bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of Moderate Alcohol Exposure During Pregnancy and Neonatal Outcome in Rhesus Monkeys (Macaca mulatta)
Authors: Schneider Mary L. , Moore Colleen F. , Becker Elana F. 
Published: April 2006

Background: Moderate prenatal alcohol exposure can contribute to neurodevelopmental deficits in nonhuman primate offspring. The purpose of this study was to examine the effects of gestational timing of alcohol exposure on neurobehavior with a nonhuman primate model.Methods: Sixty‐three rhesus monkey infants (Macaca mulatta), from four groups of females, were assessed: (1) an early alcohol‐exposed group, in which mothers voluntarily consumed alcohol on gestational days 0 through 50; (2) a mid to late gestation alcohol‐exposed group, in which mothers consumed an identical dose on gestation days 50 through 135; (3) a continuous‐exposure group, in which mothers consumed an identical dose on days 0 through 135 or days 0 through 165; and (4) controls, in which mothers voluntarily consumed an isocaloric control solution on gestational days 0 through 50, 50 through 135, 0 through 135, or 0 through 165. Data were obtained on offspring for measures of growth and neurobehavior.Results: There were no effects of alcohol on birthweight, gestation length, or ponderal index. Prenatal exposure to alcohol during early gestation significantly decreased scores on infant neurobehavioral tests overall in multivariate tests, after controlling for birthweight. Univariate tests showed that early gestation alcohol exposure was related to reductions in infant orientation and motor maturity. Mid‐ to late‐gestation exposure also resulted in a reduction in motor maturity but did not affect overall neurobehavioral performance in the multivariate tests.Conclusions: Early‐gestation alcohol exposure is as deleterious to neonatal neurobehavior as late‐gestation or continuous exposure. Moreover, neurobehavior seems to be a more sensitive marker of early‐gestation moderate alcohol exposure than growth parameters. Women who are attempting to become pregnant should minimize frequent social drinking, because subtle neurodevelopmental effects to the fetus may be induced before pregnancy is detected.
Variation in Alcohol Pharmacokinetics as a Risk Factor for Alcohol Dependence
Authors: Whitfield J. B. , Zhu G. , Duffy D. L. , Birley A. J. , Madden P. A. F. , Heath A. C. , Martin N. G. 
Published: April 2006

Background: The significant association between alcohol dehydrogenase (ADH)‐2 genotype and alcohol‐dependence risk, demonstrated in both Asian and non‐Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence.Methods: We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979–1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992–1993.Results: Subjects who met DSM‐III‐R criteria for lifetime alcohol dependence at follow‐up had higher blood and breath alcohol values after alcohol challenge than never‐dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2‐fold higher in men and 3‐fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile.Conclusions: In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.
Chronic Ethanol Consumption Differentially Alters GABAA Receptor α1 and α4 Subunit Peptide Expression and GABAA Receptor‐Mediated 36Cl− Uptake in Mesocorticolimbic Regions of Rat Brain
Authors: Papadeas Sophia , Grobin A. Chistina , Morrow A. Leslie 
Published: April 2006

Background: Gamma‐aminobutyric acid type A (GABAA) receptors in the brain are modulated by chronic ethanol exposure via the regulation of their function and expression throughout the central nervous system. Recent studies show that chronic ethanol exposure alters subsequent ethanol self‐administration, effects that are believed to be mediated by subcortical regions of the rat brain including the amygdala (AMG), the nucleus accumbens (NAC), and the ventral tegmental area (VTA).Methods: We evaluated GABAA receptor subunit expression using subunit specific (α1 and α4) immunoblotting of small tissue punches from AMG, NAC, and VTA. GABAA receptor‐mediated 36 Cl− uptake was measured in these brain areas after chronic ethanol consumption for 2 weeks.Results: Regional differences in the effect of chronic ethanol on α1 and α4 subunit expression were found. In the AMG, α1 and α4 subunit expressions were significantly decreased by 21.1 ± 5.5% and 22.0 ± 7.1%, respectively. In the NAC, there was a decrease of 28.1 ± 1.3% in α4 subunit expression (p < 0.0001), but no change in α1 subunit expression was observed. In the VTA, there were no changes in α1 and α4 subunit expressions. Muscimol‐stimulated Cl− uptake was enhanced in the extended AMG, but not the extended NAC of ethanol‐dependent rats. The muscimol concentration response curve was left‐shifted with a 74% decrease (p < 0.01) in the EC50 and a 42% increase (p < 0.05) in the Emax in the AMG of ethanol‐dependent rats.Conclusions: These results suggest that chronic ethanol exposure alters GABAA receptor expression in the AMG and NAC. Decreased expression of α4 subunits is associated with increases in GABAA receptor function in the AMG, but not the NAC. These changes may contribute to alcohol drinking behavior and the development of ethanol dependence.
A Social Learning Perspective: A Model of Parenting Styles, Self‐Regulation, Perceived Drinking Control, and Alcohol Use and Problems
Authors: Patock‐Peckham Julie A. , Cheong JeeWon , Balhorn Michelle E. , Nagoshi Craig T. 
Published: April 2006

