bluuebunny/crossref_metadata_2025_split huggingface dataset:
Place Conditioning: Age‐Related Changes in the Rewarding and Aversive Effects of Alcohol
Authors: Philpot R. M. , Badanich K. A. , Kirstein C. L. 
Published: May 2006

Background: Alcohol abuse levels are very high in adolescents, creating a significant societal issue. It has been shown that people who begin alcohol use as adolescents are more likely to become addicts than people who initiate alcohol use as adults. It is important to note that the development of addiction in humans is more rapid with initiation in adolescence than in adulthood.Methods: To determine changes in the reinforcing efficacy of alcohol as a function of adolescent development, we used a place‐conditioning paradigm. In this study, we assessed the ability of ethanol to support a conditioned place preference (CPP) or aversion. Animals [postnatal days (PND) 25, 35, 45, and 60] were tested for alcohol‐induced conditioning in response to a range of ethanol doses (0.2, 0.5, 1.0, and 2.0 g/kg intraperitoneally) or saline.Results: In general, there was a trend for alcohol to produce an aversion to the ethanol‐paired compartment at higher doses. These patterns differed significantly as a function of age. Younger animals (PND 25) exhibited a CPP to a low dose and an aversion at high doses. Late‐adolescent (PND 45) animals exhibited a CPP at two moderate doses but a conditioned place aversion at the highest dose. PND 35 and 60 animals did not exhibit a CPP at any examined dose, and PND 60 animals exhibited a progressive aversion with increasing dose.Conclusions: The data show that the developmental processes of adolescence influence general responsiveness to alcohol. Specifically, late‐adolescent animals (PND 45) seem to prefer doses of alcohol that are either not reinforcing (0.5 g/kg) or are aversive (1.0 g/kg) at other ages. These processes need to be examined thoroughly to understand the development of addiction in adolescence. This is especially important given that alcohol abuse in adolescence may interfere with the usual pattern of brain development as it relates to alcohol reinforcement.
The Role of Neurotrophic Factors, Apoptosis‐Related Proteins, and Endogenous Antioxidants in the Differential Temporal Vulnerability of Neonatal Cerebellum to Ethanol
Authors: Heaton Marieta Barrow , Moore D. Blaine , Paiva Michael , Madorsky Irina , Mayer Joanne , Shaw Gerry 
Published: May 2006

Background: Ethanol produces abnormalities in the developing nervous system, with certain regions being vulnerable during well‐defined periods. Neonatal rodent cerebellum is particularly susceptible to ethanol during the early postnatal period [on postnatal days 4‐5 (P4‐5)], while this region is resistant to ethanol at a slightly later time (P7‐9). We assessed basal levels of several substances which may be involved in differential temporal ethanol vulnerability in neonatal cerebellum, and analyzed alterations in these substances after early ethanol exposure.Methods: Assessments were made of neurotrophic factors nerve growth factor, brain‐derived neurotrophic factor, neurotrophin‐3, and neurotrophin‐4; apoptosis‐related proteins Bcl‐2, Bcl‐xl, Bax, Bcl‐xs, Bad, phosphorylated‐Bad, phosphorylated‐Akt, and phosphorylated‐c‐Jun N‐terminal kinase; and the antioxidants superoxide dismutase, glutathione reductase, and catalase. These analyses quantified basal levels (in controls), and sequential changes following acute ethanol exposure at the vulnerable and resistant cerebellar periods (P4, P7).Results: Comparisons of basal levels of the molecules assessed between P4 and P7 revealed higher levels of total proapoptotic Bad at p4, higher levels of the protective pAkt kinase at P7, and lower levels of proapoptotic pJNK at P7. Other basal levels did not differ. While ethanol‐mediated alterations were found at both ages favoring both apoptosis and survival, the apoptosis‐promoting changes produced on P4 exceeded those on P7, and most occurred within the first 2 hr after exposure, a critical survival/death period. The number of alterations favoring survival were similar at the two ages, but at P7 most occurred within the first 2 hr after exposure, possibly acting in a protective manner.Conclusions: Differential temporal vulnerability to ethanol in the neonatal cerebellum appears to be paralleled by cellular alterations in neurotrophic factors, apoptosis‐regulatory proteins, and/or antioxidant activities which generally favor apoptosis at the most sensitive age and survival at the resistant age.
Chronic Prenatal Ethanol Exposure Alters Ionotropic Glutamate Receptor Subunit Protein Levels in the Adult Guinea Pig Cerebral Cortex
Authors: Dettmer Todd S. , Barnes Alicia , Iqbal Umar , Bailey Craig D. C. , Reynolds James N. , Brien James F. , Valenzuela C. Fernando 
Published: May 2006

