bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcoholic Hepatitis as a T‐Cell Mediated Disorder: An Hypothesis
Authors: Batey R. G. , Clancy R. L. , Pang G. T. , Cao Q. 
Published: May 2006

Background: The mechanism by which alcohol induces alcoholic hepatitis, the precursor lesion for cirrhosis, has never been elucidated. In particular, direct toxicity has not been proven. This article reviews the hypothesis that a primary target of chronic alcohol ingestion is the T lymphocyte. The lesion in the T lymphocyte is characterized by reduced baseline secretion of cytokines, including tumor necrosis factor‐α; although characterized by an exaggerated release of cytokines when stimulated by polyclonal activators such as endotoxin. High concentrations of cytokines, especially tumor necrosis factor‐α, within the liver induce necrosis/apoptosis of hepatocytes. Methods: Data supporting this hypothesis in rodent models are reviewed. Conclusion: A strategic approach for testing this concept in man is defined.
Binge Drinking and Bone Metabolism in a Young Actively Growing Rat Model
Authors: Sampson H. Wayne , Gallager Sharon , Lange Jason , Chondra Whitney , Hogan Harry A 
Published: May 2006

Background: Chronic alcohol consumption has been demonstrated to be deleterious to bone health. However, binge drinking is the prevalent form of drinking in young people, which was the impetus for the present study to determine the effect of week‐end and week‐long binge drinking on bone health in a young actively growing animal model. Methods: Four‐week‐old, female, Sprague‐Dawley rats were given the amount of 5% alcohol by gavage to be equivalent to a 63 kg woman drinking six beers a day for either 2 or 5 consecutive days per week. Results: There were no changes in the 5‐day binge animals, but the 2‐day binge animals were hypocalcemia Similarly, 2‐day binge animals had slightly increased bone chemistry and histomorphometric values for both tibia and femur, but only femur length, dry weight, and ash weight as well as femur density, presented either as g/ml or ash weight per unit volume, were increased by a statistically significant level. Cross‐section periosteal Mineral Apposition Rate (MAR) was significantly decreased in the 2‐day alcohol fed animals. Conclusions: Actively growing rats given 5% alcohol by gavage for 2 days per week have an increased bone length, bone weight, and bone density. The interpretation of these results must be viewed with great caution because studies of chronic alcohol consumption, and many studies of acute drinking, clearly indicate deleterious effects of alcohol on bone health. Those fed alcohol for 5 days per week showed no change.
Serotonergic Neuronal Activity in the Dorsal Raphe Nucleus of Selectively Bred Alcohol‐Preferring and Alcohol‐Nonpreferring Rats and Unselected Wistar Rats
Authors: Morzorati Sandra L. , Johnson Timothy B. 
Published: May 2006

Background:Selectively‐bred alcohol‐preferring (P) rats have fewer serotonin (5‐HT) neurons in the dorsal raphe nucleus (DRN) than do alcohol‐nonpreferring (NP) rats. The present study was designed to test the hypothesis that the remaining 5‐HT neurons in P rats compensated for their reduced number by increasing neuronal activity.Methods:Spontaneous activity was recorded from single‐spiking and bursting 5‐HT neurons in the DRN of unanesthetized paralyzed, alcohol‐naive P, NP, and Wistar rats. Firing frequencies, the percentages of action potentials in bursts, and the percentages of bursting neurons were evaluated.Results:There were no significant differences among the three groups of rats in any of the parameters measured. Power analyses were performed on preliminary data to determine the sample sizes necessary for detection of significant differences. The mean firing frequencies of single‐spiking 5‐HT neurons averaged 1.8 (37 neurons), 1.7 (17 neurons), and 1.8 (41 neurons) spikes per second in P, NP, and Wistar rats, respectively. For bursting 5‐HT neurons, the percentages of action potentials in bursts for P, NP, and Wistar rats were 55.0% (24 neurons), 49.7% (18 neurons), and 55.1% (21 neurons). The mean percentages of bursting 5‐HT neurons encountered per electrode penetration were 44% for P rats (n= 28), 44% for NP rats (n= 14), and 34% for Wistar rats (n= 26).Conclusions:The results indicate that the sample of 5‐HT neurons recorded in the DRN of P rats had not compensated for a reduced number by altering neuronal activity.
Naltrexone's Effect on Cue‐Elicited Craving Among Alcoholics in Treatment
Authors: Monti Peter M. , Rohsenow Damaris J. , Hutchison Kent E. , Swift Robert M. , Mueller Timothy I. , Colby Suzanne M. , Brown Richard A. , Gulliver Suzy B. , Gordon Alan , Abrams David B. 
Published: May 2006

