bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Study of Alcohol Consumption Patterns in Relation to Symptomatic Gallstone Disease in Men
Authors: Leitzmann Michael F. , Giovannucci Edward L. , Stampfer Meir J. , Spiegelman Donna , Colditz Graham A. , Willett Walter C. , Rimm Eric B. 
Published: May 2006

Although the association between alcohol intake and gallstone disease has been characterized previously, the relation between alcohol consumption patterns, specific types of alcoholic beverages, and risk for cholelithiasis has not been addressed systematically. These issues were examined prospectively in a cohort of men who were free from symptomatic gallstone disease in 1986 and were followed to 1996. During follow‐up, 2.4% of the men reported newly symptomatic gallstones that were diagnosed by ultrasonography or x‐ray, or a cholecystectomy.After adjusting for other known or suspected risk factors, an increase in the amount of alcohol consumed was associated with a decreased risk of symptomatic gallstone disease. An increase in frequency of alcohol consumption also was related to decreased risk. Combining the reports of quantity and frequency of alcohol intake, a consumption pattern that reflected frequent intake (5‐7 days/week) of any given amount of alcohol was associated with a decreased risk, as compared with nondrinkers. In contrast, infrequent alcohol intake (1‐2 days/week) showed no significant association with risk. All alcoholic beverage types were inversely associated with risk of symptomatic gallstone disease, independent of patterns of consumption.These results suggest that frequent, moderate intake of alcohol decreases the risk for symptomatic gallstone disease, in contrast to infrequent or episodic alcohol intake. Recommendations regarding the benefit of moderate quantities of alcohol for gallstone disease should be weighed against the potential health hazards of alcohol consumption.
Tissue Inhibitors of Metalloproteinases: Role in Liver Fibrosis and Alcoholic Liver Disease
Authors: Arthur Michael J. P. , Iredale John P. , Mann Derek A. 
Published: May 2006

In liver fibrosis, activated hepatic stellate cells (HSC) play a major role in the deposition of excess extracellular matrix, including fibrillar collagens type I and type III. In addition to matrix protein synthesis, HSC regulate matrix degradation in the liver. This is mediated via a combination of synthesis of matrix (pro)metalloproteinases, which activate these zymogens via specific mechanisms and by inhibiting the active matrix‐degrading enzymes via expression of tissue inhibitors of metalloproteinases (TIMPs). There are currently four members of the TIMP family described and of these, both TIMP‐1 and TIMP‐2 are synthesised by HSC. These observations have led to the suggestion that inhibition of matrix degradation mediated by a change in HSC‐expression of TIMPs relative to metalloproteinases, such as interstitial collagenase, may contribute to progression of liver fibrosis. This hypothesis is supported by studies of human liver disease in which TIMP‐1 expression is upregulated 5‐fold in cirrhotic compared with normal liver. TIMP‐1 and TIMP‐2 expression is also upregulated in animal models of progressive fibrosis, whereas expression of collagenase is unchanged. In a model which is characterized by natural resolution of liver fibrosis, degradation of the deposited fibrillar liver matrix is accompanied by rapid down‐regulation of TIMP‐1 expression.In alcoholic liver disease, the role of TIMPs has not been studied exhaustively, but the evidence currently available supports a role for inhibition of matrix degradation by TIMPs in this progressive fibrotic liver disease.
Limited Access Alcohol Drinking in High‐ and Low‐Alcohol Preferring Selected Lines of Mice
Authors: Grahame Nicholas J. , Li Ting‐Kai , Lumeng Lawrence 
Published: May 2006