Background: The superfamily of glutamate‐gated ion channels mediates fast excitatory synaptic transmission in the central nervous system and is composed of the NMDA, AMPA, and kainate receptors. Binding studies have shown that chronic prenatal and/or neonatal ethanol exposure produces persistent effects on the numbers of some of these channels. However, whether or not this chronic ethanol exposure produces long‐lasting effects on the expression of specific ionotropic receptor subunits remains an open question.Methods: Timed pregnant Dunkin‐Hartley strain guinea pigs received oral administration of one of the following regimens between gestational days 2 and 67: (1) 4 g of ethanol per kilogram of maternal body weight per day with ad libitum access to pellet food and water (ethanol group), (2) isocaloric sucrose‐ and pair‐feeding with ad libitum access to water (sucrose group), or (3) isovolumetric water with ad libitum access to food and water (water group). The maternal blood ethanol concentration produced by the ethanol regimen was 71 ± 12 mM. Adult offspring were killed on postnatal day 61, and cerebral cortical tissue was analyzed for ionotropic glutamate receptor subunit expression by Western immunoblotting.Results: There was a statistically significant decrease in NR2B subunit protein expression and an increase in GluR2/3 subunit protein expression in the ethanol group. Expression of NR1, NR2A, NR2C, GluR1, GluR6/7, and KA2 subunit proteins was not affected.Conclusions: These results demonstrate that chronic prenatal ethanol exposure produces long‐lasting effects on the subunit composition of NMDA and AMPA receptors in the cerebral cortex of the adult guinea pig.
Brain fMRI Activation Associated with Self‐Paced Finger Tapping in Chronic Alcohol‐Dependent Patients
Authors: Parks Mitchell H. , Morgan Victoria L. , Pickens David R. , Price Ronald R. , Dietrich Mary S. , Nickel Mark K. , Martin Peter R. 
Published: May 2006

Background: Fine and gross motor dysfunction in chronic alcoholic patients is prevalent, but not extensively studied. Brain autopsy studies of brain regions involved in motor movements indicate cerebellum and frontal lobes are particularly sensitive to alcohol‐induced damage, in contrast to motor cortex.Methods: Using functional magnetic resonance imaging (fMRI), we compared the pattern of activation of the cerebral cortex and cerebellum during repetitive, self‐paced dominant (DH) and nondominant (NDH) index finger tapping in eight uncomplicated alcohol‐dependent patients after approximately 2 weeks of abstinence and in nine normal controls.Results: Whereas alcoholic patients tapped significantly more slowly than normal controls, a greater percentage of pixels were activated in the ipsilateral cortex during DH tapping. Furthermore, alcoholics tapped significantly less efficiently (tapping rate divided by percent pixels activated [weighted by pixel intensity] in a given region of interest [ROI]) than normal controls in every ROI examined while using DH, but only in ipsilateral hemi‐cerebellum using NDH. Finally, the alcohol‐dependent patients did not demonstrate the greater mean pixel activation, percentage activated pixels, and lesser activation efficiency in the ipsilateral cortex during NDH compared to DH tapping that was observed in the normal control group.Conclusions: These findings are compatible with motor inefficiency and compensatory alterations of cortical‐cerebellar circuits. Further studies are needed to determine whether these deficits recover with prolonged abstinence and how they relate to cognitive inefficiency throughout the clinical course of alcoholism.
Does Price Matter? The Effect of Decreased Price on Spirits Consumption in Switzerland
Authors: Kuo Meichun , Heeb Jean‐Luc , Gmel Gerhard , Rehm Jürgen 
Published: May 2006

