bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gamma‐Hydroxybutyric Acid (GHB) in the Treatment of Alcohol Withdrawal Syndrome: A Randomized Comparative Study Versus Benzodiazepine
Authors: Addolorato Giovanni , Balducci Giuseppe , Capristo Esmeralda , Attilia Maria L. , Taggi Franco , Gasbarrini Giovanni , Ceccanti Mauro 
Published: May 2006

Background: Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma‐hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single‐blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.Methods: Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5–0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 ± 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males, 4 females; mean age 41.7 ± 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol‐revised scale (CIWA‐Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self‐rating Depression Scale for current depression assessment were performed.Results: Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA‐Ar total score at baseline and at the different times of observation. Considering the CIWA‐Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p< 0.02), agitation on day 5 (p< 0.02) and time of recovery of depression on day 5 (p< 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.Conclusions: GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well‐tolerated in AWS management.
Ethanol‐Induced Alterations in Neurotrophin Expression in Developing Cerebellum: Relationship to Periods of Temporal Susceptibility
Authors: Heaton Marieta Barrow , Mitchell J. Jean , Paiva Michael 
Published: May 2006

Background: The developing cerebellum has been shown to be profoundly affected by exposure to ethanol and to exhibit a temporal pattern of vulnerability. Cerebellar Purkinje cells are particularly susceptible to ethanol on postnatal day 4 or day 5 (P4‐5), whereas this population is much less vulnerable to similar ethanol insult slightly later in the postnatal period (P7‐9). The purpose of the study was to determine whether differential alterations in neurotrophic factors might be associated with this differential susceptibility. Methods: Neonatal rats were exposed to ethanol via vapor inhalation, and enzyme‐linked immunoabsorbent assays were subsequently conducted to assess cerebellar nerve growth factor, brain‐derived neurotrophic factor, and neurotrophin‐3 protein content. These analyses were made after ethanol exposure during the period of maximal cerebellar ethanol sensitivity (postnatal days 4‐5 [P4‐5]), during a period of much lower sensitivity (P7‐8), and during the entire “brain growth spurt” (P4‐10). Results: These determinations revealed a significant ethanol‐induced decrease in cerebellar nerve growth factor after exposure on P4‐5 but not after exposure on P7‐8 or P4‐10. No significant changes in brain‐derived neurotrophic factor or neurotrophin‐3 were found with any of the exposure paradigms. Conclusions: These results suggest that alterations in nerve growth factor, which has previously been shown to support cerebellar Purkinje and granule cells, may be a mechanism contributing to the early ethanol susceptibility within these neuronal populations.
Impact of a Stimulant‐Focused Enhanced Program on the Outcome of Alcohol‐ and/or Stimulant‐Dependent Men
Authors: Smith Tom L. , Volpe Fredric R. , Hashima Jason N. , Schuckit Marc A. 
Published: May 2006

Background: The approaches to the treatment of most forms of substance dependence are similar. It is not clear whether specific treatment components need to be added to address specific substances. This study asks two questions: What is the impact of a more intense drug treatment program, and do different substance problems require different treatment interventions?Methods: The 383 veterans included in this study represent two groups of consecutive inpatient male admissions with current alcohol dependence and/or dependence on amphetamines or cocaine at the inpatient Alcohol and Drug Treatment Program of the Veterans Affairs San Diego Healthcare System. All were interviewed at intake by trained interviewers using a standardized semistructured assessment instrument, and a resource person interview also was conducted with 85% of them. The first group of men received the Standard Treatment Program (STP), whereas the second group received the Enhanced Treatment Program (ETP). The latter included an addition of 10 hr per week of intense treatment aimed at stimulants, including two newly developed manual‐driven groups (Relapse Prevention and Interpersonal Counseling), each of which met twice a week.Results: The patient follow‐up was 92% at 3 months and 83% at 12 months. Abstinence from substances of abuse for ETP and STP were 63% vs. 49% at 3 months and 43% vs. 24% at 12 months. Logistic regressions demonstrated that treatment type continued to predict outcome even in the context of other potentially predictive variables.Conclusions: Despite the ETP emphasis on stimulants, both alcohol‐ and stimulant‐dependent men appeared to benefit, suggesting a generic improvement in substance use.
Long‐Term Alcohol Consumption in the Rat Affects Femur Cross‐Sectional Geometry and Bone Tissue Material Properties
Authors: Hogan H. A. , Groves J. A. , Sampson H. W. 
Published: May 2006

