bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement and Prediction of Medication Compliance in Problem Drinkers
Authors: Feinn Richard , Tennen Howard , Cramer Joyce , Kranzler Henry R. 
Published: November 2003

Background: A variety of methods have been used to measure medication compliance. Although electronic monitoring has been considered to be the best method, it has some potential for error and its high cost may limit its feasibility. This study examined the concordance of data on medication compliance that was obtained by using an electronic monitoring system (Medication Event Monitoring System, or MEMS), daily diary reports, and tablet counts.Methods: Subjects were 150 problem drinkers participating in a pharmacotherapy trial. Subjects were randomly assigned to receive naltrexone 50 mg (n= 75) or placebo (n= 75) and to receive either daily (n= 72) or targeted (n= 78) medication administration. Comparisons between methods were conducted at the aggregate and individual daily levels, and the association between compliance and three alcohol‐related outcomes was evaluated.Results: Daily diaries showed good day‐to‐day concordance with MEMS and a higher correlation with MEMS than did tablet counts. However, high‐compliance subjects did no better than low‐compliance subjects on any of three alcohol‐related outcome measures.Conclusions: Compliance measurement using a daily diary method yielded results that are comparable to those obtained with electronic monitoring, which served as a criterion measure. In contrast, tablet counts provided data that were less concordant with the criterion measure. The unique nature of the study sample (i.e., the majority of subjects were not committed to a goal of abstinence), combined with the targeted approach to treatment, may explain the lack of association between compliance and alcohol‐related outcomes. Further research should aim to ascertain the factors affecting the relationship between compliance and outcomes.
Role of Fyn Tyrosine Kinase in Ethanol Consumption by Mice
Authors: Cowen Michael S. , Schumann Gunter , Yagi Takeshi , Spanagel Rainer 
Published: November 2003

Background: Mice deficient for the intracellular protein Fyn tyrosine kinase (fynZ/fynZ mice) have been reported to show increased alcohol sensitivity and lack of tolerance to the effects of ethanol. To further study the involvement of Fyn in neurobehavioral effects of alcohol, we examined ethanol consumption and relapse drinking behavior in fynZ/fynZ mice.Methods: FynZ/fynZ and wild‐type mice were given a free choice between water and increasing concentrations of ethanol (2‐16%). Once a stable baseline of 16% ethanol consumption was established, access to ethanol was withdrawn for 2 weeks and then reinstated, to measure the alcohol deprivation effect (ADE). Forced swim stress was performed thereafter on 2 consecutive days. In a final experiment we studied alcohol sensitivity by measuring ethanol‐induced loss of righting reflex (LORR).Results: The concentration of available ethanol had a significant effect on ethanol consumption and preference; however, there was no significant effect of genotype on these measures. Deprivation from ethanol led to a significant increase in ethanol consumption by all mice with no significant impact of genotype on ethanol consumption or water consumption during the ADE. Two consecutive days of forced swim stress led to a significant increase in ethanol consumption; again however, genotype had no effect on stress‐associated ethanol consumption. Surprisingly, however, FynZ/fynZ mice showed no differences in alcohol sensitivity when compared to wild‐type animals, in contrast to previously reported results (Miyakawa et al., 1997).Conclusions: Deletion of the Fyn tyrosine kinase gene may be involved in ethanol sensitivity but this effect may depend on a gene‐environment interaction. Fyn does not influence ethanol consumption, neither under basal conditions nor following a deprivation period or stress. This finding indicates that phosphorylation and activation of N‐methyl‐D‐aspartate (NMDA) receptors through Fyn is not a critical mechanism in alcohol drinking or relapse behavior.
Nonlinear Relation Between Alcohol Intake and High‐Density Lipoprotein Cholesterol Level: Results From the Copenhagen City Heart Study
Authors: Johansen Ditte , Andersen Per K. , Jensen Majken K. , Schnohr Peter , Grønbæk Morten 
Published: November 2003

