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1.  Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics 
Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals.
PMCID: PMC3002844  PMID: 21045074
2.  Alcohol Affects the Late Differentiation of Progenitor B Cells 
Aims: Previous studies show that alcohol exposure can affect the differentiation of progenitor B cells. Before final commitment to a B lineage, progenitor B cells usually undergo several important stages. However, it is still unclear whether alcohol alters B cell differentiation at which stages. The aim of this study was to determine which stage(s) of progenitor cell differentiation are affected by alcohol and to elucidate the mechanism(s) responsible for the effect of alcohol on B cell differentiation. Methods: Oligoclonal-neonatal-progenitor (ONP) cells from bone marrow cells of 2-week-old mice were cultured under different conditions in vitro with or without the exposure of 100 mM alcohol. Phenotype analysis was performed at different time points and expression levels of transcription factors (TFs) and cytokine receptors were measured quantitatively and kinetically. Results: After 3 days in vitro culture, ONP cells differentiated into two populations: B220−CD11b− and B220−CD11b+ cells. B220−CD11b− cells can further differentiate into B lineage cells only with the support of B220−CD11b+ cells. Cells exposed to 100 mM of alcohol during the first 3 days of culture showed no statistically significant difference in B cell formation after 12 days compared with the control group. However, cells exposed to alcohol from Day 4 till the end of culture yield very few B cells. Expression levels of TFs and cytokine receptors were down-regulated kinetically among ONP cells co-cultured with the addition of 100 mM alcohol. Conclusions: Alcohol affects the ONP cell differentiation into B lineage at a late stage. Alcohol also down-regulates the expression level of TFs and cytokine receptors resulting in the impairment of B cell differentiation.
PMCID: PMC3002845  PMID: 21098503
3.  Response Inhibition Impairments Predict Alcohol-Induced Sedation 
Aims: The aim of this study was to probe the relationship between the subjective effects of alcohol and impulsive behavior in social drinkers. Methods: Fifty social drinkers performed a response-inhibition task before consuming alcohol. A 0.8-g/kg dose of alcohol was administered in a binge-like fashion (0.2 g/kg every 30 min) to the participants over a 2-h time period. Participants then completed questionnaires measuring stimulation, sedation and mood following consumption of alcohol. Linear regression analyses were performed by examining the relationship between performance on the response inhibition impulsivity task and subjective responses to alcohol (i.e. stimulation, sedation and arousal). Results: There was a significant positive relationship found between impulsive responding and self-reported sedation following alcohol consumption. Additionally, there was a significant negative relationship between behavioral impulsivity and self-reported stimulation and arousal following alcohol consumption. Conclusion: These results suggest that higher levels of impulsivity are associated with experiencing greater sedating than stimulating effects of alcohol. Individuals with high levels of impulsivity may be less sensitive to the stimulating effects of a specified dose of alcohol, which could lead to these individuals consuming more alcohol to experience the stimulating effects of alcohol.
PMCID: PMC3002846  PMID: 21127353
4.  The Impact of Screening, Brief Intervention and Referral for Treatment in Emergency Department Patients’ Alcohol Use: A 3-, 6- and 12-month Follow-up 
Aims: This study aims to determine the impact of Screening, Brief Intervention and Referral for Treatment (SBIRT) in reducing alcohol consumption in emergency department (ED) patients at 3, 6, and 12 months following exposure to the intervention. Methods: Patients drinking above the low-risk limits (at-risk to dependence), as defined by National Institute of Alcohol Abuse and Alcoholism (NIAAA), were recruited from 14 sites nationwide from April to August 2004. A quasi-experimental comparison group design included sequential recruitment of intervention and control patients at each site. Control patients received a written handout. The Intervention group received the handout and participated in a brief negotiated interview with direct referral for treatment if indicated. Follow-up surveys were conducted at 3, 6, and 12 months by telephone using an Interactive Voice Response (IVR) system. Results: Of the 1132 eligible patients consented and enrolled (581 control, 551 intervention), 699 (63%), 575 (52%) and 433 (38%) completed follow-up surveys via IVR at 3, 6, and 12 months, respectively. Regression analysis adjusting for the clustered sampling design and using multiple imputation procedures to account for subject attrition revealed that those receiving SBIRT reported roughly three drinks less per week than controls (B = −3.00, SE = 1.06, P < 0.05) and the level of maximum drinks per occasion was approximately three-fourths of a drink less than controls (B = -0.76, SE = 0.29, P < 0.05) at 3 months. At 6 and 12 months post-intervention, these effects had weakened considerably and were no longer statistically or substantively significant. Conclusion: SBIRT delivered by ED providers appears to have short-term effectiveness in reducing at-risk drinking, but multi-contact interventions or booster programs may be necessary to maintain long-term reductions in risky drinking.
