bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Forward and Reverse Selection for Ethanol‐Induced Locomotor Response on Other Measures of Ethanol Sensitivity
Authors: Palmer Abraham A. , Phillips Tamara J. 
Published: April 2006

Background Ethanol sensitivity may be a predictor of genetic predisposition to ethanol abuse. To examine ethanol sensitivity in rodents, two lines of mice were bred in replicate for high (FAST‐1 and ‐2) and low (SLOW‐1 and ‐2) locomotor stimulant responses to ethanol. After large differences between the lines developed and further response to selection seemed to have arrested, reverse selection was initiated by breeding the slowest FAST mice with each other and the fastest SLOW mice with each other. The reverse‐selected lines, named r‐FAST and r‐SLOW, were virtually equally sensitive to the stimulant effects of the selection dose of ethanol after 16 generations of reverse selection.Methods These experiments used this unique genetic model to examine two responses, putatively genetically correlated with sensitivity to ethanol stimulation: handling‐induced convulsions during chronic ethanol withdrawal, and ethanol‐induced hypothermia. Ethanol clearance, for which a small difference was previously found between the FAST and SLOW lines, was also examined.Results Handling‐induced convulsions during chronic ethanol withdrawal were significantly greater in both FAST lines compared with both SLOW lines. Reverse selection eliminated the difference between the replicate 1 lines but did not alter the difference between the replicate 2 lines. Ethanol‐induced hypothermia was greater in both SLOW lines compared with the FAST lines. This difference was significantly reduced by reverse selection in r‐SLOW mice only. Ethanol clearance rates were similar among all lines and replicates.Conclusions These data demonstrate the usefulness of reverse‐selected lines for examining putatively genetically correlated traits. Changes in the correlated traits demonstrated the existence of persistent trait‐relevant genetic heterogeneity and some genetic overlap between the correlated traits and the selection trait. Absence of a change after reverse selection suggests that trait‐relevant genetic heterogeneity was eliminated by forward selection or, alternatively, that the trait was not influenced by genes associated with successful reverse selection.
Women Who Marry Men With Alcohol‐Use Disorders
Authors: Schuckit Marc A. , Smith Tom L. , Eng Mimy Y. , Kunovac Jelena 
Published: April 2006

Background Women who marry men with alcohol‐use disorders (AUDs) might have unique characteristics that could affect the clinical course of their partner's AUD and the risk for problems in the offspring. Most data available on spouses of such men come from subjects in treatment, which might bias results to more severely impaired individuals. Our data were gathered as part of a prospective study of an original sample of 453 sons of alcoholics and controls who were originally selected as students or nonacademic staff at a university.Methods Personal interviews were performed with 327 women who were married to men who had been personally evaluated on multiple occasions over the prior 15 years. The data compare characteristics of the 235 women (71.9%) whose husbands had never developed alcohol abuse and dependence with the 92 (28.1%) for whom these disorders had been documented.Results The women who married men with an AUD were less likely to be homemakers, were more likely to meet criteria for alcoholism (especially abuse) themselves, were more likely to report use of illicit substances, and to be current smokers. However, spouses of men with AUDs in this highly functional sample had no higher risk for other major psychiatric disorders and did not report a higher rate of alcohol abuse or dependence or psychiatric conditions in their parents.Conclusions The results demonstrate increased risks for the use of illicit substances and for AUDs in women married to alcoholics, despite the overall high level of functioning of the sample. This information may be relevant to enhancing our understanding of the environment in which their offspring are being raised. The descriptive aspects of the work might also help researchers and clinicians working with alcoholic families.
Alcohol Consumption and Incidence of Workers’ Compensation Claims: A 5‐Year Prospective Study of Urban Transit Operators
Authors: Ragland David R. , Krause Niklas , Greiner Birgit A. , Holman Barbara L. , Fisher June M. , Cunradi Carol B. 
Published: April 2006