Background: It has been suggested that the level of high‐density lipoprotein cholesterol (HDL‐C) in the blood can be used as a marker of recent alcohol intake. However, before using HDL‐C as a predictor of alcoholism, the relation between alcohol intake and HDL‐C in the entire range of consumption must be explored. Most studies model the relation between alcohol intake and HDL‐C linearly, although a threshold effect is expected. The objective of this study was to evaluate the shape of the relation between intake of alcohol and HDL‐C and to determine whether there are differential effects of beer, wine, and spirits on HDL‐C and whether they remain after adjusting for total alcohol.Method: The relation between alcohol intake and HDL‐C was investigated by means of generalized additive models using data from the Copenhagen City Heart Study.Results: A nonlinear effect of alcohol improved the model fit significantly, and the nonlinearity of alcohol was highly significant in both men and women. The relation was concave: HDL‐C was stable in men and women who drank more than approximately 35 and 20 drinks per week, respectively. We found a significant nonlinear term of wine on HDL‐C in men after adjustment for total alcohol intake.Conclusions: There was a concave relation between alcohol intake and HDL‐C, indicating a threshold effect of alcohol on HDL‐C. The association between wine and HDL‐C in men after adjusting for total alcohol intake may be due to residual lifestyle confounding.
Compromised Pontocerebellar and Cerebellothalamocortical Systems: Speculations on Their Contributions to Cognitive and Motor Impairment in Nonamnesic Alcoholism
Authors: Sullivan Edith V. 
Published: November 2003

Background: Corticopontocerebellar and cerebellothalamocortical circuits underlie a wide range of neuropsychological processes compromised by alcoholism. The analyses herein tested whether abnormalities of volumes of brain structures forming nodes of these separate feed‐forward and feedback systems are selectively related to each other and whether any of these noncortical regions can account for cognitive and motor deficits occurring as sequelae of chronic alcoholism.Methods: Regional brain measures originated from our prior neuroimaging studies, showing in alcoholics significant volume deficits in the principal structures of interest: cerebellar hemispheres, vermis, pons, and thalamus as well as prefrontal, frontal, and parietal cortex. Neuropsychological functions targeted for analysis—problem solving, visuospatial ability, and static postural stability—showed 0.6 to 1.6 SD deficits in these alcoholic men.Results: In alcoholics, the patterns of correlations were consistent with dissociation of thalamic and pontine circuitry. Pontine and thalamic volumes were not correlated with each other. Pontine volumes correlated with white matter volumes of anterior superior vermis and gray and white matter volumes of the cerebellar hemispheres but not with cortical regional volumes. Thalamic volumes correlated with gray matter volumes of the cerebellar hemispheres, parietal cortex, and inferior posterior vermian lobule, which itself correlated with parietal, prefrontal, and frontal cortical volumes. Controls did not show these correlational patterns. Brain structure‐function relationships in alcoholics examined with multiple regression identified anterior vermian but not prefrontal or parietal volume as a unique predictor of balance scores; vermian and thalamic but not prefrontal cortical volumes as predictors of card sorting scores; and cerebellar hemispheric white matter but not parietal cortical volume as a predictor of visuospatial ability.Conclusions: Each major node of frontocerebellar circuitry shows volume deficits in alcoholics but can be independently compromised. Disruption of these circuits may underlie alcoholism‐related neuropsychological deficits, either by abnormalities present in individual nodes or by disconnection via interruption of selective circuitry.
Mean Corpuscular Volume and the Aldehyde Dehydrogenase‐2 Genotype in Male Japanese Workers
Authors: Yokoyama Masako , Yokoyama Akira , Yokoyama Tetsuji , Hamana Genichi , Funazu Kazuo , Kondo Shuji , Yamashita Takeshi , Yoshimizu Haruko , Nakamura Haruo 
Published: November 2003

