bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ability of Baclofen in Reducing Alcohol Craving and Intake: II—Preliminary Clinical Evidence
Authors: Addolorato Giovanni , Caputo Fabio , Capristo Esmeralda , Colombo Glancarlo , Gessa Gian Luigi , Gasbarrini Giovanni 
Published: May 2006

Background:Accumulating evidence shows the efficacy of the γ‐aminobutyric acid (GABAB) receptor agonist baclofen in reducing alcohol intake in rats, but no studies have been performed in alcoholics. In the present preliminary study we investigated the effect of short‐term baclofen administration on craving for alcohol, ethanol intake, and abstinence from alcohol in alcoholic individuals.Methods:Ten male current alcoholic individuals were admitted to the study. Baclofen was orally administered for 4 weeks, at a dose of 15 mg/day refracted in three times per day for the first 3 days, with the dose increased to 30 mg/day for the remaining 27 days. Each subject was checked as an outpatient every week for the 4 weeks; at each visit (T0‐T4) craving level was evaluated by the Alcohol Craving Scale (ACS), and abstinence from alcohol was assessed based on the individual's self‐evaluation, family member interview, and the main biological markers of alcohol abuse. A self‐reported alcohol intake was recorded as the mean number of standard drinks consumed per day.Results:Nine subjects completed the study; of these, two subjects continued to drink alcohol although they substantially reduced their daily drinks in the first week of treatment, whereas seven maintained abstinence throughout the experimental period. Craving was significantly reduced from the first week of the drug administration (p < 0.01) and remained so throughout the entire treatment period. Participants also reported that obsessional thinking about alcohol disappeared. Values of γ‐glutamyltranspeptidase, alanine aminotransferase, and mean cellular volume significantly decreased by the end of the study. Tolerability was fair in all participants; headache, vertigo, nausea, constipation, diarrhea, abdominal pain, hypotension, increased sleepiness, and tiredness were present as side effects in the first stage of the treatment. No participants showed craving for the drug.Conclusions:With the limitations of the low number of individuals evaluated and the open design, this preliminary clinical study supports the preclinical evidence on the effect of baclofen in reducing alcohol intake. The anticraving properties of the drug suggest a possible role of baclofen in the treatment of individuals with alcohol problems.
Neurophysiological Findings and Drinking Levels in High‐Alcohol‐Drinking (HAD) and Low‐Alcohol‐Drinking (LAD) Rats
Authors: Slawecki C. J. , Betancourt M. , Li T‐K. , Ehlers C. L. 
Published: May 2006

Background:Specific neurophysiological profiles, such as reduced P300 amplitude or altered spectral power in the EEG, have been associated with a risk for alcoholism in several clinical populations. In certain rodent models, high versus low alcohol consumption is associated with similar neurophysiological differences. For example, alcohol‐preferring (P) rats have increased spectral power and decreased P300 amplitudes compared with alcohol‐nonpreferring (NP) rats. In the present study, the neurophysiological profiles of high‐alcohol‐drinking (HAD) and low‐alcohol‐drinking (LAD) rats were assessed (1) to determine if their electrophysiological profiles are similar to P and NP rats and (2) to examine the relationship of these neurophysiological indices to ethanol drinking.Methods:Ethanol‐naïve HAD and LAD rats were implanted with cortical and amygdalar recording electrodes. Baseline EEG and event‐related potentials (ERPs) then were assessed. Subsequently, all rats were trained to self‐administer ethanol by using a sucrose‐substitution procedure.Results:Baseline EEG and ERP (i.e., pre‐ethanol exposure) were assessed based on line (HAD versus LAD) and actual ethanol consumption (high drinkers versus low drinkers). At baseline, ethanol‐naïve HAD rats displayed significantly greater power in the cortical EEG and decreased amygdala N1 ERP amplitude compared with ethanol‐naïve LAD rats. Similar EEG and ERP profiles have been observed when P and NP rats are compared. No differences in P300 between lines were observed, but high‐drinking rats, independent of line, had significantly decreased P300 amplitude in the amygdala compared with low‐drinking rats.Conclusions:These data suggest there are some similarities in EEG and ERP profiles of P and HAD rats compared with NP and LAD rats. Furthermore, the data suggest that decreased P300 amplitude in the amygdala is associated with increased limited access ethanol drinking.
Efficacy of Dexfenfluramine in the Treatment of Alcohol Dependence
Authors: Romach Myroslava K. , Sellers Edward M. , Kaplan Howard L. , Somer Gail R. , Gomez‐Mancilla Baltazar 
Published: May 2006