Background:Selection studies and genetic analyses of drinking behavior in rodents often involved unlimited access to alcohol over a period of weeks, with water and food freely available. Most studies investigating the pharmacology of alcohol drinking, on the other hand, use procedures in which access to alcohol is limited to a particular time each day. Reconciliation of findings between these two conditions likely depends on their sharing common genetic mechanisms as indicated, for example, by covariation in response to selection. To this end, high‐ and low‐alcohol preferring (HAP and LAP, respectively) mice, selected for differences in 24‐hr access alcohol drinking over a 4‐week period, were subjected to a limited access alcohol drinking protocol.Method:During 2‐hr sessions, mice had access to various concentrations of alcohol (7‐15%, v/v) in the home cage for 2 hr a day, with ad libitum access to food and water. Additional sessions were conducted with no food present.Result:Although both strains consumed alcohol and water during these sessions, HAP mice drank far more alcohol than did LAP mice. HAP but not LAP mice drank alcohol at a high rate early in the session compared with later in the session. Additionally, HAP mice responded to changes in alcohol concentration, whereas LAP mice did not. Removal of food did not influence alcohol drinking, although water drinking decreased following food removal. HAP mice reached appreciable blood alcohol concentrations after limited access.Conclusions:These findings indicate that in these selectively bred mice, alcohol drinking during limited and unlimited access may be genetically related, and that drinking during limited access sessions in HAP mice is likely for the pharmacological properties of alcohol.
Impaired Sleep in Alcohol Misusers and Dependent Alcoholics and the Impact Upon Outcome
Authors: Foster John H. , Peters Timothy J. 
Published: May 2006

Background: There is very little work that has investigated the self‐reported sleep status of alcohol misusers. This study addressed that imbalance. Methods: The study consisted of two parts: 1) the outpatient study, a sample of DSM‐IV alcohol‐dependent subjects who were referred to an outpatient clinic and were given a series of questionnaires, including the Pittsburgh Sleep Quality Index (PSQI); and 2) the inpatient study, a group of DSM‐IV alcohol‐dependent subjects whose sleep was assessed by the Nottingham Health Profile (NHP) sleep subscore at the start of the study and again at the 12‐week follow‐up. Both the PSQI and NHP are self‐report indices whereby higher scores indicate a poor sleep quality. Results: In the outpatient study, the PSQI scores were significantly higher in the alcoholics (n= 31) compared with the controls (n= 49). There were no differences in the PSQI scores among mildly (n= 11), moderately (n= 10), and severely (n= 11) dependent drinkers. The PSQI total scores correlated with the Beck Depression Index but not with severity of dependence or alcohol problem scores. Sleep latency emerged as the most significant predictor of relapse, and sleeping badly was associated with poor outcome at the 12‐week follow‐up in the inpatient study. Conclusion: Self‐reported sleep disturbance can provide clinicians with information to plan better treatment for alcohol misusers.
Behavioral and Psychosocial Profiles of Alcohol‐Exposed Children
Authors: Roebuck Tresa M. , Mattson Sarah N. , Riley Edward P. 
Published: May 2006

Background: It is widely known that prenatal alcohol exposure is related to cognitive and behavioral deficits throughout childhood and adolescence. Much research has focused on understanding and quantifying the cognitive profile of children with fetal alcohol syndrome (FAS) with relatively less empirical research on behavioral or psychosocial adjustment. The primary purpose of this study was to examine the behavioral and psychosocial profile of children exposed to heavy amounts of alcohol prenatally. Method: Two groups of subjects were evaluated: an alcohol‐exposed group (ALC) and a nonexposed control group (NC) each made up of 32 subjects matched for age, gender, and ethnicity. The alcohol‐exposed group consisted of children heavily exposed to alcohol in utero, including 19 children diagnosed with FAS. The Personality Inventory for Children (PIC) was completed by the caretaker of each child. Four validity/screening scales and 12 clinical scales were scored for all subjects. Result: Analyses revealed significant group differences on four validity/screening scales and 12 substantive scales. Within the ALC group, the profile of children without FAS was similar to that of children with FAS, with the exception that their profiles were consistent with less cognitive impairment. Conclusions: These findings indicate that in addition to previously reported cognitive impairments, heavy prenatal alcohol exposure is related to significant impairments in psychosocial functioning. Even children without alcohol‐related physical anomalies suffer from impaired psychosocial functioning. Because impairments of this nature can interfere with functioning across multiple domains, effective early intervention programs should be considered for families of alcohol‐exposed children. Furthermore, given the similarities of alcohol‐exposed children with and without FAS, it is imperative to obtain prenatal alcohol exposure histories on all children experiencing cognitive or psychosocial deficits.
Effects of Ethanol Treatment on Proliferation and Differentiation in a Head and Neck Squamous Cell Carcinoma Cell Line
Authors: Kornfehl J. , Temmel A. , Formanek M. , Knerer B. 
Published: May 2006

