bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Serum Amylase Levels in Drinking Alcoholics
Authors: Maruyama Katsuya , Takahashi Hisao , Okuyama Keiji , Yokoyama Akira , Nakamura Yuji , Kobayashi Yasunori , Ishii Hiromasa
Published: November 2003

Background: We have reported that the serum level of amylase, different from other pancreatic enzymes, increases temporarily after abstinence in alcoholics. To elucidate the mechanism of this phenomenon, pancreatic isoamylase, salivary isoamylase, and amylase in urine were measured together with total serum amylase.

Methods: Total serum amylase, pancreatic isoamylase, and salivary isoamylase values were measured in 38 male patients admitted to the National Alcoholism Center, Kurihama Hospital, for alcoholism after abstinence. In an investigation of amylase secretion, amylase in urine was measured in some patients after abstinence.

Results: In the group with abnormally high total serum amylase on admission, levels were found to decrease after abstinence. In patients with pancreatic disorders in this group, abstinence leads to a decrease in total serum amylase, but in patients with no such disorders, total serum amylase increases temporarily due to increases in salivary isoamylase. In the group with normal total serum amylase on admission, levels increased sharply after abstinence, and both pancreatic isoamylase and salivary isoamylase contributed to the gains. In the group with low total serum amylase, a sharp increase of 2‐fold or more was noted after abstinence, and a major contributor was pancreatic isoamylase. The ratio of urine amylase to total serum amylase gradually declined, indicating clearly that abstinence led to a decrease in the excretion of amylase in urine.

Conclusions: In cases of heavy alcohol consumption, a decrease in the production or secretion of pancreatic isoamylase and salivary isoamylase while drinking could happen. It was thus suggested that the increase in serum amylase might be due to the fact that this situation is improved by abstinence, plus the fact that excretion of amylase in urine increases during alcohol consumption, and abstinence brings about a decline in such excretion. Measurement of total serum amylase is not appropriate for diagnosing pancreatitis in alcoholic patients or those who consume large quantities of alcohol.
Racially Related Health Disparities and Alcoholism Treatment Outcomes
Authors: Brower Kirk J. , Carey Theadia L.
Published: November 2003

Published studies comparing the outcomes of black and white patients with alcohol dependence have produced mixed results. We hypothesized that among alcoholic outpatients blacks would have worse outcomes than whites. A sample of 38 blacks and 136 whites were assessed prospectively at baseline and 6–12 months using a naturalistic study design. At baseline, blacks had less education, employment, and income than whites, and they were less likely to be married. They also were more likely to have family histories of substance abuse, previous episodes of treatment, cocaine use disorders, antisocial personality disorder, and poor physical health. Between baseline and follow‐up, blacks received less treatment for alcohol dependence than whites. Such differences would seem to favor worse outcomes which were not found. Blacks, however, reported more social support for sobriety than whites. They also had better rates of study retention than whites, suggestive of either higher levels of motivation or stronger alliances with the treatment center. Future studies of racial differences should include measures of social support for sobriety, motivation for treatment, and treatment alliance.
Conceptualizing Alcohol Treatment Research for Hispanic/Latino Adolescents
Authors: Wagner Eric F.
Published: November 2003

This paper briefly reviews the Community‐Based Intervention Research Group's ongoing efforts in conceptualizing alcohol treatment research for Hispanic/Latino adolescents. I begin by defining Empirically Supported Therapies (ESTs), Developmentally Sensitive Therapies (DSTs), and Culturally Sensitive Therapies (DSTs). I then argue that these three perspectives need to be integrated for the field to advance. Next, I discuss the complexities inherent in the integration of EST, DST, and CST, and suggest a ‘flexible core approach’ may be the most feasible and promising approach to integration. Finally, I introduce the concept of ‘amenability to treatment’ and describe how it may be applied to understanding how race/ethnicity‐related variables may influence response to treatment.
Journeys of the Circle: A Culturally Congruent Life Skills Intervention for Adolescent Indian Drinking
Authors: Marlatt G. Alan , Larimer Mary E. , Mail Patricia D. , Hawkins Elizabeth H. , Cummins Lillian Huang , Blume Arthur W. , Lonczak Heather S. , Burns Kelly M. , Chan Karen K. , Cronce Jessica M. , La Marr C. June , Radin Sandra , Forquera Ralph , Gonzales Rebecca , Tetrick Crystal , Gallion Steve
Published: November 2003