Background:A substantial body of evidence supports a role for serotonin in modulating alcohol intake, which suggests that this neurotransmitter represents a promising target for pharmacotherapy development for alcohol use disorders. Dexfenfluramine, a serotonin releaser and reuptake inhibitor, decreases alcohol self‐administration by rats. Its greater potency and several mechanisms of action suggest it should be more effective in treating alcohol dependence than drugs that only inhibit serotonin reuptake.Methods:We conducted an 11 week, randomized, double‐blind trial that compared oral placebo and dexfenfluramine 7.5, 15, 22.5, and 30 mg bid in 136 alcohol‐dependent patients. A brief behavioral intervention was offered concurrently.Results:The majority of subjects were male (72%), and the age of the group was 44 ± 11 years (mean ± SD). Both placebo‐ and drug‐treated groups significantly reduced alcohol consumption compared with baseline (a 55% decrease in mean drinks per day; p < 0.01), but there were no significant differences between drug and placebo groups or dose effects for most outcome measures.Conclusions:Our results with dexfenfluramine are further evidcnce that serotonergic medications on their own do not significantly reduce alcohol consumption in alcohol‐dependent individuals. Combination pharmacotherapy with agents that act on different receptors or neurotransmitter systems (e.g., naltrcxone plus dexfenfluramine) may be one way to enhance serotonergic effects on drinking behavior and should be considered in future medication development clinical trials.
Test Characteristics of Carbohydrate‐Deficient Transferrin and γ‐Glutamyltransferase in Alcohol‐Using Perimenopausal Women
Authors: van Pelt Johannes , Leusink Geraline L. , van Nierop Peter W.M. , Keyzer Jules J. 
Published: May 2006

Background:The application of biochemical markers to detect heavy alcohol use in women has shown disappointing results until now. We evaluated carbohydrate‐deficient transferrin (CDT) by the CDTcct® method and γ‐glutamyltransferase (GGT) in a large cohort of alcohol‐using perimenopausal women studied primarily for osteoporosis.Methods:CDT and GGT were measured in 431 women aged 46 to 54 years, who were selected from a large cohort (n= 8503) of pre‐, peri‐, and postmenopausal women. Their alcohol intake was known from questionnaires and face‐to‐face interviews. Three groups were constructed for statistical analysis: those drinking on average less than 7 alcoholic drinks per week (n= 103), those drinking 7 to 34 per week (n= 280), and those drinking at least 35 per week (n= 48).Results:The mean values of CDT and GGT of the three groups increased with an increasing alcohol intake, but there was a poor correlation between CDT and GGT in the complete study group (r= 0.3). The specificities of CDT and GGT were comparable, 83% and 78%, respectively. The sensitivities for CDT and GGT were 30% and 50%, respectively. A logistic regression model could assign, overall, 77% of the women correctly in relation to their alcohol intake: 43% of the women drinking at least 35 drinks per week and 92% of the women drinking less than 7 drinks per week.Conclusions:The test characteristics of both GGT and CDT are not good enough to be used as biochemical markers for detecting heavy alcohol use in women. The use of a logistic regression model offers an advantage, because both numeric values of CDT and GGT are taken into account instead of arbitrary cutoff values.
Alcohol and the Continuation of Early Marital Aggression
Authors: Quigley Brian M. , Leonard Kenneth E. 
Published: May 2006