Background: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high‐risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory‐based, cue‐elicited urge to drink among abstinent alcoholics in treatment. Methods: Alcohol‐dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After ∼ 1 week on medication, all received cue reactivity assessment. Results: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue‐elicited decreases in heart rate were not affected by the medication. Conclusions: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments.
Role of Yeasts in the Salivary Acetaldehyde Production From Ethanol Among Risk Groups for Ethanol‐Associated Oral Cavity Cancer
Authors: Tillonen J. , Homann N. , Rautio M. , Jousimies‐Somer H. , Salaspuro M. 
Published: May 2006

Background: Acetaldehyde, the first metabolite of alcohol, has been proposed to be the carcinogenic substance behind ethanol‐related oral cancers. High levels of acetaldehyde are formed from ethanol in saliva by the oral flora, but so far the role of certain microbial species responsible for this phenomenon is not known. Yeasts are common commensals of the oral cavity that have alcohol‐oxidizing enzymes, thus providing a potential source of acetaldehyde from ethanol. The aim of this study was to examine the contribution of oral yeasts to the production of ethanol‐derived acetaldehyde in the oral cavity. Methods: Fifty‐five saliva samples were divided into two groups, high and low, based on the in vitro salivary acetaldehyde production capacity from ethanol. Yeasts were isolated and identified from these samples, and their acetaldehyde production capacity was determined gas chromatographically by incubating intact cells with ethanol at the physiological pH of 7.4. Results: Yeast colonization was found in 78% of the high acetaldehyde‐producing salivas, compared with 47% in the low acetaldehyde‐producing salivas (p = 0.026). Among carriers, the density of yeasts was higher in the high than in low acetaldehyde producers (p = 0.025). Candida albicans was the main species isolated (88% of all oral isolates). Moreover, C. albicans strains isolated from the high acetaldehyde‐producing salivas formed significantly higher acetaldehyde levels from ethanol than C. albicans strains from low‐acctaldehyde‐producing salivas (73.1 nmol ach/10e6 colony‐forming units vs. 43.2 nmol ach/10e6 colony‐forming units, p= 0.035). Conclusions: This study shows that some C. albicans strains have a marked capacity to produce toxic and carcinogenic acetaldehyde from ethanol in vitro. Because the in vitro production of salivary acetaldehyde has been previously shown to correlate with in vivo acetaldehyde production, our finding could be an important microbial pathogenetic factor underlying cancer of the oral cavity associated with ethanol drinking.
Genetic Polymorphism of Aldehyde Dehydrogenase 2 in Patients With Upper Aerodigestive Tract Cancer
Authors: Tanabe Hiroki , Ohhira Motoyuki , Ohtsubo Tikara , Watari Jiro , Yokota Kinichi , Kohgo Yutaka 
Published: May 2006

Background: Alcohol consumption is one of the major risk factors of the upper aerodigestive tract (UADT) cancers, and combined cancers are frequently discovered in the patients with UADT cancer. The association between esophageal cancer and alcohol‐related metabolizing enzymes is well studied, but only a few examinations about the association between head and neck cancer and the enzymes were performed. Methods: Fifty‐two patients with UADT cancer (head and neck cancer in 25, esophageal cancer in 19, and multiple cancers in 8) were examined in the alcohol habit and in the polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P‐4502E1. Results: Patients with multiple cancers had significantly higher ethanol consumption than the other two groups (p < 0.001). The frequency of ALDH2* 1/2*2 heterozygote was significantly lower (p= 0.009) in patients with head and neck cancer (5/25) than patients with esophageal cancer (11/19). The allele frequency of P‐4502E1 did not show a significant difference between the groups (p= 0.700). Conclusions: These results demonstrated the difference in the frequency of ALDH2 heterozygote between the patients with esophageal cancer and patients with head and neck cancer.
Quantitative Trait Loci Affecting Ethanol Sensitivity in BXD Recombinant Inbred Mice
Authors: Browman Kaitlin E. , Crabbe John C. 
Published: May 2006

Background:Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains.Methods:We conducted a QTL analysis of ethanol‐induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen.Results:Genome‐wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p≤ 0.01). These provisional QTLs were on all chromosomes except 2,5,12,13, and X, and several map near potential candidate genes.Conclusions:These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.
Comparison of Cross‐Sectional and Daily Reports in Studying the Relationship Between Depression and Use of Alcohol in Response to Stress in College Students
Authors: Flynn Heather A. 
Published: May 2006

