bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infusion of gliotoxins or a gap junction blocker in the prelimbic cortex increases alcohol preference in Wistar rats
Authors: Miguel-Hidalgo J , Shoyama Y , Wanzo V 
Published: June 2008

Abstract Postmortem research has revealed that there is a lower density of glial cells in regions of the prefrontal cortex (PFC) of uncomplicated alcoholics when compared with control subjects. Impairment of astrocyte function in the PFC may contribute to malfunction in circuits involved in emotion- and reward-related subcortical centers, heavily connected with the PFC and directly involved in the pathophysiology of addictive behaviours. The hypothesis was tested that infusion of gliotoxins known to injure astrocytes or of a gap junction blocker into the prelimbic area of the rat PFC results in increased preference for ethanol in rats exposed to free choice between water and 10% ethanol. Fluorocitric acid, L-α-aminoadipic acid (AAD) or the gap junction blocker 18-α-glycyrrhetinic acid (AGA) were bilaterally infused once into the rat prelimbic cortex and alcohol preference (ratio of 10% ethanol consumed to total liquid ingested) was measured before and after infusion. Infusion of AAD or AGA dissolved in their vehicles, but not of their vehicles alone, resulted in significant transient increase of preference for 10% ethanol. The present data suggest that impaired integrity of glial cells or the gap junctional communication between them in the rat PFC may contribute to changes in ethanol preference.
Catatonia, neuroleptics and brain damage – a case report
Authors: Chandran M , El-Shazly M 
Published: June 2008

Abstract Catatonia is a syndrome that encompasses multiple motor signs. It can be the only presenting clinical feature in a patient with underlying multiple neuropsychiatric syndromes. The authors present a case of amisulpiride-induced catatonia, further evaluation suggested neuroleptic malignant syndrome (NMS) and showed the occurrence of temporal lobe epilepsy (TLE) and underlying brain pathology with marked frontoparietal atrophy and periventricular white matter hyperintensities. The pathological substrate of catatonia and its complex association with neuropsychiatric syndromes are discussed.
Modafinil treatment of amphetamine abuse in adult ADHD
Authors: Mann N , Bitsios P 
Published: June 2008

Abstract Substance abuse is a frequent co-morbid condition of adult attention deficit hyperactivity disorder (ADHD). Treatment with conventional psychostimulants in adult ADHD with co-morbid stimulant abuse may be problematic. In this study, we report the case of a patient with adult ADHD with co-morbid amphetamine abuse who was treated successfully with the non-stimulant alertness-promoting drug modafinil. The drug resolved both the inattention/hyperactivity symptoms as well as the amphetamine abuse. Modafinil may be a suitable candidate treatment for adults with ADHD and stimulant abuse.
Risperidone-induced sexual dysfunction in a prepubertal child - a case report
Authors: Wadoo O , Chalhoub N 
Published: June 2008

Abstract We report on a child with attention deficit hyperactivity disorder and motor tics, who developed frequent penile erections during treatment with risperidone and atomoxetine. On discontinuation of risperidone, he recovered fully. Clinicians should be alert to the adverse effects of atypical antipsychotics, which are used to treat a wide variety of paediatric psychiatric disorders.
The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment
Authors: Wilffert B , Al Hadithy AFY , Sing VJ , Matroos G , Hoek HW , van Os J , Bruggeman R , Brouwers JRBJ , van Harten PN 
Published: June 2008