Background: Husband alcohol use has frequently been found to be related to husband‐to‐wife marital violence. Research has demonstrated a prospective link between husband alcohol use before marriage and husband‐to‐wife aggression in the first year of marriage. The present study examined the relationships of husband violence, marital conflict, and couple's alcohol use in the first year of marriage to husband‐to‐wife marital violence in the second and third years of marriage.Methods: Newlywed couples were recruited at the time of marriage and were interviewed regarding alcohol use and experience with violence before marriage, 1 year after marriage, and 3 years after marriage.Results: Year l violence was predictive of subsequent marital violence. Husband and wife drinking patterns in the first year of marriage interacted to predict violence in later years. The most violence in subsequent years occurred in couples where the husband was a heavy drinker and the wife was not. Husbands who were violent in year 1 were more likely to be violent in later years. When no violence occurred in the first year, frequent use of verbal aggression in year 1 was predictive of violence in subsequent years.Conclusions: The predictive value of husband drinking patterns for subsequent violence extends beyond the transition to marriage. The fact that husband and wife alcohol use interacted to predict future aggression suggests that the relationship between husband alcohol use and marital violence is not spurious nor the result of conflict and violence promoting alcohol use. The findings may reflect multiple instances of acute intoxication and/or alcohol‐related stress and conflict within the relationship, both of which may increase the likelihood of aggression.
Ethanol Inhibition: The Humoral and Cellular Immune Response to Hepatitis C Virus NS5 Protein After Genetic Immunization
Authors: Encke J. , Wands J.R. 
Published: May 2006

Background: The combination of chronic hepatitis C virus (HCV) and ethanol may increase viral replication, impair cellular immunity, and result in severe and progressive liver disease. Because HCV nonstructural proteins play a major role in viral elimination, we examined the cellular and humoral immune responses after genetic immunization against NS5 in a chronic ethanol mouse model.Methods: Mice were fed an ethanol or isocaloric pair‐fed control liquid diet and were immunized with HCV NS5‐expression plasmid.Results: The humoral and cellular arms of the immune system were significantly impaired in ethanol‐fed mice. Abstinence partially reversed the inhibitory effects on antibody levels and the CD4+ proliferative immune response but did not restore the CD8+ cytotoxic T‐cell response to this HCV nonstructural protein. Furthermore, we determined whether murine interleukin‐2 coadministration with the NS5 expression plasmid would reverse the inhibitory effects of chronic ethanol consumption; again, partial restoration was observed for B‐cell and CD4+ T‐cell activity, but not for cytotoxic T cells.Conclusions: These results suggest that the high rate of chronic HCV infection in alcoholics may be due to ethanol's effects on antiviral immune responses.
Discriminative‐Stimulus Effects of Triazolam in Light and Moderate Drinkers
Authors: Rush Craig R. , Kelly Thomas H. , Fillmore Mark T. , Hays Lon R. 
Published: May 2006

Background:The results of previous laboratory experiments with humans suggest that light and moderate drinkers respond differentially to the effects of benzodiazepines. The aim of this study was to further assess the behavioral effects of a benzodiazepine in light and moderate drinkers.Methods:To accomplish this aim, 12 volunteers (6 light drinkers and 6 moderate drinkers) learned to discriminate 0.375 mg of triazolam, a triazolobenzodiazepine hypnotic. After they learned this discrimination, a test‐of‐novel‐doses phase was conducted in which a range of doses of triazolam (0, 0.06, 0.125, 0.25, and 0.375 mg) was tested in both groups of volunteers. The subject‐rated and performance‐impairing effects of triazolam were assessed concurrently.Results:There was not a significant difference between the groups in terms of the number of trials needed to learn the discrimination, nor did the proportion of light and moderate drinkers who learned to accurately discriminate 0.375 mg of triazolam differ significantly. The discriminative‐stimulus, subject‐rated, and performance‐impairing effects of triazolam were an orderly function of dose but did not differ across the light and moderate drinkers.Conclusions:Future studies should examine the discriminative‐stimulus effects of a lower dose of triazolam (e.g., 0.25 mg) in light and moderate drinks or use a fading procedure to determine differences in terms of the lowest discriminable dose.
Executive Functioning in Preschool‐Age Children Prenatally Exposed to Alcohol, Cocaine, and Marijuana
Authors: Noland Julia S. , Singer Lynn T. , Arendt Robert E. , Minnes Sonia , Short Elizabeth J. , Bearer Cynthia F. 
Published: May 2006

