stephen S; Xiong, Huabao; Cederbaum, Arthur I; Lu, Yongke

    2015-06-01

    Ethanol can induce cytochrome P450 2E1, an active generator of reactive oxygen species, and this cytochrome is considered a risk factor for oxidative liver injury. Recently, we found that in addition to P450 2E1 also cytochrome P450 2A5, another isoform of cytochrome P450, can be induced by ethanol, and that ethanol induction of cytochrome P450 2A5 is P450 2E1-dependent. To investigate the role of cytochrome P450 2A5 in alcohol-induced liver injury. Cytochrome P450 2A5-knockout mice and wild type mice were fed the Lieber-Decarli ethanol liquid diet to induce liver injury. Controls were fed the Lieber-Decarli control diet. After 4 weeks of feeding with Lieber-Decarli diet, ethanol-induced liver injury was enhanced in the knockout mice compared with wild type mice, as indicated by serum transaminases, hepatic fat accumulation (steatosis), and necroinflammation observed in liver sections with Haematoxylin & Eosin staining. Ethanol-induced oxidative stress was also higher in the knockout mice than the wild types. Ethanol feeding induced cytochrome P450 2A5 in wild type mice but not in the knockout mice, while induction of cytochrome P450 2E1 was comparable in the knockout and wild type mice. These results suggest that cytochrome P450 2A5 protects against ethanol-induced oxidative liver injury. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Melatonin and vitamin C attenuates alcohol-induced oxidative stress in aorta.

    PubMed

    Sönmez, Mehmet Fatih; Narin, Figen; Balcioğlu, Esra

    2009-12-01

    Epidemiological studies have shown that low to moderate doses of alcohol consumption are beneficial to cardiac health. However, chronic high doses of alcohol ingestion cause cardiovascular complications. The aim of this study was to investigate both the effects of melatonin and vitamin C and expression of endothelial nitric oxide synthase in aorta of chronic alcoholic rats. Twenty-four adult male Wistar rats weighing 200-250 g were used in the study. Rats were divided into four equal groups. Group I (control): rats were not fed on alcohol; Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40 mg/kg vitamin C were injected intraperitoneally and Group IV: rats were fed on alcohol and 4 mg/kg melatonin were injected intraperitoneally. At the end of the experiment, rats were killed and aorta tissues were removed. Some parts of the aorta tissues were used for biochemical analyses and the other parts were used at histological procedures. In the control group, endothelial nitric oxide synthase immunoreactivity was (++) in smooth muscle cells and endothelial cells. Expression of endothelial nitric oxide synthase in the alcohol group was stronger than control group. Chronic ethanol ingestion significantly increased (p < 0.05); and melatonin significantly decreased both the plasma and tissue malondialdehyde levels. The superoxide dismutase levels and catalase activity did not change significantly in the Vitamin C and melatonin groups (p > 0.05) compared to the control and alcohol groups. The present results indicate that chronic alcohol consumption increase lipid peroxidation and cause endothelial nitric oxide synthase expression in the aorta. However, melatonin and vitamin C administration provide partial protection against alcohol-induced damage.

  2. Dietary nicotinic acid supplementation ameliorates chronic alcohol-induced fatty liver in rats.

    PubMed

    Li, Qiong; Xie, Guoxiang; Zhang, Wenliang; Zhong, Wei; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang

    2014-07-01

    Alcohol abuse frequently causes niacin deficiency in association with the development of alcoholic liver disease. The objective of the present study was to determine whether dietary nicotinic acid (NA) deficiency exaggerates and whether dietary NA supplementation alleviates alcohol-induced fatty liver. Male Sprague-Dawley rats were pair-fed with 4 isocaloric liquid diets: control, ethanol (EtOH), EtOH with dietary NA deficiency, and EtOH with dietary NA supplementation, respectively, for 8 weeks. The control and EtOH diets contained normal levels of NA (7.5 mg/l). Dietary NA deficiency (0 mg NA/l) was achieved by removing NA from the vitamin mix, while NA was added to the liquid diet at 750 mg/l for dietary NA supplementation. Chronic EtOH feeding induced significant lipid accumulation in the liver, which was not worsened by dietary NA deficiency, but was ameliorated by dietary NA supplementation. Liver total NAD, NAD(+) , and NADH levels were remarkably higher in the NA supplemented group than the NA deficient or EtOH alone groups. Dietary NA supplementation to EtOH-fed rats increased the protein levels of hepatic cytochrome P450 4A1 (CYP4A1) and acyl-coenzyme A oxidase 1 without affecting their mRNA levels. Interestingly, we found dietary NA supplementation reduced the ubiquitination level of CYP4A1. In addition, hepatic fatty acid synthase expression was reduced, while the serum β-hydroxybutyrate and adiponectin concentrations were significantly elevated by dietary NA supplementation. Moreover, dietary NA supplementation modulated EtOH-perturbed liver and serum metabolite profiles. These results demonstrate that alcoholic fatty liver was not exaggerated by dietary NA deficiency, but was ameliorated by dietary NA supplementation. Increased hepatic fatty acid oxidation and decreased hepatic de novo lipogenesis contribute to the effects of dietary NA supplementation. Copyright © 2014 by the Research Society on Alcoholism.

  3. Impact of smoking images in magazines on the smoking attitudes and intentions of youth: an experimental investigation

    PubMed Central

    Carter, Owen B J; Donovan, Robert J; Weller, Narelle M; Jalleh, Geoffrey

    2007-01-01

    Objective To determine the effect of magazine incidental smoking imagery on youths' smoking intentions. Methods A magazine was developed incorporating photographs of smokers (Smoking Magazine). A second version of the magazine (Non‐smoking Magazine) included these photographs with the tobacco paraphernalia digitally erased. Equal numbers of smokers and non‐smokers aged 14–17 years (n = 357) were randomly assigned to look through one version of the magazine and then asked a series of questions. Results Smokers made more unprompted mention of smoking imagery than non‐smokers after viewing Smoking Magazine (52% vs 34%; p<0.05). Smokers viewing Smoking Magazine were more likely to report an urge to smoke (54% vs 40%; p<0.05). Female non‐smokers who viewed Smoking Magazine were more likely than those who viewed Non‐smoking Magazine to state a future intention to smoke (13% vs 0%; p<0.05). Female smokers were more attracted to the male models appearing in Smoking Magazine than Non‐smoking Magazine (49% vs 24%; p<0.05) and the opposite was true for female non‐smokers (28% vs 52%; p<0.05). Female smokers were also marginally more likely to desire looking like the female models in Smoking Magazine (64% vs 46%; p = 0.06) but no difference was observed in the non‐smoking females (46% vs 46%). Male smokers and non‐smokers did not differ in their responses by magazine type. Conclusions Incidental positive smoking imagery in magazines can generate the same sorts of consumer effects attributed to advertising in general, including tobacco advertising. Sex specific results of our study may be explained by the choice of smoking images used. PMID:18048611

  4. Impact of smoking images in magazines on the smoking attitudes and intentions of youth: an experimental investigation.

    PubMed

    Carter, Owen B J; Donovan, Robert J; Weller, Narelle M; Jalleh, Geoffrey

    2007-12-01

    To determine the effect of magazine incidental smoking imagery on youths' smoking intentions. A magazine was developed incorporating photographs of smokers (Smoking Magazine). A second version of the magazine (Non-smoking Magazine) included these photographs with the tobacco paraphernalia digitally erased. Equal numbers of smokers and non-smokers aged 14-17 years (n = 357) were randomly assigned to look through one version of the magazine and then asked a series of questions. Smokers made more unprompted mention of smoking imagery than non-smokers after viewing Smoking Magazine (52% vs 34%; p<0.05). Smokers viewing Smoking Magazine were more likely to report an urge to smoke (54% vs 40%; p<0.05). Female non-smokers who viewed Smoking Magazine were more likely than those who viewed Non-smoking Magazine to state a future intention to smoke (13% vs 0%; p<0.05). Female smokers were more attracted to the male models appearing in Smoking Magazine than Non-smoking Magazine (49% vs 24%; p<0.05) and the opposite was true for female non-smokers (28% vs 52%; p<0.05). Female smokers were also marginally more likely to desire looking like the female models in Smoking Magazine (64% vs 46%; p = 0.06) but no difference was observed in the non-smoking females (46% vs 46%). Male smokers and non-smokers did not differ in their responses by magazine type. Incidental positive smoking imagery in magazines can generate the same sorts of consumer effects attributed to advertising in general, including tobacco advertising. Sex specific results of our study may be explained by the choice of smoking images used.

  5. Do Emotional Eating Urges Regulate Affect? Concurrent and Prospective Associations and Implications for Risk Models of Binge Eating

    PubMed Central

    Haedt-Matt, Alissa A.; Keel, Pamela K.; Racine, Sarah E.; Burt, S. Alexandra; Hu, Jean Yueqin; Boker, Steven; Neale, Michael; Klump, Kelly L.

    2014-01-01

    Objective Emotional eating (EE) reflects an urge to eat in response to emotional rather than physical cues and is a risk factor for the development of binge eating. EE has been conceptualized as an attempt to regulate negative affect (NA), a posited maintenance factor for binge eating. However, no study has examined whether EE urges regulate affect. Further, no studies have examined longitudinal associations between EE urges and positive affect (PA). Method We examined within-subject longitudinal associations between affect and EE urges in a community-based sample of female twins (mean age=17.8 years). Participants (N=239) completed ratings of affect and EE urges for 45 consecutive days. Results Greater NA was concurrently associated with greater EE urges. Additionally, greater EE urges predicted worse NA for both concurrent and prospective (next-day) analyses. Finally, lower PA was associated with greater EE urges in concurrent analyses, but there were no prospective associations between changes in PA and EE urges. Discussion EE urges do not appear to effectively regulate affect. EE urges in a community-based sample appears to have the same functional relationship with affect as binge eating in clinical samples, further supporting EE as a useful dimensional construct for examining processes related to binge eating. PMID:24431328

  6. Do emotional eating urges regulate affect? Concurrent and prospective associations and implications for risk models of binge eating.

    PubMed

    Haedt-Matt, Alissa A; Keel, Pamela K; Racine, Sarah E; Burt, S Alexandra; Hu, Jean Yueqin; Boker, Steven; Neale, Michael; Klump, Kelly L

    2014-12-01

    Emotional eating (EE) reflects an urge to eat in response to emotional rather than physical cues and is a risk factor for the development of binge eating. EE has been conceptualized as an attempt to regulate negative affect (NA), a posited maintenance factor for binge eating. However, no study has examined whether EE urges regulate affect. Further, no studies have examined longitudinal associations between EE urges and positive affect (PA). We examined within-subject longitudinal associations between affect and EE urges in a community-based sample of female twins (mean age = 17.8 years). Participants (N = 239) completed ratings of affect and EE urges for 45 consecutive days. Greater NA was concurrently associated with greater EE urges. Additionally, greater EE urges predicted worse NA for both concurrent and prospective (next-day) analyses. Finally, lower PA was associated with greater EE urges in concurrent analyses, but there were no prospective associations between changes in PA and EE urges. EE urges do not appear to effectively regulate affect. EE urges in a community-based sample appear to have the same functional relationship with affect as binge eating in clinical samples, further supporting EE as a useful dimensional construct for examining processes related to binge eating. © 2014 Wiley Periodicals, Inc.

  7. [Smoking cessation].

    PubMed

    Mori, Masahide; Maekura, Ryoji

    2011-10-01

    Smoking has been determined as a cause of chronic obstructive pulmonary disease (COPD) in most patients. Smoking cessation should be stressed above everything else for COPD patients under all conditions. A smoking habit is determined not as a preference but as a dependency on tobacco; therefore, smoking cessation is difficult solely based on one's motivation. Smoking cessation therapy is employed with cessation aids. Now, we can use nicotine-containing gum, patches, and the nicotine-receptor partial agonist varenicline. First, nicotine from tobacco is replaced with a nicotin patch, or a nicotine-free condition is induced by varenicline. Subsequently, the drugs are gradually reduced. In Japan, smoking cessation therapy is covered by public health insurance as definite requirements.

  8. A Multifaceted Hypnosis Smoking-Cessation Program: Enhancing Motivation and Goal Attainment.

    PubMed

    Green, Joseph P; Lynn, Steven Jay

    2017-01-01

    Smoking cessation remains a major health priority. Despite public campaigns against smoking and widespread availability of smoking-cessation treatments, many people continue to smoke. The authors argue that the "problem of motivation," that is, suboptimal or fluctuating motivation to resist smoking urges and to comply with the demands of treatment, commonly undermines treatment seeking and adherence, appreciably reducing the success rates of smoking-cessation programs. The authors describe the history of the Winning Edge smoking-cessation program and discuss ways to enhance motivation before, during, and after formal treatment. They illustrate how hypnotic suggestions, administered in the context of their program, can promote cognitive, behavioral, and emotional commitment to treatment and enhance motivation to live a smoke-free life.

  9. Can smoking initiation contexts predict how adult Aboriginal smokers assess their smoking risks? A cross-sectional study using the ‘Smoking Risk Assessment Target’

    PubMed Central

    Gould, Gillian Sandra; Watt, Kerrianne; West, Robert; Cadet-James, Yvonne; Clough, Alan R

    2016-01-01

    Objectives Smoking prevalence is slow to reduce among Indigenous Australians of reproductive age. We analysed the relationships between age of smoking initiation, recalled initiation influences and self-assessment of smoking risks in Aboriginal smokers. Design, setting and participants A community-based cross-sectional survey of Aboriginal smokers aged 18–45 years (N=121; 58 men) was undertaken, using single-item measures. The Smoking Risk Assessment Target (SRAT) as the primary outcome measure enabled self-assessment of smoking risks from 12 options, recategorised into 3 groups. Participants recalled influences on their smoking initiation. Multinomial logistic regression modelling included age, gender, strength of urges to smoke, age at initiation (regular uptake) and statistically significant initiation influences on χ2 tests (‘to be cool’, alcohol and cannabis). Results Frequent initiation influences included friends (74%; SD 0.44), family (57%; SD 0.5) and alcohol (40%; SD 0.49). 54% (n=65) of smokers had the highest risk perception on the SRAT, selected by those who cared about the smoking risks and intended to quit soon. On multivariate analyses, compared with the highest level of SRAT, male gender, lower age of uptake and strong urges to smoke were significantly associated with the lowest level of SRAT, selected by those who refuted risks or thought they could not quit. Lower age of uptake and alcohol were associated with mid-level of SRAT, selected by those who cared about smoking risks, but did not consider quitting as a priority. Conclusions Characteristics of smoking initiation in youth may have far-reaching associations with how smoking risks are assessed by adults of reproductive age, and their intentions to quit smoking. Becoming a regular smoker at under the age of 16 years, and influences of alcohol on smoking uptake, were inversely associated with high-level assessment of smoking risks and intention to quit in regional Aboriginal smokers

  10. Secondhand Smoke

    MedlinePlus

    ... Life Smoking and Asthma How Can I Quit Smoking? Contact Us Print Resources Send to a friend Permissions Guidelines Note: Clicking these links will take you to a site outside of KidsHealth's control. About TeensHealth Nemours.org Reading BrightStart! Contact Us ...

  11. [Youth Smoking.

    ERIC Educational Resources Information Center

    Stare, Russell K., Ed.

    1994-01-01

    This issue of the newsletter "Prevention Forum" focuses on smoking among adolescents. The articles are as follows: (1) "Where There's Smoke--Will Prevention Put Out the Fire?" (Joanne Burgess), an overview of the Surgeon General's report "Preventing Tobacco Use among Young People," including interviews with prevention…

  12. Secondhand Smoke

    MedlinePlus

    ... Income 8 Secondhand smoke exposure is higher among people with low incomes. During 2011–2012, more than 2 out of every 5 (43.2%) nonsmokers who lived below the poverty level were exposed to secondhand smoke. Occupation 10 ...

  13. [Youth Smoking.

    ERIC Educational Resources Information Center

    Stare, Russell K., Ed.

    1994-01-01

    This issue of the newsletter "Prevention Forum" focuses on smoking among adolescents. The articles are as follows: (1) "Where There's Smoke--Will Prevention Put Out the Fire?" (Joanne Burgess), an overview of the Surgeon General's report "Preventing Tobacco Use among Young People," including interviews with prevention…

  14. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis and apoptosis

    PubMed Central

    Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Jang, Sehwan; Yoo, Seong-Ho; Yun, Jun-Won; Gonzalez, Frank J.; Keshavarzian, Ali; Song, Byoung-Joon

    2013-01-01

    Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed to investigate the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6 g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria while liver histology obtained at 6 h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria and triglycerides. All these changes including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetyl-cysteine, both of which suppressed the oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1 and lipid peroxidation with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of pro-apoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK and peroxisome proliferator-activated receptor-alpha (PPAR-α), all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seem critical in the binge alcohol-mediated increased nitroxidative stress, gut leakage, endotoxemia, and

  15. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis.

    PubMed

    Abdelmegeed, Mohamed A; Banerjee, Atrayee; Jang, Sehwan; Yoo, Seong-Ho; Yun, Jun-Won; Gonzalez, Frank J; Keshavarzian, Ali; Song, Byoung-Joon

    2013-12-01

    Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed at investigating the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria, and liver histology obtained at 6h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria, and triglycerides. All these changes, including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetylcysteine, both of which suppressed oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1, and lipid peroxidation, with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of proapoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK, and peroxisome proliferator-activated receptor-α, all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seems critical in binge alcohol-mediated increased nitroxidative stress, gut leakage, and endotoxemia; altered fat

  16. Schisandra chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats

    PubMed Central

    Park, Hyoung Joon; Lee, Soo-Jung; Song, Yuno; Jang, Sun-Hee; Ko, Yeoung-Gyu; Kang, Suk Nam; Chung, Byung Yeoup; Kim, Hong-Duck; Kim, Gon-Sup

    2014-01-01

    Abstract Schisandra chinensis (SC), a traditional herbal medicine, has been prescribed for patients suffering from various liver diseases, including hepatic cancer, hypercholesterolemia, and CCl4-induced liver injury. We investigated whether SC extract has a protective effect on alcohol-induced fatty liver and studied its underlying mechanisms. Rats were fed with ethanol by intragastric administration every day for 5 weeks to induce alcoholic fatty liver. Ethanol treatment resulted in a significant increase in alanine aminotransferase, aspartate aminotransferase, and hepatic triglyceride (TG) levels and caused fatty degeneration of liver. Ethanol administration also elevated serum TG and total cholesterol (TC) and decreased high-density lipoprotein (HDL) cholesterol levels. However, after administration of ethanol plus SC extracts, the ethanol-induced elevation in liver TC and TG levels was reversed. Elevation in serum TG was not observed after treatment with SC. Moreover, compared with the ethanol-fed group, the rats administered ethanol along with SC extracts for 5 weeks showed attenuated fatty degeneration and an altered lipid profile with decreased serum TC and TG, and increased HDL cholesterol levels. Chronic ethanol consumption did not affect peroxisome proliferator-activated receptor γ (PPARγ) levels, but it decreased PPARα and phospho-AMP-activated protein kinase (AMPK) levels in the liver. However, SC prevented the ethanol-induced decrease in PPARα expression and induced a significant decrease in sterol regulatory element-binding protein-1 expression and increase in phospho-AMPK expression in rats with alcoholic fatty liver. SC administration resulted in a significant decrease in intracellular lipid accumulation in hepatocytes along with a decrease in serum TG levels, and it reversed fatty liver to normal conditions, as measured by biochemical and histological analyses. Our results indicate that the protective effect of SC is accompanied by a

  17. Reversal of Alcohol-Induced Dysregulation in Dopamine Network Dynamics May Rescue Maladaptive Decision-making.

    PubMed

    Schindler, Abigail G; Soden, Marta E; Zweifel, Larry S; Clark, Jeremy J

    2016-03-30

    Alcohol is the most commonly abused substance among adolescents, promoting the development of substance use disorders and compromised decision-making in adulthood. We have previously demonstrated, with a preclinical model in rodents, that adolescent alcohol use results in adult risk-taking behavior that positively correlates with phasic dopamine transmission in response to risky options, but the underlying mechanisms remain unknown. Here, we show that adolescent alcohol use may produce maladaptive decision-making through a disruption in dopamine network dynamics via increased GABAergic transmission within the ventral tegmental area (VTA). Indeed, we find that increased phasic dopamine signaling after adolescent alcohol use is attributable to a midbrain circuit, including the input from the pedunculopontine tegmentum to the VTA. Moreover, we demonstrate that VTA dopamine neurons from adult rats exhibit enhanced IPSCs after adolescent alcohol exposure corresponding to decreased basal dopamine levels in adulthood that negatively correlate with risk-taking. Building on these findings, we develop a model where increased inhibitory tone on dopamine neurons leads to a persistent decrease in tonic dopamine levels and results in a potentiation of stimulus-evoked phasic dopamine release that may drive risky choice behavior. Based on this model, we take a pharmacological approach to the reversal of risk-taking behavior through normalization of this pattern in dopamine transmission. These results isolate the underlying circuitry involved in alcohol-induced maladaptive decision-making and identify a novel therapeutic target. One of the primary problems resulting from chronic alcohol use is persistent, maladaptive decision-making that is associated with ongoing addiction vulnerability and relapse. Indeed, studies with the Iowa Gambling Task, a standard measure of risk-based decision-making, have reliably shown that alcohol-dependent individuals make riskier, more maladaptive

  18. Urges for food and money spill over into motor system excitability before action is taken

    PubMed Central

    Gupta, Nitin; Aron, Adam R

    2015-01-01

    Much human behavior is driven by urges. Yet research into urges is hampered by a paucity of tools to objectively index their strength, timing and control. Here we used Transcranial Magnetic Stimulation (TMS) and concurrent electromyography to examine whether urges for food and money are detectable via motor system excitability. In Experiment 1, we used a naturalistic food paradigm to show that food items that were most strongly wanted elicited the largest motor excitability, even before participants knew which response to make to get them. In Experiment 2a, we replicated the results using money – motor excitability was greater for larger monetary amounts. In Experiment 2b we show that monetary amount does not modulate motor excitability when participants simply observe, without having to take action. As the main effect occurred prior to the subject knowing which motor response to make it is not merely related to response preparation, and as the effect was present only when action was required, it is not merely related to increased arousal. Instead, the increased motor excitability likely indexes the degree of motivation a subject has to perform an action. Thus, we have used TMS to demonstrate that urges for food and money “spill over” into the motor system. This is likely mediated by interactions between the limbic system (including the orbital frontal cortex) and the motor system, probably at the level of the basal ganglia. Implications are discussed for theories of embodied cognition and for methodological progress in studying urge control. PMID:21091805

  19. [Current diagnostics and therapy of the overactive bladder and urge incontinence].

    PubMed

    Badawi, J K; Langbein, S

    2005-06-17

    Urinary incontinence affects millions of people worldwide and also represents a social problem. Costs of urinary incontinence and overactive bladder are very high. Urge incontinence is the involuntary loss of urine associated with a strong desire or urge to urinate. There are two types of urge incontinence: One is associated with involuntary detrusor contractions leading to a loss of urine, the other is characterized by a hypersensitive bladder in which micturition reflexes are induced due to an increased afferent activity. It is important to distinguish between an idiopathic type of urge incontinence and a symptomatic type possibly caused by infections, tumours, bladder stones or foreign bodies. Diagnostics is based on a careful medical history, clinical examination and urodynamic evaluation. The use of a voiding diary is necessary. Current agents for drug therapy rely upon their anticholinergic properties. Their use is limited by side effects such as blurred vision, dizziness, constipation and dryness of the mouth. Additionally, patients refractory to anticholinergic medication can be treated by endoscopic direct injection of botulinum toxin into the detrusor muscle. These patients can also be treated by intravesical application of vanilloid derivatives in the bladder leading to a desensitization of bladder sensory fibers. In some cases of refractory urge incontinence, electrical neuromodulation is effective. Other pharmacological approaches could be selective b-adrenoceptor agonists, calcium antagonists and potassium channel openers, but these substances are not yet available for clinical use.

  20. Effects of tic suppression: ability to suppress, rebound, negative reinforcement, and habituation to the premonitory urge.

    PubMed

    Specht, Matt W; Woods, Douglas W; Nicotra, Cassandra M; Kelly, Laura M; Ricketts, Emily J; Conelea, Christine A; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2013-01-01

    The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

  1. OSTEOPONTIN BINDING TO LIPOPOLYSACCHARIDE LOWERS TUMOR NECROSIS FACTOR-α AND PREVENTS EARLY ALCOHOL-INDUCED LIVER INJURY IN MICE

    PubMed Central

    Ge, Xiaodong; Leung, Tung-Ming; Arriazu, Elena; Lu, Yongke; Urtasun, Raquel; Christensen, Brian; Fiel, Maria Isabel; Mochida, Satoshi; Sørensen, Esben S.; Nieto, Natalia

    2013-01-01

    Rationale: Although osteopontin (OPN) is induced in alcoholic patients, its role in the pathophysiology of alcoholic liver disease (ALD) remains unclear. Increased translocation of lipopolysaccharide (LPS) from the gut is key for the onset of ALD since it promotes macrophage infiltration and activation, tumor necrosis factor-α (TNFα) production and liver injury. Since OPN is protective for the intestinal mucosa, we postulated that enhancing OPN expression in the liver and consequently in the blood and/or in the gut could protect from early alcohol-induced liver injury. Results: Wild-type (WT), OPN knockout (Opn−/−) and transgenic mice overexpressing OPN in hepatocytes (OpnHEP Tg) were chronically fed either the control or the ethanol Lieber-DeCarli diet. Ethanol increased hepatic, plasma, biliary and fecal OPN more in OpnHEP Tg than in WT mice. Steatosis was lesser in ethanol-treated OpnHEP Tg mice as shown by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower ALT activity, hepatocyte ballooning degeneration, LPS levels, the inflammation score and the number of macrophages and TNFα+ cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed affinity for LPS and the binding prevented macrophage activation, reactive oxygen and nitrogen species generation and TNFα production. Treatment with milk OPN (m-OPN) blocked LPS translocation in vivo and protected from early alcohol-induced liver injury. Conclusion: Natural induction plus forced overexpression of OPN in the liver and treatment with m-OPN protect from early alcohol-induced liver injury by blocking the gut-derived LPS and TNFα effects in the liver. PMID:24214181

  2. Hepatic cannabinoid receptor type 1 mediates alcohol-induced regulation of bile acid enzyme genes expression via CREBH.

    PubMed

    Chanda, Dipanjan; Kim, Yong-Hoon; Li, Tiangang; Misra, Jagannath; Kim, Don-Kyu; Kim, Jung Ran; Kwon, Joseph; Jeong, Won-Il; Ahn, Sung-Hoon; Park, Tae-Sik; Koo, Seung-Hoi; Chiang, John Y L; Lee, Chul-Ho; Choi, Hueng-Sik

    2013-01-01

    Bile acids concentration in liver is tightly regulated to prevent cell damage. Previous studies have demonstrated that deregulation of bile acid homeostasis can lead to cholestatic liver disease. Recently, we have shown that ER-bound transcription factor Crebh is a downstream effector of hepatic Cb1r signaling pathway. In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process. We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo alongwith significant increase in Crebh gene expression and activation. Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis. Overexpression of Crebh increased the expression of key bile acid synthesis enzyme genes via direct binding of Crebh to their promoters, whereas Cb1r knockout and Crebh-knockdown mice were protected against alcohol-induced perturbation of bile acid homeostasis. Interestingly, insulin treatment protected against Cb1r-mediated Crebh-induced disruption of bile acid homeostasis. Furthermore, Crebh expression and activation was found to be markedly increased in insulin resistance conditions and Crebh knockdown in diabetic mice model (db/db) significantly reversed alcohol-induced disruption of bile acid homeostasis. Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.