PMCID: PMC3104610  PMID: 20876217
5.  Gender Differences in Drinking Practices in Middle Aged and Older Russians 
Aims: The study investigated gender differences in drinking patterns and the reasons behind them among men and women in the Russian city of Novosibirsk. Methods: A mixed method, combining quantitative and qualitative data, was conducted based on the Health, Alcohol and Psychosocial factors In Eastern Europe cohort study. The quantitative study included 4268 men and 5094 women aged 45–69 years; of those, 20 men and 24 women completed an in-depth interview. Results: The quantitative data revealed a large gap in drinking patterns in general between genders. Women drank less often and much smaller quantities than that of men. For example, 19% of men, vs. 1% of women, were classified as problem drinkers (two or more positive answers on the CAGE questionnaire). These differences were not explained by socioeconomic factors. Qualitative data have shown that gender roles and a traditional culture around women's and men's drinking were the main reasons for the reported drinking behaviour, whereby women were consistently expected to drink much less than men in terms of preference for strong beverages, drinking frequency and quantity of alcohol consumed. Conclusion: The study confirmed that large differences exist between Russian men's and women's drinking; these differences may be largely explained by gender roles.
PMCID: PMC3943390  PMID: 21075855
6.  fMRI BOLD Response in High-risk College Students (Part 1): During Exposure to Alcohol, Marijuana, Polydrug and Emotional Picture Cues† 
Aim: This functional magnetic resonance imaging (fMRI) study examined reactivity to alcohol, polydrug, marijuana and emotional picture cues in students who were referred to a college alcohol and drug assistance program. Methods: The fMRI data of 10 participants (5 females; 5 males) were collected while they viewed standardized emotional and appetitive cues. Results: Positive and negative emotional cues produced greater activity than neutral cues in the expected brain areas. Compared with neutral cues, alcohol cues produced greater brain activation in the right insula, left anterior cingulate, left caudate and left prefrontal cortex (Z = 2.01, 1.86, 1.82, 1.81, respectively; P < 0.05). Drug cues produced significantly greater left prefrontal activity compared with neutral cues, with polydrug cues activating the right insula and marijuana cues activating left anterior cingulate. Conclusions: Students at-risk for alcohol abuse showed neural reactivity to alcohol cues in four brain regions, which is consistent with their greater use of alcohol. Insula activation to appetitive cues may be an early marker of risk for progression to alcohol/drug abuse.
PMCID: PMC2930251  PMID: 20729530
7.  fMRI BOLD Response of High-risk College Students (Part 2): During Memory Priming of Alcohol, Marijuana and Polydrug Picture Cues 
Aims: This study examined brain activity using functional magnetic resonance imaging (fMRI) and reaction time (RT) during an implicit repetition priming memory task involving alcohol, polydrug, marijuana and emotional picture cues. Methods: Participants were 5 male and 5 female high-risk college students who had just participated in a cue exposure study (Ray et al., this issue). fMRI and RT data were collected while participants made decisions about previously seen and new picture cues. Results: Both behavioral RT and brain imaging data revealed strong memory priming for drug and alcohol cues. Neurologically, a repetition priming effect (suppression in neural activity for repeated cues) was observed in response to alcohol cues in the left prefrontal, bilateral occipital, and bilateral occipitotemporal regions, as well as right insula and right precuneus (Z ranged from 3.03 to 3.31 P < 0.05). Polydrug cues elicited priming in the occipital and temporal areas, and marijuana cues in the occipital area. Conclusions: Prefrontal and insular cortex involvement both in reactivity to alcohol cues (Ray et al., this issue) and subsequent implicit memory processing of these cues, as found in this study, suggests their potential role in the maintenance of high-risk alcohol use behaviors.
