bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that caspase‐1 is a negative regulator of AMPA receptor‐mediated long‐term potentiation at hippocampal synapses
Authors: Lu Chengbiao , Wang Yue , Furukawa Katsutoshi , Fu Weiming , Ouyang Xin , Mattson Mark P.
Published: March 2006

Best known for their pivotal role in a form of programmed cell death called apoptosis, caspases may also function in more subtle physiological processes. Caspases are present in synapses and dendrites of neurons where they can be activated in response to glutamate receptor stimulation and calcium influx. Here we tested the hypothesis that caspase‐1 plays a role in modulating long‐term potentiation (LTP) at hippocampal synapses. We provide evidence that caspase‐1 plays a role in regulating α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor‐mediated calcium influx and synaptic plasticity in the hippocampus. LTP of excitatory postsynaptic potentials at CA1 synapses was significantly enhanced when hippocampal slices were treated with either a pan‐caspase inhibitor or a selective inhibitor of caspase‐1, but not by an inhibitor of caspase‐6. Inhibition of caspase‐1 significantly enhanced the AMPA current‐mediated component of LTP without affecting the N‐methyl‐d‐aspartate current‐mediated component. Calcium responses to AMPA were enhanced in hippocampal neurons treated with a caspase‐1 inhibitor suggesting that caspase‐1 normally functions to reduce AMPA receptor‐mediated calcium influx. These findings suggest that, by selectively reducing AMPA currents and calcium influx, caspase‐1 functions as a negative regulator of LTP at hippocampal synapses.
NFκB in neurons? The Uncertainty Principle in neurobiology
Authors: Massa Paul T. , Aleyasin Hossein , Park David S. , Mao Xianrong , Barger Steven W.
Published: March 2006

Nuclear factor κB (NFκB) is a dynamically modulated transcription factor with an extensive literature pertaining to widespread actions across species, cell types and developmental stages. Analysis of NFκB in a complex environment such as neural tissue suffers from a difficulty in simultaneously establishing both activity and location. Much of the available data indicate a profound recalcitrance of NFκB activation in neurons, as compared with most other cell types. Few studies to date have sought to distinguish between the various combinatorial dimers of NFκB family members. Recent research has illuminated the importance of these problems, as well as opportunities to move past them to the nuances manifest through variable activation pathways, subunit complexity and target sequence preferences.
Graded response to GABA by native extrasynaptic GABAAreceptors
Authors: Lindquist Catarina E. L. , Birnir Bryndis
Published: March 2006

GABA is the main inhibitory neurotransmitter in the mammalian CNS. GABA in the brain is commonly associated with a fast, point‐to‐point form of signalling called synaptic transmission (phasic inhibition), but there is growing evidence that GABA participates in another, slower and more diffuse form of signalling often referred to as tonic inhibition. Unresolved questions regarding tonic neuronal inhibition concern activation and functional properties of extrasynaptic GABAAreceptors (GABARex) present on neurones. Extrasynaptic receptors are exposed to submicromolar GABA concentrations and may modulate the overall excitability of neurones and neuronal networks. Here, we examined GABA‐activated single‐channel currents in dentate gyrus granule neurones in rat hippocampal slices. We activated three types (I, II, III) of GABARex channels by nanomolar GABA concentrations (EC50I: 27 ± 12; II: 4 ± 3; III: 43 ± 19 nm). The channels opened after a delay and the single‐channel conductance was graded (γmaxI: 61 ± 3; II: 85 ± 8, III: 40 ± 3 pS). The channels were differentially modulated by 1 µmdiazepam, 200 nmzolpidem, 1 µmflumazenil and 50 nmTHDOC (3α, 21‐dihydroxy‐5α‐pregnan‐20‐one), consistent with the following minimal subunit composition of GABARex I α1βγ2, GABARex II α4βγ2and GABARex III αβδ channels.
Intracerebral accumulation of glutaric and 3‐hydroxyglutaric acids secondary to limited flux across the blood–brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl‐CoA dehydrogenase deficiency
Authors: Sauer Sven W. , Okun Jürgen G. , Fricker Gert , Mahringer Anne , Müller Ines , Crnic Linda R. , Mühlhausen Chris , Hoffmann Georg F. , Hörster Friederike , Goodman Stephen I. , Harding Cary O. , Koeller David M. , Kölker Stefan
Published: March 2006

Glutaric acid (GA) and 3‐hydroxyglutaric acids (3‐OH‐GA) are key metabolites in glutaryl co‐enzyme A dehydrogenase (GCDH) deficiency and are both considered to be potential neurotoxins. As cerebral concentrations of GA and 3‐OH‐GA have not yet been studied systematically, we investigated the tissue‐specific distribution of these organic acids and glutarylcarnitine in brain, liver, skeletal and heart muscle of Gcdh‐deficient mice as well as in hepatic Gcdh–/– mice and in C57Bl/6 mice following intraperitoneal loading. Furthermore, we determined the flux of GA and 3‐OH‐GA across the blood–brain barrier (BBB) using porcine brain microvessel endothelial cells. Concentrations of GA, 3‐OH‐GA and glutarylcarnitine were significantly elevated in all tissues of Gcdh–/– mice. Strikingly, cerebral concentrations of GA and 3‐OH‐GA were unexpectedly high, reaching similar concentrations as those found in liver. In contrast, cerebral concentrations of these organic acids remained low in hepatic Gcdh–/– mice and after intraperitoneal injection of GA and 3‐OH‐GA. These results suggest limited flux of GA and 3‐OH‐GA across the BBB, which was supported in cultured porcine brain capillary endothelial cells. In conclusion, we propose that an intracerebral de novo synthesis and subsequent trapping of GA and 3‐OH‐GA should be considered as a biochemical risk factor for neurodegeneration in GCDH deficiency.
Triptans—Why Once?
Authors: Ifergane Gal , Wirguin Itzhak , Shvartzman Pesach
Published: March 2006

