bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione Replacement Preserves the Functional Surfactant Phospholipid Pool Size and Decreases Sepsis‐Mediated Lung Dysfunction in Ethanol‐Fed Rats
Authors: Velasquez Alvaro , Bechara Rabih I. , Lewis James F. , Malloy Jaret , McCaig Lynda , Brown Lou Ann S. , Guidot David M. 
Published: April 2006

Background Alcohol abuse increases the incidence of acute respiratory distress syndrome (ARDS). Previous evidence from our laboratory links ethanol‐mediated glutathione depletion to impaired surfactant production by alveolar epithelial cells in vitro and to endotoxin‐mediated edematous injury in isolated lungs ex vivo. ARDS patients have an imbalance between the inactive small aggregate (SA) and the bioactive large aggregate (LA) forms of surfactant phospholipid (as reflected by increased SA/LA ratios). Therefore, we hypothesized that ethanol ingestion, via glutathione depletion, could alter surfactant phospholipid distribution between LA and SA forms and thereby exacerbate sepsis‐mediated lung dysfunction in vivo.Methods Rats fed an isocaloric diet with or without ethanol (36% total calories) for 6 weeks were made septic via cecal ligation and perforation. Some ethanol‐fed rats had their diets supplemented with the glutathione precursor procysteine (l‐2‐oxothiaxolidine‐4‐carboxylate). Sepsis physiology was assessed by determining respiratory rates, arterial blood pressures, and plasma lactate levels, and lung dysfunction was assessed by determining lung lavage fluid protein levels (index of alveolar endothelial/epithelial barrier disruption), arterial hypoxemia (index of impaired gas exchange) and surfactant phospholipid SA and LA fractions (index of the alveolar epithelium's ability to maintain a functional surfactant pool during sepsis).Results Ethanol ingestion decreased (p < 0.05) lung lavage fluid glutathione levels, and this defect was prevented by procysteine. Although ethanol ingestion had no effect (p < 0.05) on any of the indices of sepsis, it increased (p < 0.05) lung lavage fluid protein levels, worsened hypoxemia, and decreased the functional (LA) surfactant phospholipid pool after sepsis, all of which was prevented by procysteine.Conclusions Ethanol ingestion, via glutathione depletion, increased sepsis‐mediated lung dysfunction, and these effects could contribute to the increased risk of ARDS seen in alcoholic patients.
The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats
Authors: Reed Adam H. , McCarty Heidi L. , Evans Glenda L. , Turner Russell T. , Westerlind Kim C. 
Published: April 2006

Background Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise.Methods Six‐month‐old male Sprague Dawley® rats were assigned to one of five groups: baseline, exercise‐alcohol diet, exercise‐normal diet, sham‐alcohol diet, and sham‐normal diet. Alcohol‐fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair‐fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone.Results Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol‐treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol‐fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross‐sectional areas were also significantly lower in the alcohol‐fed groups compared with the non‐alcohol‐fed groups. Exercise had no significant effect on cancellous or cortical bone measurements.Conclusions Chronic alcohol consumption significantly reduced bone formation. Exercise had no effect on the bone and did not attenuate any of the negative effects of alcohol. The results suggest that alcohol consumption weakens the skeleton and increases the incidence of endurance‐exercise‐related bone injuries. Thus, individuals who are participating in endurance exercise and consuming alcohol may be at greater risk for exercise‐related skeletal injuries. Further investigation of the potential for alcohol to induce detrimental effects on the hearts of individuals participating in endurance exercise is indicated.
Ethanol Induces Morphological and Dynamic Changes on In Vivo and In Vitro Neural Crest Cells
Authors: Rovasio Roberto A. , Battiato Natalia L. 
Published: April 2006

