bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Administration of Alcohol to Adult Rats Inhibits Leydig Cell Activity: Time Course of Effect and Role of Nitric Oxide
Authors: Herman Melissa , Kang Sang Soo , Lee Soon , James Peter , Rivier Catherine 
Published: August 2006

Background: Alcohol has been shown to interfere with testosterone (T) release from Leydig cells. However, the mechanisms responsible for this phenomenon, which may include decreased activity of the luteinizing hormone‐releasing hormone (LHRH)–LH axis, as well as a direct influence of the drug on the testes, are not fully understood. In this work, we investigated the influence of alcohol, administered intragastrically (i.g.) or delivered via vapors, on Leydig cell activity and T release. Leydig cell function was studied by measuring changes in the levels of the steroidogenic proteins steroidogenic acute regulatory (StAR), the peripheral‐type benzodiazepine receptor (PBR), and the cytochrome P450 side‐chain cleavage enzyme (P450scc). Testosterone release was studied under basal conditions or in response to human chorionic gonadotropin (hCG). Finally, to identify potential factors mediating the influence of alcohol, we measured the testicular variant of the neuronal nitric oxide (NO) synthase (NOS), TnNOS, in semipurified Leydig cells.Methods: Adult male Sprague–Dawley rats were either injected with alcohol i.g. once or exposed to alcohol vapors (4 h/d) for 1 or 5 days. Controls received the vehicle (i.g. model) or were kept in boxes through which no vapors were circulated. Following these treatments, one series of experiments was devoted to investigate Leydig cell responsiveness by measuring plasma T levels before or after the intravenous injection of hCG (1 U/kg). In another series of experiments, we used semipurified Leydig cell preparations to measure StAR, PBR, P450scc, and TnNOS by Western blot analysis.Results: In the i.g. model, the T response to hCG was blunted for 12 hours following alcohol injection, but showed a rebound at 48 hours. Levels of StAR protein and of PBR, but not of P450scc, were significantly decreased within 10 minutes of drug administration. While StAR then remained depressed for 24 hours, PBR values were variable over this time course. By 48 hours, StAR, PBR, and P450scc levels had increased above control values. Both StAR and PBR levels showed correlations with plasma T levels. In the alcohol vapor models, both regimens of the drug also significantly depressed StAR and PBR protein concentrations, blunted the T response to hCG, and did not alter P450scc. Finally, we observed that alcohol delivered i.g. or via vapors up‐regulated TnNOS levels in Leydig cells, but that blockade of NO formation failed to restore a normal T response to hCG.Conclusions: Collectively, these results suggest that (a) the ability of Leydig cells to release T does not show a simple correlation with changes in StAR, PBR, and P450scc levels; (b) the time course of the alcohol‐induced changes were protein‐specific; and (c) despite the ability of alcohol to stimulate TnNOS expression, NO does not appear to mediate the inhibitory influence of this drug on testicular steroidogenesis in the models that we studied.
Effects of Acamprosate on Sleep During Alcohol Withdrawal: A Double‐Blind Placebo‐Controlled Polysomnographic Study in Alcohol‐Dependent Subjects
Authors: Luc Staner , Peter Boeijinga , Thierry Danel , Isabelle Gendre , Muriel Muzet , Frédéric Landron , Rémy Luthringer 
Published: August 2006

Background:Sleep disturbances are frequently encountered in alcohol‐dependent patients. Drugs improving sleep during abstinence from alcohol may play an important role in the recovery process.Methods:In the present study, the effects of acamprosate, a drug successfully used in maintaining abstinence following alcohol withdrawal, were assessed by polysomnographic recordings. A parallel double‐blind placebo‐controlled study was conducted in 24 male DSM‐IV alcohol‐dependent subjects aged 35.9±1.2 years. Treatments (2 tablets of 333 mg acamprosate vs placebo t.i.d.) were initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Polysomnographic assessments were recorded during acute withdrawal (the first 2 nights following withdrawal) and during postwithdrawal abstinence (the last 2 nights of the trial).Results:Results show that, compared with placebo, acamprosate decreased wake time after sleep onset and increased stage 3 and REM sleep latency (all treatment effects with ap<0.05 significance). Withdrawal effects themselves were also demonstrated as sleep efficiency (p<0.01) and total sleep time (p<0.05) were lower in abstinence nights versus withdrawal nights, whereas no significant treatment × withdrawal effect could be evidenced. Acamprosate was well tolerated during the entire course of the study.Conclusions:The present study shows that acamprosate ameliorates both sleep continuity and sleep architecture parameters classically described as disturbed in alcohol‐dependent patients. From a clinical perspective, it suggests that an 8‐day acamprosate prewithdrawal treatment is well tolerated and can attenuate the sleep disturbances engendered by alcohol withdrawal in alcohol‐dependent subjects.
Enzymatic Mechanisms of Ethanol Oxidation in the Brain
Authors: Zimatkin Sergey M. , Pronko Sergey P. , Vasiliou Vasilis , Gonzalez Frank J. , Deitrich Richard A. 
Published: August 2006