  3. Protection of Xenopus laevis embryos against alcohol-induced delayed gut maturation and growth retardation by peroxiredoxin 5 and catalase.

    PubMed

    Peng, Ying; Yang, Pai-Hao; Ng, Samuel S M; Lum, Ching Tung; Kung, Hsiang-Fu; Lin, Marie C

    2004-07-16

    Accumulated evidence indicates that maternal alcohol consumption causes fetal enteric damage and growth retardation. In this study, we investigated the underlying molecular mechanisms in a Xenopus model of fetal alcohol exposure. We established a condition of transient alcohol exposure that produces tadpoles with delayed gut maturation and decreased body length. We then investigated the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by microinjecting plasmids expressing catalase and peroxiredoxin 5 (PRDX5) into two-cell stage embryos. Finally, the effects of these enzymes on the expression of key gut developmental genes were determined by animal cap explant assay. We showed that exposure of Xenopus embryos to 0.5% alcohol from stage 13 to stage 22 produced tadpoles with delayed gut maturation, reduced growth, and down-regulation in several gut developmental genes, with VegT, Pax6 and Sox17 most vulnerable. We further demonstrated that microinjection of catalase attenuated alcohol-induced ROS production and restored the expression of VegT and Pax6, but protected the embryos from delayed gut development and retarded growth only partially. By contrast, microinjection of PRDX5 reduced both ROS and RNS production, and prevented the gut and growth defects, and restored VegT, Pax6 and Sox17 gene expression. A positive correlation was found between delayed gut maturation and reduced body length. These results indicate the crucial roles of both the ROS-Pax6 and RNS-Sox17 signaling axes in alcohol-induced fetal gut defects and growth retardation. In addition, they suggest strongly a cause-and-effect relationship between alcohol-induced delayed gut maturation and growth retardation.

  4. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity

    PubMed Central

    Ary, Alexis W.; Cozzoli, Debra K.; Finn, Deborah A.; Crabbe, John C.; Dehoff, Marlin H.; Worley, Paul F.; Szumlinski, Karen K.

    2012-01-01

    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. PMID:22444953

  5. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex

    PubMed Central

    Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S.; Smolka, Michael N.

    2014-01-01

    Background A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. Methods We measured inhibitory control in fifty young adults with a stop-signal task (SST) during functional magnetic resonance imaging (fMRI). In a single-blind placebo-controlled cross-over design, all participants performed the SST once under alcohol with a breath alcohol concentration (BrAC) of 0.6 g/kg, and once under placebo. In addition, alcohol consumption was assessed using a free-access alcohol self-administration (ASA) paradigm in the same participants. Results Inhibitory control was robustly decreased under alcohol compared to placebo indicated by longer stop-signal reaction times (SSRTs). On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals, and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. Conclusion We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control may enhance alcohol consumption in young adults which might promote future alcohol problems. PMID:24560581

  6. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex.

    PubMed

    Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S; Smolka, Michael N

    2014-11-01

    A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

    PubMed

    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.

  8. Alcohol-induced morbidity and mortality by occupation: a population-based follow-up study of working Finns.

    PubMed

    Kaila-Kangas, Leena; Koskinen, Aki; Pensola, Tiina; Mäkelä, Pia; Leino-Arjas, Päivi

    2016-02-01

    To justify alcohol-related health promotion programs and target them at the correct workplaces, it is important to identify occupations with increased risk of severe health outcomes caused by alcohol. Data on hospital admissions (854,555 men and 801,653 women) from the Finnish health care register and data on deaths from Statistics Finland from 1 January 2001 to 31 December 2004 were merged with information from the 2000 population census. We assessed the age- and education-adjusted relationship between occupation and the sum of hospitalizations and death primarily caused by alcohol, using Cox proportional hazards regression. We also estimated the fraction of incidence of severe alcohol-induced health outcomes that are attributable to factors related to one's occupation (population attributable fraction). Most of the cases were men (80%), middle-aged and usually had no more than a secondary level of education. When the reference was professionals, who were at the lowest risk, those at increased risk were mostly manual workers in craft work, construction and service. However, we also found several non-manual occupations at a high risk. According to population attributable fraction, the proportion of severe alcohol-induced health outcomes would have been 31% lower among men and 20% lower among women if all occupational groups had been at the same risk as professionals. We detected considerable occupational differences in alcohol-induced morbidity and mortality among a nationally representative working population. This indicates a need for alcohol-focused health promotion programs in these high-risk occupations. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  9. Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.

    PubMed

    Zhong, Qian; Shi, Ganggang; Zhang, Yanmei; Lu, Lei; Levy, Daniel; Zhong, Shuping

    2015-02-01

    Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer.

  10. A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

    PubMed

    Lv, Bei; Duan, Haishui

    2016-08-25

    Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve

  11. Predictors of smoking relapse by duration of abstinence: findings from the International Tobacco Control (ITC) Four Country Survey

    PubMed Central

    Herd, N; Borland, R; Hyland, A

    2015-01-01

    Aim To explore predictors of smoking relapse and how predictors vary according to duration of abstinence. Design, setting and participants A longitudinal survey of 1296 ex-smokers recruited as part of the International Tobacco Control (ITC) Four Country Survey (Australia, Canada, UK, and USA). Measurements Quitters were phone interviewed at varying durations of abstinence (from one day to approximately three years) and then followed-up approximately one year later. Theorised predictors of relapse (i.e., urges to smoke; outcome expectancies of smoking and quitting; and abstinence self-efficacy) and nicotine dependence were measured in the survey. Findings Relapse was associated with lower abstinence self-efficacy and a higher frequency of urges to smoke, but only after the first month or so of quitting. Both of these measures mediated relationships between perceived benefits of smoking and relapse. Perceived costs of smoking and benefits of quitting were unrelated to relapse. Conclusions Challenging perceived benefits of smoking may be an effective way to increase abstinence self-efficacy and reduce frequency of urges to smoke (particularly after the initial weeks of quitting), in order to subsequently reduce relapse risk. PMID:19922574

  12. Involvement of Insula and Cingulate Cortices in Control and Suppression of Natural Urges

    PubMed Central

    Bagic, Anto; Hanakawa, Takashi; Boudreau, Eilis A.; Pagan, Fernando; Mari, Zoltan; Bara-Jimenez, William; Aksu, Murat; Sato, Susumu; Murphy, Dennis L.; Hallett, Mark

    2009-01-01

    The physiology of control and suppression of natural urges is not well understood. We used [15O]H2O positron-emission tomography imaging to identify neural circuits involved in suppression of spontaneous blinking as a model of normal urges. Suppression of blinking was associated with prominent activation of bilateral insular-claustrum regions, right more than left; activation was also found in bilateral anterior cingulate cortex (ACC), supplementary motor areas, and the face area of the primary motor cortex bilaterally. These results suggest a central role for the insula possibly together with ACC in suppression of blinking. PMID:18469316

  13. Neurobiology of the premonitory urge in Tourette syndrome: Pathophysiology and treatment implications

    PubMed Central

    Cavanna, Andrea E.; Black, Kevin J; Hallett, Mark; Voon, Valerie

    2017-01-01

    Motor and vocal tics are relatively common motor manifestations identified as the core features of Tourette syndrome. Although traditional descriptions have focused on objective phenomenological observations, such as anatomical location, number and frequency of tics, patients’ first-person accounts have consistently reported characteristic subjective correlates. These sensory phenomena are often described as a feeling of mounting inner tension or urge to move (“premonitory urge”), which is transiently relieved by tic expression. This paper reviews the existing literature on the clinical and neurobiological aspects of the premonitory urge in patients with Tourette syndrome, with focus on its pathophysiology and possible treatment implications. PMID:28121259

  14. The design of controlled-release formulations resistant to alcohol-induced dose dumping--a review.

    PubMed

    Jedinger, N; Khinast, J; Roblegg, E

    2014-07-01

    The concomitant intake of alcoholic beverages together with oral controlled-release opioid formulations poses a serious safety concern since alcohol has the potential to alter the release rate controlling mechanism of the dosage form which may result in an uncontrolled and immediate drug release. This effect, known as alcohol-induced dose dumping, has drawn attention of the regulatory authorities. Thus, the Food and Drug Administration (FDA) recommends that in vitro drug release studies of controlled-release dosage forms containing drugs with narrow therapeutic range should be conducted in ethanolic media up to 40%. So far, only a limited number of robust dosage forms that withstand the impact of alcohol are available and the development of such dosage forms is still a challenge. This review deals with the physico-chemical key factors which have to be considered for the preparation of alcohol-resistant controlling dosage forms. Furthermore, appropriate matrix systems and promising technological strategies, which are suitable to prevent alcohol-induced dose dumping, are discussed.

  15. Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder.

    PubMed

    Liput, Daniel J; Hammell, Dana C; Stinchcomb, Audra L; Nixon, Kimberly

    2013-10-01

    Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In Experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p=0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/day). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p<0.05), while IP CBD resulted in a 50.6% (p<0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.

  16. Crepidiastrum denticulatum Extract Protects the Liver Against Chronic Alcohol-Induced Damage and Fat Accumulation in Rats

    PubMed Central

    Yoo, Ji-Hye; Kang, Kyungsu; Yun, Ji Ho; Kim, Mi Ae

    2014-01-01

    Abstract Alcohol is a severe hepatotoxicant that causes liver abnormalities such as steatosis, cirrhosis, and hepatocarcinoma. Crepidiastrum denticulatum (CD) is a well-known, traditionally consumed vegetable in Korea, which was recently reported to have bioactive compounds with detoxification and antioxidant properties. In this study, we report the hepatoprotective effect of CD extract against chronic alcohol-induced liver damage in vivo. The rats that were given CD extract exhibited decreased alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase activities, which are liver damage markers that are typically elevated by alcohol consumption. The results were confirmed by histopathology with hematoxylin and eosin staining. Chronic alcohol consumption induced the formation of alcoholic fatty liver. However, treatment with CD extract dramatically decreased the hepatic lipid droplets. Treatment with CD extract also restored the antioxidative capacity and lipid peroxidation of the liver that had been changed by alcohol consumption. Furthermore, treatment with CD extract normalized the activities of the antioxidative enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase, which had been decreased by alcohol consumption. The results indicate that CD extract has protective effects against chronic alcohol hepatotoxicity in rats by increasing the liver's antioxidant capacity, and has potential as a dietary supplement intervention for patients with alcohol-induced liver damage. PMID:24650230

  17. Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201

    PubMed Central

    Cho, Jae Youl; Choi, Jongwon; Park, Jae Gwang; Yi, Young-Su; Hossen, Muhammad Jahangir; Kim, Hyeongmin; Ro, Jieun; Cha, Bae Cheon; Yoo, Eun Sook

    2014-01-01

    DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside isolated from Sanguisorba officinalis, a medicinal plant prescribed for various diseases, such as duodenal ulcers and bleeding in East Asian counties. We demonstrated that this compound is able to normalize the altered lipid metabolism induced by hyperglycemia and a high fat diet. In this study, we determined whether hyperlipidemic conditions induced with chronically treated alcohol can also be restored by DWP208. Similar to our previous results, orally administered DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i) up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride, and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as absolute body weight, superoxide dismutase (SOD) activity, and high-density lipoprotein (HDL) in serum and liver. According to our data, the ameliorative activity of DWP208 is due to its indirect anti-oxidative activity as a result of which lipid peroxide and hydroxyl radical levels were reduced and the activity of SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as a remedy against alcohol-induced hyperlipidemia. PMID:25598660

  18. Zinc Deprivation Mediates Alcohol-Induced Hepatocyte IL-8 Analog Expression in Rodents via an Epigenetic Mechanism

    PubMed Central

    Zhao, Yantao; Zhong, Wei; Sun, Xiuhua; Song, Zhenyuan; Clemens, Dahn L.; Kang, Y. James; McClain, Craig J.; Zhou, Zhanxiang

    2011-01-01

    Neutrophil infiltration caused by IL-8 production is a central mechanism in alcohol-induced hepatitis. This study was performed to examine if an epigenetic mechanism is involved in alcohol-induced IL-8 production. Mice were pair-fed an alcohol-containing liquid diet for 4 weeks. Alcohol exposure induced hepatitis as indicated by increased expression of keratinocyte-derived cytokine (mouse IL-8) and neutrophil infiltration. Alcohol exposure induced histone 3 hyperacetylation owing to inhibition of histone deacetylase (HDAC) in association with NF-κB activation. Cell culture studies showed that alcohol exposure induced IL-8 and cytokine-induced neutrophil chemoattractant-1 (CINC-1, rat IL-8) production in human VL-17A cells and rat H4IIEC3 cells, respectively, dependent on acetaldehyde production, oxidative stress, and zinc release. Zinc deprivation alone induced CINC-1 production and acted synergistically with lipopolysaccharide or tumor necrosis factor-α on CINC-1 production. Zinc deprivation induced histone 3 hyperacetylation at lysine 9 through suppression of HDAC activity. Zinc deprivation caused nuclear translocation of NF-κB, and reduced HDAC binding to NF-κB. Chromatin immunoprecipitation (ChIP) showed that zinc deprivation caused histone 3 hyperacetylation as well as increased NF-κB binding to the CINC-1 promoter. In conclusion, inactivation of HDAC caused by zinc deprivation is a novel mechanism underlying IL-8 up-regulation in alcoholic hepatitis. PMID:21708112

  19. Therapeutic effect of green tea extract on alcohol induced hepatic mitochondrial DNA damage in albino wistar rats.

    PubMed

    Reddyvari, Hymavathi; Govatati, Suresh; Matha, Sumanth Kumar; Korla, Swapna Vahini; Malempati, Sravanthi; Pasupuleti, Sreenivasa Rao; Bhanoori, Manjula; Nallanchakravarthula, Varadacharyulu

    2017-05-01

    The present study principally sought to investigate the effect of green tea extract (GTE) supplementation on hepatic mitochondrial DNA (mtDNA) damage in alcohol receiving rats. MtDNA was isolated from hepatic tissues of albino wistar rats after alcohol treatment with and without GTE supplementation. Entire displacement loop (D-loop) of mtDNA was screened by PCR-Sanger's sequencing method. In addition, mtDNA deletions and antioxidant activity were measured in hepatic tissue of all rats. Results showed increased frequency of D-loop mutations in alcoholic rats (ALC). DNA mfold analysis predicted higher free energy for 15507C and 16116C alleles compared to their corresponding wild alleles which represents less stable secondary structures with negative impact on overall mtDNA function. Interestingly, D-loop mutations observed in ALC rats were successfully restored on GTE supplementation. MtDNA deletions were observed in ALC rats, but intact native mtDNA was found in ALC + GTE group suggesting alcohol induced oxidative damage of mtDNA and ameliorative effect of GTE. Furthermore, markedly decreased activities of glutathione peroxidise, superoxide dismutase, catalase and glutathione content were identified in ALC rats; however, GTE supplementation significantly (P < 0.05) restored these levels close to normal. In conclusion, green tea could be used as an effective nutraceutical against alcohol induced mitochondrial DNA damage.

  20. Identification of Noninvasive Biomarkers for Alcohol-Induced Liver Disease Using Urinary Metabolomics and the Ppara-null Mouse

    PubMed Central

    Manna, Soumen K.; Patterson, Andrew D.; Yang, Qian; Krausz, Kristopher W.; Li, Henghong; Idle, Jeffrey R.; Fornace, Albert J.; Gonzalez, Frank J.

    2010-01-01

    Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively non-specific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study the metabolic changes associated with alcohol-induced liver disease were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-β-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. PMID:20540569

  1. Alcohol-induced apoptosis of canine cerebral vascular smooth muscle cells: role of extracellular and intracellular calcium ions.

    PubMed

    Li, Wenyan; Li, Jianfeng; Liu, Weiming; Altura, Bella T; Altura, Burton M

    2004-01-16

    Exposure of canine cerebral vascular smooth muscle cells (VSMCs) to ethanol (10, 25 and 100 mM) for 1, 3 and 5 days induced apoptosis with its typical characteristics of nuclear shrinkage, condensation, and DNA breakage as well as formation of apoptotic bodies observed by fluorescence staining, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling and comet assays. Such effects of alcohol on cerebral VSMCs were time- and concentration-dependent. The threshold ethanol concentration for induction of the apoptotic process was found to be 10 mM. Extracellular and intracellular Ca2+ chelators, i.e. ethylglycol-bisbeta-aminoethylether-N,N,N'N'-tetraacetic acid (EGTA, 5 mM) and 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid AM (BAPTA, 10(-6) M), respectively, ameliorated greatly the number of cerebral VSMCs which underwent apoptosis. Verapamil, however, failed to inhibit apoptosis of cerebral VSMCs. From these new findings, we suggest that alcohol-induced apoptosis may contribute to alcohol-induced brain-vascular damage and stroke. In addition, our findings point to potential caution for humans who imbibe two or more standard drinks per day or who undergo 'binge drinking'.

  2. Executive dysfunction in Korsakoff's syndrome: Time to revise the DSM criteria for alcohol-induced persisting amnestic disorder?

    PubMed

    Van Oort, Roos; Kessels, Roy P C

    2009-01-01

    Objective. This study examines the profile of executive dysfunction in Korsakoff's syndrome. There is accumulating evidence of executive deficits in Korsakoff patients that may greatly affect activities of daily living. However, the DSM-IV criteria for "alcohol-induced persisting amnestic disorder" do not take this into account. In addition, existing studies have failed to determine the type of executive deficits in this syndrome. Methods. Executive functioning was assessed in 20 Korsakoff patients using the Behavioural Assessment of the Dysexecutive Syndrome (BADS), an ecologically valid neuropsychological assessment battery consisting of various subtests that assess planning, organisation, inhibition, shifting, cognitive estimation and monitoring. Results. Sixteen patients (80%) had executive deficits, i.e. impairments on at least one BADS subtest compared to a normative control group. Overall, the profile is characterized by planning deficits on unstructured tasks. Conclusions. Next to amnesia, executive deficits are a prominent characteristic of cognitive impairment in Korsakoff patients. It is argued that the new DSM criteria should consider incorporating executive dysfunction as an important feature of alcohol-induced persistent cognitive disorder.

  3. Transdermal Delivery of Cannabidiol Attenuates Binge Alcohol-Induced Neurodegeneration in a Rodent Model of an Alcohol Use Disorder

    PubMed Central

    Liput, Daniel J.; Hammell, Dana C.; Stinchcomb, Audra L.; Nixon, Kimberly

    2013-01-01

    Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p = 0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/d). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p < 0.05), while IP CBD resulted in a 50.6% (p < 0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration. PMID:24012796

  4. Coordinated regulation of scopoletin at adipose tissue-liver axis improved alcohol-induced lipid dysmetabolism and inflammation in rats.

    PubMed

    Lee, Hae-In; Lee, Mi-Kyung

    2015-09-17

    There is increasing evidence that alcohol-induced white adipose tissue (WAT) dysfunction contributes to disturbance of hepatic lipid metabolism. This study investigated the effects of scopoletin on lipid homeostasis and inflammation at the WAT and liver in chronic alcohol-fed rats. Rats were fed a liquid diet containing 5% alcohol with or without two doses of scopoletin (0.001% and 0.005%) for 8 weeks. Scopoletin decreased serum triglyceride and cytokines (TNFα and IL-6) levels and hepatic and WAT lipid levels, whereas it increased WAT adiponectin mRNA and serum adiponectin levels, up-regulated hepatic gene and protein expression of AdipoR2 and activated AMPK. Additionally, scopoletin inhibited the expression of lipogenic genes (SREBP-1c and Fasn) and increased the expression of fatty acid oxidative genes (PPARα, Acsl1, CPT, Acox, and Acaa1a) in both WAT and liver. Alcohol led to significant up-regulation of WAT lipolysis and hepatic Cidea gene expression, whereas it decreased the WAT Cidea gene level; however, scopoletin reversed these changes. Scopoletin significantly down-regulated TLR4 signaling genes such as MyD88, TRIF, NFκB, TNFα and IL-6 in WAT and liver. These results indicated that coordinated regulation of scopoletin at the WAT-liver axis may play an important role in improvement of alcohol-induced lipid dysregulation and inflammation. Copyright © 2015. Published by Elsevier Ireland Ltd.

  5. Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice

    PubMed Central

    Chattopadhyay, Abhijnan; Pinkaew, Decha; Doan, Hung Q.; Jacob, Reed B.; Verma, Sunil K.; Friedman, Hana; Peterson, Alan C.; Kuyumcu-Martinez, Muge N.; McDougal, Owen M.; Fujise, Ken

    2016-01-01

    Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans. PMID:26726832

  6. Neuroprotective effect of vitamin E isoforms against chronic alcohol-induced peripheral neurotoxicity: possible involvement of oxidative-nitrodative stress.

    PubMed

    Tiwari, Vinod; Kuhad, Anurag; Chopra, Kanwaljit

    2012-11-01

    Small-fiber painful peripheral neuropathy is one of the long-term complications of alcohol for which there is no reliable successful therapy available. The precise mechanisms by which chronic alcohol consumption produces peripheral nerve fiber damage and loss remain unclear. Emerging data from clinical and preclinical studies suggest that increased oxidative-nitrodative stress mediated release of proinflammatory cytokines from damaged neural tissues may play a central role in the pathogenesis of alcoholic neuropathy. The present study investigated the effect of both the isoforms of vitamin E (α-tocopherol and tocotrienol) against chronic alcohol-induced peripheral neuropathy in rats. Ethanol treated rats showed a significant decrease in paw-withdrawal threshold in both Randall-Selitto and von-Frey hair tests along with a significant reduction in tail flick latency in the tail-immersion test. A decreased pain threshold was associated with significant alterations in oxidative-nitrodative stress markers and an increase in proinflammatory cytokines (TNF-α and IL-1β). The 4-week treatment with tocotrienol significantly ameliorated behavioral, biochemical and molecular alterations in alcohol treated rats. However, α-tocopherol failed to produce any protective effect. The results of the present study suggest that oxidative-nitrodative stress mediated cytokine signaling may be responsible for alcohol-induced peripheral neurotoxicity and tocotrienol treatment might be beneficial in chronic alcoholics exhibiting neuropathy. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Fructose 1, 6-diphosphate prevents alcohol-induced liver injury through inhibiting oxidative stress and promoting alcohol metabolism in mice.

    PubMed

    Li, Ling; Wu, Yifei; Yin, Fangyuan; Feng, Qin; Dong, Xiaoliang; Zhang, Ruhui; Yin, Zhimin; Luo, Lan

    2017-09-21

    Fructose 1, 6-diphosphate (FDP), a glycolytic intermediate,has been identified to possess antioxidant activities. Here we show the protective effect of FDP against alcohol-induced liver injury in mice and the underlying mechanisms. The in vivo experiments demonstrated that FDP, orally administered to mice, dose-dependently suppressed alcohol (50%, v/v, 12ml/kg)-induced increase of serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum triglyceride (TG) level and hepatic malondialdehyde (MDA) level. FDP also inhibited liver histological lesions induced by seven-day administration of alcohol to mice. In vitro study indicated that FDP inhibited ethanol-induced L02 cell apoptosis via reducing pro-caspase3 protein level and increasing poly ADP-ribose polymerase (PARP) cleavage. The mechanism analysis showed that FDP prevented ethanol-induced decrease of mouse antioxidant capability through inhibiting the reducion of the level of glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-PX) in mouse livers, and suppressing the reducion of GSH level and SOD activity in L02 cells. FDP also enhanced alcohol metabolic rate through increasing alcohol dehydrogenase (ADH) activity and acetaldehyde dehydrogenase (ALDH) protein level, and down-regulating cytochrome p450 2E1 (CYP2E1). These results displayed that FDP protected mice from alcohol-induced liver injury, suggesting the potential activity of FDP in preventing alcoholic liver disease (ALD). Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Social Smoking

    PubMed Central

    Schane, Rebecca E.; Glantz, Stanton A.; Ling, Pamela M.

    2009-01-01

    Background Social smoking is increasingly prevalent and poses a challenge to traditional cessation practices. Tobacco companies conducted extensive research on social smokers long before health authorities did and marketed products to promote this smoking behavior. Purpose Research is described and mechanisms identified that are used to promote social smoking to help improve cessation strategies in this growing group. Evidence acquisition Searches from 2006 to 2008 of previously secret tobacco industry documents using keywords social smoker, light smoker, casual smoker, youth smoker, and occasional smoker, followed by snowball searching. Data analysis was conducted in 2008. Evidence synthesis Tobacco industry research identified characteristics of social smokers that include: (1) denial of personal nicotine addiction; (2) self-categorization as a nonsmoker; (3) propensity for decreased tobacco use in response to smoke-free laws; (4) variations in age, education, ethnicity, and socioeconomic backgrounds; and (5) a perceived immunity to personal health effects of tobacco but fear of consequences to others. Tobacco companies developed marketing strategies aimed at social smokers, including “non–habit forming” cigarettes. Conclusions Previously considered a transient behavior, social smoking is also a stable consumption pattern. Focused clinical questions to detect social smoking are needed and may include, “Have you smoked any cigarettes or used any tobacco products in the past month?” as opposed to “Are you a smoker?” Clinicians should recognize that social smokers might be motivated to quit after education on the dangers of secondhand smoke rather than on personal health risks or with pharmacotherapy. PMID:19589449

  9. Use of varenicline for 4 weeks before quitting smoking: decrease in ad lib smoking and increase in smoking cessation rates.

    PubMed

    Hajek, Peter; McRobbie, Hayden J; Myers, Katie E; Stapleton, John; Dhanji, Al-Rehan

    2011-04-25

    The use of varenicline tartrate alleviates postquit withdrawal discomfort, but it also seems to reduce the "reward" associated with smoking. The current treatment schedule, which commences 1 week before quitting, relies primarily on the first mechanism. We set out to determine whether increasing the prequit medication period renders cigarettes less satisfying and facilitates quitting. One hundred one smokers attending a stop-smoking clinic in London, United Kingdom, were randomly allocated to receive varenicline for 4 weeks before the target quit date (TQD) or to receive placebo for 3 weeks before the TQD, followed by varenicline for 1 week before the TQD. In both groups, standard varenicline treatment was given for 3 months after the TQD. Measures included smoking satisfaction and smoke intake before quitting, urges to smoke and withdrawal discomfort after quitting, and sustained abstinence from the TQD to 3 months. Varenicline preloading reduced prequit enjoyment of smoking (P = .004) and smoke intake (P < .001), with 36.7% of participants reducing their cotinine concentrations by more than 50% (reducers). Varenicline preloading did not affect postquit withdrawal symptoms, but it increased 12-week abstinence rates (47.2% in the varenicline arm vs 20.8% in the placebo arm, P = .005). The effect was particularly strong among the reducers in the varenicline arm (66.7% in reducers vs 22.6% in nonreducers, P = .002). Varenicline preloading was well tolerated. Although several issues remain to be clarified, varenicline preloading can generate a substantial reduction in ad lib smoking and enhance 12-week quit rates. Current treatment schedules may lead to suboptimal treatment results. Trials with longer follow-up periods are needed to corroborate these findings. Trial Registration clinicaltrials.gov Identifier: NCT00789074.