Background: Increased mean corpuscular volume (MCV) is common in alcohol abusers and alcoholics. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase‐2 (ALDH2) encoded by ALDH2*1/2*2 than among those with active ALDH2 encoded by ALDH2*1/2*1. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. Because moderate and heavy drinkers with ALDH2*1/2*2 have very high risks for esophageal cancer, MCV might serve as an indicator of these high‐risk drinkers.Methods: In this investigation of the association of red cell values with the ALDH2 genotype and possible confounding factors, the drinking, smoking, and dietary habits reported on a structured questionnaire by 163 Japanese working men were subjected to multivariate analyses.Results: Aging, lower body mass index (BMI), more alcohol consumption, and more smoking were positively associated with increased MCV. Among moderate to heavy drinkers (≥9 units/week; 1 unit = 22 g of ethanol), both MCV and mean corpuscular hemoglobin were higher and the red cell count was lower in those with ADLH2*1/2*2 than in those with ALDH2*1/2*1. Multiple linear regression analysis after adjustment for age, BMI, and smoking revealed that a positive relationship between the amount of drinking and MCV but inverse relationships for drinking and red cell count, as well as hemoglobin and hematocrit values, were significantly stronger for men with ALDH2*1/2*2 than for those with ALDH2*1/2*1, demonstrating a gene‐environment interaction. Drinking accounted for 19.9% of interindividual MCV variance among men with ALDH2*1/*2*2 but for only 1.3% of variance among those with ALDH2*1/2*1. Age, BMI, drinking, and smoking accounted for 52.1 and 34.7% of the variation among those with ALDH2*1/2*2 and ALDH2*1/2*1, respectively. Macrocytosis (MCV ≥100.0 fl) was observed in 18 subjects (11.0%), and use of macrocytosis as a biomarker of moderate to heavy drinkers with ALDH2*1/2*2 had a sensitivity of 54.5% (6 of 11) and a specificity of 92.1% (140 of 152).Conclusions: Alcohol‐related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehyde's role in increasing MCV and the potential for using MCV as a marker for high‐risk drinkers for esophageal cancer.
Lactulose Reduces Intracolonic Acetaldehyde Concentration and Ethanol Elimination Rate in Rats
Authors: Zidi Sémia H. , Linderborg Klas , Väkeväinen Satu , Salaspuro Mikko , Jokelainen Kalle 
Published: November 2003

Background: Normal colonic bacteria possessing alcohol dehydrogenase activity can oxidize ethanol to acetaldehyde. Acetaldehyde recently has been shown to be a local carcinogen in humans. The aim of the study was to examine the effect of lactulose feeding on fecal and cecal pH, intracolonic acetaldehyde concentration, and total ethanol elimination rate in rats.Methods: Sixty Wistar rats were divided into four groups. Groups 2 and 4 received lactulose daily (11 g/kg body weight for 14 days). On days 7 and 14, groups 1 and 2 received ethanol (1.5 g/kg body weight) intraperitoneally, whereas groups 3 and 4 received saline.Results: Fecal and cecal pH values decreased significantly after lactulose treatment compared with the controls. Lactulose feeding reduced the total ethanol elimination rate by 13.8% (257 ± 0.008 mg/kg/hr vs. 298 ± 0.003 mg/kg/hr, p < 0.001) and the intracecal acetaldehyde concentration by 66.2% after ethanol (49 ± 29 μM vs. 145 ± 47 μM, p= 0.03) compared with the controls.Conclusion: Lactulose feeding to rats significantly reduces ethanol elimination rate and intraluminal acetaldehyde concentration in the colon after ethanol administration. This prebiotic thus could be used as an effective agent to block the microbial production of carcinogenic acetaldehyde in the large intestine.
Effect of Duration of Alcohol Consumption on Calcium and Bone Metabolism During Pregnancy in the Rat
Authors: Keiver Kathy , Weinberg Joanne 
Published: November 2003