PMCID: PMC2930252  PMID: 20729527
8.  Alcohol Use Disorders Affect Antimicrobial Proteins and Anti-pneumococcal Activity in Epithelial Lining Fluid Obtained via Bronchoalveolar Lavage 
Aims: Our overall objective was to examine whether characteristics of epithelial lining fluid (ELF) from subjects with alcohol use disorders (AUDs) obtained via bronchoalveolar lavage (BAL) contribute to their predisposition to pneumococcal pneumonia. We sought to compare the anti-pneumococcal activity of acellular human BAL from subjects with AUDs to matched controls. Further, differences in BAL lysozyme activity and lactoferrin concentrations between these two groups were examined to determine the effect of AUDs on these antimicrobial proteins. Methods: BAL was performed in subjects with AUDs and matched controls. Acellular BAL was used at varying concentrations in an in vitro killing assay of Streptococcus pneumoniae, type 2, and the percent kill of organisms per microgram per milliliter total BAL protein was ascertained. Lysozyme activity and lactoferrin concentrations were measured in BAL from subjects and controls at measured concentrations of BAL protein. Results: AUD subjects (n = 15) and controls (n = 10) were enrolled in these investigations who were balanced in terms of smoking history. Using a mixed effect model, across the range of BAL protein concentrations, killing of pneumococcus tended to be less potent with BAL fluid from AUD subjects. Additionally, lysozyme activity and lactoferrin concentrations were significantly lower in the AUD group. Conclusions: The predisposition for pneumococcal pneumonia among those with AUDs may be in part mediated through effects of alcohol on substances within ELF that include antimicrobial proteins. Clarifying the composition and activity of ELF antimicrobial proteins in the setting of AUDs via investigations with human BAL fluid can help establish their contribution to the susceptibility for pulmonary infections in these individuals.
PMCID: PMC2930253  PMID: 20729531
9.  Changes in Alcohol Availability, Price and Alcohol-related Problems and the Collectivity of Drinking Cultures: What Happened in Southern and Northern Sweden?† 
Aims: The aims of this study were to study whether alcohol-related self-reported problems follow the same pattern of changes in alcohol consumption in southern Sweden, assumed to be affected by a decrease in Danish spirits tax and by an increase in Swedish travellers’ import quotas, and to study whether the results obtained for southern and northern Sweden follow the predictions of Skog's theory of collectivity of drinking cultures. Methods: Analysis was carried out on a sample from the  Swedish general population from southern and northern Sweden separately. Two indices such as impaired self-control/dependent behaviour and extrinsic problems for alcohol-related problems were computed and analysed in terms of sex, age, income and alcohol consumption level. Results: Although there were no huge changes in the number of persons reporting alcohol-related problems, the general trend in data for various subpopulations was a decrease in the southern site and an increase in the northern site. In the northern site, the increase in alcohol consumption among men also showed an increase in alcohol-related problems. However, various population subgroups changed in different directions and did not move in concert over the population distribution. Conclusions: Analysis confirmed that alcohol-related problems, according to the two indices used, followed a similar pattern to alcohol consumption, but less divergent. A version of Skog's theory applied on alcohol-related problems could not confirm that alcohol-related problems did not change collectively within the population.
PMCID: PMC2930254  PMID: 20739440
10.  Long-Term Modulations in the Vertebral Transcriptome of Adolescent-Stage Rats Exposed to Binge Alcohol 
Aims: Dangerous alcohol consumption practices are common in adolescents, yet little is known about their consequences on attainment of peak bone mass and long-term skeletal integrity. We previously demonstrated that binge alcohol-exposed adolescent rats showed site-specific reductions in accruement of bone mineral density and bone strength, which were incompletely recovered following prolonged alcohol abstinence. Currently, we analysed the vertebral transcriptome of adolescent rats following alcohol treatment and abstinence to identify long-term molecular changes in the lumbar spine. Methods: Sixty male adolescent Sprague-Dawley rats were assigned to one of six treatment groups receiving binge alcohol (3 g/kg) or saline i.p., 3 consecutive days (acute binge), 4 consecutive weekly (3-day) binge cycles (chronic binge) or 4 weekly binge cycles followed by a 30-day abstinence period (chronic binge with abstinence). Following treatment, lumbar vertebrae were assayed for global transcriptional changes using gene array technology. Results: Analysis of the adolescent rat vertebral transcriptome identified clusters of binge alcohol-sensitive genes displaying differential expression patterns starting before bone damage was seen and persisting after alcohol treatment was discontinued. Functional grouping of these gene clusters identified candidate cellular pathways affected following acute and chronic binge treatment, as well as pathways remaining modulated following abstinence. Conclusions: These results demonstrate that binge alcohol exposure can produce disruptions of normal bone gene expression patterns in the adolescent rat that persist well beyond the period of active intoxication. This data may have relevance to peak bone mass attainment and future risk of skeletal disease in adolescents engaging in repeated binge-drinking episodes.