  10. Acupuncture attenuates autonomic responses to smoking-related visual cues.

    PubMed

    Chae, Younbyoung; Park, Hi-Joon; Kang, O-Seok; Lee, Hwa-Jin; Kim, Song-Yi; Yin, Chang-Shik; Lee, Hyejung

    2011-01-01

    In smokers, smoking-associated cues produce smoking urges and cravings, which are accompanied by autonomic dysfunction in response to these cues. We investigated whether or not acupuncture ameliorated cigarette withdrawal symptoms, as well as attenuated the autonomic responses to smoking-related visual cues in smokers using a power spectrum analysis of heart rate variability (HRV). Fifteen subjects were treated with real acupuncture (RA) at HT7 and 14 subjects received sham acupuncture (SA) at LI10 using the Park Sham Device. The cigarette withdrawal scale (CWS) was measured on the third day after the subjects had quit smoking. We compared the low-frequency/high-frequency (HF/LF) ratio in the HRV of the RA and SA groups during a distraction task using neutral and smoking visual cues. The CWS of the RA group was significantly lower than that of the SA group. The increase in the LF/HF ratio of HRV induced by the smoking-related visual cues was also significantly lower in the RA group when compared with the SA group. Acupuncture not only ameliorated cigarette withdrawal, but also weakened the autonomic responses to smoking cues during withdrawal. These findings suggest that acupuncture might help in smoking cessation by attenuating withdrawal symptoms and smoking cues-induced autonomic responses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Association of URG11 and Twist with clinical pathological characteristics and prognosis in patients with IgA nephropathy.

    PubMed

    Du, Rui; Zhao, Lu; Xia, Lin; Liu, Limin; Sun, Wenjuan; Zhao, Ali; Yu, Yan; Han, Hua; Sun, Shiren

    2013-09-01

    Our previous studies demonstrated that URG11 is involved in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. The objective of this study was to determine the expression levels of URG11 in kidneys with IgA nephropathy (IgAN), and the association of URG11 with various clinical parameters. We analysed the degree of expression and localization of URG11 in biopsies from kidneys with IgAN, and correlated their immunostaining levels with various clinical and histological parameters. We also analysed the correlation between the expression of URG11 and Twist in the renal interstitium with renal survival. URG11 was strongly expressed in the cytoplasm of tubular epithelial cells obtained from kidneys of patients with IgAN. However, there was little positive staining for URG11 in the renal tubules of normal kidneys (P = 0.024). URG11 protein levels in the tubulointerstitium were inversely correlated with estimated glomerular filtration rates (eGFRs) (r = -0.305, P = 0.038) and the percentage of tubulointerstitial fibrosis (r = 0.350, P = 0.023). Moreover, a high level of URG11 correlated with the activation of Twist expression and E-cadherin repression in patients with IgAN (P = 0.000 and 0.041, respectively). Multivariate analyses indicated that a combination of high URG11 and Twist expression was an independent prognostic factor [relative ratio, RR 4.738 (95% CI: 1.040, 21.591), P = 0.044] of IgAN. Our findings suggest that URG11 staining in renal biopsy specimens might be a novel histological marker for progression in IgAN patients.

  12. Brain activity associated with placebo suppression of the urge-to-cough in humans.

    PubMed

    Leech, Jennifer; Mazzone, Stuart B; Farrell, Michael J

    2013-11-01

    Antitussive therapies are accompanied by a substantial placebo effect, indicating that inhibitory circuits in the brain have a significant capacity to regulate cough neural processing. However, essentially nothing is known about the identity of these inhibitory circuits or how they reduce coughing. Understanding these processes may help develop more effective antitussive therapies in the future. To identify regional changes in human brain activity related to the urge-to-cough after placebo antitussive administration. Seventeen healthy participants undertook functional magnetic resonance imaging while completing a series of inhalations of capsaicin to induce the urge-to-cough. The resultant brain responses associated with capsaicin inhalation without any treatment were compared with those induced by capsaicin after placebo antitussive administration. There was a significant decrease in participants' ratings of urge-to-cough after the placebo antitussive administration. Brain activity associated with capsaicin inhalation was less in the somatosensory, primary motor, insula, and cingulate cortices during placebo antitussive trials compared with no treatment control subjects. By contrast, placebo trials were associated with increased activation in the prefrontal and left parietal cortices. Placebo-related decreases in urge-to-cough are accompanied by commensurate decreases in several brain regions activated during capsaicin inhalation, suggesting that beliefs about treatment can modify the central processing of inputs arising from the airways. The prefrontal cortex and posterior parietal cortex are likely to play an active role in the modification of airway sensory processing after administration of a placebo.

  13. U.S. Ed-Tech Plan Urges Rethinking in K-12 Schools

    ERIC Educational Resources Information Center

    Ash, Katie

    2010-01-01

    The Obama administration urged educators and policymakers last week to embrace a host of digital-learning approaches it says will make K-12 schools better, including putting a computing device in the hands of every student. Guided by an overarching goal set by President Barack Obama to raise national college-completion rates from 40 percent to 60…

  14. U.S. Ed-Tech Plan Urges Rethinking in K-12 Schools

    ERIC Educational Resources Information Center

    Ash, Katie

    2010-01-01

    The Obama administration urged educators and policymakers last week to embrace a host of digital-learning approaches it says will make K-12 schools better, including putting a computing device in the hands of every student. Guided by an overarching goal set by President Barack Obama to raise national college-completion rates from 40 percent to 60…

  15. The effect of codeine on the Urge-to-Cough response to inhaled capsaicin

    PubMed Central

    Davenport, P.W.; Bolser, D.C.; Vickroy, T.; Berry, R.B.; Martin, A.D.; Hey, John A.; Danzig, M.

    2011-01-01

    We have shown previously in normal subjects that a sensory measure, the Urge-to-Cough rating, increases at concentrations of inhaled capsaicin that are lower than those necessary to elicit reflex cough. This finding suggests that the Urge-to-Cough may represent an index of the cough response. Research on cough in the human has most often employed challenge with inhaled capsaicin to induce reflex cough. Current measures of cough sensitivity in the human provide no information regarding the intensity of cough. The influence of codeine on cough perceptual sensitivity and the relationship to cough intensity with capsaicin-induced cough in normal subjects has not been evaluated. This study determined the effect of codeine on capsaicin-induced cough perceptual sensitivity and motor response in normal subjects in a double-blind, placebo-controlled, crossover study. This approach investigated the relevance of cough sensitivity, intensity, and sensory modalities in the assessment of cough suppression in humans. This study consisted of three experimental trials: administration of placebo, 30 mg codeine and 60 mg codeine. The study was double-blinded. The order of the three trials was randomized. Respiratory motor pattern was recorded with EMGs from the rectus abdominis, lateral abdominal muscles and eighth intercostal space. The subjects leaned into a fume hood to inspire deeply for 2 s once through a mouthpiece connected to the nebulizer. A modified Borg scale was used to estimate their Urge-to-Cough. The experimental trial consisted of eight test solutions of 0–200 μM capsaicin. Each solution was presented three times in a randomized block order for a total of 24 presentations. The lowest capsaicin concentration to elicit a cough was determined. The lowest capsaicin concentration to elicit an Urge-to-Cough greater than zero was identified. The Urge-to-Cough sensitivity was determined from the log–log slope. For placebo, the Urge-to-Cough was zero with inhalation of

  16. Brain Activity During Cocaine Craving and Gambling Urges: An fMRI Study.

    PubMed

    Kober, Hedy; Lacadie, Cheryl M; Wexler, Bruce E; Malison, Robert T; Sinha, Rajita; Potenza, Marc N

    2016-01-01

    Although craving states are important to both cocaine dependence (CD) and pathological gambling (PG), few studies have directly investigated neurobiological similarities and differences in craving between these disorders. We used functional magnetic resonance imaging (fMRI) to assess brain activity in 103 participants (30 CD, 28 PG, and 45 controls) while they watched videos depicting cocaine, gambling, and sad scenarios to investigate the neural correlates of craving. We observed a three-way urge type × video type × diagnostic group interaction in self-reported craving, with CD participants reporting strong cocaine cravings to cocaine videos, and PG participants reporting strong gambling urges to gambling videos. Neuroimaging data revealed a diagnostic group × video interaction in anterior cingulate cortex/ventromedial prefrontal cortex (mPFC), activating predominantly to cocaine videos in CD participants, and a more dorsal mPFC region that was most strongly activated for cocaine videos in CD participants, gambling videos in PG participants, and sad videos in control participants. Gender × diagnosis × video interactions identified dorsal mPFC and a region in posterior insula/caudate in which female but not male PG participants showed increased responses to gambling videos. Findings illustrate both similarities and differences in the neural correlates of drug cravings and gambling urges in CD and PG. Future studies should investigate diagnostic- and gender-specific therapies targeting the neural systems implicated in craving/urge states in addictions.

  17. Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

    PubMed

    Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D; Resnick, Neil M

    2015-09-01

    Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement

  18. Sacral Nerve Stimulation For Urinary Urge Incontinence, Urgency-Frequency, Urinary Retention, and Fecal Incontinence

    PubMed Central

    2005-01-01

    Executive Summary Objective The aim of this review was to assess the effectiveness, safety, and cost of sacral nerve stimulation (SNS) to treat urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence. Background: Condition and Target Population Urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence are prevalent, yet rarely discussed, conditions. They are rarely discussed because patients may be uncomfortable disclosing their symptoms to a health professional or may be unaware that there are treatment options for these conditions. Briefly, urge incontinence is an involuntary loss of urine upon a sudden urge. Urgency-frequency is an uncontrollable urge to void, which results in frequent, small-volume voids. People with urgency-frequency may or may not also experience chronic pelvic pain. Urinary retention refers to the inability to void despite having the urge to void. It can be caused by a hypocontractile detrusor (weak or no bladder muscle contraction) or obstruction due to urethral overactivity. Fecal incontinence is a loss of voluntary bowel control. The prevalence of urge incontinence, urgency-frequency, and urinary retention in the general population is 3.3% to 8.2%, and the prevalence of fecal incontinence is 1.4% to 1.9%. About three-quarters of these people will be successfully treated by behaviour and/or drug therapy. For those who do not respond to these therapies, the options for treatment are management with diapers or pads, or surgery. The surgical procedures are generally quite invasive, permanent, and are associated with complications. Pads and/or diapers are used throughout the course of treatment as different therapies are tried. Patients who respond successfully to treatment may still require pads or diapers, but to a lesser extent. The Technology Being Reviewed: Sacral Nerve Stimulation Sacral nerve stimulation is a procedure where a small device attached to an electrode is

  19. Urges for food and money spill over into motor system excitability before action is taken.

    PubMed

    Gupta, Nitin; Aron, Adam R

    2011-01-01

    Much human behavior is driven by urges. Yet research into urges is hampered by a paucity of tools to objectively index their strength, timing and control. Here we used transcranial magnetic stimulation (TMS) and concurrent electromyography to examine whether urges for food and money are detectable via motor system excitability. In Experiment 1, we used a naturalistic food paradigm to show that food items that were most strongly wanted elicited the largest motor excitability, even before participants knew which response to make to get them. In Experiment 2a, we replicated the results using money - motor excitability was greater for larger monetary amounts. In Experiment 2b we show that monetary amount does not modulate motor excitability when participants simply observe, without having to take action. As the chief effect occurred prior to the subject knowing which motor response to make, it is not merely related to response preparation, and as the effect was present only when action was required, it is not merely related to increased arousal. Instead, the increased motor excitability likely indexes the degree of motivation a subject has to perform an action. Thus, we have used TMS to demonstrate that urges for food and money 'spill over' into the motor system. This is likely mediated by interactions between the limbic system (including the orbital frontal cortex) and the motor system, probably at the level of the basal ganglia. Implications are discussed for theories of embodied cognition and for methodological progress in studying urge control. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  20. Impaired urge-to-cough in elderly patients with aspiration pneumonia

    PubMed Central

    Yamanda, Shinsuke; Ebihara, Satoru; Ebihara, Takae; Yamasaki, Miyako; Asamura, Takaaki; Asada, Masanori; Une, Kaori; Arai, Hiroyuki

    2008-01-01

    Background The down-regulation of the cough reflex in patients with aspiration pneumonia can involve both cortical facilitatory pathways for cough and medullary reflex pathways. In order to study the possible involvement of the supramedullary system in the down-regulation of cough reflex, we evaluated the urge-to-cough in patients with aspiration pneumonia. Methods Cough reflex sensitivity and the urge-to-cough to inhaled citric acid were evaluated in patients with at least a history of aspiration pneumonia and age-matched healthy elderly people. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough scores at the concentration of C2 and C5, and at the concentration of two times dilution of C2 (C2/2) and C5 (C5/2) were estimated for each subject. Results Both C2 and C5 in the control subjects were significantly greater than those for patients with aspiration pneumonia. There were no significant differences in the urge-to-cough at C2 and C5 between control subjects and patients with aspiration pneumonia. However, the urge-to-cough scores at both C2/2 and C5/2 in patients with aspiration pneumonia were significantly lower than those in control subjects. The number of coughs at C5/2 was significantly greater in the control subjects than those in the patients with aspiration pneumonia whereas the number of coughs at C2/2 did not show a significant difference between the control subjects and the patients with aspiration pneumonia. Conclusion The study suggests the involvement of supramedullary dysfunction in the etiology of aspiration pneumonia in the elderly. Therefore, restoration of the cough motivation system could be a new strategy to prevent aspiration pneumonia in the elderly. PMID:19019213

  1. Influence of the CXCL1 rs4074 A allele on alcohol induced cirrhosis and HCC in patients of European descent.

    PubMed

    Nischalke, Hans Dieter; Berger, Cordula; Lutz, Philipp; Langhans, Bettina; Wolter, Franziska; Eisenhardt, Marianne; Krämer, Benjamin; Kokordelis, Pavlos; Glässner, Andreas; Müller, Tobias; Rosendahl, Jonas; Fischer, Janett; Berg, Thomas; Grünhage, Frank; Leifeld, Ludger; Soyka, Michael; Nattermann, Jacob; Sauerbruch, Tilman; Stickel, Felix; Spengler, Ulrich

    2013-01-01

    CXCL1 (CXC chemokine-ligand-1) is a ligand for CXC chemokine receptor 2 expressed on hepatic stellate cells (HSC). Thus, CXCL1 might contribute to HSC activation and fibrogenesis. In the present study, we investigated the influence of the CXCL1 rs4074 polymorphism on the occurrence of alcohol induced liver cirrhosis and hepatocellular carcinoma (HCC). The study involved 458 patients with alcoholic cirrhosis (170 with HCC), 115 alcoholics without liver disease and 342 healthy controls. All subjects were genotyped for the CXCL1 rs4074 polymorphism and CXCL1 serum levels of 132 patients were measured. In vitro CXCL1 secretion in TLR-transfected cell lines were studied by ELISA. Distribution of the CXCL1 genotypes (GG/GA/AA) was 159/219/80 in patients with alcoholic cirrhosis, 52/44/19 in alcoholic controls and 158/140/44 in healthy controls. Patients with alcohol-induced cirrhosis were significantly more often carriers of the CXCL1 rs4074 A allele (65.3%) than alcoholics without liver disease (54.8%, OR=1.55; 95%CI=1.025-2.350; p=0.04) and healthy controls (53.8%, OR=1.62; 95%CI=1.212-2.151; p=0.001). Accordingly, the frequency of the CXCL1 rs4074 A allele was significantly higher in the cirrhotic patients than in the subjects without cirrhosis (41.4% vs. 33.9%, OR=1.38, 95% CI:1.14-1.66, p=0.001). Furthermore cirrhotic carriers of the CXCL1 rs4074 A allele had significantly higher CXCL1 serum levels than carriers of the GG genotype. In contrast to sera from healthy controls, sera from patients with alcoholic cirrhosis induced CXCL1 secretion in TLR2- (p=0.016) and TLR4- (p=0.008) transfected HEK293 cells. This finding indicates that sera from patients with alcoholic cirrhosis contain soluble ligands that can induce CXCL1 production via stimulation of TLRs. The enhanced CXCL1 serum levels in carriers of the rs4074 A allele together with their increased frequency in patients with alcohol induced cirrhosis suggest the CXCL1 rs4074 A allele as a genetic risk factor for

  2. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis.

    PubMed

    Bala, Shashi; Csak, Timea; Saha, Banishree; Zatsiorsky, James; Kodys, Karen; Catalano, Donna; Satishchandran, Abhishek; Szabo, Gyongyi

    2016-06-01

    Alcoholic liver disease (ALD) ranges from fatty liver to inflammation and cirrhosis. miRNA-155 is an important regulator of inflammation. In this study, we describe the in vivo role of miR-155 in ALD. Wild-type (WT) (C57/BL6J) or miR-155 knockout (KO) and TLR4 KO mice received Lieber DeCarli diet for 5weeks. Some mice received corn oil or CCl4 for 2 or 9weeks. We found that miR-155 KO mice are protected from alcohol-induced steatosis and inflammation. The reduction in alcohol-induced fat accumulation in miR-155 KO mice was associated with increased peroxisome proliferator-activated receptor response element (PPRE) and peroxisome proliferator-activated receptors (PPAR)α (miR-155 target) binding and decreased MCP1 production. Treatment with a miR-155 inhibitor increased PPARγ expression in naïve and alcohol treated RAW macrophages. Alcohol increased lipid metabolism gene expression (FABP4, LXRα, ACC1 and LDLR) in WT mice and this was prevented in KO mice. Alcohol diet caused an increase in the number of CD163(+) CD206(+) infiltrating macrophages and neutrophils in WT mice, which was prevented in miR-155 KO mice. Kupffer cells isolated from miR-155 KO mice exhibited predominance of M2 phenotype when exposed to M1 polarized signals and this was due to increased C/EBPβ. Pro-fibrotic genes were attenuated in miR-155 KO mice after alcohol diet or CCl4 treatment. Compared to WT mice, attenuation in CCl4 induced hydroxyproline and α-SMA was observed in KO mice. Finally, we show TLR4 signaling regulates miR-155 as TLR4 KO mice showed no induction of miR-155 after alcohol diet. Collectively our results demonstrated the role of miR-155 in alcohol-induced steatohepatitis and fibrosis in vivo. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Trait Mindfulness, Problem-Gambling Severity, Altered State of Awareness and Urge to Gamble in Poker-Machine Gamblers.

    PubMed

    McKeith, Charles F A; Rock, Adam J; Clark, Gavin I

    2016-09-12

    In Australia, poker-machine gamblers represent a disproportionate number of problem gamblers. To cultivate a greater understanding of the psychological mechanisms involved in poker-machine gambling, a repeated measures cue-reactivity protocol was administered. A community sample of 38 poker-machine gamblers was assessed for problem-gambling severity and trait mindfulness. Participants were also assessed regarding altered state of awareness (ASA) and urge to gamble at baseline, following a neutral cue, and following a gambling cue. Results indicated that: (a) urge to gamble significantly increased from neutral cue to gambling cue, while controlling for baseline urge; (b) cue-reactive ASA did not significantly mediate the relationship between problem-gambling severity and cue-reactive urge (from neutral cue to gambling cue); (c) trait mindfulness was significantly negatively associated with both problem-gambling severity and cue-reactive urge (i.e., from neutral cue to gambling cue, while controlling for baseline urge); and (d) trait mindfulness did not significantly moderate the effect of problem-gambling severity on cue-reactive urge (from neutral cue to gambling cue). This is the first study to demonstrate a negative association between trait mindfulness and cue-reactive urge to gamble in a population of poker-machine gamblers. Thus, this association merits further evaluation both in relation to poker-machine gambling and other gambling modalities.

  4. Correlates of Continued Tobacco Use and Intention to Quit Smoking Among Russian Cancer Patients

    PubMed Central

    Schnoll, Robert A.; Subramanian, Somasundaram; Martinez, Elisa; Engstrom, Paul F.

    2011-01-01

    Background Tobacco use among cancer patients is associated with adverse health outcomes. Little attention has been paid to tobacco use among cancer patients in developing countries, including Russia, where tobacco use is extremely high, and there is little public health infrastructure to address this issue. Purpose This study examined medical, socio-demographic, and psychological correlates of smoking status and intention to quit smoking among newly diagnosed Russian cancer patients. Method A cross-sectional study was conducted with 294 current or former smokers newly diagnosed with cancer. Results Compared with patients who quit smoking, patients who continued to smoke were more likely to report urges to smoke to satisfy positive reinforcing aspects of tobacco use. Compared with patients who were smoking and reported no intention to quit smoking in the next 3 months, patients who were smoking but intended to quit smoking reported higher levels of perceived risks associated with continued smoking and higher levels of self-efficacy to quit smoking. Conclusion As commitment to developing smoking cessation treatment programs for caner patients in Russia emerges, these data can help guide the development of behavioral interventions to assist patients with quitting smoking, enhancing their chances for improved clinical outcomes. PMID:21076900

  5. Smoke detection

    DOEpatents

    Warmack, Robert J. Bruce; Wolf, Dennis A.; Frank, Steven Shane

    2015-10-27

    Various apparatus and methods for smoke detection are disclosed. In one embodiment, a method of training a classifier for a smoke detector comprises inputting sensor data from a plurality of tests into a processor. The sensor data is processed to generate derived signal data corresponding to the test data for respective tests. The derived signal data is assigned into categories comprising at least one fire group and at least one non-fire group. Linear discriminant analysis (LDA) training is performed by the processor. The derived signal data and the assigned categories for the derived signal data are inputs to the LDA training. The output of the LDA training is stored in a computer readable medium, such as in a smoke detector that uses LDA to determine, based on the training, whether present conditions indicate the existence of a fire.

  6. Smoke detection

    SciTech Connect

    Warmack, Robert J. Bruce; Wolf, Dennis A.; Frank, Steven Shane

    2016-09-06

    Various apparatus and methods for smoke detection are disclosed. In one embodiment, a method of training a classifier for a smoke detector comprises inputting sensor data from a plurality of tests into a processor. The sensor data is processed to generate derived signal data corresponding to the test data for respective tests. The derived signal data is assigned into categories comprising at least one fire group and at least one non-fire group. Linear discriminant analysis (LDA) training is performed by the processor. The derived signal data and the assigned categories for the derived signal data are inputs to the LDA training. The output of the LDA training is stored in a computer readable medium, such as in a smoke detector that uses LDA to determine, based on the training, whether present conditions indicate the existence of a fire.

  7. Smoke Mask

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Smoke inhalation injury from the noxious products of fire combustion accounts for as much as 80 percent of fire-related deaths in the United States. Many of these deaths are preventable. Smoke Mask, Inc. (SMI), of Myrtle Beach, South Carolina, is working to decrease these casualties with its line of life safety devices. The SMI personal escape hood and the Guardian Filtration System provide respiratory protection that enables people to escape from hazardous and unsafe conditions. The breathing filter technology utilized in the products is specifically designed to supply breathable air for 20 minutes. In emergencies, 20 minutes can mean the difference between life and death.

  8. Smoke generator

    NASA Technical Reports Server (NTRS)

    Rogers, J. R. (Inventor)

    1976-01-01

    A smoke generator is disclosed which is particularly suitable for mounting on the wing tips of an aircraft and for conducting airflow studies. The device includes a network of thermally insulated tubes for carrying a fluid which is used to produce smoke. The fluid, which need not be combustible, is heated above its vaporization temperature by electric current which is passed through the fluid conduit tubes, so that the tubes serve both as fluid conduits and resistance heating elements. Fluid supply and monitoring systems and electrical control systems are also disclosed.

  9. Inflammatory responses to alcohol in the CNS: nuclear receptors as potential therapeutics for alcohol-induced neuropathologies.

    PubMed

    Kane, Cynthia J M; Drew, Paul D

    2016-11-01

    Fetal alcohol spectrum disorder (FASD), which results from ethanol exposure during pregnancy, and alcohol use disorder (AUD), which includes both binge and chronic alcohol abuse, are strikingly common and costly at personal and societal levels. These disorders are associated with significant pathology, including that observed in the CNS. It is now appreciated in both humans and animal models that ethanol can induce inflammation in the CNS. Neuroinflammation is hypothesized to contribute to the neuropathologic and behavioral consequences in FASD and AUD. In this review, we: 1) summarize the evidence of alcohol-induced CNS inflammation, 2) outline cellular and molecular mechanisms that may underlie alcohol induction of CNS inflammation, and 3) discuss the potential of nuclear receptor agonists for prevention or treatment of neuropathologies associated with FASD and AUD. © Society for Leukocyte Biology.

  10. Randomized crossover trial of the acceptability of snus, nicotine gum, and Zonnic therapy for smoking reduction in heavy smokers.

    PubMed

    Caldwell, Brent; Burgess, Carl; Crane, Julian

    2010-02-01

    Novel approaches to nicotine replacement therapy (NRT) are needed to improve the modest long-term quit rate of 10%. Snus (Swedish tobacco) and Zonnic (oral nicotine sachet) rapidly deliver nicotine via buccal absorption and have potential as NRTs. As a prelude to formal evaluation of either product as a smoking cessation therapy, it is necessary to determine their acceptability and the willingness of smokers to use them in populations with no history of access to oral tobacco products. An open-label crossover study of ad libitum snus, Zonnic, and nicotine gum among 63 smokers for 2 weeks each, and smoking reduction if the subjects did not feel the desire to smoke. Diary cards recorded use of products and cigarettes; formal and ad hoc scales measured urges to smoke, withdrawal symptoms, and the sensory quality of the products. Subjects preferred snus and Zonnic over gum. Snus and Zonnic were superior to gum in reducing urges to smoke and caused fewer side effects. All three products suppressed withdrawal symptoms. Subjects reduced their smoking by Ms of 33%, 37%, and 42% during the gum, snus, and Zonnic fortnights, respectively. Most subjects reported a strong desire to use Zonnic or snus to quit smoking. Subjects preferred snus and Zonnic, which both had significantly fewer gastrointestinal side effects than gum and resulted in greater reductions in smoking. Snus and Zonnic are effective in suppressing desires to smoke and reducing smoking, and further studies are warranted to investigate their effect on long-term quit rates.

  11. Expectancies Regarding the Interaction between Smoking and Substance Use in Alcohol-Dependent Smokers in Early Recovery

    PubMed Central

    Carmody, Timothy P.; Delucchi, Kevin; Simon, Joel A.; Duncan, Carol L.; Solkowitz, Sharon N.; Huggins, Joy; Lee, Sharon K.; Hall, Sharon M.

    2011-01-01

    The purpose of this study was to investigate expectancies regarding the interaction between cigarette smoking and use of alcohol among alcohol-dependent smokers in early recovery, using the Nicotine and Other Substances Interaction Expectancies Questionnaire (NOSIE). Participants were 162 veterans, 97% male, with a mean age of 50 years, enrolled in a clinical trial aimed at determining the efficacy of an intensive smoking cessation intervention versus usual care. At baseline, participants were assessed on measures of smoking behavior, abstinence thoughts about alcohol and tobacco use, symptoms of depression, and smoking-substance use interaction expectancies. In addition, biologically-verified abstinence from tobacco and alcohol was assessed at 26 weeks. Participants reported that they expected smoking to have less of an impact on substance use than substance use has on smoking (p<.001). Severity of depressive symptoms was significantly associated with the expectancy that smoking provides a way of coping with the urge to use other substances (p<.01). The expectation that smoking increases substance urges/use was predictive of prospectively-measured and biologically-verified abstinence from smoking at 26 weeks (p<.03). The results add to our knowledge of smoking-substance use interaction expectancies among alcohol-dependent smokers in early recovery and will inform the development of more effective counseling interventions for concurrent alcohol and tobacco use disorders. PMID:21707127

  12. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice

    PubMed Central

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R.

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8–10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  13. Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.