Background: Little is known about the consequences of drinking during pregnancy for the long‐term health of the mother. Alcohol (ethanol) has been shown to disrupt calcium (Ca) homeostasis and is known to have deleterious effects on bone. During pregnancy, bone turnover is increased to maintain Ca homeostasis; therefore, pregnancy may be a time of life when maternal bone is particularly susceptible to the effects of ethanol. This study investigated the effect of duration of ethanol consumption on Ca homeostasis and bone during pregnancy in the rat.Methods: Rats were fed ethanol (36% ethanol‐derived calories) in liquid diets for 3 (21 days gestation only) or 6 (3 weeks before and throughout 21 days gestation) weeks. Maternal blood was analyzed for Ca (total and ionized Ca [iCa]), the Ca‐regulating hormones (parathyroid hormone [PTH], 1,25(OH)2D, calcitonin), and osteocalcin (a marker for bone formation). Bone was analyzed for ash (mineral) content.Results: Dams consuming ethanol (E dams) had decreased blood Ca levels (total and iCa) at both 3 and 6 weeks, but iCa was lower in E dams after 6 compared with 3 weeks. Importantly, ethanol seemed to interfere with the normal compensatory response to these decreased Ca levels. In contrast to pair‐fed controls, serum PTH levels actually were decreased, 1,25(OH)2D levels failed to increase, and calcitonin levels were increased in ethanol‐consuming dams, regardless of duration. Moreover, ethanol decreased bone formation, as indicated by serum osteocalcin levels, after both 3 and 6 weeks consumption, and after 6 weeks, the ash content of bone also was decreased. In addition, a relationship was found between the blood alcohol concentration (BAC) and some measures of Ca and bone metabolism. Serum 1,25(OH)2D and osteocalcin levels varied inversely, whereas serum calcitonin varied directly with BAC, suggesting that time of sampling after drinking may be an important variable for interpreting ethanol's effects on Ca and bone metabolism. In all rats, serum osteocalcin levels varied directly with PTH and 1,25(OH)2D levels.Conclusions: Ethanol consumption during pregnancy impaired Ca homeostasis in the dam, regardless of duration of consumption, and resulted in decreased bone formation and ash content of bone. Significant relationships among the Ca‐regulating hormones, BAC, and osteocalcin support the hypothesis that ethanol's effects on the Ca‐regulating hormones may mediate some of its effects on bone.
Dietary Cholate Is Required for Antiatherogenic Effects of Ethanol in Mouse Models
Authors: Deeg Mark A. 
Published: November 2003

Background: Human consumption of moderate amounts of ethanol is associated with reduced cardiovascular events. Studies examining the effect of ethanol on atherosclerosis in mouse models have yielded conflicting results that may be due to differences in dietary fat and cholate content. To determine if dietary cholate influences ethanol's effect on atherosclerosis, we fed apolipoprotein E−/− and low‐density lipoprotein receptor (LDLR)−/− mice different liquid diets with or without ethanol.Methods: Apolipoprotein E−/− mice were fed a low‐fat or high saturated fat, cholate‐containing diet with or without ethanol for 3 to 10 weeks, and LDLR−/− mice were fed a low‐fat, high saturated fat, or high saturated fat diet with cholate with or without ethanol for 7 weeks. At the end of the feeding study, aortic root lesion size was determined and compared with serum cholesterol, triglycerides, and high‐density lipoprotein cholesterol. Because dietary cholate increases hepatic nuclear factor (NF)‐κB and ethanol inhibits NF‐κB, we also examined the effect of ethanol on aortic NF‐κB binding activity.Results: Adding ethanol to a low‐fat diet had no effect on lesion size. Similarly, ethanol had no effect on lesion size in LDLR−/− mice consuming a high saturated fat diet. Adding ethanol to a high‐fat, cholate‐containing diet for either strain resulted in a 25% to 50% reduction in lesion size. Dietary cholate increased and ethanol reduced NF‐κB binding activity in the aorta.Conclusions: These results suggest that ethanol inhibits atherosclerosis in the presence of dietary cholate, which may occur via an anti‐inflammatory mechanism.
Long‐Term Influence of an Initial Exposure to Alcohol on the Rat Hypothalamic‐Pituitary Axis
Authors: Lee Soon , Rivier Catherine 
Published: November 2003

Objective: We have previously shown that adult male rats injected with alcohol daily for 3 consecutive days displayed a significantly blunted ACTH to a second alcohol injection, given 3 to 7 days later. The purpose of the present work was to determine the maximum duration over which the ACTH response remained blunted after an initial alcohol treatment.Methods: Male rats were exposed to alcohol (intragastrically or via vapors for 4 hr) on three consecutive days, starting when they were 22 (group A), 34 (group B), or 50 days old (group C). Control animals were injected with the vehicle intragastrically or kept in chambers through which normal air was circulated. At 60 days of age, the animals were injected with the vehicle or alcohol (4.5 g/kg intragastrically) to determine whether the initial treatment had long‐term consequences on the ACTH response to a second alcohol challenge.Results: Rats of group C, pretreated with alcohol via intragastric injections or vapors, all exhibited a blunted ACTH response to the second acute alcohol challenge. In contrast, the second alcohol challenge only attenuated ACTH responses in rats of group B that had received intragastric injections, but not vapors. Group A showed a comparable response to acute intragastric alcohol injection at 60 days of age regardless of whether they had been preexposed to the drug. This was not due to a lack of neuroendocrine response because alcohol vapors significantly increased plasma ACTH levels and up‐regulated paraventricular nucleus neuronal activity regardless of the age at which it was initially administered.Conclusions: Repeated (daily for 3 consecutive days) administration of alcohol by the gastric route induces a long‐lasting (up to 24 days) but not permanent blunting of the ACTH response to a second (acute) alcohol challenge. The fact that alcohol delivered by inhalation only caused a relatively brief (≤8 days) decrease in the ability of a second intragastric alcohol challenge to release ACTH suggests that the mode of alcohol delivery influences its long‐term consequences.
Cellular Adaptation to Chronic Ethanol Results in Altered Compartmentalization and Function of the Scaffolding Protein RACK1
Authors: Vagts Alicia J. , He Dao‐Yao , Yaka Rami , Ron Dorit 
Published: November 2003