Background: The exact enzymatic mechanisms of ethanol oxidation in the brain are still unclear. The catalase‐mediated oxidation of ethanol was demonstrated in rat brain using incubation of brain homogenates with catalase inhibitors. The role of the alcohol dehydrogenase (ADH) or cytochrome P450–dependent system in this process is possible, but has not been confirmed. The objective of the study was to determine the contribution of the different enzymatic pathways to ethanol oxidation in brain homogenates from mice and rats.Methods: Three approaches were used to investigate the enzymatic mechanisms of ethanol oxidation in the brain of rats and mice: (1) preincubation of brain homogenates with inhibitors of the ethanol‐metabolizing enzymes (catalase, CYP2E1, ADH, and ALDH); (2) utilization of mice with genetic deficiency in ethanol‐metabolizing enzymes (catalase, CYP2E1, or both enzymes); and (3) determination of ethanol oxidation in brain subcellular fractions known to have differential activity of ethanol‐metabolizing enzymes. The ethanol‐derived acetaldehyde (AC) and acetate were determined in brain samples by gas chromatography.Results: The catalase inhibitors sodium azide (5 mM) and aminotriazole (5 mM) as well as CYP2E1 inhibitors diallyl sulfide (2 mM) and β‐phenethyl isothiocyanate (0.1 mM) lowered significantly the accumulation of the ethanol‐derived AC and acetate in brain homogenates. The ADH inhibitor 4‐methyl pyrazole (5 mM) significantly decreased the acetate but not the AC accumulation. Ethanol‐derived AC accumulation in brain homogenates of acatalasemic mice was 47% of the control value, 91% in CYP2E1‐null mice, and 24% in double mutants (with deficiency of both catalase and CYP2E1). The highest levels of ethanol oxidation were found in microsomal and peroxisomal subcellular brain fractions, where CYP2E1 and catalase are located, respectively.Conclusions: Catalase is the key enzyme of ethanol oxidation in the brain of rodents: it may be responsible for about 60% of the process. CYP2E1 plays an important role in ethanol oxidation in the rodent brains. Alcohol dehydrogenase plays a minor role, if any, in this process. Aldehyde dehydrogenase plays the crucial role in the further oxidation of ethanol‐derived AC in the brain homogenates.
Infantile Sensitivity to Ethanol's Motivational Effects: Ethanol Reinforcement During the Third Postnatal Week
Authors: Molina Juan Carlos , Ponce Luciano Federico , Truxell Eric , Spear Norman E. 
Published: August 2006