    PubMed

    Rajayer, Salil R; Jacob, Asha; Yang, Weng-Lang; Zhou, Mian; Chaung, Wayne; Wang, Ping

    2013-01-01

    Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP), a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT) mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP(-/-)) mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH) were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP(-/-) mice. Brain TNF-α mRNA and protein expressions along with IL-1β protein levels were significantly increased in WT mice, which was not seen in the CIRP(-/-) mice. In cultured BV2 cells (mouse microglia), ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-α and IL-1β were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation.

  14. Reductive beta-scission of the hydroperoxides of fatty acids and xenobiotics: role of alcohol-inducible cytochrome P-450.

    PubMed Central

    Vaz, A D; Roberts, E S; Coon, M J

    1990-01-01

    As shown previously in this laboratory, purified rabbit liver microsomal cytochrome P-450 form 2 (P-450 IIB4) catalyzes the reductive cleavage of hydroperoxides to yield hydrocarbons and either aldehydes or ketones. We have proposed that lipid hydroperoxides are the physiological substrates for the cleavage reaction and have shown that with 13-hydroperoxy-9,11-octadecadienoic acid the formation of pentane is roughly equimolar with respect to the NADPH consumed. In the present study, the other product was isolated and identified as 13-oxo-9,11-tridecadienoic acid. Of particular interest, the alcohol-inducible form of liver microsomal cytochrome P-450 form 3a (P-450 IIE1) is the most active of the isozymes examined in the reductive beta-scission of the 13-hydroperoxide derived from linoleic acid and the 15-hydroperoxide derived from arachidonic acid as well as the model compounds cumyl hydroperoxide (alpha, alpha-dimethylbenzyl hydroperoxide) and t-butyl hydroperoxide. In general, the forms of P-450 with lower activity, as judged by the rate of NADPH oxidation in the reconstituted system, give less of the cleavage products (hydrocarbon and oxo compound) and catalyze direct reduction of the hydroperoxides to the corresponding hydroxy compounds. The occurrence of the reductive cleavage reaction in liver microsomal membranes was demonstrated, and microsomes from animals treated with ethanol or acetone (P-450 IIE1 inducers) or phenobarbital (a P-450 IIB4 inducer) were more active than those from untreated animals. We suggest that the alcohol-inducible P-450, in addition to its known deleterious effects in chemical toxicity and chemical carcinogenesis, may enhance the reductive cleavage of lipid hydroperoxides with a resultant loss in membrane integrity. Images PMID:2371285

  15. Suppression of neuro-inflammatory signaling cascade by tocotrienol can prevent chronic alcohol-induced cognitive dysfunction in rats.

    PubMed

    Tiwari, Vinod; Kuhad, Anurag; Chopra, Kanwaljit

    2009-11-05

    Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in neuronal apoptosis and thus dementia. In the present study, we investigated the comparative effect of both the isoforms of vitamin E, alpha-tocopherol and tocotrienol against chronic alcohol-induced cognitive dysfunction in rats. Male Wistar rats were given ethanol (10g/kg; oral gavage) for 10 weeks, and treated with alpha-tocopherol and tocotrienol for the same duration. The learning and memory behavior was assessed using Morris water maze and elevated plus maze test. The rats were sacrificed at the end of 10th week and cytoplasmic fractions of cerebral cortex and hippocampus were prepared for the quantification of acetylcholinesterase activity, oxidative-nitrosative stress parameters, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). From the 6th week onwards, ethanol-treated rats showed significant increase in transfer latency in both the behavioral paradigms which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, TNF-alpha and IL-1beta levels in different brain regions of ethanol-treated rats. Co-administration of alpha-tocopherol as well as tocotrienol significantly and dose-dependently prevented these behavioral, biochemical and molecular changes in the brains of ethanol-treated rats. However, the effects were more pronounced with tocotrienol. The current study thus demonstrates the possible involvement of oxidative-nitrosative stress mediated activation of inflammatory cascade in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of vitamin E isoforms, of which tocotrienol being more potent, in preventing the cognitive deficits associated with chronic alcohol consumption.

  16. Subjective and autonomic responses to smoking-related visual cues.

    PubMed

    Chae, Younbyoung; Lee, Jeung-Chan; Park, Kyung-Mo; Kang, O-Seok; Park, Hi-Joon; Lee, Hyejung

    2008-04-01

    Nicotine, like several other abused drugs, is known to act on the reward system in the brain. Smoking-associated cues produce smoking urges and cravings accompanied by autonomic dysfunction to these cues in smokers. The present study was aimed at investigating whether cues related to smoking elicit the autonomic response in smokers. The subjective and physiological reactivity of 7 smokers and 12 nonsmokers in a supine position to smoking-related visual cues was assessed under indirect dim light using a self-assessment manikin and a specially designed pupillometer. The experimental procedure consisted of the elicitation and measurement of pupil size (PS) while the subjects viewed a smoking image and images from three valence-defined categories (i.e., pleasant, unpleasant, and neutral), based on normative affective ratings selected from the International Affective Picture System. Both groups produced significantly larger PS increases in response to pleasant or unpleasant images compared to neutral images. Smokers, viewing smoking-related visual cues but no other affective images, produced significantly larger PS's compared to nonsmokers. Moreover, smokers rated the smoking image with more pleasure and arousal than nonsmokers. These findings suggest that cues related to smoking induce not only a subjective emotional alteration, but also sympathetic activation, measured by the time-series PS data in smokers.

  17. Secondhand Smoke

    MedlinePlus

    ... about exposure to secondhand smoke (SHS) in these places: At work The workplace is a major source of SHS ... the only way to prevent SHS exposure at work. Separating smokers from non-smokers, cleaning ... public places Everyone can be exposed to SHS in public ...

  18. Urge incontinence

    MedlinePlus

    ... and night Needing to urinate suddenly and urgently Exams and Tests During a physical exam, your health ... foods that may irritate the bladder, such as: Caffeine Highly acidic foods, such as citrus fruits and ...

  19. Combination analysis of NOS3, ABCB1 and IL23R polymorphisms with alcohol-induced osteonecrosis of the femoral head risk in Chinese males.

    PubMed

    Wang, Yuan; Yang, Xuejun; Shi, Jianping; Zhao, Yan; Pan, Linlin; Zhou, Jinqiu; Wang, Guoqiang; Wang, Jianzhong

    2017-05-16

    Common variants of multiple genes played a crucial role in osteonecrosis of the femoral head (ONFH) onset which was proved by many previous reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related to individual differences in alcohol sensitivity and the development of alcohol-induced ONFH. In this case-control study, we evaluated 8 SNPs in three genes in the Chinese Han population including 355 male cases and 355 healthy male controls. These SNPs were genotyped by Sequenom MassARRAY RS1000. To identify their relationship with alcohol-induced ONFH susceptibility using χ2 test and genetic model analysis. We found an association with alcohol-induced ONFH susceptibility for 4 SNPs (rs743506, rs3918184, rs13233308 and rs6693831) in three genes after adjusted by age. The genotype "G/A" of rs743506 in NOS3 gene acts as a risk factor in genotype (P = 0.003), dominant (P = 0.048), recessive (P = 0.005) and additive model(P = 0.006); The genotype "T/C" of rs3918184 in NOS3 gene acts as a risk factor in genotype (P = 0.012) and recessive model (P = 0.009); The genotype "T/C" of rs13233308 in ABCB1 gene acts as a risk factor in genotype (P = 0.038) and additive model(P = 0.041); The genotype "T/C" of rs6693831 in IL23R gene acts as a protective factor in genotype model (P = 0.046). This study provides evidence for three alcohol-induced ONFH susceptibility genes (NOS3, ABCB1 and IL23R) in Chinese males and polymorphisms of them may be associated with alcohol-induced ONFH risk.

  20. Inconsistencies in place definition: How different operational place definitions affect estimates of adolescent smoking and drinking risk.

    PubMed

    Brady, Joanne E; Weitzman, Beth C

    2007-06-01

    We find that estimates of the prevalence of teenage smoking and drinking in "urban," "suburban," and "rural" areas vary with different definitions of these types of geographic units. Given the salience of youth risk behavior to the public debate, we urge researchers to purposefully choose their definitions of geographic areas and to be explicit about those choices.

  1. Repetitive urges to inflict burns: An unusual presentation of impulse control disorder

    PubMed Central

    Pal, Arghya; Parmar, Arpit; Pattanayak, Raman Deep

    2016-01-01

    Impulse control disorders (ICDs) are characterized by an inability to resist an intense impulse or drive to perform a particular act that is excessive and/or harmful to self/others. Till date, there is no published report of an ICD presenting with repetitive urges to inflict burns. We describe the case of an adult male in regular follow-up for 6 months who presented with intense, irresistible, and repetitive urges and acts of causing burns on his skin for past 1 year. The phenomenology shared the core qualities described for ICDs and patient showed adequate response to treatment. The case report describes an unusual type of ICD classifiable as not otherwise specified. More clinical and research attention is warranted toward ICDs in general, with implications for ICD-11. PMID:28163418

  2. Desensitization of Triggers and Urge Reduction for Paruresis: A Case Report

    PubMed Central

    Park, Hyoin; Jang, Eun Young; Bae, Hwallip

    2016-01-01

    Paruresis is a special type of non-generalized social phobia that involves fear and avoidance of urination in public restrooms. We administered eight 60-minute sessions of desensitization of triggers and urge reduction (DeTUR), an addiction protocol of eye movement desensitization and reprocessing (EMDR) therapy, to a 29-year old man with paruresis of 10 year duration. Because phobic avoidance is the hallmark of any anxiety disorder, we applied DeTUR targeting the urge to avoid each anxiety-provoking situation in succession. After treatment, the participant no longer met the requirements for a diagnosis of social anxiety disorder, and the self-reported symptoms of social anxiety had decreased to non-clinical levels; furthermore, these treatment gains were maintained at the one-year follow-up. Further clinical studies are needed to generalize this finding. PMID:26766960

  3. Desensitization of Triggers and Urge Reduction for Paruresis: A Case Report.

    PubMed

    Park, Hyoin; Kim, Daeho; Jang, Eun Young; Bae, Hwallip

    2016-01-01

    Paruresis is a special type of non-generalized social phobia that involves fear and avoidance of urination in public restrooms. We administered eight 60-minute sessions of desensitization of triggers and urge reduction (DeTUR), an addiction protocol of eye movement desensitization and reprocessing (EMDR) therapy, to a 29-year old man with paruresis of 10 year duration. Because phobic avoidance is the hallmark of any anxiety disorder, we applied DeTUR targeting the urge to avoid each anxiety-provoking situation in succession. After treatment, the participant no longer met the requirements for a diagnosis of social anxiety disorder, and the self-reported symptoms of social anxiety had decreased to non-clinical levels; furthermore, these treatment gains were maintained at the one-year follow-up. Further clinical studies are needed to generalize this finding.

  4. Desensitization of triggers and urge reprocessing for pathological gambling: a case series.

    PubMed

    Bae, Hwallip; Han, Changwoo; Kim, Daeho

    2015-03-01

    This case series introduces the desensitization of triggers and urge reprocessing (DeTUR), as a promising adjunctive therapy in addition to comprehensive treatment package for pathological gambling. This addiction protocol of eye movement desensitization and reprocessing was delivered to four male inpatients admitted to a 10-week inpatient program for pathological gambling. The therapist gave three 60-min weekly sessions of the DeTUR using bilateral stimulation (horizontal eye movements or alternative tactile stimuli) focusing on the hierarchy of triggering situations and the urge to initiate gambling behaviors. After treatment, self-reported gambling symptoms, depression, anxiety, and impulsiveness were all improved, and all the participants reported satisfaction with the therapy. They were followed up for 6 months and all maintained their abstinence from gambling and their symptomatic improvements. Given the efficiency (i.e., brevity and efficacy) of the treatment, a controlled study to confirm the effects of the DeTUR on pathological gambling would be justified.

  5. Plain packaging of cigarettes and smoking behavior: study protocol for a randomized controlled study.

    PubMed

    Maynard, Olivia M; Leonards, Ute; Attwood, Angela S; Bauld, Linda; Hogarth, Lee; Munafò, Marcus R

    2014-06-25

    Previous research on the effects of plain packaging has largely relied on self-report measures. Here we describe the protocol of a randomized controlled trial investigating the effect of the plain packaging of cigarettes on smoking behavior in a real-world setting. In a parallel group randomization design, 128 daily cigarette smokers (50% male, 50% female) will attend an initial screening session and be assigned plain or branded packs of cigarettes to smoke for a full day. Plain packs will be those currently used in Australia where plain packaging has been introduced, while branded packs will be those currently used in the United Kingdom. Our primary study outcomes will be smoking behavior (self-reported number of cigarettes smoked and volume of smoke inhaled per cigarette as measured using a smoking topography device). Secondary outcomes measured pre- and post-intervention will be smoking urges, motivation to quit smoking, and perceived taste of the cigarettes. Secondary outcomes measured post-intervention only will be experience of smoking from the cigarette pack, overall experience of smoking, attributes of the cigarette pack, perceptions of the on-packet health warnings, behavior changes, views on plain packaging, and the rewarding value of smoking. Sex differences will be explored for all analyses. This study is novel in its approach to assessing the impact of plain packaging on actual smoking behavior. This research will help inform policymakers about the effectiveness of plain packaging as a tobacco control measure. Current Controlled Trials ISRCTN52982308 (registered 27 June 2013).

  6. Cerebral control of the bladder in normal and urge-incontinent women

    PubMed Central

    Griffiths, Derek; Tadic, Stasa D.; Schaefer, Werner; Resnick, Neil M.

    2007-01-01

    Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase. Conclusion: Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO). PMID:17574871

  7. The effects of suicide ideation assessments on urges to self-harm and suicide.

    PubMed

    Eynan, Rahel; Bergmans, Yvonne; Antony, Jesmin; Cutcliffe, John R; Harder, Henry G; Ambreen, Munazzah; Balderson, Ken; Links, Paul S

    2014-01-01

    Participants' safety is the primary concern when conducting research with suicidal or potentially suicidal participants. The presence of suicide risk is often an exclusion criterion for research participants. Subsequently, few studies have examined the effects of research assessments on study participants' suicidality. The purpose of this research was to examine the patterns of postassessment changes in self-harm and suicide urges of study participants who were recently discharged from an inpatient psychiatric service. Study participants (N = 120) were recruited from patients with a lifetime history of suicidal behavior admitted with current suicidal ideation or suicide attempt to an inpatient psychiatric service and/or a crisis stabilization unit. Participants were assessed for suicidal ideation with the Suicide Ideation Scale at 1, 3, and 6 months following their discharge from hospital. The risk assessment protocol was administered at the start and at the end of each of the study follow-up assessments. Changes in self-harm and suicide urges following study assessments were small, infrequent, and were most likely to reflect a decrease in suicidality. Similarly, participants rarely reported worsening self-control over suicidal urges, and when they did, the effect was minimal. By the end of the 6-month follow-up period, increases in self-harm and suicidal urges postassessment were not seen. The inclusion of suicidal participants in research interviews rarely increased suicide risk. Research involving suicidal individuals is possible when study protocols are well planned and executed by trained assessors and clinicians who are able to identify participants at risk and provide intervention if necessary. The few participants that required intervention had high levels of suicide ideation and behavior at baseline and almost all reported symptoms of posttraumatic stress disorder. Further study is needed to better characterize this subgroup of participants.

  8. A Naturalistic Examination of Social Comparisons and Disordered Eating Thoughts, Urges, and Behaviors in College Women

    PubMed Central

    Fitzsimmons-Craft, Ellen E.; Ciao, Anna C.; Accurso, Erin C.

    2015-01-01

    Objective We examined the effects of body, eating, and exercise social comparisons on prospective disordered eating thoughts and urges (i.e., restriction thoughts, exercise thoughts, vomiting thoughts, binge eating urges) and behaviors (i.e., restriction attempts, exercising for weight/shape reasons, vomiting, binge eating) among college women using ecological momentary assessment (EMA). Method Participants were 232 college women who completed a two-week EMA protocol, in which they used their personal electronic devices to answer questions three times per day. Generalized estimating equation models were used to assess body, eating, and exercise comparisons as predictors of disordered eating thoughts, urges, and behaviors at the next report, adjusting for body dissatisfaction, negative affect, and the disordered eating thought/urge/behavior at the prior report, as well as body mass index. Results Body comparisons prospectively predicted more intense levels of certain disordered eating thoughts (i.e., thoughts about restriction and exercise). Eating comparisons prospectively predicted an increased likelihood of subsequent engagement in all disordered eating behaviors examined except vomiting. Exercise comparisons prospectively predicted less intense thoughts about exercise and an increased likelihood of subsequent vomiting. Discussion Social comparisons are associated with later disordered eating thoughts and behaviors in the natural environment and may need to be specifically targeted in eating disorder prevention and intervention efforts. Targeting body comparisons may be helpful in terms of reducing disordered eating thoughts, but eating and exercise comparisons are also important and may need to be addressed in order to decrease engagement in actual disordered eating behaviors. PMID:26610301

  9. Alcohol-induced blackouts as predictors of other drinking related harms among emerging young adults

    PubMed Central

    Hingson, Ralph; Zha, Wenxing; Simons-Morton, Bruce; White, Aaron

    2016-01-01

    Background Alcohol-related blackouts are periods of amnesia that reflect the failure of the brain to record memories of what transpires while drinking. This paper examined the incidence, predictors, and behavioral correlates of blackouts among emerging adults and examined whether questions about blackouts could serve as better markers of risk for other alcohol related harms than questions about levels of consumption. Methods In 2012-2013, 1,463 (68%) of 2,140 respondents one-year past high school reported having consumed alcohol. They were asked whether, in the past six months because of drinking, they forgot where they were or what they did. The survey also explored demographics, substance use behaviors, and other alcohol-related problems in the past six months. Chi square and logistic regression analyses explored bivariate and multivariate predictors of blackouts and other alcohol-related problems. Results Twenty percent of respondents who ever drank alcohol reported a blackout in the past six months. Blackouts were more prevalent among females and those who, in the past 30 days, used multiple drugs, more frequently binged, were drunk, smoked, had lower body weight, and lived in college dorms. After controlling for drinking levels, having a blackout was the strongest independent predictor of most other alcohol problems examined, including in the past six months because of drinking, missing class or work, getting behind in work or school, doing something respondents later regretted, arguing with friends, experiencing an overdose, and total number of alcohol problems reported. It was also an independent predictor of hangovers, damaging property, getting hurt, and trouble with police. Conclusion Because blackouts indicate drinking at levels that result in significant cognitive and behavioral impairment, questions about blackouts could serve as important, simple screeners for the risk of experiencing other alcohol related harms. Additional work on this subject is

  10. Origin of symbol-using systems: speech, but not sign, without the semantic urge

    PubMed Central

    Sereno, Martin I.

    2014-01-01

    Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint. PMID:25092671

  11. Origin of symbol-using systems: speech, but not sign, without the semantic urge.

    PubMed

    Sereno, Martin I

    2014-09-19

    Natural language--spoken and signed--is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint.

  12. Quality of life and self-esteem for children with urinary urge incontinence and voiding postponement.

    PubMed

    Natale, N; Kuhn, S; Siemer, S; Stöckle, M; von Gontard, A

    2009-08-01

    Urge incontinence and voiding postponement are common subtypes of daytime wetting in children. We analyzed health related quality of life for children with urge incontinence and voiding postponement, and healthy controls at 2 centers. We examined a total of 49 consecutive children 5 to 13 years old who presented with urge incontinence (22) or voiding postponement (27), and 32 controls matched for age and sex. Health related and overall quality of life were measured with generic questionnaires, and self-esteem was measured with the Piers-Harris questionnaire. Health related quality of life was significantly reduced in parent rating but not in child rating in the incontinent vs control group (total mean parent score 73 vs 78, child 76 vs 76). Children with voiding postponement have the lowest health related quality of life. Overall quality of life was significantly reduced in children with incontinence, while self-esteem did not differ. Children with externalizing disorders generally have the lowest health related and overall quality of life. Health related and overall quality of life are useful constructs, and are reduced in children with daytime incontinence by parental rating. In comparison, children rate their quality of life as being higher. Quality of life is lowest with externalizing behavioral disorders, as in children with voiding postponement. Due to comorbid behavioral disturbances, children with voiding postponement often need additional assessment, counseling and treatment.

  13. Detection of intracellular bacteria in exfoliated urothelial cells from women with urge incontinence.

    PubMed

    Cheng, Ying; Chen, Zhuoran; Gawthorne, Jayde A; Mukerjee, Chinmoy; Varettas, Kerry; Mansfield, Kylie J; Schembri, Mark A; Moore, Kate H

    2016-10-01

    The role of subclinical infection in patients with urge incontinence has been largely ignored. The aim of this study was to test for the presence of intracellular bacteria in exfoliated urothelial cells obtained from the urine of patients with detrusor overactivity or mixed incontinence +/- a history of UTI, and compare this to a control group of patients with stress incontinence and no history of infection. Bacterial cystitis was assessed by routine microbiology and compared to microscopic analysis of urine by Wright staining. Subsequent analysis of urothelial cells by confocal microscopy was performed to determine the existence of intracellular bacteria. Bacterial cystitis was seen in 13% of patients based on routine microbiology. Wright staining of concentrated urothelial cells demonstrated the presence of bacteria in 72% of samples. Filamentous bacterial cells were observed in 51% of patients and were significantly more common in patients with detrusor overactivity. Intracellular Escherichia coli were observed by confocal microscopy. This study supports the possibility that a subset of patients with urge incontinence may have unrecognised chronic bacterial colonisation, maintained via an intracellular reservoir. In patients with negative routine microbiology, application of the techniques used in this study revealed evidence of infection, providing further insights into the aetiology of urge incontinence. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Effects of the Opioid Receptor Antagonist Naltrexone on Smoking and Related Behaviors in Smokers Preparing to Quit: A Randomized Controlled Trial

    PubMed Central

    King, Andrea; Cao, Dingcai; Zhang, Lingjiao; Rueger, Sandra Yu

    2013-01-01

    Aims To determine if naltrexone affects smoking behaviours in smokers preparing to quit, and whether such pre-quit responses predict post-quit date outcomes. Design Double-blind, placebo-controlled, randomized study. Current study focused on smoking-related outcomes in the pre-quit phase, which was one week prior to the quit date, and these findings were linked with reductions in same outcomes demonstrated in the post-quit phase previously published for this RCT in mediation analyses. Setting Community sample of adult smokers desiring to quit in Chicago, Illinois USA. Participants Participants were 315 smokers randomized to naltrexone (n=161; mean age=42.6 years; 60% white) or placebo (n=154; mean age=41.3 years; 55% white). Measurements Difference from baseline in the number of cigarettes smoked during pre-quit phase interval was the primary outcome. Secondary pre-quit outcomes were assessed using Likert scales of subjective responses and consumption of cigarettes, alcohol, and food. Number of cigarettes smoked, alcoholic drinks consumed, and the Brief Questionnaire of Smoking Urges were assessed in the post-quit phase. Findings Relative to placebo, naltrexone decreased the number of cigarettes smoked (−4.21 vs. −2.93, p<.05), smoking urge (p=.02), and number of alcoholic drinks consumed (p=.04). Exploratory mediation analyses linking outcomes of the pre quit and post quit phases found that naltrexone’s effects on reducing smoking urge, cigarettes smoked and alcoholic drinks consumed in the pre-quit phase demonstrated full mediation of their respective effects during the post-quit phase. Conclusions Naltrexone taken in the week before a quit attempt appears to reduce cigarette consumption, urges to smoke and alcohol consumption relative to placebo. The size of the effect statistically mediates the size of similar effects after the quit date. PMID:23714324

  15. [Spanish opinions on tobacco smoke-free areas].

    PubMed

    Clemente Jiménez, María Lourdes; Bartolomé Moreno, Cruz; Rubio Aranda, Encarnación; Martín Cantera, Carlos; Puente, Diana; Sobradiel Sierra, Natalia

    2012-03-01

    To determine the number of passive smokers, the environments where exposure to second-hand smoke (SHS) is higher, the opinion of smokers and non-smokers with regard to these spaces and their influence on smoking. Descriptive and cross-sectional observational study of a convenience sample. Multi-centre, Spanish Health-care Centres. A total of 9733 people older than 16 years who were seen or were working in Spanish Health-care Centres in April 2008. Smoker condition, gender, profession and their opinion with regard to second-hand smoke (SHS) exposure. A total of 42.4% of participants considered themselves second-hand (passive) smokers in public places and 96.8% in indoor areas. Almost all of them (91.8%) considered SHS exposure harmful for non-smokers, Smoke-free environments were considered to be good for discouraging people from starting to smoke (70.3%), and for quitting smoking (71.8%). Smoke-free environments were preferred by 81.1%. They felt more exposed SHS inside a car (79.8%) and in cafes (34.7%). Non-smokers, both men and women, shared these opinions significantly (P<.05). Altogether, those surveyed considered themselves as second-hand smokers and think that smoke-free environments reduce the impact of smoking and help in quitting smoking. Besides, they prefer living in those environments. Considering the preferences of most of the population, this stresses the need to urge governments to establish legislative measures promoting smoke-free environments. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  16. Smoke Detector

    NASA Technical Reports Server (NTRS)

    1979-01-01

    In the photo, Fire Chief Jay Stout of Safety Harbor, Florida, is explaining to young Richard Davis the workings of the Honeywell smoke and fire detector which probably saved Richard's life and that of his teen-age brother. Alerted by the detector's warning, the pair were able to escape their burning home. The detector in the Davis home was one of 1,500 installed in Safety Harbor residences in a cooperative program conducted by the city and Honeywell Inc.

  17. Alcohol-induced electrical remodeling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium.

    PubMed

    Laszlo, Roman; Eick, Christian; Schwiebert, Mareike; Schreiner, Birgit; Weig, Hans-Joerg; Weretka, Slawomir; Bosch, Ralph F; Schreieck, Juergen

    2009-10-01

    In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. Ethanol infusion did not alter current densities of I(to) [58.7 +/- 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 +/- 5.0 pA/pF (EG, n = 24)], I(sus) [11.3 +/- 1.4 pA/pF (PG, n = 20) vs. 10.2 +/- 1.0 pA/pF (EG, n = 24)], and I(K1) [-1.6 +/- 0.3 pA/pF (PG, n = 17) vs. -2.0 +/- 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of I(Ca,L) current densities [-28.4 +/- 1.8 pA/pF (PG, n = 20) vs. -15.2 +/- 1.4 pA/pF (EG, n = 22)] and I(Na) [-75.4 +/- 3.6 pA/pF (PG, n = 17) vs. -35.4 +/- 4.4 pA/pF (EG, n = 21)], respectively. Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

  18. Alcohol-Induced Behaviors Require a Subset of Drosophila JmjC-Domain Histone Demethylases in the Nervous System.

    PubMed

    Pinzón, Jorge H; Reed, Addison R; Shalaby, Nevine A; Buszczak, Michael; Rodan, Aylin R; Rothenfluh, Adrian

    2017-09-21

    Long-lasting transcriptional changes underlie a number of adaptations that contribute to alcohol use disorders (AUD). Chromatin remodeling, including histone methylation, can confer distinct, long-lasting transcriptional changes, and histone methylases are known to play a role in the development of addiction. Conversely, little is known about the relevance of Jumonji (JmjC) domain-containing demethylases in AUDs. We systematically surveyed the alcohol-induced phenotypes of null mutations in all 13 Drosophila JmjC genes. We used a collection of JmjC mutants, the majority of which we generated by homologous recombination, and assayed them in the Booze-o-mat to determine their naïve sensitivity to sedation and their tolerance (change in sensitivity upon repeat exposure). Mutants with reproducible phenotypes had their phenotypes rescued with tagged genomic transgenes, and/or phenocopied by nervous system-specific knock down using RNA interference (RNAi). Four of the 13 JmjC genes (KDM3, lid, NO66 and HSPBAP1) showed reproducible ethanol-sensitivity phenotypes. Some of the phenotypes were observed across doses, e.g. the enhanced ethanol-sensitivity of KDM3(KO) and NO66(KO) , but others were dose-dependent, such as the reduced ethanol sensitivity of HSPBAP1(KO) , or the enhanced ethanol tolerance of NO66(KO) . These phenotypes were rescued by their respective genomic transgenes in KDM3(KO) and NO66(KO) mutants. While we were unable to rescue lid(k) mutants, knock down of lid in the nervous system recapitulated the lid(k) phenotype, as was observed for KDM3(KO) and NO66(KO) RNAi-mediated knock down. Our study reveals that the Drosophila JmjC-domain histone demethylases Lid, KDM3, NO66, and HSPBAP1 are required for normal ethanol-induced sedation and tolerance. Three of three tested of those four JmjC genes are required in the nervous system for normal alcohol-induced behavioral responses, suggesting that this gene family is an intriguing avenue for future research. This

  19. Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

    PubMed Central

    Bonthius, Daniel J.; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J.