Introduction: Epidemiologic studies have provided evidence that chronic ethanol consumption is an independent risk factor in upper aerodigestive tract cancer, but the underlying mechanisms are largely unknown. Method: To examine ethanol effects on mucosal keratinocytes in vitro, we used a squamous cell carcinoma of the head and neck (SCCHN) cell line as a model and, to exclude line specific effects, two other cell lines. The influence of ethanol on proliferation (using [3H]thymidine uptake/cell number), cell cycle distribution, cytokeratin pattern, and growth factor receptor expression (using FACS analyses) was investigated. Result: Ethanol increased in a dose dependent manner (tested range 10‐3M to 10‐10 M) the [3H]thymidine uptake and cell number, with unaltered viability (>95%) in all concentrations. In ail tested cell lines, addition of 10‐3 M ethanol caused: (a) a significant increase of cells in the S‐phase of the cell cycle; (b) a shift of cytokeratin pattern that suggested inhibition of differentiation; and (c) significant upregulation of EGF, IL‐4, and PDGF receptors. Conclusions: Our results demonstrated an increased proliferation and reduced differentiation induced by ethanol in mucosa derived neoplastic cells, which may enhance further growth of neoplastic cells. These effects may also be involved in the carcinogenesis of upper aerodigestive tract malignancies.
Prenatal Alcohol Use Among Teenagers: Effects on Neonatal Outcomes
Authors: Cornelius Marie D. , Goldshmidt Lidush , Taylor Paul M. , Day Nancy L 
Published: May 2006

Background:This longitudinal study examines the effects of alcohol use during pregnancy on the growth and gestational age at birth of 413 offspring of adolescents. Methods:Data were collected during 1990 to 1994. The adolescents were from a prenatal clinic in Pittsburgh, PA. They were interviewed at mid‐pregnancy and at delivery to obtain information on alcohol and other substance use before and during pregnancy. Infants were examined 24 to 36 hr after birth. Results:The average maternal age was 16.3 (12‐18) years; 68% were African American. Prenatal exposure to alcohol during the second trimester was significantly related to decreases in head circumference, birthweight, and chest circumference. There was also a significant relationship between alcohol exposure in each trimester and lower Apgar scores. All of the analyses controlled for other prenatal substance use and covariates of drinking during pregnancy. Conclusion:Prenatal alcohol exposure is associated with decreases in fetal growth and in APGAR scores in the offspring of adolescents.
Effects of Continuous Versus Intermittent Ethanol Exposure on Rat Sympathetic Neurons
Authors: Riikonen Jamo , Jaatinen Pia , Karjala Kirsi , Rintala Jyrki , Pörsti Llkka , Wu Xiumin , Eriksson C.J. Peter , Hervonen Antti 
Published: May 2006

Background:Binge ethanol exposure is known to induce degeneration of central nervous system (CNS) neurons. Sympathetic hyperactivity has been related to ethanol withdrawal symptoms, but the effects of repeated withdrawals on peripheral sympathetic neurons have not been studied previously.Methods:The effects of continuous versus intermittent ethanol consumption on sympathetic neurons of the superior cervical ganglion (SCG) were studied in male Wistar rats. Two‐month‐old rats were divided into three groups: one group with ethanol (10% v/v) as the drinking fluid throughout the 5½‐month experiment (continuous, n=9), one group drinking ethanol on 4 days/week and water on 3 days/week (intermittent, n=9), and a control group (n=9) with water as the only available fluid. All groups had food ad libitum. SCG volume, neuron density, and total number of neurons were measured by using unbiased morphometric methods.Results:As the mean daily ethanol consumption did not differ between the two ethanol‐exposed groups (continuous5.7 g/kg/day versusintermittent5.8 g/kg/day), the total dose of ethanol consumed was 42% smaller in theintermittentgroup. The total number of SCG neurons decreased by 28%, and neuron density by 23%, in theintermittentgroup compared with the control group, whereas no significant neuron loss was observed in thecontinuousgroup. The volume of the SCG was similar in all study groups. The results suggest that repeated ethanol withdrawals, rather than ethanol exposure per se, are deleterious to sympathetic neurons.Conclusions:Ethanol‐induced degeneration of neurons is not only related to the amount of ethanol consumed, but also to the patterns of drinking.
Neonatal Ethanol Exposure Alters bcl‐2 Family mRNA Levels in the Rat Cerebellar Vermis
Authors: Moore D. Blaine , Walker Don W. , Heaton Marieta Barrow 
Published: May 2006