Objective.—To evaluate triptan use patterns in a large Israeli HMO district.

Background.—Triptans, 5HT1B/1D agonists, provide an effective and safe relief of headache and accompanying symptoms during an acute migraine attack.

Method.—We retrospectively reviewed the computerized prescription filling data of 1498 patients who filled a first triptan prescription between July 2003 and June 2004.

Results.—During a 1‐year follow‐up period, 841 patients (56.1%) purchased triptans only once. Single‐time users were significantly more prevalent among men and in patients younger than 30 or older than 70 years.

Conclusions.—It seems that many migraine patients choose not to use triptans after their first experience with the drug.
Acute Migraine Treatment: Patterns of Use and Satisfaction in a Clinical Population
Authors: Malik Shahram N. , Hopkins Mary , Young William B. , Silberstein Stephen D.
Published: March 2006

Background.—The sequence and timing of taking migraine medications, whether prescription or over‐the‐counter, and the patient's response to their treatment, is unknown.

Objective.—To describe the use of, response to, and satisfaction with acute medications for 1 migraine attack.

Methods.—We performed a clinic‐based survey of 127 patients at Jefferson Headache Center, Philadelphia. Adult patients who met the International Headache Society criteria for migraine with or without aura were included in the study. Patients were asked to complete a questionnaire.

Results.—Of 109 participants who met the inclusion criteria, most waited 1 hour or more after the onset of symptoms to take medication. Triptans were most commonly used as first, second, and third medications. Triptan use was associated with higher 2‐hour pain‐free response rates compared with other agents, whether the triptan was used as the first, second, or third medication. Patients who were treated with medications other than triptans were more likely to have pain at 2 hours (P= .36). NSAIDs had relatively low pain‐free and headache relief response rates at 2 hours. Sixty‐two participants (56.9%) had to treat a second time and 31 (28.4%) had to treat a third time. Some participants (17.6%) had headache recurrence within 24 hours after becoming headache free following initial medication and some (23.5%) had recurrence after becoming headache free following their second medication. Sixty‐six percent of participants reported being very satisfied/satisfied with their initial medication and 33% were somewhat dissatisfied/dissatisfied to some degree. Even though most patients were satisfied with their medication, 88% reported that they would be willing to try a new antimigraine medication. Most patients (60 [55%]) preferred a long‐acting agent versus a rapid‐onset, short‐acting agent (which was preferred by 49 [45%] patients).

Conclusion.—Migraine patients have treatment preferences. They generally want a drug that provides complete headache relief, and they are often satisfied with the current treatment options.
Serotonin Transporter Protein Polymorphism and Harm Avoidance Personality in Migraine without Aura
Authors: Park Jeong Wook , Han Si Ryung , Yang Dong Won , Kim Yeong In , Lee Kwang Soo
Published: March 2006

Objective.—To investigate polymorphisms in the serotonin transporter protein gene and harm avoidance personality dimension in patients with migraine without aura (MWOA).

Background.—The serotonin transporter protein is a key modulator of serotonergic synaptic neurotransmission. Two polymorphic regions of the gene for serotonin transporter protein have been found, and are associated with variations in the functional activity of serotonin caused by differing transcriptional efficiency. The harm avoidance (HA) personality trait may also be heritable and associated with altered serotonergic neurotransmitter activity.

Design.—We amplified the polymorphism in the promoter of serotonin transporter protein (5‐HTTLPR) and the variable number of tandem repeats polymorphism within intron 2 (VNTR) using the polymerase chain reaction and performed genotype polymorphism analyses in 97 patients with MWOA and 100 healthy controls. We investigated serotonin‐related personality traits by evaluating the HA personality dimension using a tridimensional questionnaire.

Results.—The genotype frequencies and allele distributions of 5‐HTTLPR did not differ between patients with MWOA and controls. The VNTR genotype STin2.12/STin2.12 was significantly more common in patients with MWOA (90%) than in controls (77%; P= .017). Patients with MWOA also had HA scores (21.9 ± 6.4) significantly higher than those of controls (16.3 ± 6.1; P < .001).

Conclusions.—Serotonergic activity might be involved in the development of MWOA and VNTR of serotonin transporter gene might be one of the genetically contributing factors.
Myofascial Trigger Points and Their Relationship to Headache Clinical Parameters in Chronic Tension‐Type Headache
Authors: Fernández‐de‐las‐Peñas César , Alonso‐Blanco Cristina , Cuadrado Maria Luz , Gerwin Robert D. , Pareja Juan A.
Published: March 2006

Objective.—To assess the presence of trigger points (TrPs) in several head and neck muscles in subjects with chronic tension‐type headache (CTTH) and in healthy subjects; and to evaluate the relationship of these TrPs with forward head posture (FHP), headache intensity, duration, and frequency.