Background: Alcohol consumption previously has been demonstrated to reduce the density and strength of cortical bone of young, actively growing rats. Osteoblast activity and trabecular bone volume were also significantly lower. A germane question arising from these studies is whether the detrimental effects would persist into adulthood. To address this issue, a long‐term study was undertaken with animals that consumed alcohol throughout their life and into old age.Methods: One‐month‐old female Sprague‐Dawley rats were divided into three diet groups: alcohol‐fed, pair‐fed, and chow‐fed. The alcohol‐fed animals received a modified Lieber‐DeCarli diet that contained 35% ethanol‐derived calories. The pair‐fed group served as a caloric‐equivalent control, and the chow‐fed animals served as a completely untreated control. Animals were euthanized after five time periods on the diets that represented three stages of the life span: young (3 months), adult (6, 9, 12 months), and aged (18 months). The left femur was isolated and mechanically tested in 3‐point bending for mechanical properties.Results: In the young animals, alcohol consumption produced dramatic reductions in both extrinsic (whole bone) and intrinsic (tissue material) properties, which is consistent with results from previous studies on growing rats. For the adult animals, however, the alcohol groups were only slightly lower and the differences were not statistically significant. The aged animals showed diminished properties due to alcohol, but only for the intrinsic material properties. The extrinsic properties remained similar to controls as a result of greater radial expansion in the femur diaphysis. Despite the cross‐sectional areas being the same, this expansion gave rise to higher cross‐sectional moment of inertia values in the alcohol animals. The thickness of the cortical wall was lowest in the alcohol group at all time points.Conclusions: Long‐term alcohol consumption produced two major effects in the oldest animals studied: the quality of the cortical bone tissue was diminished, as evidenced by reduced elastic modulus and ultimate strength values, and the bone seemed to compensate for this by expanding the cross‐section to produce larger cross‐sectional moment of inertia values. The reduced bone tissue quality is consistent with the lower ash percent values in the alcohol animals, but other factors such as the quality of the collagen and mineral crystal may also be important contributors.
Ethanol Pretreatment Enhances NMDA Excitotoxicity in Biogenic Amine Neurons: Protection by Brain Derived Neurotrophic Factor
Authors: Crews Fulton T. , Waage Heather G. , Wilkie Mary Beth , Lauder Jean M. 
Published: May 2006

Background: Biogenic amine neurons are involved in a number of mental diseases including addiction and alcohol dependence. Because chronic ethanol is known to cause supersensitivity to NMDA excitotoxicity in cortical neurons, this study sought to determine the effect of ethanol treatment on biogenic amine neurons.Methods: To determine if ethanol exposure alters the vitality of hiogenic amine neurons, cultures were prepared from E14 rat brain. After 24 hr in culture, cells were divided into control or ethanol (100 mM) treatment groups, cultured an additional 48 hr, and then half of them exposed to NMDA for 25 min. The NMDA was then removed and cells cultured in fresh media for an additional 24 hr to allow for excitotoxic delayed neuronal death. Cultures were then stained with antibodies to 5‐hydroxytryptamine or tyrosine hydroxylase to identify serotonin and dopamine neurons, respectively. Cultures were analyzed for cell number and neuronal morphology.Results: Ethanol treatment alone had no effect on hiogenic amine cell number, soma area, number of neurites, or terminal segments, although the field area of dopamine neurons was decreased. Treatment with 30 μM NMDA had no effect on controls, but significantly decreased dopamine neurons in ethanol‐treated cultures as well as reduced soma area, field area, number of neurites and number of terminal segments. Treatment with higher concentrations of NMDA reduced dopamine and serotonin neurons in both controls and ethanol‐treated groups, and ethanol treatment significantly enhanced NMDA excitotoxic effects. Treatment with Brain Derived Neurotrophic Factor (BDNF) prevented ethanol sensitization to NMDA excitotoxicity.Conclusions: These studies suggest that ethanol treatment sensitizes biogenic amine neurons to excitotoxic insults. Ethanol sensitization of biogenic amine neurons to insults could contribute to the development of mental disease.
Birth Cohort Differences in Features of Antisocial Alcoholism Among Men and Women
Authors: Stoltenberg S.F. , Hill E.M. , Mudd S.A. , Blow F.C. , Zucker R.A. 
Published: May 2006