Background Numerous studies have linked alcohol impairment on the job to occupational injury. Few studies have looked at the association of nonwork drinking and occupational injury.Methods This study examines first workers’ compensation claims after a baseline assessment of alcohol consumption and other occupational variables in 1836 transit operators participating in a medical examination for driver's license renewal. A proportional hazard model was used for the analysis.Results Individuals with higher alcohol consumption were more likely to be male, have more years of driving, and have a higher job‐stress score. When these variables were controlled for, individuals with higher alcohol consumption were more likely to have a workers’ compensation claim over the follow‐up period. Individuals reporting a consumption of 10 to 14 drinks per week had a hazard of 1.30 (p= 0.03), and those reporting 15 or more drinks per week had a hazard of 1.27 (p= 0.05) compared with individuals reporting no drinks consumed per week.Conclusions This study indicates that drinking off the job is associated with workers’ compensation injury claims. Because it is presumed that most drinking was done outside work, due to high public scrutiny of city transit operators, these results suggest that experience in life outside of work may influence work outcomes. Research should be conducted to identify the mechanisms (e.g., drinking before work, hangover, fatigue) of such effects.
Mouse Cerebellar Adenosine‐Glutamate Interactions and Modulation of Ethanol‐Induced Motor Incoordination
Authors: Dar M. Saeed 
Published: April 2006

Background It was demonstrated previously that cerebellar adenosine modulates ethanol‐induced motor incoordination via A1 subtype of adenosine receptors. Several reports suggest the involvement of brain glutamate mechanisms, in particular N‐methyl‐d‐aspartate (NMDA) receptor sites, in the central nervous system (CNS) actions of ethanol. Mutually antagonistic functional responses as a result of glutamate and adenosine within the brain regions have also been well documented.Methods With the use of rotorod performance as the test response, this study was conducted to evaluate possible functional interactions between cerebellar adenosine and glutamate and its consequence on ethanol‐induced motor incoordination. Except for ethanol, which was injected intraperitoneally, all drugs used were microinfused directly into the cerebellum.Results Direct intracerebellar microinfusion of glutamate (125, 250, and 500 ng) and the antagonist l‐glutamic acid diethyl‐ester (125, 250, and 500 ng) markedly and dose‐dependently attenuated and accentuated, respectively, ethanol‐induced motor incoordination, suggesting an involvement of glutamate. Subsequently, intracerebellar microinfusions of NMDA (125, 250, and 500 ng) and its antagonists AP‐5 [(+)‐2‐amino‐5‐phosphoropentanoic acid; 125, 250, and 500 ng] and (+)‐MK‐801 [(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a. d]‐cyclo‐hepten‐5,10‐imine hydrogen maleate; 25, 50, and 100 ng] significantly attenuated and accentuated, respectively, ethanol‐induced motor incoordination in a dose‐related manner, indicating participation of NMDA receptor. The attenuation of ethanol‐induced motor incoordination by glutamate and NMDA was receptor mediated as it was antagonized by their receptor antagonists. Adenosine A1‐selective agonist N6‐cyclohexyladenosine and antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine functionally opposed the attenuation by glutamate and NMDA and the accentuation by L‐glutamic acid diethyl‐ester, AP‐5, and (+)‐MK‐801, respectively, of ethanol‐induced motor incoordination.Conclusions These results suggest a functional antagonism between glutamate NMDA and adenosine A1 receptors exhibiting a co‐modulation of ethanol‐induced motor incoordination within the cerebellum.
Ethanol Induces Hyperprolactinemia by Increasing Prolactin Release and Lactotrope Growth in Female Rats
Authors: De Alok , Boyadjieva Nadka , Oomizu Souichi , Sarkar Dipak K. 
Published: April 2006