Background: Although tests specific to newborn rats have frequently verified their susceptibility to the reinforcing properties of ethanol, demonstration of comparable reinforcing effects in older infants has been elusive. Using a second‐order conditioning procedure, the present study assessed in preweanling rats whether pairing with early postabsorptive effects of ethanol would render intraorally delivered gustatory stimuli capable of positive reinforcement for association with a salient texture. Direct reinforcing effects of ethanol were also evaluated through intake tests of gustatory stimuli previously paired with the drug. Blood ethanol levels (BELs) were determined for each of the ethanol doses used.Methods: Pups (14 days old) were stimulated with intraoral infusion of sucrose (10% v/v), water, or quinine (0.0045% w/v) 5 minutes after being intragastrically (i.g.) administered 0.00, 0.25, 0.50, or 2.00 g/kg ethanol (Experiments 1 and 2). These stimuli were then briefly presented while pups experienced a rough texture (sandpaper). Rats were subsequently evaluated in a 2‐way texture location test (sandpaper vs smooth surface). In Experiment 3, sucrose, water, or quinine was paired with early postabsorptive effects of ethanol (0.00, 0.50, or 2.0 g/kg). Consumption of these stimuli was later assessed. Motor activity patterns during the intake test were also evaluated. In Experiment 4, BELs corresponding to 0.25, 0.50, or 2.0 g/kg ethanol were determined 5 and 20 minutes after i.g. administration (time periods were in accord with the onset and offset of intraoral stimulation used in the previous experiments).Results: Intraoral infusion of sucrose, water, or quinine, while under a state of sobriety and paired with sandpaper, resulted in roughly 50% preference for this texture. Sandpaper preferences were significantly elevated in pups that had experienced sucrose or water in a nonsober state—while under the effects of ethanol (Experiments 1 and 2). This indicated reinforcing effects of the ethanol intoxication. Pairing ethanol intoxication directly with consumption of sucrose, water, or quinine did not affect their later consumption. Yet, there were clear indications that this pairing resulted in conditioned behavioral activity patterns. Blood ethanol levels corresponding to the ethanol doses used here ranged between 10 and 150 mg%.Conclusions: Infants appear sensitive to pharmacological reinforcing properties of low and relatively high ethanol doses. This sensitivity was revealed indirectly, by pairing gustatory stimuli with ethanol intoxication and then allowing these stimuli to act as second‐order reinforcement for a quite different (tactile) stimulus. Behavioral activation elicited by the gustatory stimuli previously paired with a state of intoxication seems to compete with the expression of ethanol's motivational properties as assessed through intake tests.
Barriers to Treatment of Hepatitis C in HIV/HCV‐Coinfected Adults with Alcohol Problems
Authors: Nunes David , Saitz Richard , Libman Howard , Cheng Debbie M. , Vidaver John , Samet Jeffrey H. 
Published: August 2006

Background:Alcohol use and human immune deficiency virus (HIV) infection are both associated with accelerated progression of hepatitis C virus (HCV) disease and reduced response rates to interferon therapy. In this study, we assessed the prevalence of barriers to interferon treatment in a population of HIV/HCV‐coinfected patients with current or past alcohol problems and the extent to which they received treatment to address the barriers.Methods:This is a cross‐sectional, descriptive analysis of baseline data from a prospective study assessing the impact of HCV and alcohol use on HIV disease progression. Using consensus guidelines, subjects were categorized as having absolute, relative, or no contraindications to interferon therapy for HCV. Absolute contraindications to treatment included heavy alcohol use, decompensated liver disease, CD4 cell count <100 cells/μL, recent needle sharing, and suicidal ideation. Relative contraindications included moderate alcohol use, recent injection drug use, depressive symptoms, and CD4 cell count from 100 to 199 cells/μL.Results:Of 401 HIV‐infected subjects, 200 were HCV RNA‐positive. Fifty‐three percent had an absolute contraindication to interferon therapy, 35% a relative but no absolute contraindication, and only 12% had no contraindication. Of those with an absolute contraindication, 61% reported heavy drinking and the majority (88%) had multiple contraindications. These contraindications were present despite the fact that over 50% were in receipt of substance abuse and mental health treatment.Conclusions:Continued alcohol and drug use as well as depressive symptoms are the major barriers to interferon therapy in HCV/HIV‐coinfected subjects and these barriers persist despite high treatment rates for these problems. Therefore, more intensive treatments of alcohol, drug, and mental health issues are needed to improve HCV treatment eligibility in HCV/HIV‐coinfected persons.
Effects of Alcohol on Polysomnographically Recorded Sleep in Healthy Subjects
Authors: Feige Bernd , Gann Horst , Brueck Rigo , Hornyak Magdolna , Litsch Simone , Hohagen Fritz , Riemann Dieter 
Published: August 2006