Background Fetal alcohol syndrome (FAS) is an embryopathology related to maternal alcohol drinking. The information concerning the factors involved in the prenatal mechanisms of ethanol action at the cellular and molecular levels is scarce. Because several abnormal changes in FAS involve regions colonized by cell lineages derived from neural crest cells (NCCs), it is reasonable to propose that epigenetic alteration of this cell population can represent an important component of the etiopathogeny. The aim of this work was to evaluate the direct effect of ethanol on a chick embryo model, as well as on in vitro NCC morphology and dynamic behavior.Methods After ethanol treatment, in ovo or cultured chick embryos were used to determine the anatomical development of and to quantify the migratory parameters and apoptosis of NCCs. Scanning electron microscopy was performed on ethanol‐perfused (and control) cultures of cephalic and trunk NCCs; the actin cytoskeleton was evaluated, and morphometric and dynamic parameters were determined after time‐lapse videorecording. Recovery capacity after ethanol treatment was also determined.Results Chick embryos submitted to conditions sufficient to induce FAS in mammals displayed developmental disruptions frequently accompanied by cephalic/facial anomalies. In vitro studies also indicated that cephalic and trunk NCCs exposed to ethanol exhibited significant and permanent changes regarding cell shape, surface morphology, apoptotic cell death, cytoskeleton, and distance and velocity traveled, as well as an abnormal pattern of migration.Conclusions Taking into account that even a limited period of abnormal behavior may imply serious consequences in the final cues of an embryonic cell population, our results indicate that the biological effects of ethanol on early development—even during a short time—could induce permanent ontogenetic perturbations of NCCs, with potentially dramatic effects on embryonic morphogenesis. These results support an important participation of NCCs in the etiopathogeny of FAS.
Reduced Adrenal Activation in a Rat Line Selected for High Alcohol Sensitivity
Authors: Raatesalmi Kristina , Virtanen Antti , Sarviharju Maija , Pelto‐Huikko Markku , Korpi Esa R. 
Published: April 2006

Background A rat line developed by selective breeding for high alcohol sensitivity has blunted corticosterone responses to alcohol and stress. In the present study, we determined possible differences in adrenal activation after alcohol and motor performance testing between the alcohol‐sensitive alcohol‐nontolerant and alcohol‐insensitive alcohol‐tolerant rats.Methods The animals received ethanol (2 g/kg, intraperitoneally), and 30 min later they were subjected to a motor function test (i.e., normal selection test used in the breeding of the lines); the control animals for both rat lines received no treatment and minimal handling. Blood corticosterone and ACTH levels at the single time point were determined by radioimmunoassay, and adrenal activation was determined by in situ hybridization of the immediate early gene c‐fos, nor1, nurr1, and NGFI‐B mRNA expression.Results The alcohol nontolerant rats had lower corticosterone but normal ACTH levels after ethanol and motor testing. Adrenal early gene expression of all of the genes studied was strongly induced by the treatment in both rat lines, but the inductions of c‐fos, nor1, and nurr1 were significantly lower in the alcohol‐sensitive animals. Acute treatment with a high dose of ACTH also induced less adrenal gene expression in the alcohol‐sensitive animals.Conclusions The results suggest that the reduced adrenal activation is associated with high alcohol sensitivity in a genetic animal model, which is in agreement with the human findings of alcohol insensitivity during glucocorticoid treatment.
Substance Use–Related Outpatient Consultations in Specialized Health Care: An Underestimated Entity
Authors: Sillanaukee Päivi , Kääriäinen Janne , Sillanaukee Pekka , Poutanen Pauli , Seppä Kaija 
Published: April 2006

Background To study the occurrence and documentation of substance use related outpatient visits in specialized health care.Methods The diagnosis recorded in retrospective discharge data in Tampere University Hospital for 6 years was compared with the prospective data gathered from separately completed forms added during an 8‐week period to every outpatient's discharge data. In this form, the relation of substance use and the actual reason for the consultation were specifically elicited.Results On the basis of diagnoses, retrospectively, 0.4% (6,666 of 1,555,898) of outpatient visits were caused by substance use. In the prospective part of the study, 5.6% of visits (1,401/25,014) were related to substance use. Retrospective study demonstrated 2% prevalence of substance use, whereas prospective study showed 36% substance use–related visits at the emergency room. According to the retrospective discharge data, alcohol‐related organ damages were the major reason for substance use–related outpatient visits. In the prospective study, the proportion of acute traumas was most prevalent.Conclusions Our study indicates that substance use–related visits often remain undetected in specialized health care. Substance use–related visits were underdocumented/undetected in the emergency room. Using a simple separate form could dramatically increase the detection of substance use–related visits.
Serum Sialic Acid Levels Are Increased During Relapse to Alcohol Drinking: A Pilot Study
Authors: Pönniö Maritta , Sillanaukee Pekka , Franck Johan 
Published: April 2006