    2014-01-01

    The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS−/− mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS−/− mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS−/− mice and their wild type controls received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days 4–9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS−/− and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS−/− mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS−/− mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS−/− mice, but not

  20. Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits.

    PubMed

    Bonthius, Daniel J; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J

    2015-01-01

    The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS-/- mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS-/- mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS-/- mice and their wild type controls received alcohol (0.0, 2.2, or 4.4mg/g) daily over postnatal days 4-9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS-/- and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS-/- mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS-/- mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS-/- mice, but not in wild type. Thus, homozygous

  1. Smoking Programs for Youth.

    ERIC Educational Resources Information Center

    Ellis, Bernard H., Jr., Ed.; And Others

    The youth smoking problem is discussed and assistance is provided for teachers in developing smoking prevention and cessation programs. Four chapters serve as guides to understanding and working with the youth smoking problem. "Teenage Smoking in America" reviews trends in teenage smoking behavior and the factors that influence the initiation of…

  2. Increased Urge to Gamble Following Near-Miss Outcomes May Drive Purchasing Behaviour in Scratch Card Gambling.

    PubMed

    Stange, Madison; Graydon, Candice; Dixon, Mike J

    2016-12-24

    Previous research into scratch card gambling has highlighted the effects of these games on players' arousal and affective states. Specifically, near-miss outcomes in scratch cards (uncovering 2 of 3 needed jackpot symbols) have been associated with high levels of physiological and subjective arousal and negative emotional evaluations, including increased frustration. We sought to extend this research by examining whether near-misses prompted increases in gambling urge, and the subsequent purchasing of additional scratch cards. Participants played two scratch cards with varying outcomes with half of the sample experiencing a near-miss for the jackpot prize, and the other half experiencing a regular loss. Players rated their urge to continue gambling after each game outcome, and following the initial playing phase, were then able to use their winnings to purchase additional cards. Our results indicated that near-misses increased the urge to gamble significantly more than regular losses, and urge to gamble in the near-miss group was significantly correlated with purchasing at least one additional card. Although some players in the loss group purchased another card, there was no correlation between urge to gamble and purchasing in this group. Additionally, participants in the near-miss group who purchased additional cards reported higher levels of urge than those who did not purchase more cards. This was not true for the loss group: participants who experienced solely losing outcomes reported similar levels of urge regardless of whether or not they purchased more scratch cards. Despite near-misses' objective status as monetary losses, the increased urge that follows near-miss outcomes may translate into further scratch card gambling for a subset of individuals .

  3. Interactive effects of contextual cues and acute alcohol intoxication on the associations between alcohol expectancy activation and urge to drink.

    PubMed

    Wardell, Jeffrey D; Read, Jennifer P

    2014-10-01

    This study examined the joint effects of contextual cues and alcohol intoxication on the associations between activation of positive and negative alcohol expectancies in memory and self-reported urges to drink alcohol after a laboratory alcohol administration. Young adult heavy drinkers were randomly assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation), and then listened to positive or negative drinking scenarios (cue manipulation). Before and after these manipulations, participants completed an alcohol expectancy Stroop task assessing positive and negative expectancy activation, as well as self-report measures of urges to drink. Regression analyses revealed that the alcohol and cue manipulations had a joint, moderating impact on the associations between expectancy activation and postcue changes in urge to drink. Specifically, both increased activation of negative expectancies and decreased activation of positive expectancies predicted decreases in urges to drink, but only for intoxicated participants in the negative cue condition. There were no associations between expectancy activation and urges to drink for those in the positive cue condition regardless of beverage condition. Results suggest that whether memory activation of alcohol expectancies has an impact on urge to drink after alcohol is on board may depend on the relevance of the activated expectancies to the current drinking context. This process appears to be influenced by a complex interaction between contextual cues in the environment and the pharmacological effects of alcohol.

  4. Investigating the effects of tic suppression on premonitory urge ratings in children and adolescents with Tourette's syndrome.

    PubMed

    Himle, Michael B; Woods, Douglas W; Conelea, Christine A; Bauer, Christopher C; Rice, Kevin A

    2007-12-01

    Tics represent a complex class of behaviors that have a neurobiological origin and are influenced by factors both internal and external to the individual. One factor that has gained recent attention is the premonitory urge. Contemporary behavioral models suggest that some tics are preceded by aversive somatic urges that increase in severity when tics are suppressed and are attenuated by performance of the tic. It has been proposed that the removal of premonitory urges may strengthen or maintain tics via negative reinforcement. This investigation is the first to empirically evaluate the effect of tic suppression on the premonitory urge phenomenon. Five children and adolescents, ages 8-17years, participated in the study. Using an ABAB reversal design, tic frequency and subjective premonitory urge ratings were recorded under conditions of free-to-tic baseline (BL) and reinforced tic suppression (differential reinforcement of zero-rate behavior). Results show that four of the five children demonstrated reliable suppression. Of the four children who achieved suppression, three demonstrated a pattern in which subjective urge ratings were higher during suppression than during BL. Results provide preliminary support for the negative reinforcement view of tic function for some children.

  5. Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on acute alcohol-induced liver injury in mice

    PubMed Central

    2013-01-01

    The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-α in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the function of its health care. PMID:24090365

  6. A failure to replicate alcohol-induced laboratory aggression among college men without evidence of personality disturbance.

    PubMed

    Bailly, Matthew D; King, Alan R

    2004-06-01

    The effect of acute alcohol intoxication on laboratory-induced aggression among men has been fairly well established. The present study hypothesized that alcohol effects on Point Subtraction Aggression Paradigm (PSAP) responding would not be replicated among "low-risk' college men distinguished by their absence of personality disorder features. Participants were assigned to either Alcohol (n=18), Placebo (n=7), or Time (n=8) comparison groups with each completing 25-min. sessions during the baseline, ascent, peak (70 mg%), and descent (40 mg%) phases of absorption and elimination process. Participants assigned to the Alcohol condition received a .80 ml/kg dose of 95% ethanol mixed with soda in a 1:5 ethanol/soda ratio. As hypothesized, alcohol was associated with stable Point Subtraction Aggression Paradigm responding across the course of absorption, peak, and elimination for all three groups. Aggression Paradigm responding was least variable among the men administered alcohol. The present procedure served to identify a subset of "low-risk" college men whose Point Subtraction Aggression Paradigm responding was not adversely affected by alcohol. The extent to which aggressive personality dispositions contribute to alcohol-induced laboratory aggression remains to be identified. Low-risk college drinkers warrant systematic examination to specify what factors attenuate their reactions to alcohol and other situational provocations.

  7. Using PG-Liposome-Based System to Enhance Puerarin Liver-Targeted Therapy for Alcohol-Induced Liver Disease.

    PubMed

    Zhao, Ying-Zheng; Zhang, Lu; Gupta, Pardeep K; Tian, Fu-Rong; Mao, Kai-Li; Qiu, Kai-Yan; Yang, Wei; Lv, Chuan-Zhu; Lu, Cui-Tao

    2016-12-01

    A critical issue for alcohol-induced liver disease (ALD) therapeutics is the lack of a highly efficient delivery system. In this study, a Puerarin-propylene glycol-liposome system was prepared for the purpose of targeting puerarin, an isoflavon, to the liver. Transmission electron microscope (TEM) results showed the liposomes to be spherical in shape with an average diameter of 182 nm with a polydispersity index of 0.239. The zeta potential of the particles was about -30 mV. The entrapment efficiency of puerarin was above 90%. MTT-based assay in HpeG2 cells showed no significant cytotoxicity in the presence of up to 25% concentration of the system containing 3% puerarin. In vivo performance of this system was studied in mice. Pharmacokinetics and distribution of puerarin-PG-liposome system was studied relative to puerarin solution at the same dose levels. The results show that puerarin-PG-liposome prolonged drug retention time and decreased elimination of puerarin in mice (AUC of liposome system and solution was 9.5 and 4.0 mg h L(-1), respectively). Furthermore, propylene glycol (PG)-liposome system enhanced puerarin distribution into liver and spleen, while decreasing puerarin distribution in other tissues. Overall, the puerarin-PG-liposome system showed enhanced therapeutic effect in mice with ALD.

  8. Gentiana manshurica Kitagawa reverses acute alcohol-induced liver steatosis through blocking sterol regulatory element-binding protein-1 maturation.

    PubMed

    Lian, Li-Hua; Wu, Yan-Ling; Song, Shun-Zong; Wan, Ying; Xie, Wen-Xue; Li, Xin; Bai, Ting; Ouyang, Bing-Qing; Nan, Ji-Xing

    2010-12-22

    This study was undertaken to investigate the protective effects of Gentiana manshurica Kitagawa (GM) on acute alcohol-induced fatty liver. Mice were treated with ethanol (5 g/kg of body weight) by gavage every 12 h for a total of three doses to induce acute fatty liver. Methanol extract of GM (50, 100, or 200 mg/kg) or silymarin (100 mg/kg) was gavaged simultaneously with ethanol for three doses. GM administration significantly reduced the increases in serum ALT and AST levels, the serum and hepatic triglyceride levels, at 4 h after the last ethanol administration. GM was also found to prevent ethanol-induced hepatic steatosis and necrosis, as indicated by liver histopathological studies. Additionally, GM suppressed the elevation of malondialdehyde (MDA) levels, restored the glutathione (GSH) levels, and enhanced the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities. The concurrent administration of GM efficaciously abrogated cytochrome P450 2E1 (CYP2E1) induction. Moreover, GM significantly reduced the nuclear translocation of sterol regulatory element-binding protein-1 (nSREBP-1) in ethanol-treated mice. These data indicated that GM possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through blocking CYP2E1-mediated free radical scavenging effects and SREBP-1-regulated fatty acid synthesis. Especially, GM may be developed as a potential therapeutic candidate for ethanol-induced oxidative damage in liver.

  9. Alcohol-induced performance impairment: a 5-year re-examination study in heavy and light drinkers.

    PubMed

    Brumback, Ty; Cao, Dingcai; McNamara, Patrick; King, Andrea

    2017-06-01

    The theory of behavioral tolerance to alcohol posits that greater experience with drinking to intoxication leads to less impaired cognitive and psychomotor performance. However, the degree to which behavioral tolerance develops or changes over time in adults due to repeated heavy alcohol drinking has not been clearly demonstrated. We examined data from the first 6 years of the Chicago Social Drinking Project to test whether chronic heavy drinkers (HDs; n = 86) and light drinkers (LDs; n = 69) exhibit behavioral tolerance or changes in perceived impairment at two testing phases in early adulthood. Tasks were the Grooved Pegboard and Digit Symbol Substitution Test (DSST) given at initial testing and then repeated in a re-examination phase 5 years later. Alcohol (0.8 g/kg) and placebo were administered at separate sessions in each phase for a total of 620 individual laboratory sessions. HDs exhibited less impairment over time on the Pegboard task but not on the DSST, while LDs did not exhibit behavioral tolerance on either task. HDs reported persistently lower perceived impairment compared to LDs. These findings demonstrate that behavioral tolerance in HDs is evident over time on rote fine motor skills (Pegboard) but not more complex skills integrating motor speed, encoding, and short-term memory (DSST). The results have implications for our understanding of alcohol-induced impairments across neurobehavioral processes in heavy drinkers and their ongoing risks for alcohol-related consequences over time.

  10. The protective effect of Agaricus blazei Murrill, submerged culture using the optimized medium composition, on alcohol-induced liver injury.

    PubMed

    Wang, Hang; Li, Gang; Zhang, Wenyu; Han, Chunchao; Xu, Xin; Li, Yong-Ping

    2014-01-01

    Agaricus blazei Murrill (ABM), an edible mushroom native to Brazil, is widely used for nonprescript and medicinal purposes. Alcohol liver disease (ALD) is considered as a leading cause for a liver injury in modern dietary life, which can be developed by a prolonged or large intake of alcohol. In this study, the medium composition of ABM was optimized using response surface methodology for maximum mycelial biomass and extracellular polysaccharide (EPS) production. The model predicts to gain a maximal mycelial biomass and extracellular polysaccharide at 1.047 g/100 mL, and 0.367 g/100 mL, respectively, when the potato is 29.88 g/100 mL, the glucose is 1.01 g/100 mL, and the bran is 1.02 g/100 mL. The verified experiments showed that the model was significantly consistent with the model prediction and that the trends of mycelial biomass and extracellular polysaccharide were predicted by artificial neural network. After that, the optimized medium was used for the submerged culture of ABM. Then, alcohol-induced liver injury in mice model was used to examine the protective effect of ABM cultured using the optimized medium on the liver. And the hepatic histopathological observations showed that ABM had a relatively significant role in mice model, which had alcoholic liver damage.

  11. The Protective Effect of Agaricus blazei Murrill, Submerged Culture Using the Optimized Medium Composition, on Alcohol-Induced Liver Injury

    PubMed Central

    Wang, Hang; Li, Gang; Zhang, Wenyu; Han, Chunchao; Xu, Xin; Li, Yong-Ping

    2014-01-01

    Agaricus blazei Murrill (ABM), an edible mushroom native to Brazil, is widely used for nonprescript and medicinal purposes. Alcohol liver disease (ALD) is considered as a leading cause for a liver injury in modern dietary life, which can be developed by a prolonged or large intake of alcohol. In this study, the medium composition of ABM was optimized using response surface methodology for maximum mycelial biomass and extracellular polysaccharide (EPS) production. The model predicts to gain a maximal mycelial biomass and extracellular polysaccharide at 1.047 g/100 mL, and 0.367 g/100 mL, respectively, when the potato is 29.88 g/100 mL, the glucose is 1.01 g/100 mL, and the bran is 1.02 g/100 mL. The verified experiments showed that the model was significantly consistent with the model prediction and that the trends of mycelial biomass and extracellular polysaccharide were predicted by artificial neural network. After that, the optimized medium was used for the submerged culture of ABM. Then, alcohol-induced liver injury in mice model was used to examine the protective effect of ABM cultured using the optimized medium on the liver. And the hepatic histopathological observations showed that ABM had a relatively significant role in mice model, which had alcoholic liver damage. PMID:25114908

  12. Effects of alcohol-induced human peripheral blood mononuclear cell (PBMC) pretreated whey protein concentrate (WPC) on oxidative damage.

    PubMed

    Tseng, Yang-Ming; Chen, Sheng-Yi; Chen, Chien-Hung; Jin, Yi-Ru; Tsai, Shih-Meng; Chen, Ing-Jun; Lee, Jang-Hwa; Chiu, Chzng-Cheng; Tsai, Li-Yu

    2008-09-10

    Excessive alcohol consumption can induce apoptosis in a variety of tissues and influence the antioxidant status in peripheral blood mononuclear cells (PBMC). This paper investigates the effects of whey protein concentrate (WPC) pretreated in PBMC on the apoptosis and antioxidant status after the treatment of alcohol. The results show that the percentages of apoptotic cells in the alcohol-treated group were higher than those in the group without alcohol treatment. Additionally, there was higher glutathione (GSH) peroxidase (GPx) activity when the PBMC were treated with 300 mg/dL of alcohol. With regard to the activity of GSH reductase (GRx), there was higher activity in the group pretreated with WPC than in the group with the treatment of alcohol only. On the contrary, the levels of GSH were reduced after the treatment of alcohol, but there was a higher level of GSH in the group pretreated with WPC. In this study, it was found that the increased level of GSH in PBMC might not be attributed to the effect of GRx because there was still a higher level of GSH in the group with the treatment of WPC and BCNU (a GRx inhibitor) in this study. The results indicated that PBMC pretreated with WPC might ameliorate alcohol-induced effects such as imbalance of the antioxidant status.

  13. Severity of Alcohol-Induced Painful Peripheral Neuropathy in Female Rats: Role of Estrogen and Protein Kinase (A and Cε)

    PubMed Central

    Dina, Olayinka A.; Gear, Robert W.; Messing, Robert O.; Levine, Jon D.

    2007-01-01

    Small-fiber painful peripheral neuropathy, a complication of chronic ethanol ingestion, is more severe in women. In the present study, we have replicated this clinical finding in the rat and evaluated for a role of estrogen and second messenger signaling pathways. The alcohol diet (6.5% ethanol v:v in Lieber-DeCarli formula) induced hyperalgesia with more rapid onset and severity in females. Following ovariectomy, alcohol failed to induce hyperalgesia in female rats, well past its time to onset in gonad intact males and females. Estrogen replacement reinstated alcohol neuropathy in the female rat. The protein kinase A (PKA) inhibitor (WIPTIDE) only attenuated alcohol-induced hyperalgesia in female rats. Inhibitors of protein kinase Cε (PKCε-I) and ERK1/2 (PD98059 and U0126) attenuated hyperalgesia in males and females, however the degree of attenuation produced by PKCε-I was much greater in females. In conclusion, estrogen plays an important role in the expression of pain associated with alcohol neuropathy in the female rat. In contrast to inflammatory hyperalgesia, in which only the contribution of PKCε signaling is sexually dimorphic, in alcohol neuropathy PKA as well as PKCε signaling is highly sexually dimorphic. PMID:17204374

  14. Laboratory models available to study alcohol-induced organ damage and immune variations; choosing the appropriate model

    PubMed Central

    D’Souza El-Guindy, Nympha B.; Kovacs, Elizabeth J.; De Witte, Philippe; Spies, Claudia; Littleton, John M.; de Villiers, Willem J. S.; Lott, Amanda J.; Plackett, Timothy P.; Lanzke, Nadine; Meadows, Gary G.

    2010-01-01

    The morbidity and mortality resulting from alcohol-related diseases impose a substantive cost to society globally. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, researchers in the alcohol field are focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most is performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium “Methods of Ethanol Application in Alcohol Model – How Long is Long Enough” at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans. PMID:20586763

  15. Melatonin and vitamin C ameliorate alcohol-induced oxidative stress and eNOS expression in rat kidney.

    PubMed

    Sönmez, Mehmet Fatih; Narin, Figen; Akkuş, Derya; Türkmen, Ayşegül Burçin

    2012-01-01

    The aim of this study was to investigate the preventive effects of melatonin and vitamin C as antioxidants on renal injury in chronic alcohol consumption. A total of 24 adult male Wistar rats weighing 200-250 g were used in the study. Rats were divided into four equal groups. Group I (control): rats were not fed on alcohol; Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40 mg/kg vitamin C; and Group IV: rats were fed on alcohol and 4 mg/kg melatonin. Light microscopic examination revealed atrophic renal corpuscles, dilatation and congestion of the peritubular vessels, and renal corpuscles with obscure Bowman's space and a few foamy-appearing tubules due to alcohol consumption were observed. Expression of endothelial nitric oxide synthase (eNOS) was localized to glomerulus, distal, and collector tubules. eNOS staining decreased in alcohol treatment group and melatonin and vitamin C encore increased expression pattern of eNOS. Alcohol consumption increased malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities significantly in the alcohol consumption groups compared with that in the control group, while in melatonin give group just MDA level was decreased statistically significant and SOD and CAT activities were also decreased numerically compared with the alcohol consumption groups. These results indicated that chronic alcohol consumption caused renal damage by increased lipid peroxidation and melatonin and vitamin C administration produced in some degree protection against alcohol-induced damage.

  16. [Absenteeism attributable to smoking in the Mexican Social Security Institute, 2006-2009].

    PubMed

    Guerrero-López, Carlos Manuel; Reynales-Shigematsu, Luz Myriam; Jiménez-Ruiz, Jorge Alberto; Karam-Araujo, Roberto; Maldonado-Cruz, César Augusto; Camacho-Solís, Rafael

    2012-06-01

    To calculate the absenteeism costs by lung cancer, cerebrovascular disease, chronic obstructive pulmonary disease and acute myocardial infarction attributable to smoking in the Mexican Social Security Institute (IMSS) and the occupied population from 2006 to 2009. Productivity loss data from selected illnesses were obtained from IMSS records. The smoking attributable fraction was used, and extrapolation to occupied population was conducted. IMSS paid $143.9 million pesos (2009 prices) attributable to smoking between 2006 and 2009. The productivity loss was $298.2 million pesos and $437.8 million pesos in the occupied population, attributable to smoking. Tobacco smoking implies costs to the individual, families and society, which urge to strengthen policies contained in the Framework Convention on Tobacco Control by the WHO.

  17. Smoking and surgery

    MedlinePlus

    Surgery - quitting smoking; Surgery - quitting tobacco; Wound healing - smoking ... Tar, nicotine, and other chemicals from smoking can increase your risk of many health problems. These include heart and blood vessel problems, such as: Blood clots and aneurysms in ...

  18. Smoking Stinks! (For Kids)

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Smoking Stinks! KidsHealth > For Kids > Smoking Stinks! Print A ... more about cigarettes and tobacco. continue What Are Smoking and Smokeless Tobacco? Tobacco (say: tuh-BA-ko) ...

  19. Smoking and Bone Health

    MedlinePlus

    ... supported by your browser. Home Bone Basics Lifestyle Smoking and Bone Health Publication available in: PDF (85 ... late to adopt new habits for healthy bones. Smoking and Osteoporosis Cigarette smoking was first identified as ...

  20. Smoking Stinks! (For Kids)

    MedlinePlus

    ... Emergency Room? What Happens in the Operating Room? Smoking Stinks! KidsHealth > For Kids > Smoking Stinks! A A ... more about cigarettes and tobacco. continue What Are Smoking and Smokeless Tobacco? Tobacco (say: tuh-BA-ko) ...

  1. All about Quitting Smoking

    MedlinePlus

    Toolkit No. 7 All About Quitting Smoking Are you ready to quit smoking? You can find a way to do it. Once you’ ... bad for your health. But do you know all the benefits of quitting? When you quit smoking, ...

  2. Individual differences in smoking-related cue reactivity in smokers: an eye-tracking and fMRI study.

    PubMed

    Kang, O-Seok; Chang, Dong-Seon; Jahng, Geon-Ho; Kim, Song-Yi; Kim, Hackjin; Kim, Jong-Woo; Chung, Sun-Yong; Yang, Seung-In; Park, Hi-Joon; Lee, Hyejung; Chae, Younbyoung

    2012-08-07

    Measures of cue reactivity provide a means of studying and understanding addictive behavior. We wanted to examine the relationship between different cue reactivity measures, such as attentional bias and subjective craving, and functional brain responses toward smoking-related cues in smokers. We used eye-tracking measurements, a questionnaire for smoking urges-brief and functional magnetic resonance imaging to assess the responses to smoking-related and neutral visual cues from 25 male smokers after 36 h of smoking abstinence. Regression analyses were conducted to determine the correlation between cue-evoked brain responses and the attentional bias to smoking-related cues. The eye gaze dwell time percentage was longer in response to smoking-related cues than neutral cues, indicating significant differences in attentional bias towards smoking-related cues. The attentional bias to smoking-related cues correlated with subjective craving ratings (r=0.660, p<0.001). The dorsolateral prefrontal cortex, the putamen, the posterior cingulate cortex and the primary motor cortex were associated with the attentional bias to smoking-related cues, whereas the orbitofrontal cortex, the insula and the superior temporal gyrus were associated with smoking-related cue-induced craving and smoking urges. These results suggest that attentional mechanisms in combination with motivational and reward-related mechanisms play a role in smoking-related cue reactivity. We confirmed a positive correlation between different smoking-related cue reactivities, such as attentional bias and subjective craving, and functional brain responses in various individuals. Further studies in this field might contribute to a better individualized understanding of addictive behavior. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. Parental Smoking Exposure and Adolescent Smoking Trajectories

    PubMed Central

    Gilman, Stephen E.; Rende, Richard; Luta, George; Tercyak, Kenneth P.; Niaura, Raymond S.

    2014-01-01

    OBJECTIVE: In a multigenerational study of smoking risk, the objective was to investigate the intergenerational transmission of smoking by examining if exposure to parental smoking and nicotine dependence predicts prospective smoking trajectories among adolescent offspring. METHODS: Adolescents (n = 406) ages 12 to 17 and a parent completed baseline interviews (2001–2004), and adolescents completed up to 2 follow-up interviews 1 and 5 years later. Baseline interviews gathered detailed information on parental smoking history, including timing and duration, current smoking, and nicotine dependence. Adolescent smoking and nicotine dependence were assessed at each time point. Latent Class Growth Analysis identified prospective smoking trajectory classes from adolescence into young adulthood. Logistic regression was used to examine relationships between parental smoking and adolescent smoking trajectories. RESULTS: Four adolescent smoking trajectory classes were identified: early regular smokers (6%), early experimenters (23%), late experimenters (41%), and nonsmokers (30%). Adolescents with parents who were nicotine-dependent smokers at baseline were more likely to be early regular smokers (odds ratio 1.18, 95% confidence interval 1.05–1.33) and early experimenters (odds ratio 1.04, 95% confidence interval 1.04–1.25) with each additional year of previous exposure to parental smoking. Parents’ current non-nicotine–dependent and former smoking were not associated with adolescent smoking trajectories. CONCLUSIONS: Exposure to parental nicotine dependence is a critical factor influencing intergenerational transmission of smoking. Adolescents with nicotine-dependent parents are susceptible to more intense smoking patterns and this risk increases with longer duration of exposure. Research is needed to optimize interventions to help nicotine-dependent parents quit smoking early in their children’s lifetime to reduce these risks. PMID:24819567

  4. Parental smoking exposure and adolescent smoking trajectories.

    PubMed

    Mays, Darren; Gilman, Stephen E; Rende, Richard; Luta, George; Tercyak, Kenneth P; Niaura, Raymond S

    2014-06-01

    In a multigenerational study of smoking risk, the objective was to investigate the intergenerational transmission of smoking by examining if exposure to parental smoking and nicotine dependence predicts prospective smoking trajectories among adolescent offspring. Adolescents (n = 406) ages 12 to 17 and a parent completed baseline interviews (2001-2004), and adolescents completed up to 2 follow-up interviews 1 and 5 years later. Baseline interviews gathered detailed information on parental smoking history, including timing and duration, current smoking, and nicotine dependence. Adolescent smoking and nicotine dependence were assessed at each time point. Latent Class Growth Analysis identified prospective smoking trajectory classes from adolescence into young adulthood. Logistic regression was used to examine relationships between parental smoking and adolescent smoking trajectories. Four adolescent smoking trajectory classes were identified: early regular smokers (6%), early experimenters (23%), late experimenters (41%), and nonsmokers (30%). Adolescents with parents who were nicotine-dependent smokers at baseline were more likely to be early regular smokers (odds ratio 1.18, 95% confidence interval 1.05-1.33) and early experimenters (odds ratio 1.04, 95% confidence interval 1.04-1.25) with each additional year of previous exposure to parental smoking. Parents' current non-nicotine-dependent and former smoking were not associated with adolescent smoking trajectories. Exposure to parental nicotine dependence is a critical factor influencing intergenerational transmission of smoking. Adolescents with nicotine-dependent parents are susceptible to more intense smoking patterns and this risk increases with longer duration of exposure. Research is needed to optimize interventions to help nicotine-dependent parents quit smoking early in their children's lifetime to reduce these risks. Copyright © 2014 by the American Academy of Pediatrics.