Background: After studying the sleep of alcohol‐dependent patients at the beginning and over the course of abstinence in earlier studies, our interest in the current study focused on the direct effect of 2 doses of alcohol [0.03 and 0.1% blood alcohol level (BAL)] on healthy sleep. This is the first polysomnographic study testing the impact of 2 doses of alcohol ingestion (thus reflecting “normal” social drinking and alcohol abuse) in a single‐blind randomized design in healthy volunteers. The study evaluated a short‐term acute drinking period for 3 and 2 days of withdrawal from alcohol not only for polysomnographic variables but also for subjective estimates of sleep quality.Methods: In a crossover design with a 1‐week interval, healthy subjects received alcohol to raise their blood alcohol to either 0.03 or 0.1% BAL at bedtime for 3 consecutive nights after an alcohol‐free baseline night. Objective (polysomnography) and subjective sleep (questionnaires) was recorded each night. During the following 2 days, alcohol was discontinued with simultaneous measurements of sleep to gauge withdrawal effects.Results: At a dose of alcohol leading to BAL of 0.03%, no clear effects could be detected. Following an evening BAL of 0.1%, a hypnotic‐like effect (shortened sleep latency, reduced number of wake periods, decreased stage 1 sleep) occurred primarily during the first half of the night with signs of rebound effects being already present during the second half of the night (increased stage 1 sleep). At this dose, alcohol significantly increased slow‐wave sleep (SWS) in the first half of the night and reduced REM density in the beginning of the night. After discontinuation of the higher alcohol dose, REM sleep amount increased. No significant withdrawal or rebound effects could be observed for parameters of sleep continuity during the 2 nights after discontinuation from alcohol at a BAL of 0.1%.Conclusions: Owing to the small sample size, the results of this study need to be interpreted with caution. Short‐term moderate alcohol consumption (BAL 0.03%) did not significantly alter objective or subjective parameters of sleep. Higher doses of alcohol resulting in a BAL level of 0.10% immediately before going to bed mainly influenced sleep in the first half of the night, resembling the effects of a short‐acting hypnotic drug, including a suppression of phasic aspects of REM sleep (REM density). Interestingly, analysis of the latter part of these nights indicated the immediate presence of withdrawal effects (increased light sleep). No statistically significant effects on sleep parameters were observable during the 2 nights of withdrawal from alcohol at the higher BAL. Interpreted carefully, our data indicate that negative effects on sleep occur already with short‐term use of alcohol at doses of BAL of 0.10%, despite hypnotic‐like effects during the first hours of sleep, especially during the latter part of the night.
Cognitive Performance in Long‐Term Abstinent Alcoholic Individuals
Authors: Fein George , Torres Jennifer , Price Leonard J. , Di Sclafani Victoria 
Published: August 2006

Background: There are few investigations of the potential recovery of neurocognitive function in chronic alcoholic samples after very‐long‐term abstinence. The current study examined cognitive abilities in middle‐aged (mean age 46.8 years), long‐term abstinent alcoholic individuals (LTAA). Twenty‐five LTAA men and 23 LTAA women abstinent for an average of 6.7 years were compared with an equal number of gender and age‐comparable normal controls (NC). We examined the association of neurocognitive variables with age, duration of abstinence, alcohol use measures, and the density of a family history of problem drinking.Methods: Long‐term abstinent alcoholic individuals and NC underwent comprehensive neuropsychological assessment. Performance was measured in the following 9 domains: abstraction/cognitive flexibility, attention, auditory working memory, immediate memory, delayed memory, psychomotor function, reaction time, spatial processing, and verbal skills.Results: Long‐term abstinent alcoholic individuals performed similarly to NC, except for deficits in the spatial processing domain. The spatial processing results must be interpreted with caution because of multiple comparison issues; however, spatial processing deficits are among the impairments most often reported in abstinent alcoholic individuals. None of the cognitive measures were associated with length of abstinence, any alcohol use variable, or family history measure.Conclusions: Very‐long‐term abstinence resolves most neurocognitive deficits associated with alcoholism, except for the suggestion of lingering deficits in spatial processing.
A Theoretical Argument for Inherited Thiamine Insensitivity as One Possible Biological Cause of Familial Alcoholism
Authors: Manzardo Ann M. , Penick Elizabeth C. 
Published: August 2006

