bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Ethanol Exposure Is Associated With Decreased Plasma Zinc and Increased Fetal Abnormalities in Normal but Not Metallothionein‐Null Mice
Authors: Carey Luke C. , Coyle Peter , Philcox Jeffrey C. , Rofe Allan M. 
Published: May 2006

Background:Ethanol profoundly affects fetal development, and this is proposed to be due primarily to a transient fetal zinc (Zn) deficiency that arises from the binding of Zn by metallothionein (MT) in the maternal liver. Zn homeostasis and fetal outcome were investigated in normal (MT+/+) and metallothionein‐null (MT‐/‐) mice in response to ethanol exposure.Methods/Results:Mice were treated with saline or ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) on day 8 of gestation (Gd8), and the degree of fetal dysmorphology was assessed on Gd18. The incidence of external abnormalities was significantly increased in offspring from MT+/+ dams exposed to ethanol, where 27.4% of fetuses were affected. MT‐/‐ ethanol‐, MT+/+ saline‐, and MT‐/‐ saline‐treated dams had fetuses in which the frequencies of abnormalities were 2.2, 6.4, and 6.9%, respectively. To investigate Zn homeostasis, nonpregnant mice were killed at intervals over 16 hr after ethanol injection. Liver MT concentrations in MT+/+ mice were increased 20‐fold by 16 hr, with a significant elevation evident by 4 hr, whereas liver Zn levels were also significantly increased by 2 hr and maintained for 16 hr. In parallel with these changes, plasma Zn concentrations in MT+/+ mice decreased by 65%, with minimum levels of 4.5±0.3 μmol/liter at 8 hr. Conversely, MT‐/‐ mice exhibited increased plasma Zn concentrations, with peak values of 20.8±0.3 observed at 4 hr.Conclusion:These findings link the teratogenic effect of ethanol to the induction of maternal MT and the limitation of fetal Zn supply from the plasma.
Effect of Chronic Alcohol Consumption on Total Plasma Homocysteine Level in Rats
Authors: Stickel Felix , Choi Sang‐Woon , Kim Young‐In , Bagley Pamela J. , Seitz Helmut K. , Russell Robert M. , Selhub Jacob , Mason Joel B. 
Published: May 2006

Background: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6, Population‐based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcoholrelated hyperhomocysteinemia.Methods: In the present study, 10 male Sprague Dawley® rats were fed ethanol‐containing Lieber‐ DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair‐fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin.Results: At the end of 4 weeks, alcohol‐fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal‐5′‐phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol‐fed rats were significantly hyperhomocysteinemic (17.24 ± 4.63 μmol/liter,p < 0.01) compared to the nonalcohol group (10.73 ± 2.76 μmol/liter). Alcohol‐fed rats also had a significantly lower hepatic S‐adenosylmethionine and higher hepatic S‐adenosylhomocysteine levels.Conclusions: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one‐carbon metabolism, and not through vitamin depletion.
Early Postnatal Ethanol Exposure Has Long‐Term Effects on the Performance of Male Rats in a Delayed Matching‐to‐Place Task in the Morris Water Maze
Authors: Girard T. A. , Xing H.‐C. , Ward G. R. , Wainwright P. E. 
Published: May 2006

Background: There is concern that, in the absence of full‐blown fetal alcohol syndrome, binge drinking during pregnancy might produce long‐term cognitive deficits in offspring. Spatial working memory might be particularly vulnerable in this regard. This is the first study to address this issue in an animal model of binge exposure during the brain growth spurt using a delayed matching‐to‐place (DMTP) task in the Morris water maze.Methods: Infant male rats were gastrostomized and reared artificially from postnatal days (PD) 5 to 18. From PD 6 to 9 they were fed either 6.5 g · kg−1· d−1 ethanol (EtOH) in a binge exposure model (BAC 302 mg/dl) or an isocaloric maltose‐dextrin solution (MD). The study included a third suckled control group (SC) that was reared normally. The rats were tested on a series of problems in the DMTP task, first as juveniles (PD 35) and then twice again as adults. Each problem included an initial search trial and a subsequent test trial. The first two phases of testing used delays of either 0 sec or 60 sec between these two trials. The third phase increased this delay to 60 sec and 2 hr. In addition, the rats were tested on a cued task in the water maze.Results: EtOH rats were impaired relative to controls in their ability to relocate the hidden platform on the second trial, which followed the search trial. In Phases I and 2, there was no differential effect of ethanol on performance across the 0‐sec and 60‐sec delay conditions. However, EtOH rats were more affected by the longer 2‐hr delay in Phase 3. There were no group differences on the search trial, in swimming speed, or cued‐task performance.Conclusions: These findings establish that binge exposure to ethanol during the brain growth spurt results in a long‐lasting impairment on the DMTP performance of rats in the water maze.
Avian Genetic Background Modulates the Neural Crest Apoptosis Induced by Ethanol Exposure
Authors: Debelak Katherine A. , Smith Susan M. 
Published: May 2006