Background.—Tension‐type headache (TTH) is a headache in which myofascial TrPs in head and neck muscles might play an important etiologic role.

Design.—A blinded, controlled, pilot study.

Methods.—Twenty‐five CTTH subjects and 25 matched controls without headache were studied. TrPs in bilateral upper trapezius, sternocleidomastoids, and temporalis muscles were identified according to Simons et al's diagnostic criteria: tenderness in a hyperirritable spot within a palpable taut band, local twitch response elicited by snapping palpation, and elicited referred pain with palpation. A TrP was considered active if the subject recognized the evoked referred pain as familiar headache. If the evoked referred pain was not recognized as familiar headache, the TrP was considered as latent. Side‐view pictures of each subject were taken in both sitting and standing positions in order to assess FHP by measuring the cranio‐vertebral angle. Both measurements were made by a blinded assessor. A headache diary was kept for 4 weeks in order to assess headache intensity, frequency, and duration.

Results.—The mean number of TrPs on each CTTH subject was 3.9 (SD: 1.2), of which 1.9 (SD: 1.2) were active TrPs and 1.9 (SD: 0.8) were latent TrPs. Control subjects only exhibited latent TrPs (mean: 1.4; SD: 0.8). There was a significant difference between the CTTH group and the controls for active TrPs (P < .001), but not for latent TrPs (P > .05). Differences in the distribution of active and latent TrPs within each muscle were also significant for all the analyzed muscles (P < .01). CTTH subjects with active TrPs in the right upper trapezius muscle or left sternocleidomastoid muscle showed a greater headache intensity and duration, but not headache frequency, compared to those with latent TrPs (P < .05). Active TrPs in the right temporalis muscle were associated with longer headache duration (P < .01), whereas active TrPs in the left temporalis muscle were associated with greater headache intensity (P < .05). CTTH subjects with active TrPs in the analyzed muscles had a greater FHP than those with latent TrPs in both sitting and standing positions. Differences were only significant for TrPs in the left sternocleidomastoid and FHP in the sitting position (P < .01).

Conclusions.—Active TrPs in upper trapezius, sternocleidomastoid, and temporalis muscles were associated with CTTH. CTTH subjects with active TrPs usually reported a greater headache intensity and longer headache duration than those with latent TrPs. CTTH subjects with active TrPs tended to have a greater FHP than CTTH subjects with latent TrPs.
Evaluation of an Electronic Diary as a Diagnostic Tool to Study Headache and Premenstrual Symptoms in Migraineurs
Authors: Goldberg Jay , Wolf Abigail , Silberstein Stephen , Gebeline‐Myers Cheryl , Hopkins Mary , Einhorn Kim , Tolosa Jorge E.
Published: March 2006

Objective.—To evaluate an electronic diary as a tool to evaluate the occurrence and relationship of headaches and premenstrual syndrome (PMS) symptoms throughout the menstrual cycle in women with migraine.

Background.—Menstrually related headache and PMS significantly impact the quality of life of many women. The time relationship of these 2 menstrually related problems is not well understood and not well described.

Methods.—Twenty women with migraine experiencing regular menstrual cycles were enrolled in a prospective study designed to date‐ and time‐stamp data, both self‐ and computer‐prompted, headache and PMS symptoms, for 3 consecutive months. A previously validated PMS score was calculated by grading 23 PMS criteria on a scale of 0 to 3 (0 = no symptoms, 3 = severe symptoms).

Results.—The total number of data entries recorded was 2009, composed of 56 menstrual cycles in 20 migraineurs. Five hundred forty‐four entries reported a current, prodromal, or previous headache. The mean daily occurrence of headache increased beginning on cycle day –5, peaked on days +1 to +5, and returned to baseline by day +7. Mean daily PMS scores ranged from 2.4 to 12. Mean daily PMS scores peaked on days –6 to +2 and returned to baseline by day +8.

Conclusions.—An electronic diary may have potential as a diagnostic tool in studying headaches and PMS symptoms throughout the menstrual cycle. The occurrence of headache and PMS symptoms in migraineurs follows similar time courses.
Effect of Hyperoxia on Neurogenic Plasma Protein Extravasation in the Rat Dura Mater
Authors: Schuh‐Hofer Sigrid , Siekmann Wiebke , Offenhauser Nikolas , Reuter Uwe , Arnold Guy
Published: March 2006

Objective.—We aimed to study the effect of normobaric hyperoxia on neurogenic inflammation of the rat dura mater.

Background.—Inhalation of 100% oxygen is a first‐line therapy for the treatment of acute cluster headache (CH). However, the mechanisms underlying the antinociceptive effect of oxygen are poorly understood. Sumatriptan, which is also effective in aborting CH attacks, is known to inhibit neurogenic inflammation of the dura mater. We hypothesized that hyperoxia reduces dural plasma protein extravasation in the model of electrically stimulating the rat trigeminal ganglion.