Background Sialic acid has been suggested to be a potential marker for alcohol abuse. A previous study showed that sialic acid levels were significantly higher in serum among alcoholics as compared with social drinkers. In addition, serum sialic acid concentrations decreased after a treatment program aiming at abstinence. In this study, sialic acid was investigated as a possible marker for relapse to alcohol drinking.Methods Serum from alcohol‐dependent patients in outpatient treatment (n= 8) was analyzed for sialic acid by a colorimetric assay. A baseline sample was taken when the subject had been abstinent for longer than 4 weeks. A second sample was taken after relapse within 3 days after cessation of drinking. A relapse was defined as two or more days with daily drinking of more than 60 g of pure alcohol.Results The sialic acid levels were significantly increased by 21% (median; range, 6–33%;p < 0.01;n= 8) after a relapse as compared with the level after 4 weeks or longer of abstinence.Conclusions This study suggests that serum sialic acid levels are significantly increased even after a short period of heavy drinking and may be a potential marker for relapse.
A Double‐Blind, Placebo‐Controlled Study of Naltrexone in the Treatment of Alcohol‐Dependence Disorder: Results from a Multicenter Clinical Trial
Authors: Guardia José , Caso Carlos , Arias Francisco , Gual Antoni , Sanahuja Jordi , Ramírez Marisa , Mengual Ildefonso , Gonzalvo Begoña , Segura Lidia , Trujols Joan , Casas Miguel 
Published: April 2006

Background A 12‐week, multicenter, double‐blind, randomized, parallel‐group clinical trial to compare naltrexone and placebo was carried out to determine the efficacy, safety, and tolerability of naltrexone together with a psychosocial intervention in the treatment of alcoholism.Methods A total of 202 alcohol‐dependent patients were assigned to 12 weeks’ treatment with either naltrexone or placebo. The relapse rate was evaluated by means of intention‐to‐treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were evaluated in the 192 patients who were considered to be assessable.Results The survival function for patients who were treated with naltrexone was significantly better than that of the patients who were treated with placebo (Kaplan‐Meier log rank = 4, df = 1, p < 0.05). In addition, 7.9% of patients who were treated with naltrexone relapsed as compared with 18.8% of those who received placebo [χ2= 5.89, df = 2, p= 0.050]. In comparing naltrexone with placebo‐treated patients, the most common adverse events were abdominal pain [8.6% vs. 1%; (χ2= 6.1, df = 1, p < 0.05)] and headache [7.5% vs. 1% (χ2= 5.1, df = 1, p < 0.05)].Conclusions Naltrexone was well‐tolerated, as the rate of adverse events was low, and safe, as it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Naltrexone seemed to reduce relapse rate to heavy drinking, but we found no differences in other alcohol consumption variables between naltrexone‐ and placebo‐treated groups. Although the naltrexone group showed a tendency to consume fewer drinks per drinking day and had a longer time to first drink, differences were not statistically significant.
Fractionated Simple and Choice Reaction Time in Children with Prenatal Exposure to Alcohol
Authors: Simmons Roger W. , Wass Tara , Thomas Jennifer D. , Riley Edward P. 
Published: April 2006

Background The present study investigated central and peripheral processing speed using simple reaction time (SRT) and choice reaction time (CRT) tasks in children who were exposed to alcohol in utero compared with control subjects. Each RT interval was fractionated into premotor and motor components to assess the central processing of stimulus information and peripheral motor unit recruitment, respectively.Methods Eleven children with confirmed prenatal alcohol exposure (ALC) and 13 control subjects (NC), aged 5 to 10 years, completed 20 trials of both SRT and CRT tasks. Muscle activity was recorded from the biceps brachii muscle of each arm using electromyography to facilitate the fractionating of RT into premotor and motor components.Results ALC children exhibited significantly slower premotor RTs during the CRT task. Motor RTs were also slower for the ALC group during both SRT and CRT tasks. ALC children exhibited greater response variability compared with control subjects; however, the magnitude of this variability was not greater than would be predicted, given their lengthened RTs. In contrast, response variability was greater for young children of both groups even after accounting for mean RT. Significant age‐related differences in premotor and motor RTs were also observed.Conclusions Alcohol‐related increases in CRT were attributable to longer premotor and motor components, reflecting both reduced speed of information processing and peripheral delays in responding. These alterations likely are associated with alcohol‐related changes in the central and peripheral nervous systems that could impede or slow neuronal transmission.
Differential Effects of T‐Cell Activation on Gastric and Small Bowel Permeability in Alcohol‐Consuming Mice
Authors: Alnadjim Ziad , Kayali Zeid , Haddad Wael , Holmes Earl W. , Keshavarzian Ali , Mittal Navdha , Ivancic David , Koehler Ronald , Goldsmith David , Waltenbaugh Carl , Barrett Terrence A. 
Published: April 2006