There has been an increasing call for and development of culturally appropriate substance prevention/intervention for ethnic minorities in schools and communities, especially among reservation and in urban American Indian and Alaska Native (AIAN) communities. Past attempts to intervene in and reduce misuse of alcohol and other drugs have not had great success. The Journeys of the Circle Project utilized innovative programs with a strong emphasis on historic cultural traditions.
Accessibility of Alcohol‐Related Attitudes: A Cross‐Lag Panel Model With Young Adults
Authors: Kelly Adrian B. , Witkiewitz Katie
Published: November 2003

Background: In the alcohol literature, most cognition research has focused on alcohol expectancies. Overall scores on alcohol expectancy questionnaires predict longitudinal changes in drinking behavior. However, the association between expectancy subscale scores and drinking behavior is inconsistent and modest. Attitudinal information may vary in accessibility (i.e., the ease or speed with which attitudinal information is evaluated), and more accessible (i.e., faster) attitudinal evaluations may predict heavier alcohol consumption. An alternative hypothesis arising from response competition theory is that heavy drinkers will show slow attitudinal evaluations, given that heavy drinkers frequently show mixed, inconsistent, or opposing alcohol‐related beliefs. In this study we examined the degree to which speed of processing of alcohol‐related evaluative judgments longitudinally predicted alcohol consumption in university students.

Methods: Response latencies for alcohol‐ and non‐alcohol‐related attitudinal inquiries and measures of alcohol use were administered at two intervals 4 months apart.

Results: The key findings were that response times for tension reduction and cognitive impairment items at time 1 positively predicted alcohol consumption at time 2. These results held after we accounted for autocorrelation in drinking and individual variability in reactivity.

Conclusion: For items relating to tension reduction, response times fit a response competition hypothesis better than the attitude accessibility hypothesis.
Using the Cue‐Availability Paradigm to Assess Cue Reactivity
Authors: Davidson Dena , Tiffany Stephen T. , Johnston William , Flury Leah , Li Ting‐Kai
Published: November 2003

Background: A recent meta‐analysis on cue‐reactivity research revealed that cue‐specific craving for alcohol is substantially less robust than craving measured for other drugs of abuse. The small effect sizes for alcohol underscore the need for more powerful methods of assessing cue reactivity in humans. The cue‐availability paradigm is a modification of the conventional cue‐reactivity paradigm and is intended to increase the sensitivity of measuring cue‐reactivity to alcohol in humans.

Methods: Seventeen non‐treatment‐seeking alcoholics were tested individually on two different sessions (after priming with alcohol and after priming with placebo‐alcohol). Subjects were presented with a total of 32 cue‐availability trials. On each trial, subjects were presented with either a target cue (alcohol) or a neutral cue (water). Each cue was available for drinking on 50% of the trials (availability condition). Cue‐reactivity measures were self‐reports of craving and mood.

Results: The alcohol prime had a robust effect on craving. Irrespective of the availability of the cue for consumption or the type of cue, craving was consistently higher when subjects were primed with alcohol than with placebo‐alcohol. Negative mood was also higher when it was assessed after the alcohol prime. Negative mood decreased in alcohol‐primed subjects when the alcohol cue was available for consumption. The alcohol cue also had a significant, although more modest effect on craving. The alcohol cue consistently elicited higher levels of craving relative to the water cue.

Conclusions: These data suggest that the priming effects of alcohol may be a significant factor contributing to the experience of craving and maintenance of drinking. The study also introduces the cue‐availability as an additional new method for investigating manipulations of cue‐reactivity in alcoholics.
The Relationship Between Educational Attainment and Relapse Among Alcohol‐Dependent Men and Women: A Prospective Study
Authors: Greenfield Shelly F. , Sugarman Dawn E. , Muenz Larry R. , Patterson Marcus D. , He David Y. , Weiss Roger D.
Published: November 2003

Background: We investigated the relationship between educational attainment and drinking outcomes after discharge from inpatient treatment for alcohol dependence.