Background: This investigation sought to determine how different parenting styles are related to general self‐regulatory processes that are linked to alcohol use and abuse. Self‐regulation and, more specifically, thoughts of control over drinking are forms of positive self‐control mechanisms. Parenting styles are known determinants of both negative and positive self‐control mechanisms in offspring. According to social learning theory, stronger relationships between parenting style and self‐regulatory processes would be expected from the parent who is the same sex as the respondent.Methods: A total of 144 female and 107 male college students currently using alcohol were administered a questionnaire on their alcohol use and problems, perceived style of parenting (authoritarian, permissive, or authoritative) of their parents, self‐regulation, and perceived control of drinking. A model linking parenting styles, self‐regulatory processes, and control over drinking with alcohol use and alcohol problems was tested across sex groups by using structural equation modeling.Results: In general, the parenting style of the parent of the same sex as the respondent's was found to be significantly related to self‐regulation, which is known to be protective against alcohol use and abuse. A permissive parent of the same sex as the respondent was negatively associated with good self‐regulatory processes for both men and women. Having an authoritative mother was also shown to be related to higher levels of self‐regulation for women.Conclusions: Self‐regulation mediated the pathway from a permissive parenting style to perceived drinking control, which, in turn, mediated the pathway from self‐regulation to alcohol use and problems. Finally, self‐regulation mediated the positive pathway from an authoritative mother to perceived control over drinking for women.
Alcohol Use Disorders and Anxiety Disorders: Relation to the P300 Event‐Related Potential
Authors: Enoch Mary‐Anne , White Kenneth V. , Harris Claudia R. , Rohrbaugh John W. , Goldman David 
Published: April 2006

Background: The robust association of alcoholism with reduced P300 event‐related potential amplitude has been largely established in severely affected alcoholics and their offspring. Few studies have examined the relationship of increased arousal, anxiety, and P300. In this study, we sought to determine whether P300 group differences could be discerned in well functioning individuals with less severe forms of alcohol use disorders and anxiety disorders. We were particularly interested in looking at the subgroup of alcohol use disorders accompanied by anxiety disorders. This subgroup has previously been found to have diminished α amplitude in the resting EEG.Methods: Male and female community volunteers (99 unrelated index participants and 78 relatives) and 21 unrelated volunteers from an anxiety disorder clinic were interviewed by using the Schedule for Affective Disorders and Schizophrenia, Lifetime version. Blind‐rated lifetime psychiatric diagnoses were assigned according to DSM‐III‐R criteria. Auditory and visual P300 event‐related potentials were elicited with an oddball paradigm and were recorded at the midparietal (Pz) site.Results: As expected, auditory P300 amplitudes were significantly reduced in participants with alcohol use disorders and significantly increased in participants with lifetime anxiety disorders. However, more detailed analysis revealed that, in an apparent paradox, auditory P300 amplitudes were lowest in individuals with comorbid alcohol use and anxiety disorders and highest in individuals with anxiety disorders alone. Visual P300 amplitudes followed the same trends but were generally not significant.Conclusions: Even in a sample of largely community‐ascertained individuals, auditory P300 amplitude is reduced in alcoholics, particularly those with anxiety disorders, and is highest in nonalcoholics with anxiety disorders.
Acute, Rapid, and Chronic Tolerance During Ontogeny: Observations When Equating Ethanol Perturbation Across Age
Authors: Silveri Marisa M. , Spear Linda Patia 
Published: April 2006

Background: Sensitivity to the motor‐impairing and hypnotic effects of ethanol (EtOH) increases notably during development. Less is known, however, about the ontogeny of EtOH tolerance and the ontogenetic relationship among different types of tolerance. Consequently, we compared the ontogenetic development of acute, rapid, and chronic tolerance to EtOH‐induced motor impairment and hypothermia in a swim task.Methods: Preweanling, adolescent, and adult female and male Sprague‐Dawley rats were given chronic saline (control group), five daily EtOH exposures before EtOH on test day (chronic group), one EtOH exposure before test day (rapid group), or EtOH exposure only on test day (acute groups). Separate groups of animals in the acute groups were tested at 15, 60, or 105 min after injection to estimate acute tolerance development via calculating slopes of the linear regression of impairment relative to brain alcohol levels at each postinjection interval. Initial EtOH perturbation of swim performance was equated across age by varying EtOH dose.Results: Acute tolerance was evident to the motor‐impairing effects of EtOH at all ages. When impairment was indexed relative to brain alcohol levels, rapid and chronic tolerance to the motor‐impairing effects of EtOH on latency to reach the start was seen across age, although this tolerance tended to be more pronounced in adults. Somewhat different ontogenetic patterns of tolerance development were observed with EtOH‐induced hypothermia, a dependent measure for which EtOH perturbation was not equated across age.Conclusions: The degree of initial perturbation by EtOH seems to be an important predictor of tolerance expression during ontogeny. That is, ontogenetic profiles of tolerance development differ significantly when EtOH‐induced motor impairment is equated across age rather than dose of EtOH administered . The role of target response measures and context stress should also be considered when exploring ontogenetic expression of EtOH tolerance.
Divalproex Sodium in Alcohol Withdrawal: A Randomized Double‐Blind Placebo‐Controlled Clinical Trial
Authors: Reoux Joseph P. , Saxon Andrew J. , Malte Carol A. , Baer John S. , Sloan Kevin L. 
Published: April 2006

