bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractGlutaric 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.