  5. Behavior Therapy to Enable Drug Discontinuation in the Treatment of Urge Incontinence: A Randomized Controlled Trial

    PubMed Central

    Burgio, Kathryn L.; Kraus, Stephen R.; Menefee, Shawn; Borello-France, Diane; Corton, Marlene; Johnson, Harry W.; Mallett, Veronica; Norton, Peggy; FitzGerald, Mary P.; Dandreo, Kimberly J.; Richter, Holly E.; Rozanski, Thomas; Albo, Michael; Zyczynski, Halina M.; Lemack, Gary E.; Chai, Toby C.; Khandwala, Salil; Baker, Jan; Brubaker, Linda; Stoddard, Anne M.; Goode, Patricia S.; Nielsen-Omeis, Betsy; Nager, Charles W.; Kenton, Kimberly; Tennstedt, Sharon L.; Kusek, John W.; Chang, T. Debuene; Nyberg, Leroy M.; Steers, William

    2010-01-01

    Background Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy. Objective To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared to drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to and sustain these improvements after discontinuing medication. Design Two-stage, multi-center, randomized clinical trial (BE-DRI trial) (July 2004 – January 2006). Setting Nine university-affiliated outpatient clinics. Patients 307 women with urge predominant incontinence. Interventions Ten weeks of open-label, extended-release tolterodine alone (N = 153) or combined with behavioral training (N = 154) (Stage 1), followed by discontinuation of therapy and follow-up at 8 months (Stage 2); 237 participants completed the trial. Measurements The primary outcome, measured at 8 months, was defined as not taking drug or receiving any other therapy for urge incontinence and ≥70% reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress/bother and health-related quality-of-life. Study staff who performed outcome evaluations were blinded to group assignment, but participants and interventionists were not. Results At 8 months, there was no difference in successful discontinuation of drug therapy between combined therapy and drug alone (41% in both groups, 95% confidence interval on difference: -12% to +12%). A higher proportion of patients in combined therapy achieved ≥70% reduction of incontinence than in drug therapy alone at 10 weeks (69% vs. 58%; difference = 11%; 95% confidence interval: -0.3 to +22.1). Combined therapy yielded better outcomes over time on the Urogenital Distress Inventory and Overactive Bladder Questionnaire

  6. The effect of energy drinks on the urge to drink alcohol in young adults.

    PubMed

    McKetin, Rebecca; Coen, Alice

    2014-08-01

    Recently, Marczinski and colleagues (2013) showed that energy drinks combined with alcohol augment a person's desire to drink more alcohol relative to drinking alcohol alone. The current study replicates the findings of Marczinski and colleagues (2013) using a robust measure of alcohol craving. Seventy-five participants aged 18 to 30 years were assigned to an alcohol only or alcohol+energy drink condition in a double-blind randomized pre- versus posttest experiment. Participants received a cocktail containing either 60 ml of vodka and a Red Bull(®) Silver Edition energy drink (alcohol+energy drink condition) or 60 ml of vodka with a soda water vehicle (alcohol-only condition); both cocktails contained 200 ml of fruit drink. The primary outcome measure was the Alcohol Urge Questionnaire taken at pretest and at 20 minutes (posttest). Other measures taken at posttest were the Biphasic Alcohol Effects Questionnaire, the Drug Effects Questionnaire, and breath alcohol concentration (BAC). The alcohol+energy drink condition showed a greater pre- versus posttest increase in urge to drink alcohol compared with the alcohol-only condition (B = 3.24, p = 0.021, d = 0.44). Participants in the alcohol+energy drink condition had significantly higher ratings on liking the cocktail and wanting to drink more of the cocktail, and lower BACs, than the alcohol-only condition. When examined at specific BACs, the effect of the energy drink on the pre- to posttest increase in urge to drink was largest and only significant at BACs of 0.04-0.05 (cf. < 0.04 g/dl).There were no significant differences in stimulation, sedation, feeling the effects of the cocktail, or feeling high. Combining energy drinks with alcohol increased the urge to drink alcohol relative to drinking alcohol alone. More research is needed to understand what factors mediate this effect and whether it increases subsequent alcohol consumption. Copyright © 2014 by the Research Society on Alcoholism.

  7. Minimum important difference for validated instruments in women with urge incontinence

    PubMed Central

    Xu, Yan; Brubaker, Linda; Nygaard, Ingrid; Markland, Alayne; Rahn, David; Chai, Toby C.; Stoddard, Ann; Lukacz, Emily

    2017-01-01

    Aims Minimum important difference (MID) estimates the minimum degree of change in an instrument’s score that correlates with subjective sense of improvement. The aim of this study was to estimate the MID for the Urogenital Distress Inventory(UDI), Incontinence Impact Questionnaire(IIQ) and Overactive Bladder Questionnaire(OAB-q) using anchor and distribution-based approaches in patients with urge-predominant incontinence and whether MID changes over time. Methods This was a sub-analysis of a multi-center trial of 307 women with pure urge (11) or urge-predominant (296) incontinence who completed condition-specific instruments 10 weeks and 8 months after randomization to anticholinergic medication with or without behavioral therapy. We applied anchor-based methods only when the Kendall’s rank correlations between the anchors (Global Perception of Improvement(GPI), Patient Satisfaction Questionnaire(PSQ) and incontinence episodes(IE)) and the incontinence instruments (UDI, UDI irritative subscale, IIQ and OAB-q subscales) were ≥0.3. We applied 3 distribution-based methods to all instruments: effect sizes of ±0.2 SD (small) and ±0.5 SD (medium) and standard error of measurement (SEM) of ±1. Analyses were performed at both time points. Results Anchor-based MIDs for the UDI ranged from -35 to -45 and -15 to -25 for the irritative subscale Distribution-based methods MIDs for UDI and IIQ ranged between -10 to -25 and -19 to -49 respectively, reflective of a reduction in bother and symptom severity. OAB-q subscale MIDs ranged from +5 to +12, denoting improved quality of life (HRQL) and -13 to -25, consistent with a reduction in symptom severity (SS). Conclusions The MID in women with urge-predominant UI for the UDI and UDI irritative are -35 and -15. Our findings are consistent with previously reported MIDs for the OAB-q subscales. Distribution-based method MIDs are lower values than anchor-based values. The MID did not typically change over the time. PMID:21563210

  8. Minimum important difference for validated instruments in women with urge incontinence.

    PubMed

    Dyer, Keisha Y; Xu, Yan; Brubaker, Linda; Nygaard, Ingrid; Markland, Alayne; Rahn, David; Chai, Toby C; Stoddard, Ann; Lukacz, Emily

    2011-09-01

    Minimum important difference (MID) estimates the minimum degree of change in an instrument's score that correlates with subjective sense of improvement. The aim of this study was to estimate the MID for the Urogenital Distress Inventory (UDI), Incontinence Impact Questionnaire (IIQ) and Overactive Bladder Questionnaire (OAB-q) using anchor and distribution-based approaches in patients with urge-predominant incontinence and whether MID changes over time. This was a sub-analysis of a multi-center trial of 307 women with pure urge (11) or urge-predominant (296) incontinence who completed condition-specific instruments 10 weeks and 8 months after randomization to anticholinergic medication with or without behavioral therapy. We applied anchor-based methods only when the Kendall's rank correlations between the anchors (Global Perception of Improvement (GPI), Patient Satisfaction Questionnaire (PSQ), and incontinence episodes) and the incontinence instruments (UDI, UDI irritative subscale, IIQ, and OAB-q subscales) were ≥ 0.3. We applied three distribution-based methods to all instruments: effect sizes of ± 0.2 SD (small) and ± 0.5 SD (medium), and standard error of measurement of ± 1. Analyses were performed at both time points. Anchor-based MIDs for the UDI ranged from -35 to -45 and -15 to -25 for the irritative subscale distribution-based methods MIDs for UDI and IIQ ranged between -10 to -25 and -19 to -49, respectively, reflective of a reduction in bother and symptom severity (SS). OAB-q subscale MIDs ranged from +5 to +12, denoting improved quality of life (HRQL) and -13 to -25, consistent with a reduction in SS. The MID in women with urge-predominant UI for the UDI and UDI irritative are -35 and -15. Our findings are consistent with previously reported MIDs for the OAB-q subscales. Distribution-based method MIDs are lower values than anchor-based values. The MID did not typically change over the time. Copyright © 2011 Wiley-Liss, Inc.

  9. Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

    PubMed

    Wang, Junming; Zhang, Yueyue; Liu, Ruixin; Li, Xiaobing; Cui, Ying; Qu, Lingbo

    2015-04-01

    Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver.

  10. Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

    PubMed

    Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

    2017-12-01

    Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.

  11. An attentional control task reduces intrusive thoughts about smoking.

    PubMed

    May, Jon; Andrade, Jackie; Willoughby, Kimberley; Brown, Chris

    2012-04-01

    Attentional control tasks such as body scanning and following isometric exercise instructions have been shown to reduce smoking cravings, apparently by reducing stress (Ussher, M., Cropley, M., Playle, S., Mohidin, R., & West, R. [2009]. Effect of isometric exercise and body scanning on cigarette cravings and withdrawal symptoms. Addiction, 104, 1251-1257. doi:10.1111/j.1360-0443.2009.02605.x). Related work based upon elaborated intrusion theory (Kavanagh, D. J., Andrade, J., & May, J. [2005]. Imaginary relish and exquisite torture: The elaborated intrusion theory of desire. Psychological Review, 112, 446-467. doi:10.1037/0033-295X.112.2.446) has shown that similar tasks can reduce hungry participants' involuntary food-related thoughts (May, J., Andrade, J., Batey, H., Berry, L.-M., & Kavanagh, D. [2010]. Less food for thought: Impact of attentional instructions on intrusive thoughts about snack foods. Appetite, 55, 279-287. doi:10.1016/j.appet.2010.06.014). This study tests the effect of body scanning instructions upon smoking-related thoughts as well as craving. Twenty-seven smokers took part in 2 counterbalanced sessions, on different days, having been asked to abstain from smoking for 2 hr. In each session, they followed audio instructions for three 10-min blocks during which their thoughts were probed 10 times. In the first and third blocks, they were instructed to let their mind wander; during the second block of the control session, they also let their mind wander, but in the experimental session, they followed body scanning instructions. "Smoking thought frequency" was assessed using thought probes; "Craving" was measured using Factor 1 of the Questionnaire on Smoking Urges (Tiffany, S. T., & Drobes, D. J. [1991]. The development and initial validation of a questionnaire on smoking urges. British Journal of Addiction, 86, 1467-1476. doi:10.1111/j.1360-0443.1991.tb01732.x). Participants reported fewer smoking-related thoughts and lower smoking cravings in

  12. Anxiety Sensitivity and Pre-Cessation Smoking Processes: Testing the Independent and Combined Mediating Effects of Negative Affect–Reduction Expectancies and Motives

    PubMed Central

    Farris, Samantha G.; Leventhal, Adam M.; Schmidt, Norman B.; Zvolensky, Michael J.

    2015-01-01

    Objective: Anxiety sensitivity appears to be relevant in understanding the nature of emotional symptoms and disorders associated with smoking. Negative-reinforcement smoking expectancies and motives are implicated as core regulatory processes that may explain, in part, the anxiety sensitivity–smoking interrelations; however, these pathways have received little empirical attention. Method: Participants (N = 471) were adult treatment-seeking daily smokers assessed for a smoking-cessation trial who provided baseline data; 157 participants provided within-treatment (pre-cessation) data. Anxiety sensitivity was examined as a cross-sectional predictor of several baseline smoking processes (nicotine dependence, perceived barriers to cessation, severity of prior withdrawal-related quit problems) and pre-cessation processes including nicotine withdrawal and smoking urges (assessed during 3 weeks before the quit day). Baseline negative-reinforcement smoking expectancies and motives were tested as simultaneous mediators via parallel multiple mediator models. Results: Higher levels of anxiety sensitivity were related to higher levels of nicotine dependence, greater perceived barriers to smoking cessation, more severe withdrawal-related problems during prior quit attempts, and greater average withdrawal before the quit day; effects were indirectly explained by the combination of both mediators. Higher levels of anxiety sensitivity were not directly related to pre-cessation smoking urges but were indirectly related through the independent and combined effects of the mediators. Conclusions: These empirical findings bolster theoretical models of anxiety sensitivity and smoking and identify targets for nicotine dependence etiology research and cessation interventions. PMID:25785807

  13. Anxiety sensitivity and pre-cessation smoking processes: testing the independent and combined mediating effects of negative affect-reduction expectancies and motives.

    PubMed

    Farris, Samantha G; Leventhal, Adam M; Schmidt, Norman B; Zvolensky, Michael J

    2015-03-01

    Anxiety sensitivity appears to be relevant in understanding the nature of emotional symptoms and disorders associated with smoking. Negative-reinforcement smoking expectancies and motives are implicated as core regulatory processes that may explain, in part, the anxiety sensitivity-smoking interrelations; however, these pathways have received little empirical attention. Participants (N = 471) were adult treatment-seeking daily smokers assessed for a smoking-cessation trial who provided baseline data; 157 participants provided within-treatment (pre-cessation) data. Anxiety sensitivity was examined as a cross-sectional predictor of several baseline smoking processes (nicotine dependence, perceived barriers to cessation, severity of prior withdrawal-related quit problems) and pre-cessation processes including nicotine withdrawal and smoking urges (assessed during 3 weeks before the quit day). Baseline negative-reinforcement smoking expectancies and motives were tested as simultaneous mediators via parallel multiple mediator models. Higher levels of anxiety sensitivity were related to higher levels of nicotine dependence, greater perceived barriers to smoking cessation, more severe withdrawal-related problems during prior quit attempts, and greater average withdrawal before the quit day; effects were indirectly explained by the combination of both mediators. Higher levels of anxiety sensitivity were not directly related to pre-cessation smoking urges but were indirectly related through the independent and combined effects of the mediators. These empirical findings bolster theoretical models of anxiety sensitivity and smoking and identify targets for nicotine dependence etiology research and cessation interventions.

  14. Preliminary characterization, antioxidant activity in vitro and hepatoprotective effect on acute alcohol-induced liver injury in mice of polysaccharides from the peduncles of Hovenia dulcis.

    PubMed

    Wang, Mingchun; Zhu, Peilei; Jiang, Changxing; Ma, Liping; Zhang, Zhanjun; Zeng, Xiaoxiong

    2012-09-01

    The fresh fleshy peduncles of Hovenia dulcis have been used as a food supplement and traditional herbal medicine for the treatment of liver diseases and alcoholic poisoning for more than a millennium. The objectives of the present study, therefore, were to determine the antioxidant activity of polysaccharides from the peduncles of H. dulcis (HDPS) and to evaluate its hepatoprotective effect on acute alcohol-induced liver injury in mice. HDPS, prepared by hot water extraction, ethanol precipitation and treatment of macroporous resin, was found to be non-starch polysaccharide and mainly composed of galactose, arabinose, rhamnose and galacturonic acid. In in vitro antioxidant assay, HDPS exhibited high superoxide radical scavenging activity, strong inhibition effect on lipid peroxidation and a medium ferrous ion-chelating activity. For hepatoprotective activity in vivo, the administration of HDPS significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, significantly decreased the liver level of malondialdehyde and remarkably restored the liver activities of superoxide dismutase and glutathione peroxidase in alcohol-induced liver injury mice. The results suggested that HDPS had a significant protective effect against acute alcohol-induced liver injury possibly via its antioxidant activity to protect biological systems against the oxidative stress.

  15. Antioxidative and Anti-Inflammatory Activities of Akebia quinata Extracts in an In Vitro Model of Acute Alcohol-Induced Hepatotoxicity.

    PubMed

    Lee, Sang Hoon; Song, Young Sun; Jeong, Yoonhwa; Ko, Kwang Suk

    2017-09-01

    This study investigated the effects of Akebia quinata (AQ) leaf and fruit extract on acute alcohol-induced hepatotoxicity in AML12 cells. Different concentrations of AQ extracts (250 and 2500 μg/mL) were used to treat the AML12 cells with or without ethanol for 24 h for inducing acute alcohol cytotoxicity. AQ extract-treated AML12 cells showed enhanced expression of GSH-synthesizing enzymes and suppressed expression of oxidative stress makers such as NOX4, and decreased expression of tumor necrosis factor-α, inflammatory marker, in acute alcohol-induced hepatotoxicity. Furthermore, it was observed that 100 mM ethanol treatment of AML12 cells resulted in global change of mRNA expression in microarray, but AQ leaf extract treatment reversed the global change of mRNA expression pattern into normal condition. In conclusion, AQ extract or functional component from AQ can be useful therapeutic agent in acute alcohol-induced hepatotoxicity by reducing oxidative stress and inflammation responses.

  16. Modulatory effect of pineapple peel extract on lipid peroxidation, catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

    PubMed Central

    Okafor, OY; Erukainure, OL; Ajiboye, JA; Adejobi, RO; Owolabi, FO; Kosoko, SB

    2011-01-01

    Objective To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma. Methods Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations. Results Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities. Conclusions The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity. PMID:23569717

  17. Modulatory effect of pineapple peel extract on lipid peroxidation, catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats.

    PubMed

    Okafor, O Y; Erukainure, O l; Ajiboye, J A; Adejobi, R O; Owolabi, F O; Kosoko, S B

    2011-01-01

    To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma. Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations. Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities. The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.

  18. Depression and Smoking

    MedlinePlus

    ... Who Quit Community Helping Someone Quit Stress & Mood Stress & Mood Smoking & Mood Stress Depression Anger Weight Management Weight Management Smoking and Weight Healthy Weight Loss Being Comfortable in ...

  19. Smoking in movies: impact on adolescent smoking.

    PubMed

    Sargent, James D

    2005-06-01

    This article examines the evidence that supports an association between seeing smoking depictions in movies and adolescent smoking. The portrayal of tobacco use is common in movies and often is modeled by stars, who, from a social influences standpoint, should be powerful behavior change agents. The results of studies that assess audience responses to tobacco portrayal in movies are remarkably consistent in showing a moderate to strong association between seeing movie smoking and more positive attitudes toward smoking and adolescent smoking initiation. The two published longitudinal studies show an independent link between exposure to movie smoking at baseline and initiation in the future, with estimates of the effect size being remarkably consistent with their cross-sectional counterparts. Pediatricians should support public health campaigns to pressure the movie industry to voluntarily reduce smoking in movies and encourage parents to adhere to the Motion Picture Ratings System to reduce adolescent exposure to this powerful social influence to smoke.

  20. What Chinese adolescents think about quitting smoking: a qualitative study.

    PubMed

    Abdullah, Abu Saleh M; Ho, Winnie W N

    2006-01-01

    The aim of this study was to investigate the attitudes of Chinese adolescents toward smoking, giving up smoking, and smoking cessation programs presently available. The study was a qualitative study carried out in 2002 by focus groups of 32 male secondary school students in Hong Kong who were either current smokers or had recently given up smoking. Subjects were students (grades 8-10) attending two full-day secondary schools in Hong Kong. Participants did not feel the need to make any serious psychological preparation for quitting. They underestimated the addictive nature of cigarette smoking and felt that they could choose to quit smoking at any time with little difficulty. Several barriers to quitting were reported, including boredom, peer influence, the urge to smoke, school work pressure, the wish to do something with their hands, difficulty in concentrating, and the ready availability of free cigarettes from peers. Those who had attempted to quit smoking (26/32) reported that peer influence and boredom were the main reasons why they started smoking and insisted that willpower and determination could have helped them in their quitting attempt. Participants were unanimous that pressure or encouragement from teachers, parents, or girlfriends did not help them to stay off cigarettes. Most (24/32) of the current smokers knew that smoking cessation services were available in Hong Kong, only 50% (12/24) of those who knew had made use of such services. None of the participants were able to identify any effective way of quitting smoking, though some suggested that the best practical measure was to avoid friends who smoked. The study suggests that attempts to persuade young people to quit smoking might benefit if they were framed to address issues such as the strong influence of their peers, the ease with which tobacco products can be obtained, the casual attitudes of young people toward smoking cessation, the perceived pros and cons of quitting, and (given that

  1. Workplace smoking ban policy and smoking behavior.

    PubMed

    Kim, Beomsoo

    2009-09-01

    To evaluate the impact of the workplace smoking ban in South Korea, where the male smoking rate is high (57%), on smoking behavior and secondhand smoke exposure. A workplace smoking ban legislation implemented in April 2003 requires offices, meeting rooms, and lobbies located in larger than 3,000 square meter buildings (or 2,000 square meter multipurpose buildings) should be smoke free. A representative cross-sectional survey, the third wave (2005) of health supplements in the National Health Nutrition Survey of South Korea, was used to measure the impact of the 2003 workplace smoking ban implementation on smoking behavior. It contained 3,122 observations of adults 20 to 65 years old (excluding self-employed and non-working populations). A multivariate statistical model was used. The self-reported workplace smoking ban policy (full workplace ban, partial workplace ban, and no workplace ban) was used as the key measure. A full workplace smoking ban reduced the current smoking rate by 6.4 percentage points among all workers and also decreased the average daily consumption among smokers by 3.7 cigarettes relative to no smoking ban. Secondhand smoke showed a dramatic decrease of 86 percent (= -1.74/2.03)from the sample mean for full workplace ban. However, public anti-smoking campaign did not show any significant impact on smoking behavior. The full workplace ban policy is effective in South Korea. Male group showed bigger impact of smoking ban policy than female group. The public antismoking campaign did not show any effectiveness.

  2. The role of emotional nonacceptance in the relation between depression and recent cigarette smoking.

    PubMed

    Adams, Claire E; Tull, Matthew T; Gratz, Kim L

    2012-01-01

    Evidence that smokers have heightened depressive symptoms and report smoking in response to negative affect has led to an interest in mindfulness- and acceptance-based strategies to help smokers respond more adaptively to depressive symptoms. More research is needed to examine the role of emotional nonacceptance (ie, the tendency to judge or negatively evaluate one's emotions) in the relation between depression and smoking, particularly among populations with elevated smoking rates (eg, individuals with substance use disorders). This study examined the mediating role of emotional nonacceptance in the relation between depression and smoking among 125 smokers in residential substance abuse treatment. Participants (mean age = 35 ± 10; 60% male; 63% White) reported how many cigarettes they smoked in the past hour and completed self-report measures of emotion dysregulation (including nonacceptance) and depression. Major depressive disorder was assessed through clinical interview. Results supported the hypothesized relevance of emotional nonacceptance to recent smoking. Specifically, emotional nonacceptance was the only dimension of emotion dysregulation uniquely associated with recent smoking and mediated the relationship between depression and recent smoking. Results suggest that depression may interfere with emotional acceptance, increasing urges to smoke to escape negative affect. Targeting emotional nonacceptance may improve smoking cessation treatments for depressed individuals.

  3. Young People Smokers' Reactions on Peer Influence Not to Smoke.

    PubMed

    Harakeh, Zeena; van Nijnatten, Carolus H C J

    2016-11-09

    Peers exert influence not to smoke but little is yet known on how this affects young people's behavior and cognitions. This experimental study investigates the impact of two types of peer influence not to smoke on the verbalized attitudes and responses of daily-smoking young people. Two conditions were conducted: 1) a peer confederate stating three times that s/he had quit smoking and was glad to have done so (covert peer influence); 2) a peer confederate making similar statements, but urging to quit smoking (overt peer influence). The participant performed a music task with the peer in order to disguise the true nature of the experiment. Thirty-one daily-smoking young people (16-24 years) participated; 44 responses in the overt and 34 responses in the covert condition were analyzed in a discourse analysis. The participants in the covert condition were more elaborative about smoking, i.e., taking an active role in a dialogue about the experiences of the peer or the participant in quitting smoking while in the overt condition participants showed more passive resistance, i.e., not showing an intention to follow the advice but avoid causing the peer embarrassment or discomfort. Open resistance, i.e., demonstration of being well-informed and indicating the redundancy of the advice, does not significantly differ in these two conditions but occurs, for both, primarily at the third discouragement. Overt and frequent discouragement seems to be less effective in stimulating young people to take an active role in the dialogue with their peers about smoking.

  4. Smoking in Movies and Adolescent Smoking Initiation

    PubMed Central

    Morgenstern, Matthis; Sargent, James D.; Engels, Rutger C.M.E.; Scholte, Ron H.J.; Florek, Ewa; Hunt, Kate; Sweeting, Helen; Mathis, Federica; Faggiano, Fabrizio; Hanewinkel, Reiner

    2013-01-01

    Background Longitudinal studies from the U.S. suggest a causal relationship between exposure to images of smoking in movies and adolescent smoking onset. Purpose This study investigates whether adolescent smoking onset is predicted by the amount of exposure to smoking in movies across six European countries with various cultural and regulatory approaches to tobacco. Methods Longitudinal survey of 9987 adolescent never-smokers recruited in the years 2009–2010 (mean age 13.2 years) in 112 state-funded schools from Germany, Iceland, Italy, The Netherlands, Poland, and the United Kingdom (UK), and followed-up in 2011. Exposure to movie smoking was estimated from 250 top-grossing movies in each country. Multilevel mixed-effects Poisson regressions were performed in 2012 to assess the relationship between exposure at baseline and smoking status at follow-up. Results During the observation period (M=12 months), 17% of the sample initiated smoking. The estimated mean exposure to on-screen tobacco was 1560 occurrences. Overall, and after controlling for age; gender; family affluence; school performance; TVscreen time; personality characteristics; and smoking status of peers, parents, and siblings, exposure to each additional 1000 tobacco occurrences increased the adjusted relative risk for smoking onset by 13% (95% CI=8%, 17%, p<0.001). The crude relationship between movie smoking exposure and smoking initiation was significant in all countries; after covariate adjustment, the relationship remained significant in Germany, Iceland, The Netherlands, Poland, and UK. Conclusions Seeing smoking in movies is a predictor of smoking onset in various cultural contexts. The results confirm that limiting young people’s exposure to movie smoking might be an effective way to decrease adolescent smoking onset. PMID:23498098

  5. Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain*

    PubMed Central

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G.; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J.; Bergeson, Susan E.; Henderson, George I.; Kruman, Inna I.