Background:Ethanol‐induced neural crest apoptosis likely contributes to the distinctive craniofacial phenotype that results from prenatal alcohol exposure. The mechanism responsible for this apoptosis is incompletely understood. A serendipitous change in poultry production flocks led to the discovery that, in chick, the embryo's genetic background modulates its susceptibility to ethanol‐induced apoptosis.Methods:We examined the level of ethanol‐induced neural crest apoptosis in 11 chick layer strains or crosses, using acridine orange uptake.Results:Holding the ethanol dose and exposure stage constant, strains were classified into very sensitive (Babcock ISA, HyLine W98, Babcock B300/Hampshire Red cross [BxHR]), moderately sensitive (Spafas, HyLine W36, Babcock B300), and nonresponsive (DeKalb White and Black, Shaver White and 2000, DeKalb White/Hampshire Red cross). Detailed examination of two susceptible strains (W98, BxHR) and a resistant strain (DeKalb White) revealed that the DeKalb's nonresponse was not caused by a shift in; timing of apoptosis, or to a lower alcohol exposure at either time of injection or time of death. Strains had identical stage distributions at the time of injection and at apoptosis; housing and diet were held constant.Conclusions:Factors within the embryo and/or egg environment can affect the susceptibility to ethanol‐induced apoptosis. These sensitive and resistant strains will be important tools to dissect the molecular mechanism of ethanol‐induced apoptosis, and for understanding how these losses affect subsequent development.
Alcohol and Aldehyde Dehydrogenase Genotypes in Korsakoff Syndrome
Authors: Matsushita Sachio , Kato Motoichiro , Muramatsu Taro , Higuchi Susumu 
Published: May 2006

Background: Previous studies have suggested a genetic predisposition to the development of Wernicke‐Korsakoff syndrome (WKS), a neuropsychiatric syndrome commonly associated with alcoholism; however, little is known about this genetic risk factor.Methods: To test the hypothesis that altcrcd alcohol or aldehyde regulation is related to the development of WKS, the genetic polymorphisms of aldehyde dehydrogenase‐2 (ALDH2) and alcohol dehydrogenase‐2 (ADH2) were examined in 47 alcoholic subjects with WKS and compared with those of 342 alcoholic subjects without any WKS symptoms and 175 nonalcoholic controls.Results: Although the frequencies of the ALDH2 genotypes and alleles did not differ significantly between alcoholic subjects with WKS and alcoholics without WKS, the ADH2*1/2*1 genotype and ADH2*1 allele were significantly increased in WKS.Conclusions: These findings suggest that the ADH2*1/2*1 genotype is a risk factor for the development of WKS in alcoholic patients.
An Association Study Between Alcoholism and the Serotonergic Receptor Genes
Authors: Himei Akio , Kono Yoshihiro , Yoneda Hiroshi , Sakai Toshiaki , Koh Jun , Sakai Jun , Inada Yasushi , Imamichi Hiroyuki 
Published: May 2006