Methods: Between 1993 and 1996, we consecutively recruited 41 women and 60 men hospitalized for alcohol dependence and followed them up monthly for 1 year. We conducted structured interviews during hospitalization and at monthly intervals after discharge for 1 year. We examined the relationship between educational attainment before treatment and postdischarge drinking outcomes, including time to relapse.

Results: After covariate adjustment, educational level was a significant predictor of drinking outcomes.

Conclusions: Lower levels of educational attainment before entry into treatment predicted shorter times to first drink and relapse in both women and men. The association of educational attainment and treatment outcome for alcohol dependence warrants further investigation.
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.
Outcome Variables and Their Assessment in Alcohol Treatment Studies: 1968‐1998
Authors: Finney John W. , Moyer Anne , Swearingen Carolyn E.
Published: November 2003

Background: This article provides a historical overview of the assessment of outcome variables in alcohol treatment studies that were first published between 1968 and 1998. The review focuses on changes over time in (1) the number of outcome variables and the number of different types of outcome variables assessed, (2) the likelihood of assessing specific types of outcome variables, (3) the methods used to assess outcome variables, and (4) the status of outcome assessment in more recent studies first published between 1990 and 1998.

Methods: Reports of 357 alcohol treatment trials with two or more treatment/control groups were coded with respect to the number and types of outcome variables assessed, sources of outcome data, and methodological aspects of outcome assessment.

Results: Although the number of outcome variables assessed in studies, on average, did not increase significantly over time, the number of different types of outcome variables did increase. An expected decrease in the assessment of categorical abstinence was not found, but another categorical variable, global ratings of drinking improvement, did decrease over time. More recent studies were more likely to assess such continuous variables as time abstinent, alcohol consumption, time drinking, dependence symptoms, and drinking‐related problems. Physiological markers of drinking/alcohol misuse also were assessed more frequently in later years. Some aspects of outcome assessment methods exhibited improvement over time; validity data were more likely to be provided or cited, and self‐reports of drinking behaviors were more likely to be corroborated in studies first published in more recent years. However, the percentages of studies that provided/cited reliability data for outcome measures, indicated that follow‐up data collectors were not affiliated with treatment and were unaware of respondents' treatment conditions, and reported that respondents were alcohol‐free at follow‐up did not rise significantly over time.

Conclusions: Although the methods of outcome assessment improved between 1968 and 1998, much room for improvement remains.
Pavlovian Conditioning With Ethanol: Sign‐Tracking (Autoshaping), Conditioned Incentive, and Ethanol Self‐Administration
Authors: Krank Marvin D.
Published: November 2003

Background: Conditioned incentive theories of addictive behavior propose that cues signaling a drug's reinforcing effects activate a central motivational state. Incentive motivation enhances drug‐taking and drug‐seeking behavior. We investigated the behavioral response to cues associated with ethanol and their interaction with operant self‐administration of ethanol.

Methods: In two experiments, rats received operant training to press a lever for a sweetened ethanol solution. After operant training, the animals were given Pavlovian pairings of a brief and localized cue light with the sweetened ethanol solution (no lever present). Lever pressing for ethanol was then re‐established, and the behavioral effects of the cue light were tested during an ethanol self‐administration session.

Results: The conditioned responses resulting from pairing cue lights with the opportunity to ingest ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol‐seeking behavior (magazine entries), and (3) signal‐directed behavior (i.e., autoshaping, or sign‐tracking). Signal‐directed behavior interacted with the other two effects in a manner predicted by the location of the cue light. These conditioned responses interact with operant responding for ethanol reinforcement.

Conclusions: These findings demonstrate the importance of Pavlovian conditioning effects on ethanol self‐administration and are consistent with conditioned incentive theories of addictive behavior.
Effects of Ethanol on the Rat Glutamate Excitatory Amino Acid Transporter Type 3 Expressed in Xenopus Oocytes: Role of Protein Kinase C and Phosphatidylinositol 3‐Kinase
Authors: Kim Jin‐Hee , Lim Young‐Jin , Ro Young‐Jin , Min Seong‐Won , Kim Chong‐Soo , Do Sang‐Hwan , Kim Yong‐Lak , Zuo Zhiyi
Published: November 2003

Background: Glutamate is a major excitatory neurotransmitter in the central nervous system. Glutamate transporters play a critical role in maintaining extracellular glutamate concentrations. We investigated the effects of ethanol on a neuronal glutamate transporter, excitatory amino acid transporter type 3 (EAAT3), and the role of protein kinase C (PKC) and phosphatidylinositol 3‐kinase (PI3 K) in mediating these effects.