Background Alcohol drinking is known to cause hyperprolactinemia in both humans and laboratory animals. The mechanism by which alcoholism causes hyperprolactinemia is not known. This study investigated whether increased pituitary production of prolactin, which leads to alcohol‐induced hyperprolactinemia, results from an increase in cell number and/or cell production of prolactin in the pituitary.Methods The effects of ethanol on lactotropes were determined in vivo using female rats as an animal model and in vitro using primary cultures of mixed rat anterior pituitary cells and enriched lactotropes. In vivo experiments involved administration of ethanol for 2 and 4 weeks using a liquid diet containing 8.7% ethanol (v/v), which provides 37% of the calories in cyclic, ovariectomized, and estradiol‐17β–treated ovariectomized Fischer‐344 rats. The control group was pair‐fed an isocaloric diet minus the ethanol or fed a normal diet ad libitum. These animals were used to determine ethanol's effects on plasma prolactin levels, pituitary wet weights, pituitary total protein levels, and the number of mitotic lactotropes. In vitro studies determined ethanol's effects in the presence and absence of estradiol on prolactin release and lactotropic cell proliferation. Prolactin levels in plasma and media samples were measured using radioimmunoassay. Mitotic lactotropes were determined using bromodeoxyuridine incorporation assay.Results Ethanol treatment increased in a time‐dependent manner the plasma levels of prolactin in cyclic, ovariectomized, and estradiol‐treated ovariectomized rats. Ethanol treatment also increased pituitary wet weight and/or pituitary total protein levels and DNA synthesis in lactotropes. Determination of ethanol's action on lactotropic cell proliferation and hormone secretion in vitro using primary cultures of mixed pituitary cells revealed that ethanol stimulated both basal and estradiol‐induced prolactin secretion and lactotropic cell proliferation. When ethanol's actions were studied in isolated lactotropes, ethanol alone or in combination with estradiol stimulated prolactin secretion but failed to increase lactotropic cell proliferation.Conclusions These results suggest that ethanol causes hyperprolactinemia by elevating prolactin release from lactotropes and by increasing the number of lactotropes in the anterior pituitary gland. The mitotic action of ethanol requires cell–cell communication between lactotropes and other pituitary cells. Furthermore, ethanol's mode of action on prolactin release and lactotrope growth is similar to that observed for estradiol.
Kinetics of HDL Cholesterol and Paraoxonase Activity in Moderate Alcohol Consumers
Authors: Sierksma Aafje , van der Gaag Martijn S. , van Tol Arie , James Richard W. , Hendriks Henk F. J. 
Published: April 2006

Background The inverse association between moderate drinking and coronary heart disease mortality is well established. This study was performed to investigate the kinetics of the alcohol‐induced increases in apo A‐1, HDL cholesterol, and paraoxonase (PON) activity, as well as to study whether the alcohol‐induced increases in PON activity differ within different PON polymorphisms, and to investigate whether moderate alcohol consumption has similar effects on the outcome measures in postmenopausal women as in middle‐aged men.Methods In a randomized, diet‐controlled, crossover study, 10 middle‐aged men and 9 postmenopausal women, all apparently healthy, nonsmoking, and moderate alcohol drinkers, consumed beer or no‐alcohol beer (control) with evening dinner during two successive periods of 3 weeks. During the beer period, alcohol intake equaled 40 and 30 g/day for men and women, respectively. The total diet was supplied to the subjects and had essentially the same composition during these 6 weeks. Before each treatment was a 1‐week washout period, in which the subjects were not allowed to drink alcoholic beverages.Results Moderate alcohol consumption significantly increased serum apo A‐I level after 5 days (3.7%, p < 0.05); after 10 days, serum HDL cholesterol level was increased (6.8%, p < 0.001), and after 15 days serum PON activity was increased (3.7%, p < 0.05), all compared with no alcohol consumption. Gene polymorphisms did not modulate the alcohol effect on PON.Conclusions Serum apo A‐I, HDL cholesterol, and PON activity were significantly increased during 3 weeks of moderate alcohol consumption as compared with no alcohol consumption. Moreover, the results suggest that there is a sequence in induction of these parameters. After an increase in apo A‐I, HDL cholesterol is increased followed by an increase in PON activity. Increased serum HDL cholesterol level and PON activity may be a mechanism of action not only in healthy middle‐aged men but also in postmenopausal women, underlying the reduced coronary heart disease risk in moderate drinkers.
Role of Endotoxin in NF‐κB Activation by Ethanol in Rat Hepatocytes
Authors: Matsumoto Hiroshi , Sato Yasuhiro , Azumi Junichi , Kato Junji , Niitsu Yoshiro , Tamaki Keiji 
Published: April 2006