Methods.—Unilateral stimulation of the trigeminal ganglion was performed in anesthetized male Sprague‐Dawley rats. We assessed plasma protein extravasation (PPE) in the ipsilateral dura mater under normoxic (group 1) and hyperoxic conditions (group 2: pO2200 mmHg; group 3: pO2300 mmHg; group 4: pO2400 mmHg). The study results were compared to the effect of sumatriptan (300 μg/kg) on dural PPE.

Results.—Under normoxic conditions, the calculated extravasation ratio was 1.72 ± 0.2. Hyperoxic treatment (groups 2, 3, 4) significantly attenuated dural PPE. At oxygen levels of 400 mmHg, the PPE ratio was 1.14 ± 0.2 (P< .01). After IV application of sumatriptan (300 μg/kg), PPE was nearly abolished (PPE ratio: 1.06 ±0.17).

Conclusion.—Our findings demonstrate that hyperoxia is able to inhibit dural PPE. Hyperoxia may play an anti‐inflammatory role in neurogenic inflammation, but further studies are needed to clarify whether this effect is either caused by prejunctional mechanisms or by modulation of the vascular permeability at postcapillary venules.
EndogenousκOpioid Receptor Systems Modulate the Responsiveness of Mesoaccumbal Dopamine Neurons to Ethanol
Authors: Zapata Agustin , Shippenberg Toni S.
Published: March 2006

Background:Endogenousκ‐opioid receptor (KOPR) systems modulate the actions of several drugs of abuse. Their role in modulating the effects of ethanol is unknown. An increase in nucleus accumbens extracellular dopamine (DA) has been implicated in mediating the rewarding and locomotor‐activating effects of ethanol and virtually all drugs of abuse. The present microdialysis studies were conducted to determine whether the lack of KOPR alters ethanol‐evoked DA levels in the nucleus accumbens of naïve mice and whether a similar effect is observed in mice repeatedly exposed to ethanol.

Methods:Gene deletion techniques were used in conjunction with in vivo microdialysis to examine the influence of lack of KOPR on ethanol‐evoked DA in the nucleus accumbens. To determine whether pharmacological inactivation of KOPR produces similar effects in naïve mice and those repeatedly exposed to ethanol, the KOPR antagonist norbinaltorphimine (n‐BNI) was administered in wild‐type mice before repeated air or ethanol vapor inhalation. Microdialysis was conducted 24 hours later.

Results:Acute ethanol administration increased DA levels in the nucleus accumbens of wild‐type mice. In littermates lacking the KOPR gene, ethanol‐evoked DA levels were enhanced. Prior ethanol exposure reduced ethanol‐evoked DA levels in vehicle‐treated and n‐BNI–treated mice. Statistical analysis, however, revealed a significant main effect of n‐BNI, indicating that KOPR blockade increased ethanol‐evoked DA levels in naïve mice and repeated ethanol exposure attenuated, but did not abolish, this effect.

Conclusions:These findings demonstrate that inhibition of KOPR leads to increased sensitivity to the DA‐releasing effects of ethanol in the nucleus accumbens.
Comparison of Ethanol Preference and Neurochemical Measures of Mesolimbic Dopamine and Adenosine Systems Across Different Strains of Mice
Authors: Short Jennifer Lynn , Drago John , Lawrence Andrew John
Published: March 2006

Background:To extend the known phenotype of strains commonly used in the development of mutant mice, ethanol, saccharin, and caffeine preferences were examined in C57Bl/6J, CD‐1, and hybrid C57Bl/6J × CD‐1 mice. As dopaminergic mechanisms are inherently involved in the neuronal processing of many drugs of abuse (including ethanol), and an important role for adenosine–dopamine interactions has also been reported, the dopaminergic and purinergic neurochemical profiles of mice were compared against the consummatory phenotype observed.

Methods:Ethanol (5% v/v), saccharin (0.1% w/v), and caffeine (0.1% w/v) consumption and preference were examined using a 2‐bottle free‐choice paradigm. Dopamine and adenosine receptor and transporter mRNA and protein density were quantified using in situ hybridization histochemistry and in vitro autoradiography, respectively.

Results:C57Bl/6J and hybrid C57Bl/6J × CD‐1 mice demonstrated a clear ethanol preference, voluntarily consuming large quantities of ethanol when given the choice between drinking vessels containing either ethanol or water. Conversely, CD‐1 mice were characterized as ethanol‐avoiding under the present paradigm. Differences in D1receptor mRNA between the strains were consistent with the observed behavioral differences in ethanol preference. The high ethanol‐preferring phenotype of C57Bl/6J mice could not be directly linked to alterations in dopamine transporter neurochemistry and/or enkephalin levels as proposed by earlier researchers. Ethanol‐seeking behavior appeared to correlate with D2receptor expression, however, with evidence that ethanol‐preferring mice also exhibit an increased density of D2receptors within limbic dopaminergic projection nuclei. Interestingly, strain differences in the expression of the ethanol‐sensitive nucleoside transporter paralleled differences in ethanol consumption, a novel finding consonant with purinergic involvement in dopamine‐related behaviors.