Thiamine deficiency has been specifically linked to the development of Wernicke–Korsakoff syndrome (WK)—a degenerative brain disorder that is typically associated with alcoholic drinking. Alcoholism‐related thiamine deficiency is a major cause of WK. However, an inherited abnormality in thiamine utilization has been identified in some WK patients that may predispose heavy drinkers to this severe neurological syndrome. Individuals who possess this variant require more thiamine throughout their lives to prevent them from experiencing thiamine deficiency. Recent prospective studies have implicated early childhood nutritional and environmental influences in the etiology of alcoholism in adults. These studies have suggested that developmental abnormalities involving brain white matter growth might precipitate the later development of alcoholism possibly by altering the emerging reward‐related brain systems. Brain white matter growth is highly sensitive to nutritional deficiency (including thiamine deficiency) and oxidative injury, especially during the perinatal period.The proposed model of familial alcoholism hypothesizes that an inherited insensitivity to thiamine can precipitate brain abnormalities very early in life that will greatly increase the risk of developing alcoholism in adulthood.This paper offers a heuristic model of a possible mechanism by which both inherited and environmental factors related to thiamine utilization might coaggregate to cause alcoholism.
Neurobehavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders in Communities from Italy: Preliminary Results
Authors: Kodituwakku Piyadasa , Coriale Giovanna , Fiorentino Daniela , Aragón Alfredo S. , Kalberg Wendy O. , Buckley David , Gossage J. Phillip , Ceccanti Mauro , May Philip A. 
Published: August 2006

Background: There has been considerable effort expended on defining neurobehavioral characteristics of children with fetal alcohol spectrum disorders (FASD). Children with FASD display a range of cognitive deficits and behavioral problems. In this article, we report on the neurobehavioral characteristics of children with FASD in selected communities in Italy. It was expected that both inattentive and hyperactive/impulsive characteristics would discriminate children with FASD from controls and that the groups would also differ on intellectual functioning, language comprehension, and academic skills.Methods: Eighty‐two children, 22 diagnosed with FASD and 60 control children, participated in this study. The children were administered tests of nonverbal reasoning, language comprehension, academic achievement, and behavior.Results: On tests of nonverbal reasoning and language comprehension, the FASD group earned lower scores than did controls. Moreover, on a test of academic achievement the FASD group scored lower. When comparing these 2 groups on disruptive behavioral symptomatology, similar results were obtained, the FASD group showing greater attentional difficulties and hyperactivity/impulsivity behaviors and more overall behavioral problems. Stepwise logistic regression analysis showed that a model containing inattention and error scores on the language comprehension task correctly classified 85% of the participants. Compared with the control group, a significantly greater proportion of children with FASD met the Diagnostic and Statistical Manual of Mental Disorders—fourth edition (DSM‐IV) criteria of ADD, inattentive type, as reported by teachers. In contrast, hyperactive symptoms among children with FASD were comparable with the control group. Teachers rated children with FASD as having more inattentive behaviors and as performing lower in academic skills than controls. The association between reported hyperactivity symptoms and achievement scores was nonsignificant for both language and math scores, suggesting that it is not the hyperactivity causing problems, but the child's inattention.Conclusions: This research indicates that a nonclinic‐referred sample of Italian children with FASD display a profile of neurobehavioral functioning consistent with that reported by other researchers. Furthermore, the neurobehavioral characteristic most identified with children diagnosed with FASD was inattention followed by hyperactivity.
Maximum Quantity Consumed and Alcohol‐Related Problems: Assessing the Most Alcohol Drunk With Two Measures
Authors: Greenfield Thomas K. , Nayak Madhabika B. , Bond Jason , Ye Yu , Midanik Lorraine T. 
Published: August 2006

Purposes: The maximum amount of alcohol consumed on any day is an important indicator of problem drinking. This study examined the ability of 2 maximum measures, taken individually and in combination, to predict alcohol‐related consequences and dependence symptoms.Method: We analyzed data from 4,296 current drinkers who participated in the 2000 National Alcohol Survey (N10) and provided complete data on several alcohol measures. Items included the most they drank in any day in the past 12 months assessed by 2 questions: a standard question with a 6‐level categorical response format and an open‐ended (continuous) question referencing the occasion that you had the most to drink that followed items on drinking contexts.Results: In a within‐subjects analysis, more than two‐thirds of the respondents provided consistent responses on both questions (69.9%), 12.4% respondents reported higher maximum quantities on the open‐ended question partitioned into equivalent categories, and 17.7% reported a higher maximum on the initial categorical question. In multiple logistic regression analyses predicting alcohol‐related consequences, the continuous open‐ended maximum or the mean of the 2 maximum items were the strongest predictors, whereas for predicting alcohol dependence symptoms, the maximum of the open‐ended and closed‐ended maximum items was a better predictor than each measure alone.Conclusion: Although categorical response formats generally capture high‐quantity drinking better than open‐ended formats, use of a second, alternatively formatted “most drunk” question may modestly improve ability to predict survey indicators of alcohol use disorders.