Abstract Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D3, serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), −1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients. One hundred and twenty-six patients under chronic antipsychotic treatment were genotyped. The assessment of TD was carried out with the abnormal involuntary movement scale (AIMS). The relationships between the carriership of the least frequent alleles and the respective orofaciolingual dyskinesia (TDof) (sum of the items 1-4 of the AIMS), limb-truncal dyskinesia (TDlt) (sum of items 5-7 of the AIMS) and TD (sum of items 1-7 of the AIMS) were analyzed with ANCOVA, comparing means with age as a covariate and stratification for carriers and non-carriers of the mutations. In addition, we conducted pre-planned t-tests to compare AIMS values of carriers of the combinations of alleles versus the corresponding non-carriers. In the study population, females with 9Ser carriership exhibited higher AIMS values than non-carriers. Male subjects with 9Ser carriership in combination with 23Ser or −1438A carriership exhibited higher AIMS values. In male patients also, the combination of 23Ser and −1438A carriership increased TD. The study clearly shows that the African-Carribean population differs from the Caucasian population with regard to the association of TD with the polymorphisms studied and suggests that the association of TD with the studied polymorphisms of the 5-HT2C and probably of the 5-HT2A receptor are the result of a changed susceptibility of the patients, independent of the action of the antipsychotics on these receptors.
Long-term effects of cannabis on oculomotor function in humans
Authors: Huestegge L , Radach R , Kunert HJ 
Published: June 2008

Abstract Cannabis is known to affect human cognitive and visuomotor skills directly after consumption. Some studies even point to rather long-lasting effects, especially after chronic tetrahydrocannabinol (THC) abuse. However, it is still unknown whether long-term effects on basic visual and oculomotor processing may exist. In the present study, the performance of 20 healthy long-term cannabis users without acute THC intoxication and 20 control subjects were examined in four basic visuomotor paradigms to search for specific long-term impairments. Subjects were asked to perform: 1) reflexive saccades to visual targets (prosaccades), including gap and overlap conditions, 2) voluntary antisaccades, 3) memory-guided saccades and 4) double-step saccades. Spatial and temporal parameters of the saccades were subsequently analysed. THC subjects exhibited a significant increase of latency in the prosaccade and antisaccade tasks, as well as prolonged saccade amplitudes in the antisaccade and memory-guided task, compared with the control subjects. The results point to substantial and specific long-term deficits in basic temporal processing of saccades and impaired visuo-spatial working memory. We suggest that these impairments are a major contributor to degraded performance of chronic users in a vital everyday task like visual search, and they might potentially also affect spatial navigation and reading.
Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression?
Authors: Ebinger M , Sievers C , Ivan D , Schneider HJ , Stalla GK 
Published: June 2008

Abstract Depression is a disease of growing incidence and economic burden worldwide. In view of increasing treatment resistance, new therapeutic approaches are urgently needed. In addition to its gonadal functions, testosterone has many effects on the central nervous system. An association between testosterone levels and depressive symptoms has been proposed. Many hormones and neurotransmitters are involved in the aetiology and the course of depression including serotonin, dopamine, noradrenaline, vasopressin and cortisol. Testosterone is known to interact with them. Preclinical data suggest that testosterone has antidepressant potential. However, the data from clinical studies have been inconsistent. This review provides a critical overview on the currently available preclinical and clinical literature and concludes with clinical recommendations.
Herpesviruses and human endogenous retroviral sequences in the cerebrospinal fluid of multiple sclerosis patients
Authors: Álvarez-Lafuente R , García-Montojo M , De Las Heras V , Domínguez-Mozo MI , Bartolome M , Benito-Martin MS , Arroyo R 
Published: June 2008

Objective To analyze the possible role of human herpesvirus (HHVs) and human endogenous retroviruses (HERVs) infection in multiple sclerosis (MS) pathogenesis. Methods A total of 92 cerebrospinal fluid (CSF) samples were collected: 48 from MS patients at the first clinically evident demyelinating event, 23 from patients with other inflammatory neurological diseases (OINDs) and 21 from patients with other non-inflammatory neurological diseases (ONINDs). Total DNA and RNA were isolated, and the prevalences and viral loads of herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), HHV-6, HERV-H and HERV-W in the CSF of MS patients and controls were evaluated using a quantitative real-time polymerase chain reaction assay. Results (i) For HSV, 1/48 (2.1%, 86 copies/ml of CSF) MS patients and 1/23 (4.3%, 115.2 copies/ml of CSF) OIND patients (a myelitis case) had HSV sequences in the CSF; (ii) for EBV, only 1/48 (2.1%, 72 copies/ml of CSF) MS patients was positive for EBV; (iii) for HHV-6, only 5/48 (10.4%) MS patients had HHV-6 genomes in their CSF (128.1 copies/ml of CSF); (iv) we did not find any positive cases for VZV, CMV, HERV-H and HERV-W among MS patients or controls; (v) no cases of co-infections were found; (vi) the whole prevalence of HHVs was 7/48 (14.6%) for MS patients and 1/44 (2.3%) for controls ( p = 0.038). Conclusion The findings described here show that HHV infection is more frequent in the CSF of MS patients than in patients with other neurological diseases; however, only HHV-6 seems to be involved in the pathogenesis of MS in a subset of patients.
Modeling the cost-effectiveness of a new treatment for MS (natalizumab) compared with current standard practice in Sweden
Authors: Kobelt G , Berg J , Lindgren P , Jonsson B , Stawiarz L , Hillert J 
Published: June 2008