Background: Linkage and association studies of alcoholism using DNA makers have been conducted without conclusive results. The comorbidity of alcoholism with affective disorder indicates that dysfunction of the serotonergic system may play an important role in developing alcoholism.Methods: We studied the genetic association between alcoholism and alleles of the HTR1A, HTR2A, and HTR2C genes. The subjects were 91 biologically unrelated alcoholics and 90 controls. Polymorphisms of these genes were determined by polymerase chain reaction restriction fragment length polymorphisms, and the data were analyzed by X2 tests.Results: We found no significant association between alcoholism and the HTR1A, HTR2A, and HTR2C genes.Conclusions: The study results suggest that these serotonergic receptor genes may not directly contribute to the etiology of alcoholism.
Differential Display of Ethanol‐Induced Gene in N18TG2 Cells
Authors: Nishida Akira , Zensho Hidenobu , Hisaoka Kazue , Miyata Masahiko , Yamawaki Shigeto 
Published: May 2006

Background:Recent advances in molecular biology, such as polymerase chain reaction (PCR) differential display, have enabled the screening of mRNAs transcriptionally regulated by chronic ethanol treatment. Screening of gene expression after ethanol exposure will be the most needed for new biological insights into alcoholism.Methods:We used PCR differential display to detect differentially expressed RNAs in N18TG2 cells treated for 4 days with physiologic concentrations of ethanol (25 mM).Results:We succeeded in identifying two differentially expressed RNAs in the ethanol‐treated cells. The increase in the expression of the two RNAs was verified by Northern hybridization analysis. Sequence analyses and searches of the sequence databases revealed that one of the RNAs was that of the heat shock cognate protein 73 (HSC73) gene and that the other was the product of a novel gene. The increase in the level of HSC73 mRNA after ethanol administration was consistent with similar reports from other laboratories, and indicated that our assay system would be applicable to the screening of up‐regulated gene expression during ethanol treatment. Rapid amplification of cDNA 5′‐ends (5′‐RACE) allowed us to determine the upstream sequence of the uncharacterized mRNA that would code for a protein of 113 amino acids. A homology search by MPsrch indicated very low homology to the calcium channel L‐type alpha 1 subunit.Conclusions:The function of this new gene product is presently unknown, but our results indicate that an investigation of the pathophysiological significance of the gene in alcoholism would be worthwhile. Identification of genes that are influenced by chronic ethanol will certainly increase of the molecular mechanisms underlying physiologic dependence.
Acute and Chronic Effect of Alcohol on Ca2+ Channels in Hepatic Stellate Cells
Authors: Oide Hirosumi , Itatsu Tomoko , Hirose Miyoko , Wang Xian‐En , Nishiyama Daisuke , Takei Yoshiyuki , Sato Nobuhiro 
Published: May 2006

Background: Hepatic stellate cells have been reported to play important roles in the regulation of hepatic microcirculation via cell contraction. Increase in intracellular calcium concentration is required to induce cell contraction. We have already reported the existence of L‐type voltage‐operated Ca2+ channels (VOCC), such as smooth muscle cells. On the other hand, alcohol has been known to disturb hepatic microcirculation. In this study, we evaluated the effect of acute and chronic treatment of alcohol on VOCC in rat hepatic stellate cells.Methods: Stellate cells isolated from rats were cultured with or without 100 mM ethanol for up to 14 days. VOCC were detected by the patch clamp technique. Cells cultured for 14 days without ethanol were exposed to ethanol to investigate calcium current during membrane depolarization. α‐Smooth muscle actin (α‐SMA) was stained by indirect immunofluorescence.Results: In the control model, VOCC were recognized in cells cultured for more than 7 days. Detection of VOCC increased from 9% on day 7 to 55% on day 14. On the other hand, VOCC in cells treated chronically with 100 mM ethanol appeared earlier than in the control and the incidences were significantly higher than those of the control accompanied with an early activation of cells. In contrast, simultaneous exposure to ethanol during the membrane depolarization inhibited Ca2+ current.Conclusions: The expression of Ca2+ channels in stellate cells were up‐regulated by the chronic treatment of alcohol accompanied with the transformation to myofibroblast‐like phenotype. However, alcohol itself inhibited Ca2+ current.
Changes in Dopamine Transporter and c‐Fos Expression in the Nucleus Accumbens of Alcohol‐Tolerant Rats
Authors: Yoshimoto Kanji , Ueda Shuichi , Nishi Mayumi , Yang Yimu , Matsushita Hiroko , Takeuchi Yoshihiro , Kato Baku , Kawai Yoko , Noritake Kanae , Kaneda Shigehiro , Sorimachi Yoshihide , Yasuhara Masahiro 
Published: May 2006