Conclusions:This study has highlighted the relevance of alterations in dopamine receptor expression and purinergic modulation within the mesolimbic pathway and predisposition toward the development of ethanol‐seeking behavior.
Enhanced Morphine‐Induced Ethanol Drinking in Alcohol‐Preferring Alko Alcohol Rats Sensitized to Morphine
Authors: Ojanen Sami P. , Hyytiä Petri , Kiianmaa Kalervo
Published: March 2006

Background: Alcohol‐preferring alko alcohol (AA) rats are more susceptible to morphine‐induced behavioral and neurochemical sensitization than alcohol nonpreferring alko nonalcohol (ANA) rats. Alko alcohol rats sensitized to morphine, however, do not show enhanced acquisition of ethanol drinking. The purpose of the present study was to clarify further interactions between morphine‐induced behavioral sensitization and voluntary ethanol drinking in the AA rats.

Methods: Alko alcohol rats drinking ethanol in a limited 6‐hour access paradigm were sensitized to morphine with repeated injections of morphine (5–15 mg/kg). Injection days alternated with days of ethanol access. Controls had access only to water and/or were given injections of saline. After a 5‐day washout period from ethanol and morphine, the rats were challenged with morphine or saline and subsequent ethanol drinking or locomotor activity was recorded.

Results: Ethanol intake was suppressed during the repeated treatment with morphine, and the morphine‐treated rats did not differ in ethanol intake from the controls when given access to ethanol after the washout. Intake of ethanol was, however, increased when the rats were challenged with morphine [1 or 10 mg/kg, subcutaneously (s.c.)], while in the controls an increase in ethanol intake was seen only after 1 mg/kg morphine. Sensitization to the locomotor stimulating effects of morphine was revealed in the morphine‐treated rats after a challenge with morphine (3 or 10 mg/kg, s.c.). The controls that had been drinking ethanol also showed a sensitized response after morphine (3 mg/kg).

Conclusions: Ethanol did not interfere with the development of sensitization to morphine. Furthermore, the neuroadaptations induced by repeated exposure to ethanol were sufficient to cause behavioral cross‐sensitization to morphine. Sensitization to the behavioral effects of morphine alone, however, neither enhances the reinforcing properties of voluntarily consumed ethanol nor contributes to increase in its intake. The increase in ethanol intake found after an acute dose of morphine was augmented in rats withdrawn from repeated treatment with morphine. The data suggest that the neuronal mechanisms underlying behavioral sensitization to morphine probably are distinct from those mediating reinforcement from ethanol and that the morphine‐induced neuroadaptations contribute to the enhancement of increase in ethanol intake by morphine.
Short‐term Prognosis of Community‐Acquired Bacteremia in Patients with Liver Cirrhosis or Alcoholism: A Population‐Based Cohort Study
Authors: Linderoth Gitte , Jepsen Peter , Schønheyder Henrik C. , Johnsen Søren Paaske , Sørensen Henrik Toft
Published: March 2006

Background: Liver cirrhosis is associated with an increased risk of infection and a poor prognosis, but the role of alcoholism in these outcomes is uncertain. This study looks at the short‐term prognosis for bacteremia in patients with alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and alcoholism, compared with the prognosis for other bacteremia cases.

Methods: All patients who were hospitalized with their first community‐acquired bacteremia in North Jutland County, Denmark, in the period 1992 to 2002 were retrieved from a population‐based bacteremia registry. Denmark's Hospital Discharge Registry then allowed us to disaggregate these patients into the following groups: 47 patients with alcoholic liver cirrhosis, 19 with nonalcoholic liver cirrhosis, 190 with alcoholism, and a comparison group of 3,535 other bacteremia cases. Using logistic regression, we estimated odds ratios (ORs) for 30‐day case fatality for the main study variable, adjusted for gender, age, focus of infection, and comorbidity.

Results: The case fatality rate (CFR) was 43% for patients with alcoholic liver cirrhosis, 32% for patients with nonalcoholic liver cirrhosis, 24% for patients with alcoholism, and 15% for other bacteremia patients. The adjusted OR estimates for patients with alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and alcoholism compared with other bacteremia cases were 6.3 (95% CI 3.3–11.7), 2.4 (95% CI 0.9–6.7), and 2.5 (95% CI 1.7–3.7), respectively. Focus of infection and group of bacteria did not noticeably affect the increased CFR.

Conclusion: Liver cirrhosis and alcoholism were associated with a poor short‐term prognosis for community‐acquired bacteremia. Liver cirrhosis and alcoholism may have independent effects on the prognosis for patients with liver cirrhosis and bacteremia.
Alcohol‐Related Social Consequences in Castille and Leon, Spain
Authors: Javier álvarez Francisco , Fierro Inmaculada , Carmen del Río Maria
Published: March 2006

Background: The purpose of this study was to examine the prevalence of alcohol‐related social problems, as well as to assess the relationship between alcohol‐related social problems and patterns of alcohol consumption in the general population during the year 2004.

Methods: A total of 2,500 individuals, age range from 14 to 70 years, in Castille and Leon, Spain, were surveyed in 2004 for their patterns of alcohol consumption and alcohol‐related social consequences during the previous year.

Results: Participants who admitted to having had some kind of social problem related to the consumption of alcohol in the previous year were 6.5%, with a mean of 2.4 alcohol‐related social problems. The most frequent problems cited were “argument, discussion, or serious conflict without physical aggression” (3%).