Background: Divalproex sodium, an anticonvulsant and antikindling agent and γ‐aminobutyric acid enhancer, has been proposed as an alternative to benzodiazepines for treating alcohol withdrawal. This study reports on a randomized, double‐blind, placebo‐controlled trial of divalproex sodium in acute alcohol withdrawal.Methods: Thirty‐six hospitalized patients experiencing moderate alcohol withdrawal as measured by a score of at least 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar) were randomized to receive either divalproex sodium 500 mg three times per day for 7 days or matched placebo in a double‐blind manner. All subjects received a baseline dose of oxazepam and had additional oxazepam available as a rescue medication in accordance with a standard, symptom‐triggered detoxification protocol. Mean total milligrams of oxazepam received, progression of withdrawal symptoms, psychological distress as measured by the Symptom Checklist‐90, side effects, and adverse outcomes were compared between groups.Results: Use of divalproex sodium resulted in less use of oxazepam (p < 0.033). Group differences seemed primarily driven by those subjects who experienced symptoms above threshold level (CIWA‐Ar ≥10) after 12 hr. The progression in severity of withdrawal symptoms (increase in CIWA‐Ar above baseline) was also significantly greater in the placebo group (p < 0.05).Conclusions: This placebo‐controlled pilot study suggests that divalproex sodium significantly affects the course of acute alcohol withdrawal and reduces the need for treatment with a benzodiazepine. A more aggressive loading dose strategy may demonstrate a more robust or earlier response.
Utility of a New Assay for Carbohydrate‐Deficient Transferrin (BIORAD %CDT TIA) to Monitor Abstinence During a Treatment Outcome Study
Authors: Myrick Hugh , Henderson Scott , Anton Raymond F. 
Published: April 2006

Background: The ability to reliably detect heavy alcohol use is important in both clinical and research populations. The current study evaluates the utility of the newest method of measuring carbohydrate deficient transferrin (CDT) in monitoring the abstinence during a treatment outcome study.Methods: Blood from 40 alcohol dependent individuals was obtained at baseline and at weeks 4, 8, and 12 of treatment. Differences in percent of baseline GGT and %CDT levels were analyzed in people who remained abstinent throughout treatment (abstainers) and in those who consumed alcohol during treatment (drinkers).Results: There was a significant decrease in the percent of baseline %CDT levels in the subjects who abstained at week 4 and a trend at weeks 8 and 12. Conversely, there were no significant differences in percent of baseline GGT levels between drinkers and abstainers at any time point.Conclusions: Although small in nature, this study provides preliminary evidence for the use of the relatively new Biorad %CDT assay to monitor drinking status during treatment outcome studies. This study is also consistent with previously reported findings that GGT appears to be less sensitive than %CDT in detecting the consumption of alcohol. A larger trial focusing on sex differences in the utility of % CDT to monitor outcome would be of interest.
Long‐Term Alcohol Exposure Changes Sensitivity of Rat Kupffer Cells to Lipopolysaccharide
Authors: Enomoto Nobuyuki , Schemmer Peter , Ikejima Kenichi , Takei Yoshiyuki , Sato Nobuhiro , Brenner David A. , Thurman Ronald G. 
Published: April 2006