PMCID: PMC2899847  PMID: 20554695
11.  Persistent High Alcohol Consumption in Alcohol-Preferring (P) Rats Results from a Lack of Normal Aversion to Alcohol 
Aims: In this study, we tested the impact of pretreatment with alcohol on subsequent alcohol drinking in outbred Sprague–Dawley and selectively bred alcohol-preferring (P) rats. Methods: As a pretreatment, male Sprague–Dawley and P rats were given a passive oral administration of either alcohol (1.0 g/kg) or tap water. Then, they were given free choice of drinking alcohol (5% v/v) or water in their home cages, which was measured over 4 weeks. Results: Without alcohol pretreatment, there was no significant strain difference in alcohol preference; both strains preferred 5% (v/v) alcohol solution. The strain difference was only apparent in the groups given alcohol pretreatment. This arose from the fact that alcohol pretreatment significantly reduced alcohol preference in the Sprague–Dawley rats to a level well below 50%, while it did not alter drinking behavior in P rats. The same effects were seen with total alcohol consumption (g/kg/day). These effects persisted throughout the 4 weeks of the study. Conclusions: The principal difference between the Sprague–Dawley and P rats was that the P rats did not show the normal aversion to alcohol after forced exposure to alcohol that the Sprague–Dawley rats showed. One of the potential contributors to high alcohol intake and preference in P rats may be lack of sensitivity to aversive effects of alcohol.
PMCID: PMC2899945  PMID: 20356869
12.  The Effect of Alcohol Consumption on Later Obesity in Early Adulthood — A Population-based Longitudinal Study 
Aims: The study aimed to determine whether alcohol use during late adolescence contributes to the weight gain from adolescence to young adulthood or risk of obesity or waist circumference at young adulthood.
Methods: A population-based, longitudinal study of 5563 Finnish twins born in 1975–1979 and surveyed at ages 16 (T1), 17 (T2), 18 (T3) and 23–27 (T4) years. Drinking habits, height and weight were self-reported at T1, T2, T3 and T4; waist circumference was self-measured at T4. As potential confounders, we used smoking, diet, physical activity, place of residence, socio-economic status and parents' body mass index (BMI).
Results: Compared to the reference group (drinking once to twice per month), the BMI increase from T3 to T4 was less among abstaining men (−0.62 kg/m2, (95% CI −1.04, −0.20)) and among women in those drinking less than monthly (−0.38 kg/m2, (−0.71, −0.04)). In women, at least weekly drinking was associated with larger waist circumference (Beta 1.55 cm, (0.48, 2.61)), but this became statistically non-significant after adjusting for potential confounders. In a multilevel model for change, drinking frequency was not associated with weight change in women; in men, a negative association was seen, but it was statistically non-significant after adjusting for potential confounders.
Conclusions: These results from a population-based study with a large set of confounding variables suggest that alcohol use during adolescence has at most a minor effect on weight gain or development of abdominal obesity from adolescence to young adulthood.
PMCID: PMC2842105  PMID: 20071348
13.  Alcohol Use Among Female Sex Workers and Male Clients: An Integrative Review of Global Literature 
Aims: To review the patterns, contexts and impacts of alcohol use associated with commercial sex reported in the global literature. Methods: We identified peer-reviewed English-language articles from 1980 to 2008 reporting alcohol consumption among female sex workers (FSWs) or male clients. We retrieved 70 articles describing 76 studies, in which 64 were quantitative (52 for FSWs, 12 for male clients) and 12 qualitative. Results: Studies increased over the past three decades, with geographic concentration of the research in Asia and North America. Alcohol use was prevalent among FSWs and clients. Integrating quantitative and qualitative studies, multilevel contexts of alcohol use in the sex work environment were identified, including workplace and occupation-related use, the use of alcohol to facilitate the transition into and practice of commercial sex among both FSWs and male clients, and self-medication among FSWs. Alcohol use was associated with adverse physical health, illicit drug use, mental health problems, and victimization of sexual violence, although its associations with HIV/sexually transmitted infections and unprotected sex among FSWs were inconclusive. Conclusions: Alcohol use in the context of commercial sex is prevalent, harmful among FSWs and male clients, but under-researched. Research in this area in more diverse settings and with standardized measures is required. The review underscores the importance of integrated intervention for alcohol use and related problems in multilevel contexts and with multiple components in order to effectively reduce alcohol use and its harmful effects among FSWs and their clients.