Background: The objective of the present work was to determine whether ethanol‐induced cerebellar cell death during development is related to alterations in the expression of bcl‐2 family genes. Methods: Rats were exposed to ethanol or control conditions during the neonatal period and transcript levels of bcl‐2 family members relative to cyclophilin were determined. Pups exposed in parallel were taken for cerebellar cell counts. Results: Ethanol exposure during the first postnatal week significantly reduced Purkinje and granule cell numbers by postnatal day 21 (P21). Acute first postnatal week ethanol exposure up‐regulated mRNA transcripts encoding the cell death‐promoting molecules bax and bcl‐xs as measured on P4. An additional day of exposure on P5 resulted in no further alterations in bcl‐2 family transcripts, likely because Purkinje cell death was detectable as early as P5. To determine whether proapoptotic gene expression changes were specific to first postnatal week ethanol neurotoxicity, we examined bcl‐2 family mRNA levels in rats exposed to ethanol during a developmental period of cerebellar insusceptibility, the second postnatal week. Exposure on P7 to P8 produced no change in cerebellar cell number, but also resulted in increased levels of bax, although only after 2‐day ethanol exposure and not after acute exposure on P7. Conclusions: These data implicate altered expression of proapoptotic members of the bcl‐2 gene family in acute ethanol‐mediated cerebellar cell death during the first postnatal week. They also suggest that the differential survival of cerebellar neurons after ethanol exposure during more mature developmental stages may be related to more successful suppression of proapoptotic processes.
Selective Effects of Alcohol Drinking on Restraint‐Induced Expression of Immediate Early Genes in Mouse Brain
Authors: Ryabinin Andrey E. , Wang Yuan‐Mei , Freeman Pierre , Risinger Fred O. 
Published: May 2006

Background:Analysis of immediate early gene expression in brain is a common contemporary method for mapping changes in neuronal activation with cellular resolution. This method has been applied previously in models of involuntary alcohol exposure. In this study, immunohistochemical expression analysis of immediate early genes c‐fos, fosB, and zif268 was performed in brain of C57BL/6J mice after voluntary alcohol consumption. Methods:Mice were trained to consume 10% ethanol/10% sucrose, using a 30‐min limited‐access paradigm. Animals consumed approximately 1.5 g/kg of ethanol per session. Control animals consumed 10% sucrose solution. Gene expression was determined in half of the animals 1.5 hr after the drinking session. Gene expression in the remaining animals was determined after 0.5 hr of restraint stress, which is known to elevate expression of immediate early genes in many brain regions. Analysis of the stressed animals was also performed 1.5 hr after the drinking session. Results:Blood alcohol concentrations were significantly reduced in animals exposed to restraint stress. However, stressed mice showed the greatest alcohol‐induced changes in gene expression. Specifically, animals consuming ethanol/sucrose with subsequent exposure to restraint stress had lower c‐Fos expression in the CA3 region of hippocampus, and higher c‐Fos expression in nucleus accumbens than mice exposed to restraint stress after drinking the sucrose solution. Consumption of the ethanol/sucrose solution also significantly reduced FosB expression in the basolateral amygdala and lateral hypothalamus, and Zif268 expression in the CA1 region of the hippocampus of stressed animals. Conclusions:These data confirm previous observations showing selective effects of alcohol administration on immediate early gene expression. Furthermore, the effects of voluntary alcohol self‐administration on immediate early gene expression differ from involuntary alcohol exposure and suggest several brain regions as substrates for alcohol consumption.
Psychometric Properties of the Penn Alcohol Craving Scale
Authors: Flannery B. A. , Volpicelli J. R. , Pettinati H. M. 
Published: May 2006