Methods: EAAT3 was expressed in Xenopus oocytes by injection of EAAT3 messenger RNA. By using a two‐electrode voltage clamp, membrane currents were recorded after the application of l‐glutamate. Responses were quantified by integration of the current trace and reported as microcoulombs. Data are mean ± SEM.

Results: Ethanol enhanced EAAT3 activity in a concentration‐dependent manner. At 25, 50, 100, and 200 mM of ethanol, the responses were significantly increased compared with control values. Kinetic study demonstrated that ethanol (50 mM) significantly increased Vmax (3.48 ± 0.2 μC for control versus 4.16 ± 0.24 μC for ethanol; n= 19; p < 0.05) without a significant change in the Km (65.6 ± 11.1 μM for control versus 55.8 ± 9.6 μM for ethanol; n= 19; p > 0.05) of EAAT3 for glutamate. Preincubation of the oocytes with phorbol‐12‐myristate‐13‐acetate (PMA) significantly increased EAAT3 activity (0.98 ± 0.08 μC for control versus 1.28 ± 0.09 μC for ethanol; n= 19; p < 0.05). However, there was no statistical difference among the responses of EAAT3 to PMA, ethanol, or PMA plus ethanol. Although the PKC inhibitors chelerythrine and staurosporine did not decrease the basal EAAT3 activity, they abolished the enhancement of EAAT3 activity by ethanol. Pretreatment with wortmannin, a PI3 K inhibitor, also abolished the ethanol‐enhanced EAAT3 activity.

Conclusions: These results suggest that acute ethanol exposure increases EAAT3 activity at clinically relevant concentrations and that PKC and PI3 K may be involved in mediating these ethanol effects.
A citation analysis of education dissertations at the Delta State University, Abraka, Nigeria
Authors: Okiy Rose B.
Published: November 2003

A total of 4,012 citations in 70 postgraduate dissertations in education submitted to the Delta State University Library between 1992 and 2002 were studied. Most post graduate students in education used more textbooks (60.3 per cent), than other forms of library materials. Four of the top ranked journals, including the most popularly used – the West African Journal of Education (WAJE) – are available in the library. A total of 12 (66.7 per cent) of the 18 most popularly used journals are US publications, thus creating the need for Delta State University Library to improve on its local journal collection. Of the 18 most cited journals, six (33.3 per cent) ranked among the list of significant journals in the field of education.
A Protein Interaction Map of
Drosophila melanogaster
Authors: Giot L. , Bader J. S. , Brouwer C. , Chaudhuri A. , Kuang B. , Li Y. , Hao Y. L. , Ooi C. E. , Godwin B. , Vitols E. , Vijayadamodar G. , Pochart P. , Machineni H. , Welsh M. , Kong Y. , Zerhusen B. , Malcolm R. , Varrone Z. , Collis A. , Minto M. , Burgess S. , McDaniel L. , Stimpson E. , Spriggs F. , Williams J. , Neurath K. , Ioime N. , Agee M. , Voss E. , Furtak K. , Renzulli R. , Aanensen N. , Carrolla S. , Bickelhaupt E. , Lazovatsky Y. , DaSilva A. , Zhong J. , Stanyon C. A. , Finley R. L. , White K. P. , Braverman M. , Jarvie T. , Gold S. , Leach M. , Knight J. , Shimkets R. A. , McKenna M. P. , Chant J. , Rothberg J. M.
Published: November 2003

Drosophila melanogaster
is a proven model system for many aspects of human biology. Here we present a two-hybrid–based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.
Identification of Sequential Viral Escape Mutants Associated with Altered T-Cell Responses in a Human Immunodeficiency Virus Type 1-Infected Individual
Authors: Geels Mark J. , Cornelissen Marion , Schuitemaker Hanneke , Anderson Kiersten , Kwa David , Maas Jolanda , Dekker John T. , Baan Elly , Zorgdrager Fokla , van den Burg Remco , van Beelen Martijn , Lukashov Vladimir V. , Fu Tong-Ming , Paxton William A. , van der Hoek Lia , Dubey Sheri A. , Shiver John W. , Goudsmit Jaap
Published: November 2003