Conclusions: The present study shows that the reporting of alcohol‐related social problems was quite frequent and that having alcohol‐related social problems was related to drunkenness episodes in the previous year, having 5 or more drinks on a single occasion in the previous year, and alcohol intake.
Effects of 8 Different NR1 Splice Variants on the Ethanol Inhibition of Recombinant NMDA Receptors
Authors: Jin Chun , Woodward John J.
Published: March 2006

Background:N‐Methyl‐d‐aspartate (NMDA) receptors are glutamate‐activated ion channels that are assembled from NR1 and NR2 subunits. These receptors are highly enriched in brain neurons and are considered to be an important target for the acute and chronic effects of ethanol. NR2 subunits (A–D) arise from separate genes and are expressed in a developmental and brain region‐specific manner. The NR1 subunit has 8 isoforms that are generated by alternative splicing of a single gene. The heteromeric subunit makeup of the NMDA receptor determines the pharmacological and biophysical properties of the receptor and provides for functional receptor heterogeneity. Although results from previous studies suggest that NR2 subunits affect the ethanol sensitivity of NMDA receptors, the role of the NR1 subunit and its multiple splice variants is less well known.

Methods:In this study, all 8 NR1 splice variants were individually coexpressed with each NR2 subunit in human embryonic kidney 293 (HEK293) cells and tested for inhibition by ethanol using patch‐clamp electrophysiology.

Results:All 32 subunit combinations tested gave reproducible glutamate‐activated currents and all receptors were inhibited to some degree by 100 mM ethanol. The sensitivity of individual receptors to ethanol was affected by the specific NR1 splice variant expressed with receptors containing the NR1‐3 and NR1‐4 subunits among the least inhibited by ethanol.

Conclusions:These results suggest that regional, developmental, or compensatory changes in the expression of NR1 splice variants may significantly affect ethanol inhibition of NMDA receptors.
Social Environmental Influences on the Development and Resolution of Alcohol Problems
Authors: McCrady Barbara S. , Zucker Robert A. , Molina Brooke S. G. , Ammon Lyndsay , Ames Genevieve M. , Longabaugh Richard
Published: March 2006

This article summarizes the proceedings of a symposium presented at the 2005 Annual Meeting of the Research Society on Alcoholism, Santa Barbara, California, June 25–30. The overall goal of the symposium was to consider the broad impact of the social environment on the development of and successful or unsuccessful resolution of drinking problems. The presentations addressed multiple social environmental influences including: the influence of children on parents (Dr. Zucker), the influence of peers and parents on adolescents (Dr. Molina), the influence of family members on adult drinking (Dr. McCrady), the influence of adult peers/friends (Dr. Kaskutas), and the influence of the occupational environment (Dr. Ames). Dr. Longabaugh, the symposium discussant, addressed models for understanding the relationships between social influences and drinking problems.
A Pilot Study of Oxcarbazepine Versus Acamprosate in Alcohol‐Dependent Patients
Authors: Croissant Bernhard , Diehl Alexander , Klein Oliver , Zambrano Sergio , Nakovics Helmut , Heinz Andreas , Mann Karl
Published: March 2006

Objectives: This pilot study has been designed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients. Oxcarbazepine (OXC) blocks voltage‐sensitive sodium channels. Its metabolite reduces high‐voltage–activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, as acamprosate (ACP) modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood‐stabilizing effect in bipolar affective disorders. We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol‐dependent patients.

Methods: We investigated the efficacy and safety of OXC (vs ACP) by conducting a 24‐week randomized, parallel‐group, open‐label, clinical trial on 30 acutely detoxified alcoholic patients. Survival analyses (Kaplan–Meier) were performed to look for evidence of a longer “survival” of patients receiving OXC. We assessed time to first severe relapse and additional secondary endpoints.

Results: After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients. Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale—German version (OCDS‐G) than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol.

Conclusion: Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample. While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated, even when alcohol is on board. Thus, in medication‐based relapse prevention, OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability. OXC certainly merits a larger placebo‐controlled trial.
Visuoperceptual Learning in Alcoholic Korsakoff Syndrome
Authors: Fama Rosemary , Pfefferbaum Adolf , Sullivan Edith V.
Published: March 2006

Relative to the characteristically profound deficits of explicit memory, components of implicit memory remain largely intact in patients with alcohol‐induced Korsakoff syndrome (KS). Perceptual priming occurs in KS and transfer of learning has been consistently observed on mirror reading, a perceptual reversal task. Although priming also occurs with fragmented pictures, a perceptual closure task, it is unclear whether transfer of learning can occur. This study examined visuoperceptual learning in 4 men with alcoholic KS, 9 recently detoxified alcoholic men (ALC), 21 healthy age‐matched normal control men (NC), and 6 young normal control men (YNC). Subjects were tested with the Gollin Incomplete Pictures Test at initial and 1‐hour and 1‐day retest sessions. Both alcoholic groups (KS, ALC) were impaired in visuoperceptual ability. All subject groups showed visuoperceptual learning. The KS group showed additional learning after continued exposure to the stimuli, despite their nonmnemonic visuospatial deficits and profound explicit memory impairment for the test stimuli. Transfer of learning to similar but new stimuli was not evident in either the KS or young healthy control subjects; learning occurred only for the specific items presented. The persistence of learning beyond the life of the percept, which was independent of declarative features (such as item recall), suggests that perceptual learning and memory reflects an intact cognitive memory process in KS. This process is likely mediated by posterior cortical networks relatively unaffected in KS and that are independent of the hippocampal–diencephalic declarative memory system.
Redistricting, Candidate Entry, and the Politics of Nineteenth‐Century U.S. House Elections
Authors: Carson Jamie L. , Engstrom Erik J. , Roberts Jason M.
Published: March 2006

