bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antioxidant Pretreatment Does Not Ameliorate Alcohol‐Induced Purkinje Cell Loss in the Developing Rat Cerebellum
Authors: Grisel Jedidiah J. , Chen Wei‐Jung A. 
Published: July 2005

Background:Recent research has suggested that oxidative stress is a potential mechanism for alcohol‐induced injury and that supplementation with antioxidants can ameliorate alcohol‐induced damage. In this study, two known antioxidants, melatonin and U83836E, were assessed for their effectiveness in blocking the expected alcohol‐induced cerebellar Purkinje cell loss in neonatal rat pups.Methods:Sprague‐Dawley rat pups were artificially reared from postnatal days (PDs) 4–9 and were exposed to either alcohol or antioxidants (melatonin or U83836E) individually or in combination. A normal control group (raised by rat dams) was included in this study. On PD 9, the brain from each pup was removed and weighed, and the cerebellar vermis was processed for stereological cell counting.Results:Alcohol exposure during the brain growth spurt produced microencephaly, in addition to significant decreases in the number and density of Purkinje cells in lobule I and the volume of lobule I. The antioxidants did not reduce any of the adverse effects observed from alcohol exposure, and they did not decrease the Purkinje cell number when administered alone. Furthermore, antioxidants did not change the only blood alcohol concentration measured on PD 6.Conclusions:The results confirmed alcohol‐induced microencephaly and cerebellar Purkinje cell loss from neonatal alcohol exposure, and they showed that neither antioxidant could attenuate these adverse effects on the developing brain. The inability of antioxidants to reduce Purkinje cell loss from neonatal alcohol exposure suggests the existence of alternative mechanisms for developmental alcohol‐induced Purkinje cell loss.
A Temporal and Dose‐Response Association Between Alcohol Consumption and Medication Adherence Among Veterans in Care
Authors: Braithwaite R Scott , McGinnis Kathleen A. , Conigliaro Joseph , Maisto Stephen A. , Crystal Stephen , Day Nancy , Cook Robert L. , Gordon Adam , Bridges Michael W. , Seiler Jason F. S. , Justice Amy C. 
Published: July 2005

Background:Previous studies have shown that alcohol consumption is associated with decreased medication adherence, but this association may be confounded by characteristics common among those who drink heavily and those who fail to adhere (e.g., illicit drug use). Our objective was to determine whether there are temporal and dose‐response relationships between alcohol consumption and poor adherence.Methods:We administered telephone interview surveys to participants in the Veterans Aging Cohort Study, an eight‐site observational study of HIV& and matched HIV‐ veterans in care, to determine whether alcohol consumption on a particular day was associated with nonadherence to prescribed medications on that same day. We used the Time Line Follow Back to measure alcohol consumption and the Time Line Follow Back Modified for Adherence to measure adherence. Individuals were categorized as abstainers (no alcohol in past 30 days), nonbinge drinkers (alcohol in past 30 days but ≤four standard drinks on each day), or binge drinkers (≥five standard drinks on at least one day).Results:Among 2702 respondents, 1582 (56.6%) were abstainers, 931 (34.5%) were nonbinge drinkers, and 239 (8.9%) were binge drinkers. Abstainers missed medication doses on 2.4% of surveyed days. Nonbinge drinkers missed doses on 3.5% of drinking days, 3.1% of postdrinking days, and 2.1% of nondrinking days (p < 0.001 for trend), and this trend was more pronounced among HIV+ individuals than HIV‐ individuals. Binge drinkers missed doses on 11.0% of drinking days, 7.0% of postdrinking days, and 4.1% of nondrinking days (p < 0.001 for trend), and this trend was comparably strong for HIV+ and HIV‐ individuals.Conclusions:Among veterans in care, self‐reported alcohol consumption demonstrates a temporal and dose‐response relationship to poor adherence. HIV+ individuals may be particularly sensitive to alcohol consumption.
Alcohol Consumption, Lung Function, and Quality of Life in Pneumoconiosis
Authors: Tang Wai Kwong , Lum C M. , Ungvari Gabor S. , Chiu Helen F. K. 
Published: July 2005