Background: On July 1st, 1999, the spirits market in Switzerland was reformed based on the World Trade Organization (WTO) agreement. The tax reform, in addition to increased competition, has resulted in a 30–50% decrease in price for foreign spirits (liquor). The purpose of the present study is to examine whether decreased prices due to the tax reform and the liberalized spirits market in Switzerland have had an effect on spirits consumption, and whether the effect differs by demographic and other correlates.Methods: The present study uses data from a longitudinal study on changes in alcohol consumption in Switzerland's resident population. The baseline survey was conducted 3 months before the tax reform and the follow‐up was conducted 28 months after the tax reform. A randomly selected sample of 4007 residents aged 15 years or older participated in the baseline survey and 73% in the follow‐up survey. The data were obtained by computer‐assisted telephone interview, including detailed questions on alcohol consumption, drinking habits, problem drinking, purchase of spirits and socio‐demographic characteristics.Results: Consumption of spirits increased after the price of spirits decreased. The increase in spirits consumption was consistent across subgroups, with the exception of the group aged 60 or older. Moreover, the increase in spirits consumption persisted even after adjustment for significant correlates of spirits consumption. Apart from age, there was no evidence that the increase in spirits consumption differed between subgroups as defined by sex, region, working status, education, smoking, drinking frequency, or average number of drinks.Conclusions: The findings demonstrate that younger people are more affected by price than older persons. This study demonstrated that price should be considered an effective policy to reduce alcohol misuse and alcohol‐related problems, especially among the younger population.
Alcohol Intoxication Induces Greater Reductions in Brain Metabolism in Male Than in Female Subjects
Authors: Wang Gene‐Jack , Volkow Nora D. , Fowler Joanna S. , Franceschi Dinko , Wong Christopher T. , Pappas Naomi R. , Netusil Noelwah , Zhu Wei , Felder Christoph , Ma Yeming 
Published: May 2006

Background: The mechanisms underlying the gender differences in alcohol drinking behavior and alcohol's effects are poorly understood and may reflect gender differences in brain neurochemistry. Alcohol decreases glucose metabolism in the human brain in a pattern that is consistent with its facilitation of GABAergic neurotransmission. We compared the regional changes in brain glucose metabolism during alcohol intoxication between female and male subjects.Methods: Ten female and 10 male healthy controls were scanned with positron emission tomography and 2‐deoxy‐2[18F]fluoro‐d‐glucose twice: 40 min after placebo (diet soda) or alcohol (0.75 g/kg mixed with diet soda).Results: Alcohol significantly and consistently decreased whole‐brain metabolism. The magnitude of these changes was significantly larger in male (−25 ± 6%) than in female (−14 ± 11%;p < 0.005) subjects. Half of the female subjects had reductions in metabolism during intoxication that were significantly lower than those in male subjects. This blunted response in the female subjects was not due to differences in alcohol concentration in plasma, because these did not differ between the genders. In contrast, the self‐reports for the perception of intoxication were significantly greater in female than in male subjects. The cognitive deterioration during alcohol intoxication, although not significant, tended to be worse in female subjects.Conclusions: This study shows a markedly blunted sensitivity to the effects of acute alcohol on brain glucose metabolism in female subjects that may reflect gender differences in alcohol's modulation of GABAergic neurotransmission. The greater behavioral effects of alcohol in female subjects despite the blunted metabolic responses could reflect other effects of alcohol, for which the regional metabolic signal may be hidden within the large decrements in metabolism that occur during alcohol intoxication.
Ethanol and Estradiol Modulate Alternative Splicing of Dopamine D2 Receptor Messenger RNA and Abolish the Inhibitory Action of Bromocriptine on Prolactin Release From the Pituitary Gland
Authors: Oomizu Souichi , Boyadjieva Nadka , Sarkar Dipak K. 
Published: May 2006

Background: Several reports show evidence for the existence of high levels of prolactin (PRL) in alcoholic men and women. Previously we have shown that ethanol increases PRL release both in vivo and in vitro. How ethanol increases PRL release is not well understood.Methods: In this study, we determined the effects of ethanol in the presence and absence of estradiol‐17β on PRL messenger RNA (mRNA) levels, dopamine D2 receptor mRNA splicing, and the PRL‐inhibitory response of a dopaminergic agent, bromocriptine, in the pituitary of Fischer‐344 rats and in primary cultures of anterior pituitary cells. Real‐time reverse transcriptase‐polymerase chain reaction was used for mRNA detection, and radioimmunoassay was used for hormone detection.Results: Estradiol and ethanol alone increased PRL mRNA expression in the pituitary gland. Ethanol also potentiated estradiol action on PRL mRNA expression in the pituitary. Determination of the D2 receptor splicing, by determining the changes in the percentage of D2 receptor mRNA expressed as its long form (D2L) and as its short form (D2S), revealed that both ethanol and estradiol altered D2 receptor splicing. Ethanol and estradiol, alone and together, increased the percentage of the D2L receptor but decreased the D2S receptor percentage. Similarly, ethanol and estradiol alone and in combination increased D2L, but decreased the D2S receptor percentage in primary cultures of pituitary cells. Evaluation of bromocriptine's inhibition of PRL release in primary cultures of pituitary cells indicated that ethanol reduced the ability of this D2 receptor agonist to inhibit PRL release.Conclusions: These results confirm estradiol's inhibition of D2 function and provide novel evidence that ethanol, like estradiol, reduces dopamine's ability to inhibit PRL release by modifying alternative splicing of the dopamine D2 receptor in the pituitary.
Interaction Between Alcohol and Nitric Oxide on ACTH Release in the Rat
Authors: Seo Dong Ook , Rivier Catherine 
Published: May 2006