Background A number of variables influence the effect(s) of alcohol on distinct segments of the intestine. In these studies, we examined the effect of T‐cell activation on gastric and small bowel permeability in alcohol‐fed mice.Methods Gastric permeability was assessed using sucrose absorption, whereas small bowel permeability was followed using the ratio of lactulose to mannitol absorption and inulin absorption. T cells were activated by injecting antigen OVA323–339 into DO11.10 T‐cell receptor transgenic mice.Results T‐cell activation increased gastric and small bowel permeability through a pathway mediated by interferon‐γ and tumor necrosis factor. In mice that were fed a liquid diet that contained 30% ethanol‐derived calories for 2 weeks, T‐cell activation increased gastric permeability to levels greater than that observed in solid diet or pair‐fed, liquid control diet. By comparison, changes in small bowel permeability induced by T‐cell activation were abrogated in alcohol‐fed mice. Analysis of intestinal cytokine mRNA levels (interferon‐γ and tumor necrosis factor) indicated that relevant mucosal T‐cell function was preserved in alcohol‐fed miceConclusions Overall, these data suggest that alcohol potentiates the effects of T‐cell activation on gastric permeability, at the same time blunting effects on small bowel permeability
Investigation of Quantitative Trait Loci in the CCKAR Gene With Susceptibility to Alcoholism
Authors: Okubo Takehito , Harada Shoji , Higuchi Susumu , Matsushita Sachio 
Published: April 2006

Background Cholecystokinin (CCK) plays an important role in the function of the central nervous system by interacting with dopamine and other neurotransmitters. We previously reported genetic variations in the promoter and coding regions of the CCKA receptor (CCKAR), CCKBR, and CCK genes and a possible association between polymorphisms of the CCKAR gene and alcoholism. In this study, association analyses were re‐examined between the polymorphisms of the promoter region of the CCKAR gene and patients with alcohol withdrawal symptoms, in addition to patients with alcoholic liver injury.Methods A total of 131 Japanese male patients with alcohol withdrawal symptoms, 70 Japanese patients with alcoholic liver injury, and 98 age‐matched Japanese male controls (nonhabitual drinkers) were examined using polymerase chain reaction‐based single strand conformational polymorphism and sequencing analyses.Results Significant differences between patients with hallucination and controls were found in the allele frequencies at the −388 and −85 loci of the CCKAR gene (p= 0.0095, p= 0.0087, respectively), but these differences were not significant after Bonferroni correction for multiple testing. In contrast, the frequency of the homozygous genotype −85 CC was significantly higher in hallucination‐positive patients than in controls (p= 0.0031) and in patients with hallucination accompanying delirium tremens than in controls (p= 0.0022), and these differences were significant after Bonferroni correction.Conclusions The data from the case control suggest that polymorphisms of the promoter region of the CCKAR gene do not play a major role in the pathogenesis of alcohol withdrawal symptoms or alcoholic liver injury. However, a significant association was found between polymorphism at the −85 locus of the CCKAR gene and patients with hallucination, and especially patients with hallucination accompanying delirium tremens.
Tandem Repeat Polymorphism of the CYP2E1 Gene: An Association Study With Esophageal Cancer and Lung Cancer
Authors: Itoga Sakae , Nomura Fumio , Makino Yasuhiko , Tomonaga Takeshi , Shimada Hideaki , Ochiai Takenori , Iizasa Toshihiko , Baba Masayuki , Fujisawa Takehiko , Harada Shoji 
Published: April 2006

Background Cytochrome P‐450 (CYP) enzymes have been shown to play important roles in chemical carcinogenesis. Reports have indicated that polymorphism in CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an important role in alcohol metabolism and participates in the metabolic activation of various carcinogens, such as N‐nitrosodimethylamine. Recently, we found repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4, and A4/A4) of the CYP2E1 gene. In the present study, we investigated whether these polymorphisms are associated with lung cancer and esophageal cancer.Methods DNA was isolated from blood samples of 192 healthy control subjects, 85 patients with lung cancer, and 82 patients with esophageal cancer in Japanese males. DNA samples were amplified by polymerase chain reaction in the 5′‐flanking region of the CYP2E1 gene and in exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were examined using fluorescence‐based single strand conformational change polymorphism analysis. Written informed consent was obtained from all the subjects.Results In the CYP2E1 gene 5′‐flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p= 0.02), but no difference was found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%;p < 0.0001; habitual alcohol drinkers).Conclusions The distribution of genotypes and allele frequencies of the tandem repeats of the 5′‐flanking region of the CYP2E1 gene was significantly different in patients with esophageal cancer.