The effects of redistricting on candidate entry patterns in contemporary House races has received growing attention in the scholarly literature, yet virtually no consideration has been given to this question in the context of historical elections. This is unfortunate as the wider variation in congressional redistricting during the nineteenth century gives us increased leverage in terms of understanding strategic candidate behavior. Utilizing a new dataset of candidate quality for nineteenth‐century House races, we examine whether candidates with prior electoral experience are more likely to run in districts that are altered during the redistricting process, and provide an account of how differences in the prevalence of redistricting may affect strategic entry decisions of politicians. Our results suggest that entry decisions and electoral outcomes are affected by redistricting in this era. Moreover, our analysis provides an opportunity to use history to test contemporary theories of congressional elections in a broader context.
States as Policy Laboratories: Emulating Success in the Children's Health Insurance Program
Authors: Volden Craig
Published: March 2006

This article illustrates the use of the directed dyad‐year event history analysis to study policy diffusion, with an application to policy changes in the Children's Health Insurance Program from 1998 to 2001. This analysis reveals strong evidence that states with successful policies are more likely to be emulated than are those with failing policies. Evidence of success is especially relevant for policy changes that lower program costs rather than those raising costs, and for changes made by legislatures rather than by administrative agencies. Moreover, this study reveals policy diffusion based on political, demographic, and budgetary similarities across states, rather than simply geographic proximity.
Building Reputation: Why Governments Fight Some Separatists but Not Others
Authors: Walter Barbara F.
Published: March 2006

This article attempts to show that future players and future stakes—two factors generally ignored by political scientists—strongly influence government decisions to cooperate or fight at least against ethnic minorities seeking self‐determination. Data on all separatist movements between 1956 and 2002 reveals that governments are significantly less likely to accommodate one challenge if the number of ethnic groups in a country and the combined value of the land that may come under dispute in the future is high. Governments that refused to accommodate one challenger were also significantly less likely to face a second or third challenge down the road. This provides some of the first systematic evidence that governments invest in reputation building a least in the domain of domestic ethnic relations.
The Institutional Context of Tolerance for Ethnic Minorities: A Comparative, Multilevel Analysis of Western Europe
Authors: Weldon Steven A.
Published: March 2006

Drawing on recent insights in the nationalism and citizenship regime literatures, this article develops a macrotheoretical framework for understanding cross‐national variations in tolerance of ethnic minorities. Specifically, it tests the hypothesis that the degree to which the dominant ethnic tradition or culture is institutionalized in the laws and policies of a nation‐state affects citizen tolerance of ethnic minorities. Employing a multilevel regression model, it systematically tests the framework, as well as competing individual and country‐level explanations, for all member states of the European Union in 1997. Results confirm a strong relationship between the laws governing the acquisition and expression of citizenship, that is, citizenship regime type, and individual tolerance judgments. Moreover, citizenship regime type has a strong mediating effect on three individual‐level variables previously shown to predict tolerance: ingroup national identity, political ideology, and satisfaction with democracy.
Beyond Welfare: Framing and the Racialization of White Opinion on Social Security
Authors: Winter Nicholas J. G.
Published: March 2006

In this article I argue that the framing of Social Security in political discourse has associated it symbolically with race. The linkages are subtle and symbolic, and they serve to associate Social Security with whiteness in a mirror image of the association of welfare with blackness. In turn, these associations have racialized white opinion on the program. After discussing the theoretical mechanism by which issue frames can unconsciously associate policies with citizens' racial predispositions, I review the frames surrounding Social Security. Then, drawing on two decades of nationally representative survey data, I demonstrate the racialization of opinion among whites. Using a variety of measures of racial predispositions, I find that racially conservative whites feel more positively about Social Security than do racial liberals. I conclude by considering the implications of these findings for our understanding of racialized politics and for the connections between race, whiteness, and contemporary American politics.
The “Race Card” Revisited: Assessing Racial Priming in Policy Contests
Authors: Huber Gregory A. , Lapinski John S.
Published: March 2006

In The Race Card (2001), Mendelberg finds support for her theory that implicit racial appeals, but not explicit ones, prime racial resentment in opinion formation. She argues that citizens reject explicit appeals, rendering them ineffective, because they violate widespread egalitarian norms. Mendelberg's innovative research, however, suffers from several limitations. We remedy these deficiencies using two randomized experiments with over 6,300 respondents. We confirm that individuals do tend to reject explicit appeals outright, but find that implicit appeals are no more effective than explicit ones in priming racial resentment in opinion formation. In accounting for the differences between previous research and our own, we show that education moderates both the accessibility of racial predispositions and message acceptance. This suggests that the necessary assumptions of Mendelberg's theory hold only for different and exclusive subsets of the general population.
Changing Sides or Changing Minds? Party Identification and Policy Preferences in the American Electorate
Authors: Carsey Thomas M. , Layman Geoffrey C.
Published: March 2006