Background: This study introduces the Penn Alcohol Craving Scale (PACS), which has been used in several clinical trials at the University of Pennsylvania's Treatment Research Center. The PACS is a five‐item, self‐report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scaled from 0 to 6. Methods: To examine the questionnaire's psychometric properties, we sampled responses from 147 individuals participating in a 9‐month combined natrexone (100 mg/day)/psychotherapy trial. The psychotherapy consisted of weekly sessions of nurse‐administered medication compliance and supportive treatment. Results: The PACS proved to have excellent internal consistency. Predictive validity was demonstrated via a logistic regression analysis of craving during the 2nd week of the study on alcohol relapse during weeks 3‐12 of the trial. Construct validity of the PACS was demonstrated via its convergence with two commonly used measures for assessing craving, the Obsessive Compulsive Drinking Scale and the Alcohol Urge Questionnaire. Lack of correlation between PACS scores and several other noncraving, self‐report measures indicates that the PACS also had good discriminant validity. Additional analyses revealed that there were significant differences in craving scores during the initial 3 weeks of the trial among those who did and those who did not relapse during weeks 3‐12. Conclusion: The PACS is a reliable and valid measure of alcohol craving and can predict which individuals are at risk for subsequent relapse.
Chronic Alcoholism Is Associated With an Imbalanced Production of Th‐1/Th‐2 Cytokines by Peripheral Blood T Cells
Authors: Laso Francisco Javier , Iglesias‐Osma Carmen , Ciudad Juana , Lopez Antonio , Pastor Isabel , Orfao Alberto 
Published: May 2006

Background: In the present study, we analyzed, at the intracellular level, the pattern of cytokine secretion by the major CD4+ and CD8strong+ peripheral blood (PB) T‐cell subsets in patients with chronic alcoholism, and we correlated it both with the ethanol (EtOH) intake status and with the presence or not of alcoholic liver disease. Methods: For that purpose, a total of 30 chronic alcoholic patients, 10 without liver disease (AWLD group) and 20 diagnosed with alcoholic liver cirrhosis (ALC) were studied. In all cases, flow cytometric measurement of intracellular expression of interferon–γ (IFN‐γ), interleukin (IL)‐2, and IL‐4 was performed on PB CD4+ and CD8strone+ T lymphocytes. Results: After studying AWLD patients, we found increased numbers of both CD4+ and CD85trong+ PB T cells with detectable cytoplasmic levels of the IL‐2 and IFN‐γ T helper (Th)‐1‐associated cytokines, the greater increase being observed for this latter cytokine (p < 0.001 for CD4+ and p < 0.01 for CD8strong+ T cells). Regarding ALC patients, the pattern of expression of intracellular cytokines by PB T cells was different depending on the status of EtOH intake at the moment of entering this study. Accordingly, as in AWLD patients, ALC individuals who were actively drinking also displayed increased numbers of both CD4+ and CD8strong+ T cells expressing Th‐1‐associated cytokines. However, in these patients, expression of IFN‐γ although being significantly greater than that observed in control individuals (p < 0.05), was significantly lower than that in AWLD patients (p < 0.01 and p < 0.05, for CD4+ and CD8strong+ T cells, respectively). After a withdrawal period of ≥ 1 yr, ALC patients did not show significant changes in the cytoplasmic expression of Th‐1‐associated cytokines compared with the control group; in contrast, these patients showed a marked increase on the proportion of CD4+ and CD8strong+ T cells expressing IL‐4, a Th‐2‐associated cytokine (p < 0.01). After considering the ratio between the number of T cells expressing Th‐1 (IFN‐γ)‐and Th‐2 (IL‐4)‐associated cytokines in each individual, we found that there was a significant imbalance in this ratio, with a predominance of IFN‐γ‐producing T cells over IL‐4+ T lymphocytes during EtOH intake. Conclusions: Our results showed that in patients with chronic alcoholism, active EtOH intake is associated with a Th‐1 pattern of cytokine production by PB T cells.