Control of viremia in natural human immunodeficiency virus type 1 (HIV-1) infection in humans is associated with a virus-specific T-cell response. However, still much is unknown with regard to the extent of CD8+cytotoxic T-lymphocyte (CTL) responses required to successfully control HIV-1 infection and to what extent CTL epitope escape can account for rises in viral load and ultimate progression to disease. In this study, we chose to monitor through full-length genome sequence of replication-competent biological clones the modifications that occurred within predicted CTL epitopes and to identify whether the alterations resulted in epitope escape from CTL recognition. From an extensive analysis of 59 biological HIV-1 clones generated over a period of 4 years from a single individual in whom the viral load was observed to rise, we identified the locations in the genome of five CD8+CTL epitopes. Fixed mutations were identified within the p17, gp120, gp41, Nef, and reverse transcriptase genes. Using a gamma interferon ELIspot assay, we identified for four of the five epitopes with fixed mutations a complete loss of T-cell reactivity against the wild-type epitope and a partial loss of reactivity against the mutant epitope. These results demonstrate the sequential accumulation of CTL escape in a patient during disease progression, indicating that multiple combinations of T-cell epitopes are required to control viremia.
ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to
cis
-Acting DNA Sequences in the Terminal Repeats
Authors: Verma Subhash C. , Robertson Erle S.
Published: November 2003

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), a human oncogenic gamma-2-herpesvirus, transforms human endothelial cells and establishes latent infection at a low efficiency in vitro. During latent infection, only a limited number of genes are expressed, and the circularized viral genome is maintained as a multicopy episome. Latency-associated nuclear antigen (LANA), exclusively expressed during latency, has been shown to have a multifunctional role in KS pathogenesis. LANA tethers the viral episome to the host chromosome, thus ensuring efficient persistence of the viral genome during successive rounds of cell division. Besides episome maintenance, LANA modulates the expression of genes of various cellular and viral pathways, including those of retinoblastoma protein and p53. Herpesvirus saimiri (HVS), another gamma-2-herpesvirus, primarily infects New World primates. Orf73, encoding the nuclear antigen of HVS, is the positional homolog of the LANA gene, and the ORF73 protein has some sequence homology to KSHV LANA. However, the function of ORF73 of HVS has not been thoroughly investigated. In this report, we show that HVS ORF73 may be important for episome persistence and colocalizes with the HVS genomic DNA on metaphase chromosomes. Furthermore, HVS terminal repeats (TRs) contain a
cis
-acting sequence similar to that in KSHV TRs, suggesting that the LANA binding sequence is conserved between these two viruses. This
cis
-acting element is sufficient to bind HVS ORF73 from strains C488 and A11, and plasmids containing the HVS C488 TR element are maintained and replicate in HVS C488 ORF73-expressing cells.
Role for Influenza Virus Envelope Cholesterol in Virus Entry and Infection
Authors: Sun Xiangjie , Whittaker Gary R.
Published: November 2003

Enveloped viruses are highly dependent on their lipid envelopes for entry into and infection of host cells. Here, we have examined the role of cholesterol in the virus envelope, using methyl-β-cyclodextrin depletion. Pretreatment of virions with methyl-β-cyclodextrin efficiently depleted envelope cholesterol from influenza virus and significantly reduced virus infectivity in a dose-dependent manner. A nonenveloped virus, simian virus 40, was not affected by methyl-β-cyclodextrin treatment. In the case of influenza virus, infectivity could be partially rescued by the addition of exogenous cholesterol. Influenza virus morphology, binding, and internalization were not affected by methyl-β-cyclodextrin depletion, whereas envelope cholesterol depletion markedly affected influenza virus fusion, as measured by a specific reduction in the infectivity of viruses induced to fuse at the cell surface and by fluorescence-dequenching assays. These data suggest that envelope cholesterol is a critical factor in the fusion process of influenza virus.