Scholars have long debated the individual‐level relationship between partisanship and policy preferences. We argue that partisanship and issue attitudes cause changes in each other, but the pattern of influence varies systematically. Issue‐based change in party identification should occur among individuals who are aware of party differences on an issue and find that issue to be salient. Individuals who are aware of party differences, but do not attach importance to the issue, should evidence party‐based issue change. Those lacking awareness of party differences on an issue should show neither effect. We test our account by examining individuals' party identifications and their attitudes on abortion, government spending and provision of services, and government help for African Americans using the 1992‐94‐96 National Election Study panel study, finding strong support for our argument. We discuss the implications of our findings both for the microlevel study of party identification and the macrolevel analysis of partisan change.
Taking It to the Next Level: The Elevation of District Court Judges to the U.S. Courts of Appeals
Authors: Savchak Elisha Carol , Hansford Thomas G. , Songer Donald R. , Manning Kenneth L. , Carp Robert A.
Published: March 2006

We address an important aspect of judicial careers: the elevation of judges from the U.S. District Courts to the Courts of Appeals. We argue that the likelihood of a judge being elevated is a function of informational cues and signals regarding the nature of the judge and the judge's compatibility with presidential preferences. We also expect norms involving the intersection between geography and Senate politics to affect a judge's elevation chances. Using data on district court judges appointed between 1946 and 1995, we find that the likelihood of a judge being elevated is a function of the judge's ideological compatibility with the president, the judge's previous ABA rating, and Senate norms involving state “ownership” of appeals court seats. Blunt indicators of policy preferences trump direct signals when presidents decide whom to elevate, leaving judges little control over their career prospects and thus less incentive to slant their decisions in the direction of the president's preferences.
Dimensions of Politics in the European Parliament
Authors: Hix Simon , Noury Abdul , Roland Gérard
Published: March 2006

We investigate the dimensionality of politics in the European Parliament by applying a scaling method to all roll‐call votes between 1979 and 2001 in the European Parliament. Contrary to most existing studies using these methods, we are able to interpret the substantive content of the observed dimensions using exogenous measures of national party policy positions. We find that the main dimension of politics in the European Union's only elected institution is the classic left‐right dimension found in domestic politics. A second dimension is also present, although to a lesser extent, which captures government‐opposition conflicts as well as national and European party positions on European integration.
Dependence of Grain Shape and Growth on PT Content in PbO‐Excess PMN–PT
Authors: Seo Chang Eui , Yoon Duk Yong , Wallace Jay S. , Blendell John E.
Published: March 2006

When Pb(Mg1/3Nb2/3)O3 (PMN) with 40 wt% excess PbO is sintered at 1050°C, the grains grow normally and have flat {100} surface segments with round edges. As PbTiO3 (PT) is added up to 8 mol%, the grain growth is still nearly normal, characterized by time invariant normalized size distributions, but the grain edges become more sharply curved. This normal growth behavior is consistent with relatively small surface step free energy as indicated by the round grain edges. As the PT content is increased above 10–35 mol%, the grain edges become sharp and abnormal grain growth occurs. This is consistent with the step free energy increasing with the PT content as indicated by the sharpening grain edges.
Pamphlets and Body‐Related Metaphors in Thomas Nashe's Pierce Penilesse and Strange Newes
Authors: Chen Chloe
Published: March 2006

This essay was runner‐up in the 2005 Literature Compass Graduate Essay Prize, Renaissance Section.

This essay explores how Thomas Nashe's Pierce Penilesse and Strange Newes describe pamphlet culture in bodily terms. Firstly, the writing of pamphlets can be understood as a type of childbirth, with the book serving as a substitute for the physical presence and the assumed voices of the author. Next, pamphlets can be considered as having to remain financially viable; if they are not, they will die. To keep the book alive, the pen must feed. Its source of food can be the rich material Nashe finds in observing fellow Londoners, or even other textual works. Nashe shows how this may be done when he performs an act of cannibalism on Gabriel Harvey's Foure Letters with his own Strange Newes. Lastly this essay compares Nashe's conception of the printing industry with Bakhtin's notion of the Rabelaisian belly as a centre of life, death, nourishment and excretion. While Nashe represents urination as a creative act, defecation becomes a metaphor for the indifferent writings sold by printers to the public. So does he regard the pamphlet industry as an ailing body which can no longer produce works of literary brilliance and intellectual substance.
In Such a State of Ink: Adolescents in the Novels of Charles Dickens
Authors: Welburn Elizabeth
Published: March 2006

This essay won the 2005 Literature Compass Graduate Essay Prize, Victorian Section.

Although Charles Dickens is known for illuminating the social issues of his time with his portrayals of children, his adolescent characters have been largely neglected by critics. Since the concept of adolescence arguably emerged for the first time in Victorian England, this article identifies the adolescents in Dickens's novels and examines their characterization in light of their historical context. In particular, this article explores Dickens's attitudes toward the political efficacy of youth and the nature of healthy personal development.