PMCID: PMC2842106  PMID: 20089544
14.  Procysteine Increases Alcohol-depleted Glutathione Stores in Rat Plantaris Following a Period of Abstinence 
Aims: To assess the effectiveness of procysteine (PRO) supplementation provided during a period of abstinence (ABS) on alcohol-induced skeletal muscle atrophy and oxidant stress. Methods: Age- and gender-matched Sprague–Dawley rats were fed the Lieber–DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 12 week. Next, subgroups of alcohol-fed rats were fed the control diet for 2 week (ABS) supplemented with either PRO (0.35%, w/v) or vehicle. Plantaris morphology was assessed by hematoxylin and eosin staining. Total, reduced and oxidized glutathione (GSH) levels and total antioxidant potential were determined by commercially available assay kits. Antibody arrays were used to determine cytokine levels. Real-time polymerase chain reaction was used to determine gene expressions of two E3 ubiquitin ligases, atrogin-1 and muscle ring finger protein-1 (MuRF-1). Results: Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased GSH levels, a trend for decreased total antioxidant potential and elevated atrogin-1 and MuRF-1 mRNA levels. GSH levels and total antioxidant potential continued to decrease during 2 weeks of ABS from alcohol, which were normalized in abstinent rats provided PRO. Gene levels of both E3 ligases returned to baseline during ABS. In parallel, plantaris cross-sectional area increased in both groups during ABS. Conclusions: PRO supplementation during ABS significantly attenuated alcohol-induced redox stress compared with untreated abstinent rats. Thus, our data may suggest that GSH restoration therapy may provide therapeutic benefits to the overall antioxidant state of skeletal muscle when prescribed in conjunction with an established detoxification program for recovering alcoholics.
PMCID: PMC2981520  PMID: 20935073
15.  Measures of Learning, Memory and Processing Speed Accurately Predict Smoking Status in Short-term Abstinent Treatment-seeking Alcohol-dependent Individuals 
Aim: Chronic cigarette smoking appears to adversely affect several domains of neurocognition in those with alcohol use disorders (AUDs). The primary goal of this study was to identify which measures commonly used to assess neurocognition in AUDs accurately predict smoking status of individuals seeking treatment of alcohol dependence. Methods: Treatment-seeking alcohol-dependent participants (ALC; n = 92) completed a comprehensive neuropsychological battery after 33 ± 9 days of abstinence. Measures significantly different between smoking and non-smoking ALC were entered as predictors in binary logistic regression and discriminant analysis models, with smoking status as the dependent variable. Results: Smoking ALC performed significantly worse than non-smoking ALC on measures assessing processing speed, auditory–verbal and visuospatial learning and memory. Using these measures as predictors, a logistic regression model accurately classified 91% of smokers and non-smokers into their respective groups overall and accounted for 68% of the variance in smoking status. The discriminant analysis confirmed the findings from the logistic regression. In smoking ALC, smoking chronicity was inversely related to performance on multiple measures after controlling for lifetime alcohol consumption. Conclusions: Measures of processing speed, learning and memory robustly predicted the smoking status of ALC with high sensitivity and specificity during early abstinence. The results identified specific measures within a comprehensive neurocognitive battery that discriminated smoking and non-smoking alcohol-dependent individuals with a high sensitivity and specificity. The association of greater smoking chronicity and poorer performance on multiple measures after control for alcohol consumption suggests that chronic smoking adds an additional burden to neurocognitive function in those with alcohol dependence.
PMCID: PMC2981519  PMID: 20923865
16.  Twelve-Month Follow-up Results from a Randomized Controlled Trial of a Brief Personalized Feedback Intervention for Problem Drinkers 
Aims: To examine the impact of a web-based personalized feedback intervention, the Check Your Drinking (CYD; screener at 12-month follow-up.
Methods: Respondents (N = 185) were recruited from a general population telephone survey of Ontario, Canadian adults (≥18 years) by asking risky drinkers if they were willing to help develop and evaluate Internet-based interventions for drinkers. Those randomly assigned to the intervention condition were provided with the web address and a unique password to a study-specific copy of the CYD. Respondents assigned to the control condition were sent a written description of the different components of the CYD and asked how useful they thought each of the components might be. Respondents were followed up at 3, 6 and 12 months.
Results: By the 12-month follow-up, the impact of the intervention previously reported at 3 and 6 months of CYD on problem drinkers’ alcohol consumption was no longer apparent (P > 0.05).
Conclusions: Recognizing that many people with alcohol concerns will never seek treatment, recent years have seen an increase in efforts to find ways to take treatment to problem drinkers. The CYD is one such intervention that has a demonstrated effect on reducing alcohol consumption in the short term (i.e. 6 months). Other more intensive Internet-based interventions or interventions via other modalities may enhance this positive outcome over the short and long term among problem drinkers who would be otherwise unlikely to access treatment for their alcohol concerns. registration #NCT00367575.
PMCID: PMC2857148  PMID: 20150170

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