Background: This work was designed to determine whether alcohol increased nitric oxide (NO) levels within the hypothalamic‐pituitary (HP) axis, whether endogenous NO participated in the known ability of alcohol to release ACTH and, conversely, whether prior alcohol treatment altered the ACTH response to NO.Methods: In a first group of experiments, intact adult male rats were injected with the vehicle or alcohol intragastrically (4.5 g/kg). The effect of alcohol on NO was studied by measuring nitrite + nitrate levels, as well as NOS activity, as indexes of formation of this gas. The role of endogenous NO then was studied by blocking the activity of NO synthase, the enzyme responsible for formation of this gas, and determining whether this treatment altered the ACTH response to alcohol. Finally, we investigated the influence of alcohol on the ACTH response to NO. These studies were done in rats exposed to alcohol vapors (4 hr/day for 1–5 days) to avoid the confounding influence of HP axis stimulation by acutely injected alcohol.Results: The acute intragastric injection of alcohol significantly (p < 0.01) increased NO levels in the paraventricular nucleus of the hypothalamus, the anterior pituitary, and peripheral blood. The ACTH response to acute intragastric alcohol injection was significantly (p < 0.01) decreased by the arginine derivative Nω‐nitro‐L‐arginine‐methylester, which nonspecifically blocks NOS activity, as well as by the specific neuronal NOS antagonist 7‐nitroindazole. A 5 but not 1 or 3 day exposure to intermittent alcohol vapors interfered with the ACTH response to the intracerebroventricular injection of the NO donor 3‐morpholino‐sydnonimine.Conclusion: Acute alcohol injection increases NO levels in blood and the HP axis, and these responses seem to facilitate the ACTH response to alcohol. Reciprocally, prolonged (5 days) exposure to ethanol vapors blunts the HP axis response to centrally administered NO.
Chronic Ethanol Ingestion Increases Expression of the Angiotensin II Type 2 (AT2) Receptor and Enhances Tumor Necrosis Factor‐α‐ and Angiotensin II‐Induced Cytotoxicity Via AT2 Signaling in Rat Alveolar Epithelial Cells
Authors: Bechara Rabih I. , Brown Lou Ann S. , Eaton Douglas C. , Roman Jesse , Guidot David M. 
Published: May 2006

Background: Alcohol abuse increases the risk of acute lung injury in critically ill patients. We have shown that alveolar epithelial cell (AEC) apoptosis in response to inflammatory mediators, including tumor necrosis factor‐α (TNF‐α), parallels endotoxin‐mediated acute lung injury in ethanol‐fed rats. Although angiotensin II mediates TNF‐α‐induced apoptosis of AECs in vitro, its role in ethanol‐mediated susceptibility to AEC apoptosis is unknown.Methods: Adult male rats were fed the Lieber‐DeCarli diet for 6 weeks. AECs were isolated, and TNF‐α‐ and angiotensin II‐induced cytotoxicity (by terminal transferase‐mediated dUTP nick end labeling staining) was determined with or without the addition of the angiotensin‐converting enzyme inhibitor (lisinopril) or a selective blocker of the angiotensin II type 1 receptor (AT1) or type 2 receptor (AT2). Finally, the relative expression of the AT1 and AT2 receptors in AECs was determined by Western blot analysis.Results: TNF‐α‐induced cytotoxicity, but not angiotensin II‐induced cytotoxicity, was prevented by lisinopril, indicating that de novo angiotensin II synthesis is required for TNF‐α‐induced apoptosis in these cells. Both TNF‐α‐ and angiotensin II‐induced cytotoxicity in AECs from control‐fed and ethanol‐fed rats were inhibited by the selective AT2 blocker, PD123319, but not by the selective AT1 blocker, losartan. In parallel, ethanol ingestion doubled AT2 expression in AECs (by Western blot) but had no significant effect on AT1 receptor expression.Conclusions: Chronic ethanol ingestion increases AT2 expression in the alveolar epithelium and enhances TNF‐α‐ and angiotensin II‐induced cytotoxicity, both of which act via AT2. Together, these findings suggest that selective AT2 receptor inhibition could limit the development of acute lung injury in alcoholic patients.
Additive Inhibition of Dendritic Cell Allostimulatory Capacity by Alcohol and Hepatitis C Is Not Restored by DC Maturation and Involves Abnormal IL‐10 and IL‐2 Induction
Authors: Dolganiuc Angela , Kodys Karen , Kopasz Andrea , Marshall Christopher , Mandrekar Pranoti , Szabo Gyongyi 
Published: May 2006