Background: This study examines the relations between birth cohort, gender, and family history of alcohol problems on alcohol dependence, and on the endorsement of alcohol abuse/dependence symptoms related to antisocial behavior. Methods: Mcn (n= 1365) and women (n= 625) were recruited from the community, hospitals, and other treatment sites and were given a structured diagnostic interview. Data were analyzed by using logistic regression. Results: Age of first regular alcohol use was lower in more recent birth cohorts for both men and women, with those born in the most recent cohort reporting earliest regular use. The decline across cohort was more dramatic in women than in men. For those participants with a diagnosis of alcohol dependence, being born in a more recent cohort was associated with increased risk of dependence onset before age 25. Among those participants with onset of alcohol dependence before age 25 (nmen= 400; nwomen= 51), being born in a more recent cohort was associated with increased risk of fights while drinking, police involvement, and drunk driving trouble as well as with increased risk for a diagnosis of abuse or dependence on another drug. Conclusions: These results suggest that the prevalence of antisocial alcoholism may be increasing for both men and women. These data exemplify how societal change may affect expression of underlying vulnerability for traits thought to be genetically influenced.
Glial Differences Between Naïve Withdrawal Seizure‐Prone and ‐Resistant Mice
Authors: Buckman J.F. , Meshul C.K. 
Published: May 2006

Background: Withdrawal seizure‐prone (WSP) and withdrawal seizure‐resistant (WSR) mice were bred in replicate (i.e., WSP‐1 and WSP‐2) to exhibit differences in handling‐induced convulsion severity during ethanol withdrawal. Methods: We examined the role of the glutamatergic system in susceptibility to ethanol‐withdrawal convulsions in naive mice by measuring the density of immunolabeling for several glutamate transporters and the glutamate‐metabolizing enzyme, glutamine synthetase. The density of glial fibrillary acidic protein immunolabeling (a marker of glial structure) and cytochrome oxidase activity (a marker of neuronal activity) were also characterized in naïve mice. Results: We observed a significantly greater density of immunolabeling for the glial transporter, gluta‐mate/aspartate transporter, in CA1 subfield of the hippocampus (CA1) of naive WSP‐2 mice as compared to WSR‐2 mice. No other significant differences were observed. However, as compared to WSR mice, naïve WSP mice exhibited a trend toward (a) greater immunolabeling for the glial glutamate transporter, glutamate transporter‐1, in CA3, (b) greater immunolabeling for glial‐specific glutamate‐metabolizing enzyme, glutamine synthetase, in CA1 (replicate‐2 only), and (c) less immunolabeling for the glial structural protein, glial fibrillary acidic protein, in all brain regions tested. In contrast, no trends or significant differences in the labeling density for the neuronal transporter, excitatory amino acid carrier 1, or the neuronal activity marker, cytochrome oxidase, were observed between the selected lines. Conclusions: These data suggest that the glutamatergic system and glia may play a pivotal role in the increased susceptibility to handling‐induced convulsions observed in WSP mice.
Time Course and Reproducibility of Urinary Excretion Profiles of Ethanol, Methanol, and the Ratio of Serotonin Metabolites After Intravenous Infusion of Ethanol
Authors: Jones A.W. , Helander A. 
Published: May 2006

Background: The aim of this study was to determine the time course and reproducibility of urinary excretion profiles of ethanol, methanol, and ratio of serotonin metabolites, 5‐hydroxytlyptophol (5HTOL) to 5‐hydroxyindoleacetic acid (5HIAA), under strictly controlled conditions. Methods: Nine healthy volunteers (6 women and 3 men) received 0.40 g of ethanomg of body weight on two occasions by constant rate intravenous infusion 30 min. Urine was voided before administration of ethanol and thereafter every 60 min for a total of 8 hr. Concentrations of ethanol and methanol in urine were determined by headspace gas chromatography, and the serotonin metabolites 5HTOL and 5HIAA were measured by gas chromatography‐mass spectrometry and high‐performance liquid chromatography, respectively. Results: The peak concentration of ethanol in urine occurred at 30 or 60 min after the infusion ended. The peak concentration of methanol and the 5HTOL/5HIAA ratio developed more gradually, reaching a plateau at 213 to 220 min and 200 to 220 min postinfusion, respectively. The concentration‐time profiles of ethanol and the 5HTOL/5HIAA ratio varied more between subjects than within subjects (p < 0.001), whereas the inter‐ and intraindividual variation in the pharmacokinetics of methanol were not significantly different (p > 0.05). The concentration of methanol and the 5HTOL/5HIAA ratio remained above the endogenous levels at 8‐hr postinfusion despite the fact that urinary ethanol was no longer measurable (<0.01 g/liter) after 5 to 6 hr. Conclusions: Measuring the concentrations of methanol and the ratio of serotonin metabolites (5HTOL/5HIAA) in urine is a more sensitive way to monitor recent drinking, compared with analysis of ethanol in body fluids. Moreover, the concentration‐time profiles of methanol and the 5HTOl/5HIAA ratio showed a good test‐retest stability. The present intravenous infusion experiment confirms previous work on these markers when ethanol was given perorally. The urinary methanol and the 5HTOL/5HIAA ratio have applications in forensic and clinical medicine as indicators of acute alcohol consumption.
Alcohol at Moderate Levels Decreases Fibrinogen Expression In Vivo and In Vitro
Authors: Wang Zhiqing , Barker Thomas H. , Fuller Gerald M. 
Published: May 2006