Background: We have shown that neurochemical functions of 5‐HT3 receptors in regulating dopamine (DA) release in the nucleus accumbens (ACC) after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance, and that the development of alcohol dependence may be mediated by ACC 5‐HT3 receptors. In the present study, the effects of chronic alcohol consumption on the functions of the dopamine transporter (DAT) and the expression of c‐Fos proteins were investigated using in vivo brain microdialysis and immunocytochemistry.Methods: Perfusion of cocaine and 1‐(2‐Bis‐(4‐fluorophenyl) methoxy) ethyl)‐4‐(3‐phenylpropyl) piperizine (GBR 12909) through the microdialysis probe membrane increased the extracellular levels of DA in ACC of alcohol‐treated rats that had developed alcohol tolerance by drinking 10% EtOH for 30 days.Results: The magnitudes of DA reuptake or DAT inhibitors, cocaine, and GBR 12909 that induced DA availability in the ACC were significantly higher in alcohol‐treated rats than in controls. When compared with control rats, the alcohol‐treated rats exhibited higher levels of DA and its metabolite, DOPAC, in the ACC. Increased expression of the c‐Fos‐like protein was found in the ACC of alcohol‐treated rats. These results show that (1) chronic alcohol consumption desensitizes or decreases the DAT of DA terminals in the ACC and that (2) EtOH causes cellular hyperexcitability of ACC dopaminergic neurons with increased Fos expression during alcohol tolerance.Conclusion: The findings suggested that an abnormality of the dopaminergic neurons in the ACC that are involved with DAT dysfunction is associated with the development of alcohol tolerance.
Before‐Discharge Intervention Method in the Treatment of Alcohol Dependence
Authors: Ino Aro , Hayasida Motoi 
Published: May 2006

Background: Alcoholics have the fundamental problem of denying dependence on alcohol and minimizing their alcohol‐related problems. Therapeutic interventions often fail to help alcoholics become aware of their drinking problem and remain in long‐range treatment programs, which is a prerequisite for recovery from alcohol dependence.Methods: Inpatients were assigned to either group 1 or 2 depending on which day of the week they were admitted to the hospital. A newly developed structured intervention method (Before‐Discharge Intervention Method, or BDIM) was employed with select (nonrandomized) hospitalized alcoholics in group 1 and their family members before the patients were discharged from the hospital. None of the patients in group 2 received the BDIM. With this intervention method, the alcoholic's family members delivered to him or her verbal messages that conveyed concern about the alcoholic's problem drinking, their observations of the alcoholic's past episodes of drinking problems, and wishes and support for abstinence. Unless patients died during hospitalization or would not be able to attend the hospital follow‐up clinic and local self‐help groups (Danshukai) after discharge, outcome evaluations were carried out on all patients in groups 1 and 2 during two calendar months, 3 months after the last BDIM patient left the hospital. Outcome measures included patient's and family members' attendance at hospital outpatient follow‐up sessions and self‐help group meetings, and patient's abstinence.Results: Family members' attendance at hospital follow‐up sessions and/or self‐help group meetings was significantly higher in group 1 than in group 2. Among the three subgroups of discharged patients in either group 1 or 2—that is, those who lived with their spouse, those who lived with someone other than their spouse, and those who lived alone—only those in group 1 who lived with their spouse did significantly better than their counterparts in group 2 in three treatment outcome measures. However, patients' maintenance of abstinence was significantly better only when they and their family members both attended hospital outpatient follow‐up sessions and/or self‐help group meetings. We noted no other statistically significant difference between groups 1 and 2 in any of the other two subgroups of discharged or patients in any of the three treatment outcome variables. Irrespective of the BDIM, patients who lived alone did significantly more poorly than either those who lived with their spouse or those who lived with someone other than their spouse in terms of attendance at hospital follow‐up sessions and local self‐help group meetings and abstinence.Conclusions: This intervention method can help the alcoholic face the reality of his or her drinking problems and alcohol dependence and thus remain longer in long‐range rehabilitation programs, which is a prerequisite for successful recovery from alcohol dependence.
Effect of Acute Ethanol Administration on the Intestinal Absorption of Endotoxin in Rats
Authors: Tamai Hironao , Kato Shinzo , Horie Yoshinori , Ohki Eiji , Yokoyama Hirokazu , Ishii Hiromasa 
Published: May 2006