Background:To our knowledge, there are no previous data on drinking problems in patients with pneumoconiosis. The aim of this study was to examine drinking patterns and the impact of drinking on lung function and health‐related quality of life (HRQOL) in Chinese patients with pneumoconiosis.Methods:Three hundred patients with pneumoconiosis were recruited from a community‐based case registry. The HRQOL was measured with the St. George's Respiratory Questionnaire (SGRQ). Pulmonary function, comorbidity, and psychosocial variables were also assessed. The alcohol use of the patients was evaluated with the Alcohol Use Disorders Identification questionnaire.Results:Of the 300 patients, 72.3% (217) reported that they had not consumed any alcohol during the past year, whereas 83 patients (27.7%) did report drinking alcohol. In the drinking group, 88.0% (73) consumed <7 standard drinks per week, and none of them exceeded the safety limit of 21 standard drinks per week. The drinking group (n= 83) was younger, had less concurrent medical diseases, and lower (i.e., better) unadjusted SGRQ symptom, activity, impact, and total scores than the nondrinking group (n= 217). The SGRQ scores, which were adjusted for age, duration of occupation, concurrent medical diseases, smoking status, and forced expiratory volume in 1 sec predicted tests (FEV1%), remained significantly lower for the drinking group. Although the drinking group had a higher unadjusted FEV1% predicted, the difference between the FEV1% of the two groups, after adjustment for covariates, was of borderline significance only.Conclusions:Most Chinese patients with pneumoconiosis in this study did not consume alcohol, and among those who did, the level of alcohol consumption was low. This low level of alcohol consumption was associated with a better HRQOL and possibly with better lung function.
Manipulations of Serotonin Function in the Nucleus Accumbens Core Produce Differential Effects on Ethanol and Sucrose Seeking and Intake
Authors: Czachowski Cristine L. 
Published: July 2005

Objective:Behaviorally relevant stimuli, including alcohol, are processed through the nucleus accumbens/ventral tegmental area (VTA)/prefrontal cortex circuit. It is hypothesized that serotonin affects ethanol‐directed behaviors by interacting with this system via projections from the dorsal raphe to the nucleus accumbens and VTA. The current studies utilized two different operant paradigms, one focusing on reinforcer seeking and one focusing on reinforcer self‐administration (both with an ethanol and a sucrose solution as the reinforcer) to elucidate serotonin‐specific regulation of these behaviors.Methods:The present experiments assessed the effects of microinjections of a serotonin1B agonist (CGS12066B) and a serotonin1A agonist (8‐OH‐DPAT) in the nucleus accumbens core on ethanol‐ and sucrose‐reinforced seeking and intake. In four separate experiments, male Long‐Evans rats were trained to complete a single response requirement that resulted in access to 10% ethanol or 2% sucrose for a 20‐min drinking period.Results:Before microinjections, ethanol‐reinforced subjects were consuming an average of 0.5‐0.95 g/kg ethanol and making 50‐100 responses during intermittent nonreinforced sham (no drug) sessions (sucrose groups had similar baseline response levels). In summary, findings from the four experiments showed the following: (1) manipulations of serotonin function that had effects on ethanol‐reinforced responding had either no effect or less pronounced effects on sucrose‐reinforced responding; (2) administration of the serotonin1B agonist decreased seeking behaviors to a greater degree than drinking behaviors; and (3) administration of the serotonin1A agonist decreased ethanol intake but not seeking with no impact at all on sucrose‐reinforced behaviors.Conclusions:Manipulations of serotonin activity in the nucleus accumbens core had little effect on sucrose‐reinforced behaviors and differential effects on ethanol seeking versus intake, suggesting that this area may play a complex but selective role in the stimulus processing of external and internal alcohol‐associated cues.
The −159C/T Polymorphism in the Promoter Region of the CD14 Gene Is Associated With Advanced Liver Disease and Higher Serum Levels of Acute‐Phase Proteins in Heavy Drinkers
Authors: Campos Joaquin , Gonzalez‐Quintela Arturo , Quinteiro Celsa , Gude Francisco , Perez Luis‐Fernando , Torre Jose‐Antonio , Vidal Carmen 
Published: July 2005