Background: Reports from clinical and experimental (animal) research converge on the suggestion that prenatal exposure to alcohol, cocaine, or marijuana undermines executive functioning (EF) and its neurological underpinnings. However, large, adequately controlled, prospective studies of alcohol and marijuana effects on EF have reported conflicting findings, and there have been no such studies of cocaine exposure.Methods: EF was investigated in a cohort (n= 316) of 4‐year‐old children the majority of whose mothers had used varying combinations of cocaine, alcohol, and marijuana during pregnancy. With use of postpartum maternal report and biological assay, children were assigned to overlapping prenatal cocaine‐exposed, alcohol‐exposed, and marijuana‐exposed groups and to complementary control groups. The postnatal environmental assessment included measures of maternal intellectual and psychosocial functioning, current drug or alcohol use, and home environment.Results: The children in the alcohol‐exposed group had worse tapping‐inhibition performance than children in the non‐alcohol‐exposed group, and this effect persisted when potential confounding environmental variables, other drug variables, and concurrent verbal intelligence were controlled for.Conclusions: Prenatal alcohol is predictive of decreased EF in early childhood that could not be attributed to environmental factors. The results are discussed in terms of the age and overall high‐risk status of the children.
Effects of Alcohol, Personality, and Provocation on the Expression of Anger in Men: A Facial Coding Analysis
Authors: Parrott Dominic J. , Zeichner Amos , Stephens Dana 
Published: May 2006

Background: Research has demonstrated that alcohol‐related aggression is modulated by anger‐based personality traits. However, it is unclear how anger, as a concomitant of aggression, is affected by an interaction among these variables. The present study evaluated the effects of alcohol, anger‐based traits, and physical provocation on anger.Methods: Participants were 136 male social drinkers who completed measures designed to assess trait anger and anger expression styles and were assigned to an alcohol or no‐alcohol control beverage group. Participants engaged in a competitive reaction time task in which electric shocks were received from a fictitious opponent. Participants’ experience of anger was assessed unobtrusively via the Facial Action Coding System.Results: Intoxicated participants displayed more facial expressions of anger than sober participants. Interactive effects between anger expression styles and beverage group also were detected in that, among intoxicated participants, a positive relationship between facial expressions of anger and the tendency to express anger outwardly was found after high, but not low, provocation. This relationship was not observed at either provocation level in the no‐alcohol control group. Similarly, whereas participants’ tendency to control anger resulted in fewer facial expressions of anger by intoxicated participants, no such relationship was found among sober participants.Conclusions: Findings suggest that alcohol intoxication facilitates the experience of anger after provocation and enhances the relationship between state anger and behavioral tendencies to control anger expression.
Sensitivity of Concentration and Risk Predictions in the PRESTO and MMSOILS Multimedia Models: Regression Technique Assessment
Authors: Mills William B. , Lew Christine S. , Hung Cheng Y. 
Published: May 2006

This paper describes the application of two multimedia models, PRESTO and MMSOILS, to predict contaminant migration from a landfill that contains an organic chemical (methylene chloride) and a radionuclide (uranium‐238). Exposure point concentrations and human health risks are predicted, and distributions of those predictions are generated using Monte Carlo techniques. Analysis of exposure point concentrations shows that predictions of uranium‐238 in groundwater differ by more than one order of magnitude between models. These differences occur mainly because PRESTO simulates uranium‐238 transport through the groundwater using a one‐dimensional algorithm and vertically mixes the plume over an effective mixing depth, whereas MMSOILS uses a three‐dimensional algorithm and simulates a plume that resides near the surface of the aquifer.A sensitivity analysis, using stepwise multiple linear regression, is performed to evaluate which of the random variables are most important in producing the predicted distributions of exposure point concentrations and health risks. The sensitivity analysis shows that the predicted distributions can be accurately reproduced using a small subset of the random variables. Simple regression techniques are applied, for comparison, to the same scenarios, and results are similar. The practical implication of this analysis is the ability to distinguish between important versus unimportant random variables in terms of their sensitivity to selected endpoints.
Longterm visual prognosis in Usher syndrome types 1 and 2
Authors: Sadeghi André M. , Eriksson Kristina , Kimberling William J. , Sjöström Anders , Möller Claes 
Published: May 2006