Background:Alcohol use in response to stress in college students may be affected by the presence of symptoms of depression. However, this is a challenging issue to study due to the various methodologies used as well as the possible effect of depressed mood on the accuracy of self‐report. This study focused on methodological issues as possible sources of equivocal findings regarding the relationship between depressed mood and alcohol use in response to stress in a college student population. Findings may differ when these variables are examined cross‐sectionally versus longitudinally.Methods:Depressed mood and alcohol coping were assessed both cross‐sectionally and repeatedly over time in 125 college students. Participants were assessed at baseline using a diagnostic self‐report measure of depression as well as a measure of typical coping style. In addition, daily measures of stress, symptoms of depression, and coping were completed for 45 consecutive days.Results:Different relationships between depressed mood and alcohol coping were found when depressed individuals were analyzed separately from those who were not depressed. Although a significant correlation between daily use of alcohol coping and daily depressed mood was found, there were no differences between depressed and nondepressed participants (as assessed at baseline) on daily alcohol coping.Conclusions:These findings have implications for research design as well as clinical assessment regarding the relationships between mood and use of alcohol for coping; the findings suggest that cross‐sectional measures of mood and alcohol use may obscure differences as assessed repeatedly over time. In addition, these findings support the utility of frequent assessment of depressive symptoms when implementing or evaluating programs that target coping skills in college students.
Differential Effects of Ethanol on Signal Transduction
Authors: Levine Gail H. , Maglio Jeff J. , Horwitz Joel 
Published: May 2006

Background:PC12 pheochromocytoma cells were used as a model to study the effect of long‐term ethanol exposure on signal transduction systems. In PC12 cells, the agonist bradykinin stimulates a phospholipase C specific for inositol‐containing phospholipids and a phospholipase D specific for phosphatidylcholine.Methods:PC12 cells were grown in monolayer and cultured in the presence and absence of 1% ethanol for 5 days. After this period, bradykinin‐stimulated phospholipase C and D were measured. The effect of long‐term ethanol on the bradykinin‐mediated activation of mitogen‐activated protein (MAP) kinase was also measured.Results:In cells exposed to 1% ethanol for 5 days, bradykinin‐stimulated phospholipase D was greatly attenuated, whereas bradykinin‐stimulated phospholipase C was not altered. The tyrosine kinase inhibitor, genistein, blocked the bradykinin‐mediated activation of phospholipase D but did not affect the stimulation of phospholipase C. However, long‐term ethanol treatment did not attenuate the ability of bradykinin to activate MAP kinase, which suggests that ethanol did not have a general effect on all tyrosine kinase pathways.Conclusions:Ethanol has a differential effect on signal transduction in PC12 cells. Activation of phospholipase D may be mediated by a kinase, whereas the activation of phospholipase C is probably mediated by the guanine nucleotide binding protein, Gq. Because of these differences in activation mechanism, the pathways may adapt differently to long‐term exposure to ethanol.
Effect of Hormone Balance on Carbohydrate‐Deficient Transferrin and Gamma‐Glutamyltransferase in Female Social Drinkers
Authors: Sillanaukee Pekka , Alho Hannu , Strid Nuria , Jousilahti Pekka , Vartiainen Erkki , Olsson Ulf , Sillanaukee Päivi 
Published: May 2006

Background:Carbohydrate‐deficient transferrin (CDT) and γ‐glutamyltransferase (GGT) are the most commonly used markers for alcohol abuse, but their sensitivity and specificity are lower and have different reference values among females compared with males. In the present study, we evaluated the effect of women's hormone balance on these two alcohol markers, as well as on their mathematical combination, named γ‐CDT.Methods:An age‐stratified random sample of 3962 women, between 25–74 years old, was drawn from the normal population. Pregnancy, the use of oral contraceptives, intrauterine device for contraception, hormone replacement therapy, and hormone treatment for infertility were considered. A comparison between fertile, peri‐ and postmenopausal women was also done.Results:Existing pregnancy increased CDT levels but decreased GGT values. Lower CDT and higher GGT levels were observed among those women using oral contraceptives and in postmenopausal women compared with women at the fertile stage. γ‐CDT was not influenced by hormone balance.Conclusions:The different hormonal status had an opposite effect on CDT and GGT. Women who were close to late menopause had levels of both markers closer to the values of men. It must be pointed out that the findings presented here are based on measurements of absolute CDT values and that no measurements of total transferrin were done. γ‐CDT, not influenced by hormone balance, indicates promising clinical utility among women.
Predictors of Compliance with Naltrexone Among Alcoholics
Authors: Rohsenow Damaris J. , Colby Suzanne M. , Monti Peter M. , Swift Robert M. , Martin Rosemarie A. , Mueller Timothy I. , Gordon Alan , Eaton Cheryl A. 
Published: May 2006