Background:Innate inflammatory responses to endotoxin (lipopolysaccharide) contribute to the development of alcoholic liver disease (ALD). A single‐nucleotide polymorphism (−159C/T) in the promoter region of the gene coding for CD14 (a lipopolysaccharide receptor) could be associated with the development of ALD. We sought too investigate the relationship between the CD14/−159C/T polymorphism and advanced ALD and acute‐phase protein levels in heavy drinkers.Methods:A total of 138 heavy drinkers consecutively admitted to an Internal Medicine department were genotyped for the CD14/−159C/T polymorphism. Serum samples were analyzed for lipopolysaccharide‐binding protein (LBP), soluble CD14 (sCD14), C‐reactive protein (CRP), and immunoglobulin (Ig) A, IgG, and IgM. Patients with ascites or liver encephalopathy (n= 35) were classified as having advanced ALD.Results:After adjusting for potential confounding variables, the CD14/‐159TT genotype was positively associated with advanced ALD (odds ratio, 2.99; 95% confidence interval, 1.09–8.24, p= 0.03) and serum LBP (p= 0.01) and sCD14 (p= 0.04) levels. The CD14/−159C/T polymorphism was not associated with serum levels of CRP, IgA, IgG, or IgM.Conclusions:Our results support the notion that CD14/−159TT homozygous heavy drinkers have higher levels of the LPS‐binding acute‐phase proteins (LBP and sCD14) than do carriers of the CD14/−159C allele. Also, the CD14/−159TT genotype may be a risk factor for advanced ALD.
Development of a Chinese Version of the Yale‐Brown Obsessive Compulsive Scale for Heavy Drinking
Authors: Gau Susan S. F. , Liu Chia‐Yih , Lee Chau‐Shoun , Chang Jung‐Chen , Chang Ching‐Jui , Li Chang‐Fang , Chen Chiao‐Chicy , Cheng Andrew T. A. 
Published: July 2005

Background:Measurement of craving is an important component in the investigation of the etiology and clinical pictures of alcoholism and dependence of other substances in different cultures. The aim of this study was to develop a Chinese version of the Yale‐Brown Obsessive Compulsive Scale for heavy drinking (YBOCS‐hd‐C), the instrument most frequently used in assessing the severity of alcohol craving in Taiwan.Methods:Four hundred twenty Han Chinese (220 with alcohol use disorders) and 218 Bunun aborigines (150 with alcohol use disorders) in Taiwan were interviewed by mental health professionals with the YBOCS‐hd‐C and a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry to establish the psychiatric diagnosis. Validity and reliability of the YBOCS‐hd‐C were examined.Results:The YBOCS‐hd‐C was found to have acceptable interrater reliability (intraclass correlation, 0.89–0.96), internal consistency (Cronbach's α= 0.99), construct validity, concurrent validity, and cross‐cultural validity. The correlations between 10 items of the YBOCS‐hd‐C and 11 items of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry adjusted for age, gender, and ethnicity ranged from 0.39 to 1.00. The YBOCS‐hd‐C also discriminated effectively among individuals with alcohol dependence, alcohol abusers, and normal drinkers.Conclusions:This study demonstrated that the YBOCS‐hd‐C is a reliable and valid instrument for assessing the extent of craving for alcohol in Taiwanese Han and Bunun individuals.
Hangover Susceptibility in Relation to Aldehyde Dehydrogenase‐2 Genotype, Alcohol Flushing, and Mean Corpuscular Volume in Japanese Workers
Authors: Yokoyama Masako , Yokoyama Akira , Yokoyama Tetsuji , Funazu Kazuo , Hamana Genichi , Kondo Shuji , Yamashita Takeshi , Nakamura Haruo 
Published: July 2005