    2012-01-01

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain. PMID:23118224

  6. Acute Alcohol-Induced Decrease in Muscle Protein Synthesis in Female Mice Is REDD-1 and mTOR-Independent.

    PubMed

    Steiner, Jennifer L; Kimball, Scot R; Lang, Charles H

    2016-05-01

    To determine the causative role of the REDD (regulated in development and DNA damage)-1 protein, a known negative regulator of mTOR kinase, in changes in muscle protein synthesis induced by acute alcohol administration. Adult female REDD1(-/-) or wild-type (WT) mice were injected IP with ethanol (alcohol; 3 g/kg BW) or saline and the skeletal muscle was removed 1 h later. In vivo protein synthesis was assessed as were selected endpoints related to the activation of mTOR and protein degradation. Acute alcohol decreased muscle protein synthesis similarly in WT and REDD1(-/-) mice. In contrast, mTORC1 signaling was largely unaffected by either EtOH or genotype as evidenced by the lack of change in the phosphorylation of its downstream targets, S6K1 T(389) and 4E-BP1 S(65). Although alcohol decreased p62 and ULK1 S(757) protein in muscle from WT and REDD1(-/-) mice, there was no change in LC3B lipidation, or beclin1, Atg7 and Atg12 protein suggesting no change in autophagy. MuRF1 and atrogin-1 mRNAs were elevated in alcohol-treated REDD1(-/-) mice compared with WT mice suggesting activation of the ubiquitin proteasome activity. While there was no genotype or alcohol effect on plasma corticosterone, REDD1(-/-) mice failed to demonstrate the alcohol-induced hyperinsulinemia seen in WT mice. REDD1 does not appear to play a role in the acute alcohol-mediated decrease in protein synthesis or mTOR activity, but may contribute to the regulation of ubiquitin-proteasome mediated protein breakdown. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  7. Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice.

    PubMed

    Zhong, Wei; Zhang, Wenliang; Li, Qiong; Xie, Guoxiang; Sun, Qian; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang

    2015-06-01

    Effective therapies for alcoholic liver disease are currently unavailable. The present study tested the efficacy of Alda-1, a specific aldehyde dehydrogenase 2 (ALDH2) activator, in treating alcoholic liver disease. Male C57BL/6J mice were exposed to alcohol for a time-course study on aldehyde metabolism. The specificity and efficacy of Alda-1 on activating hepatic ALDH2 and aldehyde clearance were determined by acute treatments. Then, mice were fed alcohol for 8 weeks with Alda-1 administration for the last 10 days to test the therapeutic potential of Alda-1. Lastly, H4IIEC3 cells were treated with ethanol, acetaldehyde, or 4-hydroxynonenal to define the link between aldehydes and hepatotoxicity. Alcohol feeding for 8 weeks induced hepatic ALDH2 dysfunction and aldehyde accumulation. One dose of Alda-1 administration elevated hepatic ALDH activity, which was blocked by the specific ALDH2 inhibitor, daidzin. Alda-1 accelerated acetaldehyde clearance after acute alcohol intoxication. Alda-1 treatment in the 8-week alcohol feeding model reversed liver damage along with reduction of hepatic aldehydes. Alda-1 re-activated transcription factors, upregulated fatty acid oxidation enzymes, and reversed steatosis. Alcohol-induced endoplasmic reticulum stress and apoptotic cell death were also attenuated by Alda-1. Acetaldehyde or 4-hydroxynonenal treatment to H4IIEC3 cells inactivated transcription factors and induced endoplasmic reticulum stress and apoptosis, while ethanol per se showed limited effects. Pharmacological activation of ALDH2 by Alda-1 reversed alcoholic steatosis and apoptosis through accelerating aldehyde clearance. This study indicates that ALDH2 is a promising molecular target and Alda-1 has therapeutic potential for treating alcoholic liver disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota.

    PubMed

    Bishehsari, Faraz; Saadalla, Abdulrahman; Khazaie, Khashayarsha; Engen, Phillip A; Voigt, Robin M; Shetuni, Brandon B; Forsyth, Christopher; Shaikh, Maliha; Vitaterna, Martha Hotz; Turek, Fred; Keshavarzian, Ali

    2016-12-02

    Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption-a frequent habit of majority of modern societies-increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption-another modern life style habit-in promoting alcohol-associated CRC. TS4Cre × adenomatous polyposis coli (APC)(lox468) mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  9. Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

    PubMed Central

    Cho, Young-Eun; Im, Eun-Ju; Moon, Pyong-Gon; Mezey, Esteban; Song, Byoung-Joon; Baek, Moon-Chang

    2017-01-01

    Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity. PMID:28225807

  10. Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

    PubMed

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

    2012-12-21

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

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

    PubMed Central

    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. PMID:26484872

  12. Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation.

    PubMed

    Lin, Xing; Zhang, Shijun; Huang, Renbin; Wei, Ling; Tan, Shimei; Liang, Shuang; Tian, Yuanchun; Wu, Xiaoyan; Lu, Zhongpeng; Huang, Quanfang

    2014-06-01

    A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen α type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-β1, TNF-α, IL-6 and IL-1β and myeloperoxidase, via down-regulation of NF-κB. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-β, platelet-derived growth factor-β and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of α-SMA and TGF-β levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima.

  13. Inactivation of hepatocyte nuclear factor-4α mediates alcohol-induced downregulation of intestinal tight junction proteins

    PubMed Central

    Zhong, Wei; Zhao, Yantao; McClain, Craig J.; Kang, Y. James

    2010-01-01

    Chronic alcohol exposure has been shown to increase the gut permeability in the distal intestine, in part, through induction of zinc deficiency. The present study evaluated the molecular mechanisms whereby zinc deficiency mediates alcohol-induced intestinal barrier dysfunction. Examination of zinc finger transcription factors in the gastrointestinal tract of mice revealed a prominent distribution of hepatocyte nuclear factor-4α (HNF-4α). HNF-4α exclusively localizes in the epithelial nuclei and exhibited an increased abundance in mRNA and protein levels in the distal intestine. Chronic alcohol exposure to mice repressed the HNF-4α gene expression in the ileum and reduced the protein level and DNA binding activity of HNF-4α in all of the intestinal segments with the most remarkable changes in the ileum. Chronic alcohol exposure also decreased the mRNA levels of tight junction proteins, particularly in the ileum. Caco-2 cell culture studies were conducted to determine the role of HNF-4α in regulation of the epithelial tight junction and barrier function. Knockdown of HNF-4α in Caco-2 cells decreased the mRNA and protein levels of tight junction proteins in association with disruption of the epithelial barrier. Alcohol treatment inactivated HNF-4α, which was prevented by N-acetyl-cysteine or zinc. The link between zinc and HNF-4α function was confirmed by zinc deprivation, which inhibited HNF-4α DNA binding activity. These results indicate that inactivation of HNF-4α due to oxidative stress and zinc deficiency is likely a novel mechanism contributing to the deleterious effects of alcohol on the tight junctions and the intestinal barrier function. PMID:20576917

  14. Effect of Emilia sonchifolia (Linn.)DC on alcohol-induced oxidative stress in pancreas of male albino rats.

    PubMed

    Sophia, Dominic; Gomathy, Murugesan; Shebin, Thomas; Ragavendran, Paramasivam; Arulraj, Chinthamony; Gopalakrishnan, Velliyur Kanniapan

    2011-12-01

    To explore the efficacy of n-hexane extract of Emilia sonchifolia (E. sonchifobia) against ethanol induced pancreatic dysfunction in the young Wistar albino rats. The rats were divided into four groups. Control rats in group received distilled water orally, group received oral administration of 20% (w/v) ethanol dissolved in drinking water, group received oral administration of 20% (w/v) ethanol in distilled water+n-hexane extract of E. sonchifolia (250 mg/kg body weight), and group received oral administration of n-hexane extract of E. sonchifolia (250 mg/kg body weight) alone. Liver marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), pancreatic enzymatic antioxidants superoxide dismutase, lipid peroxidation, catalase, glutathione peroxidase, non-enzymatic antioxidants glutathione and vitamin C were measured and compared. Administration of 20% ethanol for 16 weeks significantly increased the liver marker enzymes AST, ALT(P<0.05), reduced the pancreatic enzymatic antioxidants superoxide dismutase, lipid peroxidation, catalase, glutathione peroxidase, glutathione and vitamin C(P<0.05). Histopathological examination showed that the ethanol provoked the oxidative stress which was demonstrated as pancreatic necrosis and oedema. Simultaneous administration of n-hexane extract of E. sonchifolia (250 mg/kg body weight) protected the pancreas against the damage induced by ethanol which was confirmed by the histopathological studies and the normalization of biochemical parameters. Thus n-hexane extract of E. sonchifolia shows a promise in therapeutic use in alcohol induced oxidative stress. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  15. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

    PubMed Central

    Bishehsari, Faraz; Saadalla, Abdulrahman; Khazaie, Khashayarsha; Engen, Phillip A.; Voigt, Robin M.; Shetuni, Brandon B.; Forsyth, Christopher; Shaikh, Maliha; Vitaterna, Martha Hotz; Turek, Fred; Keshavarzian, Ali

    2016-01-01

    Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APC)lox468 mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota. PMID:27918452

  16. Alcohol-Induced miR-27a Regulates Differentiation and M2 Macrophage Polarization of Normal Human Monocytes

    PubMed Central

    Saha, Banishree; Bruneau, Johanna C.; Kodys, Karen; Szabo, Gyongyi

    2015-01-01

    Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection–mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+–expressing and IL-10–secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization. PMID:25716995

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

    PubMed

    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.

  18. The H-Impairment Index (HII): a standardized assessment of alcohol-induced impairment in the Emergency Department.

    PubMed

    Hack, Jason B; Goldlust, Eric J; Gibbs, Frantz; Zink, Brian

    2014-03-01

    Emergency Departments (EDs) care for thousands of alcohol-intoxicated patients annually. No clinically relevant bedside measures currently exist to describe degree of impairment. To assess a group of bedside tests ("Hack's Impairment Index [HII] score") that applies a numerical value to the degree of alcohol-induced impairment in ED patients. A six-month retrospective review of HII score data was performed in a convenience sample of 293 intoxicated ED patients. Patients were scored 0-4 on five tasks, divided by the maximum score (20 if all tasks completed), every 2 hours; and classified by the number of visits: Low-frequency (1 visit); Medium-frequency (2 visits); High-frequency (≥3 visits). Correlations were assessed between HII score, healthcare provider judgment of intoxication, and measured alcohol levels. Study patients had 513 visits; 236 were low-frequency, 26 middle-frequency and 31 high-frequency. Clinical assessment and HII score were strongly correlated (Spearman's rho = 0.82, p < 0.001); clinical assessment and alcohol level less strongly so (rho = 0.49, p < 0.001). Among low-frequency patients, HII score and alcohol level were weakly correlated (r = 0.324, p < 0.001), with no such correlation among high-frequency visitors (r = -0.04, p = 0.89). The mean decline between serial HII scores was 0.126 (95% CI: 0.098-0.154). This pilot study shows the HII score can be performed at the bedside of alcohol-intoxicated patients. The HII declines in a reasonably predictable manner over time; and applies a quantitative, objective assessment of alcohol impairment.

  19. Elucidation of molecular mechanism involved in neuroprotective effect of Coenzyme Q10 in alcohol-induced neuropathic pain.

    PubMed

    Kandhare, Amit D; Ghosh, Pinaki; Ghule, Arvindkumar E; Bodhankar, Subhash L

    2013-12-01

    The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol-induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K-ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative-nitrosative stress, TNF-α, IL-1β, and IL-4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α-tocopherol (100 mg/kg) combination-treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α-tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido-nitrosative stress, release of pro-inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  20. A Preliminary Examination of the Role of Emotion Differentiation in the Relationship between Borderline Personality and Urges for Maladaptive Behaviors.

    PubMed

    Dixon-Gordon, Katherine L; Chapman, Alexander L; Weiss, Nicole H; Rosenthal, M Zachary

    2014-12-01

    Impulsive, maladaptive, and potentially self-damaging behaviors are a hallmark feature of borderline personality (BP) pathology. Difficulties with emotion regulation have been implicated in both BP pathology and maladaptive behaviors. One facet of emotion regulation that may be particularly important in the relation between BP pathology and urges for maladaptive behaviors is emotion differentiation. Over one day, 84 participants high (n = 34) and low (n = 50) in BP pathology responded to questions regarding state emotions and urges to engage in maladaptive behaviors using handheld computers, in addition to a measure of emotion-related difficulties controlling impulsive behaviors. Results revealed that individuals high in BP pathology reported greater emotion-related impulsivity as well as daily urges to engage in maladaptive behaviors. However, the association between BP group and both baseline emotion-related impulsivity and daily urges for maladaptive behaviors was strongest among individuals who had low levels of positive emotion differentiation. Conversely, negative emotion differentiation did not significantly moderate the relationships between BP group and either emotion-related difficulties controlling impulsive behaviors or state urges for maladaptive behaviors. Limitations to the present study include the reliance upon an analogue sample and the relatively brief monitoring period. Despite limitations, these results suggest that, among individuals with high BP pathology, the ability to differentiate between positive emotions may be a particularly important target in the reduction of maladaptive behaviors.

  1. A Preliminary Examination of the Role of Emotion Differentiation in the Relationship between Borderline Personality and Urges for Maladaptive Behaviors

    PubMed Central

    Dixon-Gordon, Katherine L.; Chapman, Alexander L.; Weiss, Nicole H.; Rosenthal, M. Zachary

    2015-01-01

    Background and Objectives Impulsive, maladaptive, and potentially self-damaging behaviors are a hallmark feature of borderline personality (BP) pathology. Difficulties with emotion regulation have been implicated in both BP pathology and maladaptive behaviors. One facet of emotion regulation that may be particularly important in the relation between BP pathology and urges for maladaptive behaviors is emotion differentiation. Methods Over one day, 84 participants high (n = 34) and low (n = 50) in BP pathology responded to questions regarding state emotions and urges to engage in maladaptive behaviors using handheld computers, in addition to a measure of emotion-related difficulties controlling impulsive behaviors. Results Results revealed that individuals high in BP pathology reported greater emotion-related impulsivity as well as daily urges to engage in maladaptive behaviors. However, the association between BP group and both baseline emotion-related impulsivity and daily urges for maladaptive behaviors was strongest among individuals who had low levels of positive emotion differentiation. Conversely, negative emotion differentiation did not significantly moderate the relationships between BP group and either emotion-related difficulties controlling impulsive behaviors or state urges for maladaptive behaviors. Limitations Limitations to the present study include the reliance upon an analogue sample and the relatively brief monitoring period. Conclusions Despite limitations, these results suggest that, among individuals with high BP pathology, the ability to differentiate between positive emotions may be a particularly important target in the reduction of maladaptive behaviors. PMID:25750478

  2. Smoking and Pregnancy

    MedlinePlus

    Smoking and Pregnancy Smoking can cause problems for a woman trying to become pregnant or who is already pregnant, and for her baby ... too early • Pregnancy occurs outside of the womb Smoking causes these health effects. Smoking could cause these ...

  3. Smoking and The Simpsons.

    PubMed

    Eslick, Guy D; Eslick, Marielle G

    2009-06-01

    To determine the frequency of smoking on The Simpsons television show, and the relationship with the sex and age groups of characters shown smoking, and with positive, negative and neutral connotations associated with instances of smoking. Content analysis (performed from January to October 2008) of instances of smoking that appeared in the first 18 seasons of The Simpsons television show, which aired from 1989 to 2007. Frequency, impact (positive, negative, neutral) of instances of smoking; and frequency associated with age (child or adolescent versus adult characters), sex and types of characters on the show. There were 795 instances of smoking in the 400 episodes observed. Most (498; 63%) involved male characters. Only 8% of instances of smoking (63) involved child or adolescent characters. Just over a third of instances of smoking (275; 35%) reflected smoking in a negative way, compared with the majority, which reflected smoking in a neutral way (504; 63%) and the minority, which reflected smoking in a positive way (16; 2%). Child and adolescent characters were much more likely to be involved in instances of smoking reflected in a negative way compared with adult characters (odds ratio, 44.93; 95% CI, 16.15-172.18). There are a large number of instances of smoking in The Simpsons television show. Child and adolescent characters are much more likely to be portrayed in instances of smoking reflected in a negative way than adult characters. Viewing The Simpsons characters smoking may prompt children to consider smoking at an early age.

  4. Trospium chloride for the treatment of overactive bladder with urge incontinence.

    PubMed

    Singh-Franco, Devada; Machado, Caridad; Tuteja, Sony; Zapantis, Antonia

    2005-05-01

    Urinary incontinence is caused by an overactive bladder, leading to symptoms of urgency, frequency, and incontinence. Urge incontinence occurs predominantly in women as they age. This article reviews the current primary literature concerning the efficacy and tolerability of the anticholinergic agent trospium chloride (TCl) in the treatment of overactive bladder with symptoms of urge incontinence, urgency, and frequency. The pharmacokinetics of TCl are also reviewed. Pertinent articles in English were identified through a search of MEDLINE (1966-present), EMBASE Drugs & Pharmacology (1980-third quarter 2004), Current Contents/Clinical Medicine (week 42, 2003-week 41, 2004), Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder, urinary incontinence, trospium, randomized controlled clinical trial, oxybutynin, tolterodine, scopolamine, imipramine, desipramine, and propantheline. TCl, a quaternary amine, exhibits high solubility in water but low oral bioavailability (9.6%) and poor central nervous system penetration. Approximately 80% of the absorbed fraction is renally eliminated as unchanged drug via active tubular secretion, with approximately 15% hepatically metabolized into a spiroalcohol and hydrolysis/oxidation products. In 3 placebo-controlled studies, patients who received TCl had an increase in maximum bladder filling capacity and bladder compliance, with a reduction in maximum cystometric capacity (P < 0.005); however, only 1 of these studies showed an increase in bladder compliance, with reductions in maximum detrusor pressure (P < 0.001), number of voids/d (P < or = 0.001), and incontinence episodes/d (P < or = 0.001). In another placebo-controlled study, TCl reduced the number of voids/d and incontinence episodes/d (both, P < or = 0.001). In 2 double-blind studies, TCl and oxybutynin were similarly effective in significantly increasing

  5. Efficacy and safety of sacral nerve stimulation for urinary urge incontinence: a systematic review.

    PubMed

    Brazzelli, Miriam; Murray, Alison; Fraser, Cynthia

    2006-03-01

    We systematically reviewed the evidence on the efficacy and safety of sacral nerve stimulation (SNS) for severe urge incontinence. A systematic review was performed of primary studies of SNS for urge incontinence published in English between 1966 and May 2003, and identified in major electronic databases. Two reviewers independently selected studies, assessed their methodological quality and extracted data. Four randomized controlled trials and 30 case series were identified. Evidence from the randomized controlled trials, involving approximately 120 patients, showed that about 80% achieved continence or greater than 50% improvement in their main incontinence symptoms after SNS compared with about 3% of controls receiving conservative treatments while waiting for an implant. While case series were larger, they were methodologically less reliable. However, they showed similar results with 67% of patients becoming dry or achieving a greater than 50% improvement in symptoms after implantation. Incontinence episodes, leakage severity, voiding frequency and pad use were significantly lower after implantation. Benefits were reported to persist 3 to 5 years after implantation. Adverse events were documented in 27 studies. Overall the reoperation rate in implanted cases was 33%. The most common reason for surgical revision was relocation of the generator because of pain and infection. Common complications were pain at the implant or lead site in 25% of patients, lead related problems such as lead migration in 16%, replacement and repositioning of the implanted pulse generator in 15%, wound problems in 7%, adverse effects on bowel function in 6%, infection in 5% and generator problems in 5%. Permanent removal of the electrodes was reported in 9% of patients. Technical changes with time have been associated with decreased complication rates. There is evidence indicating that SNS is effective for decreasing symptoms in patients with urge incontinence. Adverse events occurred

  6. "The battered fetus syndrome". Preliminary data on the incidence of the urge to physically abuse the unborn child.

    PubMed

    Condon, J T

    1987-12-01

    Recently published reports of physical assault by women in late pregnancy upon their unborn children have elicited a response of incredulity in many professionals. This response is identical to that which followed the publication of the first cases of child abuse in the 1960s. The present paper attempts a preliminary exploration of the incidence of the urge to "hurt or punish" the unborn child using a sample of 112 normal pregnant women and their male partners. Eight percent of the women and 4% of the men acknowledged experiencing such an urge. The male partner appeared to be aware of the woman's aggressive feelings toward the fetus and the male's reports tend to validate the female findings. Despite some methodological shortcomings, the findings suggest that the urge to physically assault the fetus is not rare. The need for further investigation of the phenomenon is highlighted, as it may well represent the earliest precursor of later physical child abuse.

  7. [Alcohol induced cognitive deficits].

    PubMed

    Weiss, Elisabeth; Singewald, Evelin M; Ruepp, Beatrix; Marksteiner, Josef

    2014-01-01

    Previous studies could show a complex relationship between alcohol consumption and cognition but also with processes of ageing both social and biological. Acute effects of alcohol during intoxication include clinical signs such as excitation and reduced inhibition, slurred speech, and increased reaction time but also cognitive dysfunction, especially deficits in memory functions. However, these cognitive deficits during alcohol intoxication are reversible while patients with alcohol addiction and chronic alcohol intake show severe impairments of cognitive functions especially deficits in executive functions. Frontal executive impairments in these patients include deficits in problem solving, abstraction, planning, organizing, and working memory.Additionally, gender specific deficits are relevant for the course of the disease and its concomitant health problems with female alcoholics showing a higher vulnerability for cognitive dysfunction and brain atrophy at earlier stages of alcoholism history.

  8. Sentinel alert sounds the alarm on worker fatigue; hospitals urged to mitigate risks.

    PubMed

    2012-03-01

    Noting that there is a documented link between worker fatigue and adverse events, the Joint Commission has issued a Sentinel Alert, urging health care organizations to focus on the issue and make sure that policies and procedures are in place to mitigate risks. Experts advise hospital leaders to monitor worker shifts and make sure that people are able to leave work as scheduled when their shifts have concluded. Limit health care workers to no more than three consecutive days of 12-hour shifts, especially if these shifts are at night. Scrutinize handoff procedures so that worker fatigue does not lead to errors during this potentially hazardous time. Make sure that distractions are at a minimum during these transitions, and that patient information is conveyed in both verbal and in written form.

  9. Libet's experiment: Questioning the validity of measuring the urge to move.

    PubMed

    Dominik, Tomáš; Dostál, Daniel; Zielina, Martin; Šmahaj, Jan; Sedláčková, Zuzana; Procházka, Roman

    2017-03-01

    The time of subjectively registered urge to move (W) constituted the central point of most Libet-style experiments. It is therefore crucial to verify the W validity. Our experiment was based on the assumption that the W time is inferred, rather than introspectively perceived. We used the rotating spot method to gather the W reports together with the reports of the subjective timing of actual movement (M). The subjects were assigned the tasks in two different orders. When measured as first in the respective session, no significant difference between W and M values was found, which suggests that uninformed subjects tend to confuse W for M reports. Moreover, we found that W values measured after the M task were significantly earlier than W values measured before M. This phenomenon suggests that the apparent difference between W and M values is in fact caused by the subjects' previous experience with M measurements.

  10. Characterization of urge to cough and cough symptoms associated with the common cold: results of a US internet survey.

    PubMed

    Eccles, Ron; Dicpinigaitis, Peter; Turner, Ronald B; Druce, Howard M; Adeleke, Maryann; Mann, Ashley L

    2016-06-01

    Our knowledge of cough physiology is limited despite years of study. Even less is known about the sensation of urge to cough. Given that limited clinical data are available about urge to cough and cough attributes during a common cold, we sought to gain insights into experiences and perceptions related to these symptoms. An internet survey consisting of 51 questions was fielded in the United States. Eligible survey participants included men and women aged 18 years and older who had suffered from a cold with cough within the three months preceding the survey. Participants who confirmed suffering from recurrent cough, asthma, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, or gastrointestinal reflux were excluded. Of 19,530 initial respondents, 8011 had a cold in the past three months. Of these, 6484 (81%) had experienced cough symptoms; 2708 respondents with cough due to cold and no exclusionary condition made up the analysis sample. Most respondents (62%) reported that cough developed one to two days after the onset of cold symptoms, and 45% felt that cough worsened their other cold symptoms. In 69% of respondents, cough outlasted other cold symptoms. Urge to cough was reported by 98% of respondents, and among these respondents, 64% described it as uncontrollable and 65% rated severity as moderate. More than half of respondents (57%) considered the sensation of urge to cough and the act of coughing as equally bothersome. Although urge to cough and inability to control cough were the most bothersome aspects of cough due to cold, few (<20%) respondents asked healthcare providers for treatment recommendations. Symptoms of urge to cough and cough are common and have a significant impact on cold sufferers. Understanding attributes of these symptoms may provide insights for effective management and the development of novel treatment strategies.

  11. A Comparison of Urge Intensity and the Probability of Tic Completion During Tic Freely and Tic Suppression Conditions.

    PubMed

    Specht, Matt W; Nicotra, Cassandra M; Kelly, Laura M; Woods, Douglas W; Ricketts, Emily J; Perry-Parrish, Carisa; Reynolds, Elizabeth; Hankinson, Jessica; Grados, Marco A; Ostrander, Rick S; Walkup, John T

    2014-03-01

    Tic-suppression-based treatments (TSBTs) represent a safe and effective treatment option for Chronic Tic Disorders (CTDs). Prior research has demonstrated that treatment naive youths with CTDs have the capacity to safely and effectively suppress tics for prolonged periods. It remains unclear how tic suppression is achieved. The current study principally examines how effective suppression is achieved and preliminary correlates of the ability to suppress tics. Twelve youths, ages 10 to 17 years, with moderate-to-marked CTDs participated in an alternating sequence of tic freely and reinforced tic suppression conditions during which urge intensity and tic frequency were frequently assessed. Probability of tics occurring was half as likely following high-intensity urges during tic suppression (31%) in contrast to low-intensity urges during tic freely conditions (60%). Age was not associated with ability to suppress. Intelligence indices were associated with or trended toward greater ability to suppress tics. Attention difficulties were not associated with ability to suppress but were associated with tic severity. In contrast to our "selective suppression" hypothesis, we found participants equally capable of suppressing their tics regardless of urge intensity during reinforced tic suppression. Tic suppression was achieved with an "across-the-board" effort to resist urges. Preliminary data suggest that ability to suppress may be associated with general cognitive variables rather than age, tic severity, urge severity, and attention. Treatment naive youths appear to possess a capacity for robust tic suppression. TSBTs may bolster these capacities and/or enable their broader implementation, resulting in symptom improvement. © The Author(s) 2014.

  12. Alcohol-induced facial dysmorphology in C57BL/6 mouse models of fetal alcohol spectrum disorder.

    PubMed

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

    2010-01-01

    significantly more effects of pair feeding on these facial measures than did B6J mice, suggesting that the B6N substrain may be more vulnerable to nutritional stress during pregnancy. Overall, these data indicate that both B6N and B6J mice were vulnerable to alcohol but show differences in the severity and location of alcohol-induced dysmorphic facial features and may parallel findings from human studies comparing different ethnic groups. Furthermore, these findings suggest that discriminant analysis may be useful in predicting alcohol exposure in either mouse substrains.

  13. Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide.

    PubMed

    Ganey, P E; Barton, Y W; Kinser, S; Sneed, R A; Barton, C C; Roth, R A

    2001-07-15

    rats cotreated with LPS and allyl alcohol. NS-398 did not affect liver injury from allyl alcohol alone administered at a larger, hepatotoxic dose. In addition, ibuprofen, a nonselective inhibitor of cyclooxygenases, did not protect against liver injury from LPS plus allyl alcohol. In isolated hepatocytes PGD(2), but not PGE(2), reduced the concentration of allyl alcohol required to cause half-maximal cytotoxicity. These results suggest that products of COX-2 play a role in the augmentation of allyl alcohol-induced liver injury by LPS. Copyright 2001 Academic Press.