Objective To estimate the cost-effectiveness of a new treatment (natalizumab) for multiple sclerosis (MS) compared with current standard therapy with disease-modifying drugs (DMDs) in Sweden. Methods A Markov model was constructed to illustrate disease progression based on functional disability (the Expanded Disability Status Scale (EDSS)). The effectiveness of natalizumab was based on a 2-year clinical trial in 942 patients (AFFIRM). The effectiveness of current DMDs was estimated from a matched sample of 512 patients in the Stockholm MS registry. Patients withdrawing from treatment were assumed to follow the disease course of 824 patients with relapsing–remitting disease at onset in the Ontario natural history cohort. Costs and utilities are based on a recent observational study in 1339 patients. All data sets were available at the patient level. Main results are presented from the societal perspective, over a 20-year time frame, in 2005 Euros (€1 = 9.25 SEK). Results In the base case, treatment with natalizumab was less expensive and more effective than treatment with current DMDs. When only healthcare costs were considered, the cost per quality-adjusted life year gained with natalizumab was €38 145. Results are sensitive only to the time horizon of the analysis and assumptions about effectiveness of natalizumab beyond the trial. Conclusions This cost-effectiveness analysis used registry data, cohort and observational studies to extrapolate the efficacy findings of natalizumab from the AFFIRM clinical trial to measure effectiveness in clinical practice. The analysis results suggest that for the population considered, natalizumab provides an additional health benefit at a similar cost to current DMDs from a societal perspective.
A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome
Authors: Faderl Stefan , Ravandi Farhad , Huang Xuelin , Garcia-Manero Guillermo , Ferrajoli Alessandra , Estrov Zeev , Borthakur Gautam , Verstovsek Srdan , Thomas Deborah A. , Kwari Monica , Kantarjian Hagop M. 
Published: June 2008

AbstractWe previously reported the feasibility of clofarabine and cytarabine combinations in AML. Questions remain as to (1) the therapeutic advantage of this combination and (2) the role of lower doses of clofarabine and cytarabine in older patients. We have conducted an adaptively randomized study of lower-dose clofarabine with or without low-dose cytarabine in previously untreated patients with AML aged 60 years and older. Patients received 30 mg/m2 clofarabine intravenously daily for 5 days with or without 20 mg/m2 cytarabine subcutaneously daily for 14 days as induction. Consolidation consisted of 3 days of clofarabine with or without 7 days of cytarabine. Seventy patients were enrolled. The median age was 71 years (range, 60-83 years). Sixteen patients received clofarabine and 54 the combination. Overall, 56% achieved complete remission (CR). CR rate was significantly higher with the combination (63% vs 31%; P = .025). Induction mortality was 19% with the combination versus 31% with clofarabine alone (P = .276). The combination showed better event-free survival (7.1 months vs 1.7 months; P = .04), but not overall survival (11.4 months vs 5.8 months; P = .1). Clofarabine plus low-dose cytarabine has a higher response rate than clofarabine alone with comparable toxicity. This trial is registered at www.clinicaltrials.gov as no. NCT00088218.
Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins
Authors: Hahn Phillip , Böse Jens , Edler Stefanie , Lengeling Andreas 
Published: June 2008

Abstract

Background
The jumonji C (JmjC) domain containing gene 6 (Jmjd6, previously known as phosphatidylserine receptor) has misleadingly been annotated to encode a transmembrane receptor for the engulfment of apoptotic cells. Given the importance of JmjC domain containing proteins in controlling a wide range of diverse biological functions, we undertook a comparative genomic analysis to gain further insights in Jmjd6 gene organisation, evolution, and protein function.