Abstract.Purpose:  To estimate the age at diagnosis of retinitis pigmentosa and to determine visual acuity deterioration, visual field impairment and the frequency of cataracts in Usher syndrome types 1 and 2.Methods:  We carried out a retrospective study of 328 affected subjects with Usher syndrome types 1 and 2. Study subjects were divided into seven different age groups by decade. Data were analysed using descriptive statistics, general linear model anova and survival analysis.Results:  Retinitis pigmentosa was diagnosed significantly earlier in subjects with Usher syndrome type 1 than in those with type 2. Visual acuity was significantly more impaired in affected subjects with Usher syndrome type 1 than in those with type 2 from 50 years of age onwards. Survival analysis revealed a significant difference in visual field loss (≤ 10 degrees) between the two groups, with type 2 subjects tending to be more impaired, while comparison indicated no significant differences between the groups in any of the other visual field categories. Cataract was found to be generally more common in Usher syndrome type 1 than type 2.Conclusions:  Progressive loss of visual acuity and visual field begins to be substantial between the second and third decades of life in both Usher types. The rate of degeneration varies between individuals in both groups. The data are useful for the counselling of affected subjects with Usher syndrome types 1 and 2.
Actin Binding Activity of Subunit B of Vacuolar H+-ATPase Is Involved in Its Targeting to Ruffled Membranes of Osteoclasts
Authors: Zuo Jian , Jiang Jin , Chen Shih-Hua , Vergara Sandra , Gong Yan , Xue Jing , Huang Haobo , Kaku Masato , Holliday L Shannon 
Published: May 2006

Abstract
Adeno-associated virus was used to transduce primary mouse osteoclasts with the B1 isoform of vacuolar H+-ATPase. B1, which is not normally expressed in osteoclasts, was correctly targeted to ruffled membranes of resorbing osteoclasts. Mutant subunit B1 that lacked a functional actin-binding site did not accumulate in ruffled membranes.
Introduction: The B1 “kidney” and B2 “brain” isoforms of subunit B of vacuolar H+-ATPase (V-ATPase) have actin binding sites that mediate interactions between the intact enzyme and filamentous-actin. Accumulating data support the hypothesis that the actin binding activity in subunit B is required for targeting of V-ATPases to the ruffled plasma membrane of osteoclasts. This study was designed to directly test this hypothesis.
Materials and Methods: Osteoclasts express B2, but not B1. Adeno-associated virus vectors were used to transduce mouse osteoclasts with wildtype B1 or B1mut, a full-length B subunit that contained minor alterations that disrupted actin-binding activity. Immunofluorescence was performed using polyclonal antibodies specific for subunit E, B2, and B1 of V-ATPase. Immunoprecipitations were performed using an anti-E subunit antibody. Microfilaments were detected with phalloidin and actin rings were stained with phalloidin or anti-vinculin antibodies. Images were collected using a confocal microscope.
Results: Immunoprecipitations of transduced osteoclasts suggested that both B1 and B1mut assembled with endogenous V-ATPase subunits to form intact enzyme in osteoclasts. Both B1 and B1mut were localized like endogenous V-ATPase subunits in unactivated osteoclasts. Wildtype B1 associated with the detergent-insoluble cytoskeleton and was transported to ruffled membranes of resorbing osteoclasts. In contrast, B1mut failed to associate with the actin cytoskeleton and was not transported efficiently to ruffled membranes.
Conclusions: The B1 isoform of B subunit contains the necessary information for targeting to the ruffled membranes of osteoclasts even though it is not normally expressed in osteoclasts. The actin binding activity of B1 is involved in proper ruffled membrane targeting.