  14. Neurotrophic peptides, ADNF-9 and NAP, prevent alcohol-induced apoptosis at midgestation in fetal brains of C57BL/6 mouse.

    PubMed

    Sari, Youssef; Weedman, Jason M; Nkrumah-Abrokwah, Maxwell

    2013-01-01

    Prenatal alcohol exposure is known to induce fetal brain growth deficits at different embryonic stages. We focused this study on investigating the neuroprotective effects against alcohol-induced apoptosis at midgestation using activity-dependent neurotrophic factor (ADNF)-9, a peptide (SALLRSIPA) derived from activity-dependent neurotrophic factor, and NAP, a peptide (NAPVSIPQ) derived from activity-dependent neuroprotective protein. We used an established fetal alcohol exposure mouse model. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) group with 25 % (4.49 %, v/v) ethanol-derived calories, (2) pair-fed (PF) control group, (3) ALC combined with i.p. injections (1.5 mg/kg) of ADNF-9 (ALC/ADNF-9) group, (4) ALC combined with i.p. injections (1.5 mg/kg) of NAP (ALC/NAP) group, (5) PF liquid diet combined with i.p. injections of ADNF-9 (PF/ADNF-9) group, and (6) PF liquid diet combined with i.p. injections of NAP (PF/NAP) group. On day 15 (E15), fetal brains were collected, weighed, and assayed for TdT-mediated dUTP nick end labeling (TUNEL) staining. ADNF-9 or NAP was administered daily from E7 to E15 alongside PF or ALC liquid diet exposure. Our results show that NAP and ADNF-9 significantly prevented alcohol-induced weight reduction of fetal brains. Apoptosis was determined by TUNEL staining; NAP or ADNF-9 administration alongside alcohol exposure significantly prevented alcohol-induced increase in TUNEL-positive cells in primordium of the cingulate cortex and ganglionic eminence. These findings may pave the path toward potential therapeutics against alcohol intoxication during pregnancy stages.

  15. Catalase prevents elevation of [Ca(2+)](i) induced by alcohol in cultured canine cerebral vascular smooth muscle cells: Possible relationship to alcohol-induced stroke and brain pathology.

    PubMed

    Li, Wenyan; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-01-15

    Several studies have suggested that alcohol-induced brain injury is associated with generation of reactive oxygen species (ROS). The recent findings, that antioxidants (Vitamin E and pyrrolidine dithiocarbamate (PDTC)) prevent intracellular Ca(2+) ([Ca(2+)](i)) overload in cerebral vascular smooth muscle cells, induced by alcohol, demonstrate indirectly that ROS formation is related to cerebral vascular injury. The present experiments were designed to test the hypothesis that catalase, an hydrogen peroxide (H(2)O(2)) scavenging enzyme, can prevent or ameliorate alcohol-induced elevation of [Ca(2+)](i). Preincubation of cultured canine cerebral vascular smooth muscle cells with catalase (20-1000 units/ml) didn't produce any apparent changes from controls in resting levels of [Ca(2+)](i) after 1-3 days. Exposure of the cerebral vascular cells to culture media containing 10-100mM ethanol resulted in significant rises in [Ca(2+)](i) (p<0.01). Although exposure of these cells to a low concentration of catalase (20 units/ml) failed to prevent the increased level of [Ca(2+)](i) induced by ethanol, concomitant addition of higher concentrations of catalase (100-1000 units/ml) and ethanol (10-100mM) inhibited or ameliorated the rises of [Ca(2+)](i) induced by ethanol either at 24h or at 3 days, in a concentration-dependent manner. Catalase, in the range of 100-200 units/ml, inhibited approximately 50% of the [Ca(2+)](i) increases caused by ethanol in the first 24h. Catalase at a concentration of 1000 units/ml inhibited completely excessive [Ca(2+)](i) accumulation. The present results when viewed in light of other recently published data suggest that H(2)O(2) generation may be one of the earliest events triggered by alcohol in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.

  16. The restorative effects of smoking upon self-control resources: a negative reinforcement pathway.

    PubMed

    Heckman, Bryan W; Ditre, Joseph W; Brandon, Thomas H

    2012-02-01

    Based on a model in which self-control (SC) is considered to be a limited resource, research suggests that diminished SC resources may increase the likelihood of tobacco smoking. Yet, the inverse--how smoking may influence SC resources--has not been tested. The authors of this study utilized a randomized, 2 × 2 crossed-factorial (SC Depletion Manipulation × Smoking Manipulation), between-subjects design to test the hypothesis that smoking restores depleted SC resources. To manipulate SC depletion, experimenters instructed half of 132 nicotine dependent smokers to suppress their emotional reaction to a brief video depicting environmental damage (i.e., depletion), whereas the other half were instructed to "act natural" (i.e., no depletion) during viewing. Half of the participants in each condition then smoked a cigarette, whereas the other half sat patiently without smoking (i.e., smoke vs. no smoke). All participants then completed behavioral measures of SC. As hypothesized, an interaction occurred between the depletion and smoking manipulations for duration of time spent on a frustrating mirror-tracing task. That is, depletion reduced persistence on the task, unless depletion was followed by smoking. This effect was mediated by positive affect (PA). Thus, smoking appeared to restore depleted SC resources via modulation of PA, but independent of negative affect or smoking urges. These findings suggest that restoration of SC resources may represent another means by which smoking is negatively reinforced. The application of the self-control strength model to the study of nicotine dependence may inform the development of novel treatment modalities.

  17. Smoking and women's health.

    PubMed

    Seltzer, V

    2000-07-01

    Each year more than 600000 women have deaths associated with cigarette smoking. In addition, cigarette smoking is associated with a wide array of morbidities (such as osteoporosis, cardiovascular disease, and adverse pregnancy outcomes). Two hundred million women smoke worldwide, and this number appears to be rising, particularly in developing countries. Obstetrician-gynecologists can play a role in reducing morbidity and mortality from cigarette smoking by educating women about the dangers, advising them not to smoke, and assisting those who do smoke to quit.

  18. Young Adult Smoking Behavior

    PubMed Central

    Ling, Pamela M.; Neilands, Torsten B.; Glantz, Stanton A.

    2009-01-01

    Background Young adults have the highest smoking rate of any age group in the U.S., and new strategies to decrease young adult smoking are needed. The objective of the current study was to identify psychographic and demographic factors associated with current smoking and quitting behaviors among young adults. Methods Attitudes, social groups, and self-descriptors, including supporting action against the tobacco industry, advertising receptivity, depression, alcohol use, and other factors associated with smoking were tested for associations with smoking behaviors in a 2005 cross-sectional survey of 1528 young adults (aged 18–25 years) from a web-enabled panel. Analyses were conducted in 2007. Results Being older was associated with current smoking, whereas having some higher education and being African American or Hispanic were negatively associated with smoking. Supporting action against the tobacco industry was negatively associated with smoking (AOR=0.34 [95% CI=0.22, 0.52]). Perceived usefulness of smoking, exposure to smokers, increased perceived smoking prevalence, receptivity to tobacco advertising, binge drinking, and exposure to tobacco advertising in bars and clubs were associated with smoking. Supporting action against the tobacco industry was associated with intentions to quit smoking (AOR= 4.43 [95% CI=2.18, 8.60]). Conclusions Young adults are vulnerable to tobacco-industry advertising. Media campaigns that denormalize the tobacco industry and appeal to young adults appear to be a powerful intervention to decrease young adult smoking. PMID:19269128

  19. Snuffing out cigarette sales and the smoking deaths epidemic.

    PubMed

    Laugesen, Murray

    2007-06-15

    Smokers need new products and policies to escape smoking's risks. And the next generation needs policies that will better protect them from becoming smokers. Low-nitrosamine tobacco snuff (hereafter termed 'snuff') is 20 times less dangerous than cigarette smoking. Its sale as nasal snuff raises the question as to how long cigarettes, including cigars and pipe tobacco, should continue to be sold and allowed to hasten the deaths of 4000 New Zealanders annually. Oral snuff has helped to reduce smoking to unusually low levels in Swedish men, is much less dangerous than smoking, and does not cause lung or mouth cancer. Moreover, smokeless tobacco (which includes snuff) could reduce smoking-caused health inequity for Maori. Snuff can improve population health, and more so if more smokers switch to it. Continued bans on snuff are now regarded by some experts as unsound public policy. Added to the mountain of evidence against cigarettes, sufficient evidence now exists for Government to use snuff to create safer tobacco choices for smokers, end cigarette sales altogether, and thus end the cigarette smoking deaths epidemic--in which 200,000 New Zealanders have died so far. The New Zealand Government can: Fund media campaigns to inform smokers of their new choices, and to urge them to quit smoking. (The 2007 Budget commits an extra $11 million per year for 4 years, an excellent start.) Regulate for warnings on snuff cans stating that snuff is "addictive but much safer than smoking", and regulate imports to only permit reduced-risk low-nitrosamine products. Tax each class of tobacco products proportionate to the respective risks of each. (Tax cigarettes at 20 times the snuff rate, instead of at the same rate.) Legislate, to expand the Smoke-free Environments Act's aims to include ending the sale of cigarettes and ending smoking deaths--i.e: Allow oral snuff to compete with cigarettes for market share (and for the smoker's nicotine receptors). Reduce addiction to smoking, by

  20. Kids and Smoking (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Kids and Smoking KidsHealth > For Parents > Kids and Smoking A A ... them from these unhealthy habits. The Facts About Smoking and Tobacco One reason that smoking and chewing ...

  1. Second Hand Smoke: Danger

    MedlinePlus

    ... from exposure to secondhand smoke since 1964. Smokefree Laws Save Lives, But Many Not Protected In the ... plus the District of Columbia have passed comprehensive laws to protect nonsmokers by prohibiting smoking in indoor ...

  2. Smoking and asthma

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000504.htm Smoking and asthma To use the sharing features on this page, ... enable JavaScript. Things that make your allergies or asthma worse are called triggers. Smoking is a trigger ...

  3. Smart smoke alarm

    DOEpatents

    Warmack, Robert J. Bruce; Wolf, Dennis A; Frank, Steven Shane

    2015-04-28

    Methods and apparatus for smoke detection are disclosed. In one embodiment, a smoke detector uses linear discriminant analysis (LDA) to determine whether observed conditions indicate that an alarm is warranted.

  4. Smoking and Eye Health

    MedlinePlus

    ... that is most common in women after menopause. Smoking increases the risk of serious vision loss in people with other eye diseases. And when women smoke during pregnancy they are more likely to give birth prematurely, ...

  5. Up in Smoke.

    ERIC Educational Resources Information Center

    Black, Susan

    2002-01-01

    Reviews research on adolescent smoking and nicotine addiction. Finds, for example, that smoking is linked to depression. Describes five stages of nicotine addiction. Offers tips for prevention. (Contains 12 references.) (PKP)

  6. Up in Smoke.

    ERIC Educational Resources Information Center

    Black, Susan

    2002-01-01

    Reviews research on adolescent smoking and nicotine addiction. Finds, for example, that smoking is linked to depression. Describes five stages of nicotine addiction. Offers tips for prevention. (Contains 12 references.) (PKP)

  7. Teenagers and Smoking.

    ERIC Educational Resources Information Center

    PTA Today, 1986

    1986-01-01

    The Coalition on Smoking OR Health was established to coordinate education programs to discourage young people from smoking. Projects that could be undertaken by parent associations are suggested. (MT)

  8. Factors Affecting Smoking Tendency and Smoking Intensity

    ERIC Educational Resources Information Center

    David, Nissim Ben; Zion, Uri Ben

    2009-01-01

    Purpose: The purpose of this paper is to measure the relative effect of relevant explanatory variable on smoking tendency and smoking intensity. Design/methodology/approach: Using survey data collected by the Israeli Bureau of Statistics in 2003-2004, a probit procedure is estimated for analyzing factors that affect the probability of being a…

  9. Effects of Disasters on Smoking and Relapse: An Exploratory Study of Hurricane Katrina Victims.

    PubMed

    Lanctot, Jennifer Q; Stockton, Michelle B; Mzayek, Fawaz; Read, Mary; McDevitt-Murphy, Meghan; Ward, Kenneth

    2008-01-01

    Psychosocial stress maintains cigarette use and precipitates relapse, but little is known about how natural disasters in particular affect smoking. To determine the feasibility of recruiting victims soon after a natural disaster for a survey study, and to assess the types and determinants of changes in smoking behavior resulting from exposure to the disaster. A convenience sample of 35 Hurricane Katrina refugees who had smoked more than 100 cigarettes in their lifetime were surveyed one month after the storm to evaluate changes in smoking behavior. Among a small sample of former smokers, more than half relapsed after Katrina, citing stress, urge, and sadness. Among current smokers, 52% increased their smoking after Katrina by more than half a pack per day on average. Most individuals who increased their smoking or relapsed expressed interest in receiving cessation assistance within the next month. Stress-related increases in smoking and relapse may be common after a natural disaster. Health education professionals have an important role to play in responding to changes in tobacco use in the aftermath of disasters. Educational interventions to discourage tobacco use as a coping strategy may be especially warranted given the high level of interest expressed in smoking cessation.

  10. Adolescent first lapse following smoking cessation: situation characteristics, precipitants and proximal influences.

    PubMed

    Myers, Mark G; Gwaltney, Chad J; Strong, David R; Ramsey, Susan E; Brown, Richard A; Monti, Peter M; Colby, Suzanne M

    2011-12-01

    Despite increased attention to adolescent smoking cessation, little is known about adolescent relapse following a quit attempt. To address this issue, the present study was designed to provide initial information regarding the characteristics of adolescent lapses to smoking following abstinence. Included in the present study were 204 adolescent participants in four independent smoking cessation trials. For the full sample, participants averaged 15.99 (1.27) years of age; 56% were female and 78% were white. Lapse characteristics and precipitants were assessed using the Adolescent Smoking Relapse Review. Three domains of the lapse experience were assessed: lapse situation characteristics, precipitants of use in the situation, and proximal influences (i.e., potential precipitants occurring on the same day, prior to the lapse situation). Participant reports indicated that the modal lapse situation occurred in the evening while socializing with friends at home. Urges or cravings and social pressure were commonly endorsed as occurring in lapse situations. The most frequently reported proximal influence was desire for a cigarette, followed by abstinence-violation cognitions (okay to smoke occasionally, wanted to see what it would be like) and negative emotions. The findings indicate that a broad range of factors appear to influence adolescent smoking lapse and commend the value of incorporating content relevant to managing social and affective cues, strategies for inhibiting the prepotent response to ask for a cigarette, addressing cognitions regarding the difficulty of not smoking (i.e., cessation expectancies) and combating perceptions of the ability to smoke occasionally. Published by Elsevier Ltd.

  11. Adolescent First Lapse Following Smoking Cessation: Situation Characteristics, Precipitants and Proximal Influences

    PubMed Central

    Myers, Mark G.; Gwaltney, Chad J.; Strong, David R.; Ramsey, Susan E.; Brown, Richard A.; Monti, Peter M.; Colby, Suzanne M.

    2011-01-01

    Despite increased attention to adolescent smoking cessation, little is known about adolescent relapse following a quit attempt. To address this issue, the present study was designed to provide initial information regarding the characteristics of adolescent lapses to smoking following abstinence. Included in the present study were 204 adolescent participants in four independent smoking cessation trials. For the full sample, participants averaged 15.99 (1.27) years of age; 56% were female and 78% were white. Lapse characteristics and precipitants were assessed using the Adolescent Smoking Relapse Review. Three domains of the lapse experience were assessed: lapse situation characteristics, precipitants of use in the situation, and proximal influences (i.e., potential precipitants occurring on the same day, prior to the lapse situation). Participant reports indicated that the modal lapse situation occurred in the evening while socializing with friends at home. Urges or cravings and social pressure were commonly endorsed as occurring in lapse situations. The most frequently reported proximal influence was desire for a cigarette, followed by abstinence-violation cognitions (okay to smoke occasionally, wanted to see what it would be like) and negative emotions. The findings indicate that a broad range of factors appear to influence adolescent smoking lapse and commend the value of incorporating content relevant to managing social and affective cues, strategies for inhibiting the prepotent response to ask for a cigarette, addressing cognitions regarding the difficulty of not smoking (i.e., cessation expectancies) and combating perceptions of the ability to smoke occasionally. PMID:21903332

  12. Smoking and Pancreatic Disease

    PubMed Central

    Edderkaoui, Mouad; Thrower, Edwin

    2014-01-01

    Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells. PMID:24660091

  13. Fucoidan from Fucus vesiculosus protects against alcohol-induced liver damage by modulating inflammatory mediators in mice and HepG2 cells.

    PubMed

    Lim, Jung Dae; Lee, Sung Ryul; Kim, Taeseong; Jang, Seon-A; Kang, Se Chan; Koo, Hyun Jung; Sohn, Eunsoo; Bak, Jong Phil; Namkoong, Seung; Kim, Hyoung Kyu; Song, In Sung; Kim, Nari; Sohn, Eun-Hwa; Han, Jin

    2015-02-16

    Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg) for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1), a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

  14. The Ayurvedic drug Ksheerabala (101) ameliorates alcohol-induced neurotoxicity by down-regulating the expression of transcription factor (NFkB) in rat brain.

    PubMed

    Rejitha, S; Prathibha, P; Madambath, Indira

    2015-01-01

    Most of the pharmaceutical effects of alcohol are due to its accumulation in the brain. Ksheerabala (101) an Ayurvedic formulation mainly used against central nervous system disorders. To determine the antioxidant and neuroprotective effect of Ksheerabala (101) on alcohol-induced oxidative stress in rats. Male Albino rats of Sprague-Dawley strain were grouped into four; control, alcohol (4 g/kg), Ksheerabala (15 μL/1 ml milk/100 g) and Ksheerabala (15 μL/1 ml milk/100 g) + alcohol (4 g/kg). After the experimental period (90 days), the animals were sacrificed and the effect of Ksheerabala (101) was studied on oxidative stress, inflammatory markers, and induction of transcription factor in brain. Results were statistically analyzed by one-way ANOVA. The activities of antioxidant enzymes and reduced glutathione which were decreased in alcohol-treated rats, increased significantly in co-administered groups. The lipid peroxidation products and protein carbonyls which were increased significantly in alcohol-treated rats decreased significantly in co-administered groups. The expression of gamma-glutamyl cysteine synthase decreased significantly in alcohol-treated rats and increased significantly in co-administered groups. The transcription factor nuclear factor-κB (NFκB) which was up-regulated in alcohol-treated rats was down-regulated in co-administered rats. The histopathology reinforced these results. Ksheerabala (101) attenuates alcohol-induced oxidative stress and down-regulates the expression of NFκB in rat brain.

  15. Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

    PubMed Central

    Lim, Jung Dae; Lee, Sung Ryul; Kim, Taeseong; Jang, Seon-A; Kang, Se Chan; Koo, Hyun Jung; Sohn, Eunsoo; Bak, Jong Phil; Namkoong, Seung; Kim, Hyoung Kyu; Song, In Sung; Kim, Nari; Sohn, Eun-Hwa; Han, Jin

    2015-01-01

    Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg) for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1), a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions. PMID:25690093

  16. Scopoletin prevents alcohol-induced hepatic lipid accumulation by modulating the AMPK-SREBP pathway in diet-induced obese mice.

    PubMed

    Lee, Hae-In; Yun, Kyeong Won; Seo, Kown-Il; Kim, Myung-Joo; Lee, Mi-Kyung

    2014-04-01

    This study investigated the effects of scopoletin on alcohol-induced hepatic lipid accumulation in diet-induced obese mice and its mechanism. Alcohol (25% v/v, 5g/kg body weight) was orally administered once a day for 6 weeks to mice fed with a high-fat diet (35%kcal) with or without scopoletin (0.05%, wt/wt). Scopoletin reduced plasma acetaldehyde, fatty acid, total cholesterol, triglyceride and insulin levels, hepatic lipid and droplets and fasting blood glucose levels that were increased by alcohol. Scopoletin significantly activated hepatic AMPK and inhibited ACC and SREBP-1c and the activities of lipogenic enzymes, such as FAS, PAP and G6PD compared to the alcohol control group. Moreover, scopoletin significantly inhibited hepatic CYP2E1 activity and protein levels but elevated the activities of SOD, CAT, GSH-Px and GST and the levels of GSH compared to the alcohol control group. The hepatic lipid peroxide level was significantly lowered by scopoletin supplementation in alcohol-administered obese mice. Taken together, these results suggested that scopoletin can ameliorate alcohol-induced hepatic lipid accumulation by modulating AMPK-SREBP pathway-mediated lipogenesis in mice fed a high-fat diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    PubMed Central

    Zhong, Wei; Li, Qiong; Zhang, Wenliang; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2015-01-01

    Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation. PMID:26501337

  18. In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress.

    PubMed

    You, Yanghee; Yoo, Soonam; Yoon, Ho-Geun; Park, Jeongjin; Lee, Yoo-Hyun; Kim, Sunoh; Oh, Kyung-Taek; Lee, Jeongmin; Cho, Hong-Yon; Jun, Woojin

    2010-06-01

    The protective effects of Taraxacum officinale (dandelion) root against alcoholic liver damage were investigated in HepG2/2E1 cells and ICR mice. When an increase in the production of reactive oxygen species was induced by 300 mM ethanol in vitro, cell viability was drastically decreased by 39%. However, in the presence of hot water extract (TOH) from T. officinale root, no hepatocytic damage was observed in the cells treated with ethanol, while ethanol-extract (TOE) did not show potent hepatoprotective activity. Mice, which received TOH (1 g/kg bw/day) with ethanol revealed complete prevention of alcohol-induced hepatotoxicity as evidenced by the significant reductions of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities compared to ethanol-alone administered mice. When compared to the ethanol-alone treated group, the mice receiving ethanol plus TOH exhibited significant increases in hepatic antioxidant activities, including catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione. Furthermore, the amelioration of malondialdehyde levels indicated TOH's protective effects against liver damage mediated by alcohol in vivo. These results suggest that the aqueous extract of T. officinale root has protective action against alcohol-induced toxicity in the liver by elevating antioxidative potentials and decreasing lipid peroxidation.

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

    PubMed Central

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

    2015-01-01

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

  20. Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury

    PubMed Central

    Liu, Yange; Wang, Juan; Li, Lanzhou; Hu, Wenji; Qu, Yidi; Ding, Yipei; Meng, Lina

    2017-01-01

    In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine. PMID:28337253

  1. Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury.

    PubMed

    Liu, Yange; Wang, Juan; Li, Lanzhou; Hu, Wenji; Qu, Yidi; Ding, Yipei; Meng, Lina; Teng, Lirong; Wang, Di

    2017-01-01

    In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

  2. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats.

    PubMed

    Zhong, Wei; Li, Qiong; Zhang, Wenliang; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2015-10-16

    Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation.

  3. Plain packaging of cigarettes and smoking behavior: study protocol for a randomized controlled study

    PubMed Central

    2014-01-01

    Background Previous research on the effects of plain packaging has largely relied on self-report measures. Here we describe the protocol of a randomized controlled trial investigating the effect of the plain packaging of cigarettes on smoking behavior in a real-world setting. Methods/Design In a parallel group randomization design, 128 daily cigarette smokers (50% male, 50% female) will attend an initial screening session and be assigned plain or branded packs of cigarettes to smoke for a full day. Plain packs will be those currently used in Australia where plain packaging has been introduced, while branded packs will be those currently used in the United Kingdom. Our primary study outcomes will be smoking behavior (self-reported number of cigarettes smoked and volume of smoke inhaled per cigarette as measured using a smoking topography device). Secondary outcomes measured pre- and post-intervention will be smoking urges, motivation to quit smoking, and perceived taste of the cigarettes. Secondary outcomes measured post-intervention only will be experience of smoking from the cigarette pack, overall experience of smoking, attributes of the cigarette pack, perceptions of the on-packet health warnings, behavior changes, views on plain packaging, and the rewarding value of smoking. Sex differences will be explored for all analyses. Discussion This study is novel in its approach to assessing the impact of plain packaging on actual smoking behavior. This research will help inform policymakers about the effectiveness of plain packaging as a tobacco control measure. Trial registration Current Controlled Trials ISRCTN52982308 (registered 27 June 2013). PMID:24965551

  4. Relationship between negative affect and smoking topography in heavy drinking smokers.

    PubMed

    Green, ReJoyce; Bujarski, Spencer; Roche, Daniel J O; Ray, Lara A

    2016-10-01

    Heavy drinking smokers represent a sizeable subgroup of smokers for whom nicotine deprivation and alcohol use increases the urge to smoke in the laboratory and predicts lapses during smoking cessation. The manner in which individuals smoke a cigarette (i.e. smoking topography) provides a reliable index of smoking intensity and reinforcement, yet the effects of affect on smoking topography have not been thoroughly examined in heavy drinking smokers. The current study examined how affect and nicotine deprivation predict smoking behavior as participants (N=27) smoked one cigarette using a smoking topography device after 12-h of nicotine abstinence and after a priming dose of alcohol (target BrAC=0.06g/dl). Primary smoking topography measures were puff volume, velocity, duration, and inter-puff interval (IPI). The effect of nicotine deprivation was measured by the Minnesota Nicotine Withdrawal Scale (MNWS) and the Profile of Mood States (POMS). Measures were obtained at baseline (i.e. 12-h of nicotine abstinence and pre-alcohol) and 30-minutes after alcohol administration (i.e. peak BrAC). Results revealed post-priming negative affect significantly moderated the trajectories of puff volume, puff duration and IPI (p's<0.05) over the course of the cigarette, such that those with greater negative affect had flatter slopes for volume and duration and increasingly infrequent puffs. Our results suggest that baseline and post-priming negative affect following nicotine deprivation alters smoking patterns and increases nicotine exposure throughout a single cigarette. Future studies need to examine differential amounts of nicotine deprivation on response to alcohol and smoking in heavy drinking smokers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Epidemiology of Smoking.

    ERIC Educational Resources Information Center

    Guba, Christianne J.; McDonald, James L., Jr.

    1993-01-01

    Reviews the latest statistics relative to tobacco consumption, the health consequences of cigarette use, and future U.S. smoking trends projected through the year 2000. Smoking statistics are presented by ethnicity, gender, educational status, and brand preferences. Also provided are factors contributing to smoking initiation. (GLR)

  6. About You and Smoking.

    ERIC Educational Resources Information Center

    Houser, Norman W.; And Others

    This booklet acquaints the student with current scientific knowledge about smoking and its effects on health, with the economic aspects of smoking, with ways in which young people might help those who now have a smoking problem, and with significant health statistics. It begins, in chapter 1, with a discussion of the history of tobacco and its…

  7. About You and Smoking.

    ERIC Educational Resources Information Center

    Houser, Norman W.; And Others

    This booklet acquaints the student with current scientific knowledge about smoking and its effects on health, with the economic aspects of smoking, with ways in which young people might help those who now have a smoking problem, and with significant health statistics. It begins, in chapter 1, with a discussion of the history of tobacco and its…

  8. Parental Smoking Affects Children

    ERIC Educational Resources Information Center

    Science News, 1978

    1978-01-01

    Research done by workers at Harvard Medical School suggests that passive exposure to cigarette smoke can impair breathing in children ages five through nine. Lung flow rates (breathing ability) decreased for children with smoking parents, and significantly if the children also smoke. (MA)

  9. Wildfire Smoke Emissions webinar

    EPA Pesticide Factsheets

    This webinar presented by Wayne Cascio will highlight updates to the Wildfire Smoke Guide, as well as the Smoke Sense app, which is a mobile application that gets air quality information to people impacted by wildfire smoke, and helps those affected learn