Results
We describe here a semiautomated computational pipeline to identify and annotate JmjC domain containing proteins. Using a sequence segment N-terminal of the Jmjd6 JmjC domain as query for a reciprocal BLAST search, we identified homologous sequences in 62 species across all major phyla. Retrieved Jmjd6 sequences were used to phylogenetically analyse corresponding loci and their genomic neighbourhood. This analysis let to the identification and characterisation of a bi-directional transcriptional unit compromising the Jmjd6 and 1110005A03Rik genes and to the recognition of a new, before overseen Jmjd6 exon in mammals. Using expression studies, two novel Jmjd6 splice variants were identified and validated in vivo. Analysis of the Jmjd6 neighbouring gene 1110005A03Rik revealed an incident deletion of this gene in two out of three earlier reported Jmjd6 knockout mice, which might affect previously described conflicting phenotypes. To determine potentially important residues for Jmjd6 function a structural model of the Jmjd6 protein was calculated based on sequence conservation. This approach identified a conserved double-stranded β-helix (DSBH) fold and a HxDxnH facial triad as structural motifs. Moreover, our systematic annotation in nine species identified 313 DSBH fold-containing proteins that split into 25 highly conserved subgroups.

Conclusion
We give further evidence that Jmjd6 most likely has a function as a nonheme-Fe(II)-2-oxoglutarate-dependent dioxygenase as previously suggested. Further, we provide novel insights into the evolution of Jmjd6 and other related members of the superfamily of JmjC domain containing proteins. Finally, we discuss possibilities of the involvement of Jmjd6 and 1110005A03Rik in an antagonistic biochemical pathway.
A naturally occurring omega current in a Kv3 family potassium channel from a platyhelminth
Authors: Klassen Tara L , Spencer Andrew N , Gallin Warren J 
Published: June 2008

Abstract

Background
Voltage-gated ion channels are membrane proteins containing a selective pore that allows permeable ions to transit the membrane in response to a change in the transmembrane voltage. The typical selectivity filter in potassium channels is formed by a tetrameric arrangement of the carbonyl groups of the conserved amino-acid sequence Gly-Tyr-Gly. This canonical pore is opened or closed by conformational changes that originate in the voltage sensor (S4), a transmembrane helix with a series of positively charged amino acids. This sensor moves through a gating pore formed by elements of the S1, S2 and S3 helices, across the plane of the membrane, without allowing ions to pass through the membrane at that site. Recently, synthetic mutagenesis studies in the Drosophila melanogaster Shaker channel and analysis of human disease-causing mutations in sodium channels have identified amino acid residues that are integral parts of the gating-pore; when these residues are mutated the proteins allow a non-specific cation current, known as the omega current, to pass through the gating-pore with relatively low selectivity.

Results
The N.at-K

v

3.2 potassium channel has an unusual weak inward rectifier phenotype. Several mutations of two amino acids in the voltage sensing (S4) transmembrane helix change the phenotype to a typical delayed rectifier. The inward rectifier channels (wild-type and mutant) are sensitive to 4-aminopyridine (4-AP) but not tetra-ethyl ammonium (TEA), whereas the delayed rectifier mutants are sensitive to TEA but not 4-AP. The inward rectifier channels also manifest low cation selectivity. The relative selectivity for different cations is sensitive to specific mutations in the S4 helix,

Conclusion

N.at-K

v

3.2, a naturally occurring potassium channel of the Kv3 sequence family, mediates ion permeation through a modified gating pore, not the canonical, highly selective pore typical of potassium channels. This channel has evolved to yield qualitatively different ion permeability when compared to all other members of this gene family.
Dysregulation of Adipose Glutathione Peroxidase 3 in Obesity Contributes to Local and Systemic Oxidative Stress
Authors: Lee Yun Sok , Kim A Young , Choi Jin Woo , Kim Min , Yasue Shintaro , Son Hee Jung , Masuzaki Hiroaki , Park Kyong Soo , Kim Jae Bum 
Published: June 2008