Background:A study of Asian‐American students suggested a positive association between inactive ALDH2*2 and susceptibility to hangover. A biomarker for moderate‐to‐heavy drinking in persons with inactive aldehyde dehydrogenase‐2 (ALDH2) is increased mean corpuscular volume (MCV).Methods:Associations between hangover and ALDH2 genotype, alcohol flushing, and MCV were examined for 251 Japanese workers (139 men, 112 women).Results:Inactive ALDH2*1/2*2 heterozygotes drank less alcohol than active ALDH2*1/2*1 homozygotes (p < 0.0001), but the frequency of hangover did not significantly differ between the two groups for either gender. The amount of drinking reported to lead to hangover was significantly less for male and female ALDH2*1/2*2 heterozygotes than for their ALDH2*1/2*1 homozygous counterparts (p < 0.005). The proportion of men who had hangover three times or more during the past year increased significantly with increased daily alcohol consumption in men with the ALDH2*1/2*2 genotype (p= 0.0002) but not in those with the ALDH2*1/2*1 genotype. For men who usually consumed <44 g of ethanol/day, the median amount of drinking before hangover was significantly lower for ALDH2*1/2*2 men than for ALDH2*1/2*1 men reporting the same level of consumption. Hangover occurred with consistently high frequency among ALDH2*1/2*1 men, regardless of their daily consumption. Similar findings were observed in a comparison of men who never flushed and those who reported current or former flushing, a surrogate marker of inactive ALDH2. Assessment of hangover risk by quartiles of MCV showed that men with MCV of ≥96 had a significantly higher risk of hangover than did men with MCV of <91 (odds ratio = 5.56; 95% confidence interval = 1.69‐18.25).Conclusions:Inactive heterozygous ALDH2, alcohol flushing, and increased MCV were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover.
Hormone Responses to Social Stress in Abstinent Alcohol‐Dependent Subjects and Social Drinkers with No History of Alcohol Dependence
Authors: Munro Cynthia A. , Oswald Lynn M. , Weerts Elise M. , McCaul Mary E. , Wand Gary S. 
Published: July 2005

Background:Previous studies have described blunted stress hormone responses after pharmacological activation of the hypothalamic‐pituitary‐adrenal (HPA) axis in sober alcoholics. The aim of the present study was to compare ACTH, cortisol, and prolactin responses to a psychological stressor in abstinent alcohol‐dependent subjects matched to healthy control subjects.Methods:Individuals who met DSM‐IV diagnostic criteria for a history of alcohol dependence but not for other axis I disorders were included in the study (n= 18; mean duration of abstinence ± SEM, 3.5 ± 5.7 years). Social drinkers (n= 23) served as control subjects. The sober alcohol‐dependent and control subjects were matched for demographic measures including levels of stress symptoms. All subjects underwent the Trier Social Stress Test (TSST), a laboratory‐based psychological stressor. Prestress and poststress plasma ACTH, cortisol, and prolactin levels, as well as a self‐report measure of anxiety (State‐Trait Anxiety Inventory), were obtained.Results:Nondepressed, abstinent alcoholics and control subjects did not differ with regard to age, racial composition, or baseline or poststress ratings of anxiety. Whereas ACTH and cortisol levels increased in response to the TSST, prolactin levels did not. Stress hormone response curves for the three hormones did not differ between the alcoholics and control subjects.Conclusions:When matched for levels of stress, a laboratory‐based psychological stress test did not induce differential hormone response curves for abstinent alcoholics and control subjects.
Ethanol Triggers Neural Crest Apoptosis through the Selective Activation of a Pertussis Toxin–Sensitive G Protein and a Phospholipase Cβ–Dependent Ca2+ Transient
Authors: Garic‐Stankovic Ana , Hernandez Marcos R. , Chiang Po Jen , Debelak‐Kragtorp Katherine A. , Flentke George R. , Armant D Randall , Smith Susan M. 
Published: July 2005