Background: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity.Methods: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV‐DC) and controls (N‐DC) with IL‐4 plus granulocyte‐macrophage colony stimulating factor (GM‐CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA.Results: Allostimulatory capacity of HCV‐DCs was reduced compared to N‐DCs and it was further inhibited by alcohol treatment (p < 0.01). MLR was also decreased with alcohol‐treated N‐DCs. DC phenotypic markers and apoptosis were comparable between HCV‐DCs and N‐DCs irrespective of alcohol treatment. However, HCV‐DCs and alcohol‐treated N‐DCs exhibited elevated IL‐10 and reduced IL‐12 production. Reduced MLR with HCV‐DCs and its further inhibition by alcohol coexisted with decreasing IL‐2 levels (p < 0.017). DC maturation partially improved but failed to fully restore the reduced allostimulatory function of either alcohol‐treated or alcohol‐naïve HCV‐DCs (p < 0.018).Conclusions: Alcohol and HCV independently and together inhibit DC allostimulatory capacity, increase IL‐10, reduce IL‐12 and IL‐2 production that cannot be normalized by DC maturation. HCV and alcohol interact to modulate innate and adaptive immune responses via dendritic cells.
DETECT
Authors: Whitfield Ronald G. , VanKuiken Jack C. 
Published: May 2006

SUMMARYDETECT is an inexpensive, easy to use, general‐purpose, Monte Carlo simulation program for IBM and compatible personal computers. It can be used to quickly analyze fault trees or functions of random variables. DETECT provides a wide variety of input distributions to choose from and a dependency (correlation) option. The result of the analysis is a probability distribution over the variable of interest. We look forward to further improvements (e.g., graphics, full‐screen editing, ability to inspect intermediate results) that will make DETECT even more useful and attractive.
IMES: A System for Identifying and Evaluating Computer Models for Exposure Assessment2
Authors: Pardi Richard R. 
Published: May 2006

SUMMARYAlthough IMES is apparently a marriage of independently developed modules, the blend is nearly seamless‐there are only minor differences in “feel” between the three modules. IMES is well organized and easy to use. There are help screens at every stage in each module. Selection is efficient‐queries rarely take more than a few seconds on a 386 machine before a report can be generated. There are a few pitfalls in model selection which are difficult to avoid. Improper classification is one of them. For example, IMES lists MINTEQ as a multimedia model. It would be more appropriate from this reviewer's perspective to classify MINTEQ as a geo‐chemical model (for which this version of IMES has no classification category.)One minor concern is that in two modules (Selection and Validation)IMES queries the operator “Do you really want to exit?” or “Exit?” when one simply wants to go back one level in the screening process. It would be less disconcerting to be consistently presented (as is done in the Uncertainty module)with a pop‐up menu selection like “Do you want to return to the previous screen?”IMES was an ambitious undertaking that resulted in a useful and important contribution to Exposure Assessment Model community.
Understanding Uncertainty
Authors: Rowe William D. 
Published: May 2006

There is more information we don't know than we do know for making most critical decisions involving risks. Our focus must be on understanding and effectively dealing with what we don't know. As a first step in achieving this focus, a classification of the types of uncertainties that must be addressed and the sources of these types of uncertainties is presented. The purpose is to provide a framework for discussion about addressing uncertainty, particularly in risk analyses.Both uncertainty and variability of information are addressed using four main classes:

Metrical uncertainty and variability in measurement,
Structural uncertainty due to complexity, including models and their validation,
Temporal uncertainty in future and past states
Translational uncertainty in explaining uncertain results.

The factors that contribute uncertainty and error to these classes are identified, and their interrelationships indicated. Both subjective and objective aspects are addressed.