AbstractGlutathione peroxidase 3 (GPx3) accounts for the major antioxidant activity in the plasma. Here, we demonstrate that down-regulation of GPx3 in the plasma of obese subjects is associated with adipose GPx3 dysregulation, resulting from the increase of inflammatory signals and oxidative stress. Although GPx3 was abundantly expressed in kidney, lung, and adipose tissue, we observed that GPx3 expression was reduced selectively in the adipose tissue of several obese animal models as decreasing plasma GPx3 level. Adipose GPx3 expression was greatly suppressed by prooxidative conditions such as high levels of TNFα and hypoxia. In contrast, the antioxidant N-acetyl cysteine and the antidiabetic drug rosiglitazone increased adipose GPx3 expression in obese and diabetic db/db mice. Moreover, GPx3 overexpression in adipocytes improved high glucose-induced insulin resistance and attenuated inflammatory gene expression whereas GPx3 neutralization in adipocytes promoted expression of proinflammatory genes. Taken together, these data suggest that suppression of GPx3 expression in the adipose tissue of obese subjects might constitute a vicious cycle to expand local reactive oxygen species accumulation in adipose tissue potentially into systemic oxidative stress and obesity-related metabolic complications.
Active geometry control suspension system for the enhancement of vehicle stability
Authors: Lee U K , Lee S H , Han C S , Hedrick K , Català A 
Published: June 2008

The active control of suspension geometry has historically been a challenging perspective for chassis teams of worldwide automakers. Manufacturers and suppliers have offered different solutions, but few have succeeded in combining a marked improvement in handling performance, low-energy consumption, simplicity, and low cost. The new and revolutionary approach of an active geometry control suspension (AGCS) reinvents the possibilities of rear-suspension active toe control. This system employs the use of the complexity of a rear multi-link suspension, and a clever design layout to minimize the energy use. Additionally, because of an efficient control logic strategy, the vehicle-handling performance and stability are substantially improved. The system is the most successful in controlling vehicle transient situations initiated mainly by aggressive lane-change manoeuvres at medium to high speeds. This paper presents the most relevant actions of the development process of the AGCS. The use of different evaluation methods and accurate measurement equipment was crucial for optimization of the system. The methods presented combine subjective evaluations in different road conditions (icy, wet, and dry asphalt), suspension kinematics and elastokinematics characterization, and objective road measurements using dynamic wheel position measurement equipment. Finally, a comprehensive summary of the handling-test results are explained, which outline the efficiency of the system, and its influence on the active safety level of the vehicle.
Effect of an oxidation catalyst and a three-way catalyst on odorous emissions in internal combustion engines
Authors: Roy M M 
Published: June 2008

This study investigated the effect of an oxidation catalyst on odorous emissions in a direct-injection diesel engine at idling. In cold or low-temperature idling, where engines are started from cold condition at ambient temperatures, the effectiveness of the oxidation catalyst to reduce total hydrocarbons (THCs) and aldehydes is low owing to the low catalyst temperatures, and the odour reduction is insignificant. In hot or high-temperature idling, where exhaust temperatures exceed 200°C, THCs and aldehydes are reduced by more than 90 per cent and the odour reduction is more than one point, a significant odour reduction. Below a catalyst temperature of 200°C, objectionable exhaust odour appears. The gasoline engine also emits a strong exhaust odour when the catalyst condition is poor or there is a mismatch of air—fuel ratio. The effect of a three-way catalyst on the exhaust odour was investigated in a gasoline engine. In rich engine operation condition, there are more THCs, carbon monoxide (CO), and nitrogen oxides (NO x) before the catalyst. After the catalyst in this condition, the THCs, CO, and NO x are significantly reduced, but there is a very sharp and unpleasant odour of ammonia, which is produced inside the catalyst owing to the reduction of NO x.