Background:Alcohol is a potent neurotoxin that triggers the selective apoptosis of neuronal populations in the developing fetus. For neural crest cells, clinically relevant ethanol levels (0.3%) rapidly elicit a phospholipase C (PLC)–dependent intracellular Ca2+ transient that is sufficient to activate apoptosis. We investigated the biochemical origins of this Ca2+ transient.Methods:Three somite chick embryos (stage 8‐) were pretreated with agonists and antagonists of PLC signaling pathways before ethanol challenge. The resulting intracellular Ca2+ release was quantified using Fluo‐3; apoptosis was assessed using vital dyes.Results:Pretreatment of embryos with PLC antagonists U73122 or ET‐18‐OCH3 confirmed that a phosphoinositide‐specific PLC was required for both the ethanol‐dependent Ca2+ transient and subsequent cell death. Ethanol rapidly elevated intracellular inositol‐1,4,5‐trisphosphate Ins(1,4,5)P3 levels in the rostral portion of the embryo that contains neural crest progenitors. The Ins(1,4,5)P3 receptor antagonist xestospongin C blocked the appearance of the ethanol‐dependent Ca2+ transient. Pretreatment with the pan‐Gα protein antagonist GDPβS, but not with the tyrosine kinase antagonist genistein, suppressed ethanol's ability to elicit the Ca2+ transient, suggesting that a rise in PLC activity and Ins(1,4,5)P3 concentration originates from stimulation of heterotrimeric G proteins. To probe the identity of this G protein, embryos were treated with G protein antagonists. Pertussis toxin and NF023 suppressed the ethanol‐induced Ca2+ transient and subsequent neural crest apoptosis, whereas suramin was weakly inhibitory. C3 exoenzyme was embryolethal over a wide concentration range, consistent with suggestions that Rho family GTPases participate in neural crest development. Gαi2 was identified by immunostaining in the neural crest cells.Conclusion:We propose a role for Gαi/o protein activation and subsequent interaction of Gβγ with PLCβ in mediating the proapoptotic effects of ethanol upon the developing neural crest.
An analytical model assessing the potential threat to natural habitats from insect resistance transgenes
Authors: Kelly Colleen K , Bowler Michael G , Breden Felix , Fenner Michael , Poppy Guy M 
Published: July 2005

We examine the role of ecological interactions on effective gene flow from genetically manipulated plants to their wild relatives. We do so by constructing and applying to oilseed rape (OSR) an analytical model for interaction between plants with and without an insect resistance (IR) allele in natural communities, incorporating documented levels of herbivore variability. We find that with reasonable values of advantage to the IR allele, little concomitant disadvantage (physiological costs of the allele) restricts it to low proportions of the natural population for large numbers of generations. We conclude that OSR IR transgenes are unlikely to pose an immediate threat to natural communities.
Our model identifies those factors best able to regulate particular transgenes at the population level, the most effective being impaired viability of seeds in the period between production and the following growing season, although other possibilities exist. Because solutions rely on ratios, limiting values of regulating factors are testable under controlled conditions, minimizing risk of release into the environment and offering significant advancement on existing testing programmes. Our model addresses folivory but is easily modified for herbivory damaging the seed or directly affecting seed production by infested plants, or for pathogens altering seed survival in the seedbank.
Population genetic approaches to neurological disease: Parkinson's disease as an example
Authors: Gandhi S , Abou-Sleiman P.M , Healy D.G , Weale M , Gilks W , Ahmadi K , Goldstein D.B , Wood N.W 
Published: July 2005

Parkinson's disease (PD) is a common, progressive, incurable disabling condition. The cause is unknown but over the past few years tremendous progress in our understanding of the genetic bases of this condition has been made. To date, this has almost exclusively come from the study of relatively rare Mendelian forms of the disease and there are no currently, widely accepted common variants known to increase susceptibility.
The role that the ‘Mendelian’ genes play in common sporadic forms of PD is unknown. Moreover, most studies in PD can really be described as candidate polymorphism studies rather than true and complete assessments of the genes themselves. We provide a model of how one might tackle some of these issues using Parkinson's disease as an illustration. One of the emerging hypotheses of gene environment interaction in Parkinson's disease is based on drug metabolizing (or xenobiotic) enzymes and their interaction with putative environmental toxins. This motivated us to describe a tagging approach for an extensive but not exhaustive list of 55 drug metabolizing enzyme genes. We use these data to illustrate the power, and some of the limitations of a haplotype tagging approach. We show that haplotype tagging is extremely efficient and works well with only a modest increase in effort through different populations. The tagging approach works much less well if the minor allele frequency is below 5%. However, it will now be possible using these tags to evaluate these genes comprehensively in PD and other neurodegenerative conditions.