Objective:Naltrexone has been found to be an effective adjunct to treatment to reduce the rate of drinking among alcoholics. However, adherence to the medication has been of considerable concern; the high rates of noncompliance with the medication limits the benefits that could potentially be realized from this pharmacotherapy. Knowledge of predictors of noncompliance could result in interventions targeted at these variables.Method:Participants were 128 alcohol‐dependent patients who participated in a clinical placebocontrolled trial of naltrexone. Upon discharge from a 1‐ to 2‐week partial hospital program, patients were randomly placed into 12 weeks of naltrexone (50 mg/day) or placebo (n= 64 per condition). Patients met with a physician and a research assistant weekly for 4 weeks then biweekly for 8 weeks.Results:Compliance (number of days taking medication) was not predicted by demographic or pretreatment alcohol use variables. Number and severity of side effects in the first week, particularly nausea and fatigue, predicted early termination. Compliance was not predicted by commitment to abstinence or self‐efficacy about abstinence, but was greater among patients who believed more strongly that the medication would help them stay sober. Compliance was not predicted by general level of urge to drink during the first week on medication but compliance was greater among those with a higher urge to drink in response to alcohol stimuli in the laboratory.Conclusions:Implications for approaches to increase compliance include reducing side effects and increasing patients’beliefs in the efficacy of naltrexone.
Ethanol Exposure Enhances Apoptosis Within the Testes
Authors: Zhu Qianlong , Meisinger Jeremy , Emanuele Nicholas V. , Emanuele Mary Ann , LaPaglia Nancy , Van Thiel David H. 
Published: May 2006

Background:Chronic ethanol abuse causes testicular atrophy and male infertility in alcoholic men. It is well known that ethanol exposure disrupts the hypothalamic‐pituitary‐gonadal axis, adversely affects the secretory function of Sertoli cells, and produces oxidative stress within the testes. It is still not clear what cellular mechanisms are responsible for the morphologic alteration of the testes that results in a reduction of testicular mass as a consequence of ethanol exposure. The hypothesis tested was that ethanol enhances apoptosis of testicular germ cells.Methods:In the experiments of chronic ethanol exposure, male Sprague Dawley® rats (Harlan Sprague Dawley, Inc., Indianapolis, IN) were fed Liber‐Decarlie liquid diet for 9 weeks. In the experiments of acute ethanol exposure, a small volume of 20% ethanol solution was administered by intratesticular injection. Both 3′‐end labeling of isolated testicular deoxyribonucleic acid (DNA) and labeling of apoptotic cells in situ by the terminal deoxynucleotidyl transferase‐mediated deoxyuridine 5′‐triphosphate nick end‐labeling method were used to determine apoptosis rates within the testes. The expression of proteins involved in apoptosis was assessed by reverse transcription‐polymerase chain reaction and by Western blotting.Results:The testes of rats that were fed an ethanol‐containing liquid diet had more testicular DNA fragmentation than did those of animals that were fed an isocaloric control diet. Ethanol increased the number of apoptotic spermatogonia as well as spermatocytes. Direct intratesticular injections of ethanol solution enhanced testicular DNA fragmentation, suggesting an increase in apoptosis. Moreover, Fas ligand levels were increased within the testes of rats that were chronically fed ethanol. In vitro, ethanol treatment of cultured Sertoli cells enhanced the production of Fas ligand. In addition, testicular levels of p53 messenger ribonucleic acid were increased in rats that were chronically fed ethanol.Conclusions:All of these observations suggest that ethanol enhances testicular germ cell apoptosis.
Neuropsychological Deficits in Sober Alcoholics: Influences of Chronicity and Recent Alcohol Consumption
Authors: Beatty William W. , Tivis Rick , Stott Heather D. , Nixon Sara Jo , Parsons Oscar A. 
Published: May 2006

Background:The relationships between severity of neuropsychological (NP) deficits and quantity and duration of alcoholic drinking remain controversial. Eckardt et al. (1998) proposed that NP deficits can be observed only if chronicity of alcohol abuse equals or exceeds 10 years. In this study we tested the hypothesis of Eckardt et al. and reexamined the relationship of NP performance and alcohol consumption.Methods:One hundred sixty‐two alcoholics and 165 controls completed a NP test battery at least 3 weeks after the alcoholics attained sobriety. Chronicity varied from 4 to 9 years for 55 alcoholics and from 10 to 33 years for the remaining 107.Results:Compared to controls, both groups of alcoholics were impaired on the Shipley Vocabulary and Abstraction tests and on two versions of the Digit Symbol test, but there was no difference between the two alcoholic groups on any measure. Regression analyses that controlled for age and education showed that chronicity predicted less than 0.5% of the variance on NP measures. By contrast, a measure of recent alcohol consumption, the Quantity‐Frequency Index, contributed significantly (approximately 5% of the variance) to the prediction of alcoholics’NP performance.Conclusions:These data provide weak support for a dose effect relationship between degree of NP impairment and level of alcoholic drinking in the past 6 months but no evidence for an influence of chronicity.