Background: Endotoxin has been implicated in the pathogenesis and progression of alcoholic liver disease. Not only inactivation of reticuloendothelial function, which reduces clearance of endotoxin, but also an increase in absorption of endotoxin from the intestine may be involved in mechanisms of ethanol‐induced endotoxemia. However, it is unclear how ethanol affects absorption of endotoxin from the intestine in vivo.Methods: We gave 10 mg/kg of lipopolysaccharides to rats with water (group 1), 5% ethanol (group 2), or 20% ethanol (group 3) using an intubation tube to the stomach. Blood samples were collected and plasma endotoxin levels were measured. We used fluorescence spectrophotometer to examine permeability of the gut to macromolecules (fluorescein isothiocyanate‐dextran; 4,000 Da [FD4] or 20,000 Da [FD20]).Results: Plasma endotoxin levels were not different between group 1 (9 ± 2 pg/ml) and group 2 (14 ± 3 pg/ml), whereas they significantly increased in group 3 with a peak at 60 min (87 ± 35 pg/ml). Acute ethanol administration did not affect clearance of endotoxin in rats. Hemorrhagic erosions of the proximal small intestine with epithelial cell loss were observed in group 3 at 4 hr, but no significant histological change was observed at 30 min by light microscopy. Acute ethanol administration (20%) increased the permeability of the small intestine to FD4 and FD20 in 30 min when no hemorrhagic erosions of the proximal small intestine with epithelial cell loss were observed.Conclusions: Acute ethanol administration increases intestinal permeability before pathological changes are revealed by light microscopy. Acute ethanol ingestion, especially at high concentrations, facilitates the absorption of endotoxin from rats' small intestine via an increase in intestinal permeability, which may play an important role in endotoxemia observed in alcoholic liver injury.
Disulfiram Treatment Increases Plasma and Red Blood Cell Acetaldehyde in Abstinent Alcoholics
Authors: Rosman Alan S. , Waraich Afsar , Baraona Enrique , Lieber Charles S. 
Published: May 2006

Background: Much of alcohol's toxicity is due to its product, acetaldehyde. The role of acetaldehyde derived from endogenous sources was assessed in alcoholic patients administered disulfiram, an inhibitor of aldehyde dehydrogenase.Methods: The first part of the study included 23 subjects without biochemical or clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11 patients were started on disulfiram (250 mg/day), whereas the other 12 were not given disulfiram and served as controls. The second part of the study included 13 alcoholic patients with clinical or pathological evidence of cirrhosis who also were administered disul firam for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were measured at baseline and after 1 and 2 weeks of treatment.Results: In the disulfiram‐treated group of alcoholics without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment value of 2.98 ± 0.18 μM to 4.14 ± 0.33 μM after 1 week and to 4.14 ± 0.26 μM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment values (2.07 ± 0.24 μM), plasma acetaldehyde levels also increased after 1 week (3.18 ± 0.32 μM) and 2 weeks (3.15 ± 0.26 μM) of disulfiram treatment (p < 0.001). There were no significant differences in sequential levels measured in either plasma or RBC acetaldehyde levels in patients who were not administered disulfiram. In the group of cirrhotic patients, the mean baseline RBC acetaldehyde value (3.60 ± 0.22 μM) was significantly higher than in noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week (4.63 ± 0.27 μM, p < 0.001) and 2 weeks of treatment (4.06 ± 0.28 μM, p < 0.05). Compared with baseline values, plasma acetaldehyde levels were significantly higher after 1 week but not after 2 weeks of disulfiram. There were no significant differences among serum transaminases in alcoholics administered disulfiram, although three cirrhotic patients did have clinically significant elevations.Conclusions: In abstaining subjects given disulfiram, acetaldehyde concentrations increase, possibly due to diminished catabolism of endogenously generated acetaldehyde. Disulfiram should be given cautiously, especially in patients with cirrhosis.