Background: Previously, we found that acute ethanol induces the translocation of the scaffolding protein RACK1 to the nucleus. Recently, we found that nuclear RACK1 mediates acute ethanol induction of immediate early gene c‐fos expression. Alterations in gene expression are thought to lead to long‐term changes that ultimately contribute to the development of alcohol addiction and toxicity. Therefore, we sought to determine the effects of chronic exposure of cells to ethanol on the cellular compartmentalization of RACK1 and on c‐fos messenger RNA (mRNA) and protein expression.Methods: Rat C6 glioma cells were used as the cell culture model. Immunohistochemistry was implemented to visualize the localization of RACK1 and to monitor the protein level of c‐fos. Reverse‐transcription polymerase chain reaction was used to measure c‐fos mRNA levels. The Tat‐protein transduction method was used to transduce recombinant Tat‐RACK1 into cells as previously described.Results: Chronic exposure of cells to 200 mM ethanol for 24 and 48 hr resulted in the gradual re‐distribution of RACK1 out of the nucleus. It is interesting to note that acute ethanol re‐challenge immediately after chronic treatment did not result in RACK1 translocation to the nucleus, and nuclear compartmentalization of RACK1 in response to acute ethanol was detected only after 24 hr of withdrawal. Similar patterns were obtained for c‐fos expression. Chronic exposure to ethanol did not result in an increase in mRNA or protein levels of c‐fos. Furthermore, acute ethanol exposure did not increase c‐fos protein levels in cells that were first treated chronically with ethanol. However, transduction of exogenous RACK1 expressed as a Tat‐fusion protein was able to rescue c‐fos mRNA expression after chronic ethanol exposure.Conclusions: Our data suggest that RACK1 nuclear compartmentalization and ethanol‐induced c‐fos expression are transient and are desensitized to ethanol during prolonged exposure to high concentrations. The desensitization is temporary, and RACK1 can respond to acute ethanol treatment after a 24‐hr withdrawal period. Our data further suggest that the altered compartmentalization of RACK1 leads to differences in c‐fos expression upon acute or chronic exposure to ethanol. In summary, RACK1 is an important molecular mediator of the acute and chronic actions of ethanol on the expression of c‐fos. These findings could have implications for the molecular signaling pathways leading to pathologic states associated with alcoholism, including toxicity.
Comorbidity of Alcohol Dependence With Attention‐Deficit Hyperactivity Disorder: Differences in Phenotype With Increased Severity of the Substance Disorder, but Not in Genotype (Serotonin Transporter and 5‐Hydroxytryptamine‐2c Receptor)
Authors: Johann Monika , Bobbe Gabriela , Putzhammer Albert , Wodarz Norbert 
Published: November 2003

Background: Nearly 50% of subjects with continuing symptoms of attention‐deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5‐HTT) and the 5‐hydroxytryptamine‐2c (5‐HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities.Methods: We investigated phenotype and 5‐HTT/5‐HT2c genotype characteristics in 314 alcoholics of German descent.Results: There was no significant difference in 5‐HTT genotype or 5‐HT2c allele distribution between alcoholics and matched controls. Sixty‐seven alcoholics fulfilled DSM‐IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder‐positive subjects. There were no differences in 5‐HTT genotype or 5‐HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively.Conclusions: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so‐called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5‐HTT promoter and the 5‐HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.