Background Endotoxin plays an important role in the progression of alcoholic liver injury. However, the role of endotoxin in acute activation of NF‐κB by ethanol remains unclear.Methods In primary rat hepatocyte cultures treated with ethanol and/or endotoxin, the DNA‐binding activity of NF‐κB in the nuclear extract was estimated by electrophoretic mobility shift assay. After pretreatment of a CYP2E1 inhibitor, 4‐methyl pyrazole or diallyl sulfide, NF‐κB activity was also measured in the same manner.Results Ethanol or endotoxin caused activation of NF‐κB in primary rat hepatocytes. Taking 50 mM of ethanol and endotoxin together raised the rapid increase in NF‐κB activation, but both 100 mM of ethanol and endotoxin treatment reduced the increase. Addition of diallyl sulfide decreased the activity at rapid phase but increased it after 60 min, whereas addition of 4‐methyl pyrazole caused no change of the activity at rapid phase but raised it after 60 min. Pretreatment with both endotoxin and a CYP2E1 inhibitor raised the activation of NF‐κB constantly after ethanol addition. These findings suggest that endotoxin plays a critical role in the metabolism‐independent activation of NF‐κB by ethanol.Conclusions Endotoxin raised metabolism‐independent activation of NF‐κB by high ethanol in rat hepatocytes.
Acetaldehyde‐Induced Growth Retardation and Micro‐Heterogeneity of the Sugar Chain in Transferrin Synthesized by HepG2 Cells
Authors: Searashi Yasuyuki , Yamauchi Masayoshi , Sakamoto Kazuhiko , Ohata Mitsuru , Asakura Tadashi , Ohkawa Kiyoshi 
Published: April 2006

Background A carbohydrate‐deficient transferrin (CDT) is the most useful marker of alcohol abuse; however, the mechanism of production and the pathophysiologic roles of CDT remain obscure. The effects of alcohol and its metabolites on growth and proliferation, transferrin synthesis, and phosphomannomutase enzyme activity in a human hepatoblastoma, HepG2, were examined.Methods HepG2 cells were treated with either ethanol at 80 mM or acetaldehyde at 400 μM. Transferrin secreted by the cells was prepared from conditioned culture medium by single‐step immunoaffinity column chromatography using a goat‐specific antibody against human transferrin. Phosphomannomutase and some related enzyme activities in the cell extracts were determined. Reverse transcription‐polymerase chain reaction analysis of phosphomannomutase mRNA expression was also determined in HepG2 cultured with or without acetaldehyde (400 μM).Results HepG2 cells usually synthesized and secreted transferrin with three separated bands: main broad bands estimated to be 78 to 82 kDa, 75 kDa, and 72 kDa. The last two bands were compatible with part or the entire N‐glycans‐deficient transferrin (CDT) from alcoholic liver damage. Increased secretion of CDT from HepG2 correlated well with the extent of growth retardation to the level of confluent cell density. The activity of phosphomannomutase also decreased with prolongation of cellular doubling time. Furthermore, acetaldehyde treatment at 400 μM accelerated the inhibitory effect of cell growth compared with nontreated cells, and this condition facilitated CDT secretion from HepG2 cells. Determination of the enzyme activity and mRNA expression indicated that acetaldehyde showed competitive type inhibition of phosphomannomutase activity but not suppression of phosphomannomutase gene expression.Conclusions By culturing HepG2 cells with acetaldehyde containing media, growth inhibition‐dependent increase of CDT showed good correlation with reduced enzyme activity of phosphomannomutase. Acetaldehyde facilitated growth retardation, inhibition of phosphomannomutase activity, and increased secretion of CDT. The HepG2 cell line is useful as an in vitro model to investigate the pathophysiologic state of alcoholic liver damage and mechanisms of production as well as the physiologic role of CDT.
Ethanol‐Induced Augmentation of Annexin IV Expression in Rat C6 Glioma and Human A549 Adenocarcinoma Cells
Authors: Sohma Hitoshi , Ohkawa Hiroko , Hashimoto Eri , Sakai Rie , Saito Toshikazu 
Published: April 2006