Background: Chronic ethanol treatment enhances Kupffer cell sensitivity to lipopolysaccharide (LPS). In this model, CD14 in Kupffer cells was increased significantly 4 weeks after ethanol. Moreover, it was shown that prostaglandin E2 produced by activated Kupffer cells participated in the mechanism of ethanol‐induced fatty liver. This study was designed to elucidate the temporal effect of chronic ethanol exposure on Kupffer cell sensitization to LPS.Methods: Rats were given ethanol every 24 hr intragastrically for up to 12 weeks, and Kupffer cells were isolated 24 hr after the final ethanol administration and cultured in RPMI 1640 with 10% fetal bovine serum. After addition of LPS to Kupffer cells, intracellular calcium ([Ca2+]i) was measured.Results: CD14 in Kupffer cells was increased approximately 2‐fold, and then it decreased and returned to control levels. The LPS‐induced increases in [Ca2+]i and tumor necrosis factor‐α by Kupffer cells were also increased approximately 3‐fold over control values, but they also returned to control levels. Triglyceride content increased with the duration of chronic ethanol treatment. At 8 weeks, prostaglandin E2 produced by Kupffer cells increased approximately 3‐fold over control values and triglycerides by approximately 4‐fold before gradually decreasing to basal levels. After 12 weeks of ethanol exposure, LPS‐induced increases in [Ca2+]i and tumor necrosis factor‐α production were only approximately 50% as high as peak levels at 4 weeks. Liver triglyceride content at 12 weeks was reduced significantly compared with values at 8 weeks.Conclusions: Kupffer cells at the early stage of chronic ethanol exposure exhibited sensitization to LPS, but this sensitivity was blunted later. This correlated with triglyceride accumulation in the liver. These data indicate that long‐term alcohol exposure changes the sensitivity of rat Kupffer cells to LPS but that the magnitude of the effect is time dependent.
The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)
Authors: Eriksson C. J. Peter 
Published: April 2006

Background : Recent advances in the field of acetaldehyde (AcH) research have raised the need for a comprehensive review on the role of AcH in the actions of alcohol. This update is an attempt to summarize the available AcH research.Methods : The descriptive part of this article covers not only recent research but also the development of the field. Special emphasis is placed on mechanistic analyses, new hypotheses, and conclusions.Results : Elevated AcH during alcohol intoxication causes alcohol sensitivity, which involves vasodilation associated with increased skin temperature, subjective feelings of hotness and facial flushing, increased heart and respiration rate, lowered blood pressure, sensation of dry mouth or throat associated with bronchoconstriction and allergy reactions, nausea and headache, and also reinforcing reactions like euphoria. These effects seem to involve catecholamine, opiate peptide, prostaglandin, histamine, and/or kinin mechanisms. The contribution of AcH to the pathological consequences of chronic alcohol intake is well established for different forms of cancer in the digestive tract and the upper airways. AcH seems to play a role in the etiology of liver cirrhosis. AcH may have a role in other pathological developments, which include brain damage, cardiomyopathy, pancreatitis, and fetal alcohol syndrome. AcH creates both unpleasant aversive reactions that protect against excessive alcohol drinking and euphoric sensations that may reinforce alcohol drinking. The protective effect of AcH may be used in future treatments that involve gene therapy with or without liver transplantation.Conclusions : AcH plays a role in most of the actions of alcohol. The individual variability in these AcH‐mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcH‐metabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.
Polymorphism of the 5′‐Flanking Region of the CYP2E1 Gene: An Association Study With Alcoholism
Authors: Itoga Sakae , Harada Shoji , Nomura Fumio 
Published: April 2006

Background: Recently, a restriction fragment length polymorphism in the regulatory region of the CYP2E1 gene was identified. It has been suggested that the polymorphism is associated with the elevated activity of the cytochrome P‐450 2E1 (CYP2E1) enzyme in obese or alcoholic subjects. However, significance of the polymorphism in connection with alcoholism has not been studied. In the present study, we have characterized these repeated sequences in the 5′‐untranslated region of the CYP2E1 gene in Japanese subjects and North American white subjects and investigated whether these polymorphisms are associated with drinking habits and alcoholism.Methods: DNAs were isolated from blood samples of 192 Japanese nonalcoholics and 202 alcoholics as well as 125 North American white nonalcoholics. DNA samples were amplified by polymerase chain reaction and subjected to a fluorescent‐based single‐strand conformational change polymorphism analysis, DNA fragment analysis, and polymerase chain reaction‐direct sequencing.Results: Four alleles (A1–A4) were found, which were differentiated by the six subunits (L1, L2, L3, L4, S1, S2) based on the size difference and nucleotide replacement. A2 and A4 alleles were observed in the two ethnic groups (A2: Japanese subjects, 0.752; white subjects, 0.976;A4: Japanese subjects, 0.227; white subjects, 0.016). However, A1 allele was found only in North American white subjects (0.008), and A3 allele was detected only in Japanese subjects (0.021). Allele frequencies were significantly different between the two ethnic groups (p < 0.0001). Distribution of genotypes between Japanese nonalcoholics and alcoholics were not significantly different. Also, no significant difference for the allele frequencies was observed between Japanese moderate drinkers and heavy drinkers.Conclusions: Our data suggested no association among the polymorphic repeats, drinking behavior, and alcoholism. Allele frequencies were significantly different between Japanese subjects and North American white subjects.