Background: Consumption of moderate amounts of alcohol has been reported to exert a cardioprotective effect in individuals. The exact mechanism by which this occurs has not been fully explored. Circulating levels of the clotting protein fibrinogen have been unequivocally established as an independent risk factor for vascular diseases. This study examined the effects of moderate levels of ethanol on the expression of fibrinogen in an animal model and in hepatoma cells. Methods: Out‐bred Sprague‐Dawley rats were fed 5% ethanol (v/v) in their water for 4 weeks, and circulating levels of fibrinogen were measured weekly via quantitative immunoassay. H4IIE rat hepatoma cells, which constitutively produce fibrinogen, were exposed to 10 and 20 mM ethanol, and fibrinogen production was determined. The effects of ethanol on fibrinogen messenger ribonucleic acids were determined by northern gel analyses. Results: Our findings demonstrate that daily consumption of moderate amounts of ethanol decreases circulating levels of fibrinogen 18% to 20%. The decrease is reversible and is not gender specific. The cxposure of hepatoma cells to ethanol also diminishes fibrinogen production by 20% by decreasing the transcription of fibrinogen genes. Alcohol concentration of 10 to 20 mM did not affect hepatoma cell viability or doubling time. Conclusions: The findings indicate that one likely positive benefit of moderate ethanol consumption is to diminish the production of fibrinogen, which reduces the potential risk exerted by this protein. The site of action of ethanol is, at least in part, exerted at the level of gene transcription.
A Novel Polymorphism (‐357 G/A) of the ALDH2 Gene: Linkage Disequilibrium and an Association With Alcoholism
Authors: Harada Shoji , Okubo Takehito , Nakamura Takako , Fujii Chieko , Nomura Fumio , Higuchi Susumu , Tsutsumi Mikihiro 
Published: May 2006

Background: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads to ALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported. Method: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North‐American Caucasians using single‐strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing. Result: A novel polymorphism at‐357 with a G to A substitution was found in all the population groups, including North‐American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2* 2 allele is linked to the G promoter allele, and theALDH2*1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2* 1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A χ2 test for the entire 3 × 2 table indicated significant variations in the three genotypes (χ2=6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed. Conclusion: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.
Self‐Reported Alcohol‐Associated Symptoms and Drinking Behavior in Three ALDH2 Genotypes Among Japanese University Students
Authors: Takeshita Tatsuya , Morimoto Kanehisa 
Published: May 2006

Background: Alcohol abuse is one of the most serious health problems among young adults. Nearly half of the Japanese population is sensitive to alcohol due to a genetic polymorphism in low Km aldehyde dehydrogenase (ALDH2). In the present study, we investigated the effects of the ALDH2 genotype on both self‐reported alcohol‐associated symptoms and alcohol drinking behavior among Japanese university students. Method: The study subjects were 423 (389 males and 34 females) university students in a medical university. The subjects completed a questionnaire regarding self‐reported alcohol‐associated symptoms and alcohol drinking behavior. The ALDH2 genotype was determined through digestion of polymerase chain reaction (PCR) products by a restriction enzyme Ksp632I.The frequency of alcohol‐associated symptoms generally increased in the order ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2 among males. The frequency of those who drink <5 days/week was less than 10% in all genotype groups. However, the frequency of those who drink 1‐4 days/week was significantly higher inALDH2*1/*1 than that mALDH2*1/*2 and mALDH2*2/*2. A similar tendency also was observed in females. Mean amounts of alcohol consumption per occasion in the three ALDH2 genotypes stratified by drinking frequency generally increased significantly in the order ALDH2*2/*2, ALDH2*1/*2, ALDH2*1/*1 in both sexes. The proportion of binge drinkers defined by those who drink ethanol of > 75 ml per occasion on average also increased in the order ALDH2*2/*2 (0.0%), ALDH2*1/*2 (9.8%), ALDH2*1/*1 (22.1%) among male drinkers (> 1 day/month).Conclusions:We for the first time demonstrated clear associations between the ALDH2 genotype, self‐reported alcohol‐associated symptoms, and alcohol drinking behavior among Japanese university students.