Background We previously reported that the amount of annexin IV significantly increased in the postmortem brains of alcoholics compared with controls. To investigate further whether ethanol directly affects cellular expression of annexins in a cell, we used cell lines and compared the amounts of annexins between ethanol‐exposed and control cells.Methods Two kinds of cells (rat glioma C6 cells and human adenocarcinoma A549 cells) were used in the present study. Western blot analysis was performed to quantify expressed amounts of annexins using anti‐annexin I, IV, and V antibodies. The mitochondrial enzyme (dehydrogenase) and caspase 3 activities were measured to assess cell damage (apoptosis) by ethanol.Results Expressive augmentation of annexin IV was shown in both C6 and A549 cells after a 5‐hr exposure to 200 mM of ethanol, whereas amounts of annexins I and V were not changed. Both the mitochondrial dehydrogenase and caspase 3 activities were altered under the same conditions in C6 cells, indicating the induction of cell damage (apoptosis), whereas both of these enzyme activities were unchanged in A549 cells under the same conditions.Conclusions The amount of annexin IV seemed to increase before the induction of cell damage by ethanol. Annexin IV might be one of the specific markers for the effect of ethanol.
Outcomes of Small Nodular Lesions in Heavy Drinkers
Authors: Suzuki Michihiro , Maeyama Shiro , Nishikawa Kouji , Okuse Noriaki , Hashizume Kiyoe , Mamada Yukimitu , Kobayashi Yutaro , Okuse Chiaki , Takahashi Yasuhito , Osada Taturo , Hayashi Takeshi , Yotuyanagi Hiroshi , Suzuki Hiroshi , Ogata Seiichiro , Uchikoshi Toshiyuki , Iino Shiro 
Published: April 2006

Background Increased detection of nodular lesions in patients not yet definitively diagnosed with hepatocellular carcinoma (HCC) has occurred with the use of advanced imaging techniques. In heavy drinkers, decrease in the size of nodular lesions during on‐going observation, and negation of diagnoses of HCC after surgical resection have been reported, suggesting the need for caution in diagnosis in such cases.Methods The subjects were eight heavy drinkers with small nodular lesions, 20 mm or less in diameter. All patients were male, with a mean age of 53 years. Five had single and three had multiple nodular lesions. Five of the eight patients were followed up for more than 4 years after an initial biopsy, while three patients were recent cases. Of the three recent cases, two were positive for antibody to hepatitis C virus (HCV) and two had hypervascular nodular lesion. Biopsies were performed percutaneously, under ultrasonography, for histological diagnosis of all cases, and the recent cases were also assessed using a variety of imaging techniques.Results On initial biopsy, no atypism (NO) was found in two patients, and borderline lesions (Border) were present in six patients. Of the five cases followed up long‐term, only one of the two with NO progressed to HCC, and the three with Border showed disappearance, decrease, and no change, respectively, during the follow‐up period. Of the three recent cases, no changes in size or morphology as revealed by imaging were observed following biopsy.Conclusions In heavy drinkers, no fixed relationship was observed between initial biopsy finding and clinical course, suggesting that indication for biopsy requires reassessment, refinement, and discussion. Furthermore, tumor staining may occur in hyperplastic nodules, which are histologically similar to early HCC by needle biopsy, and care needs to be exercised for diagnosis in heavy drinkers.