bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrazolo[3,4‐d]pyrimidine Derivatives as COX‐2 Selective Inhibitors: Synthesis and Molecular Modelling Studies
Authors: Raffa Demetrio , Maggio Benedetta , Plescia Fabiana , Cascioferro Stella , Raimondi Maria Valeria , Plescia Salvatore , Cusimano Maria Grazia 
Published: May 2009

AbstractThe pyrazolo[3,4‐d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti‐inflammatory activity of 5‐benzamido‐pyrazolo[3,4‐d]pyrimidin‐4‐one derivatives and considering the easy synthesis of this class of compounds, a set of new 5‐benzamido‐1H‐pyrazolo[3,4‐d]pyrimidin‐4‐ones has been prepared in 42‐80% yields by reacting 5‐aminopyrazole‐4(N‐benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a–d, and 11a, b revealed a superior inhibitory profile against COX‐2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological results.
Synthesis and Antibacterial Activity of a New Series of 3‐[3‐(Substituted Phenyl)‐1‐Isonicotinoyl‐1H‐Pyrazol‐5‐yl]‐2H‐Chromen‐2‐one Derivatives
Authors: Aragade Prashant , Maddi Veeresh , Khode Suresh , Palkar Mahesh , Ronad Pradeepkumar , Mamledesai Shivalingarao , Satyanarayana Darbhamulla 
Published: May 2009

AbstractA novel series of 3‐[3‐(substituted phenyl)‐1‐isonicotinoyl‐1H‐pyrazol‐5‐yl]‐2H‐chromen‐2‐one derivatives 4a–k have been synthesized by the reaction of 3‐[2,3‐dibromo‐3‐(substituted phenyl) propanoyl]‐2H‐chromen‐2‐one 3a–k and isonicotinic acid hydrazide in the presence of triethylamine in absolute ethanol, characterized by spectral data and screened for their in‐vitro antibacterial activity against Gram‐positive and Gram‐negative bacteria. Among the series, compounds 4e, 4i, and 4k displayed an encouraging antibacterial activity profile as compared to the reference drug ampicillin against tested bacterial strains.
Generation and Evaluation of a Homology Model of PfGSK‐3
Authors: Kruggel Sebastian , Lemcke Thomas 
Published: May 2009

AbstractPlasmodial GSK‐3 is a potential new target for malaria therapy. For a structure‐based design project, the three‐dimensional information of the designated target is needed. Unfortunately, experimental structure data for plasmodial GSK‐3 is not yet available. Homology building can be used to generate such three‐dimensional structure data using structure information of a homologous protein. GSK‐3 possesses a very flexible ATP‐binding site, a fact reflected in the variety of X‐ray structures of the human GSK‐3β which are deposited in the protein data base and are crystallized with different ligands. We used ten different HsGSK‐3β templates for the model building of plasmodial GSK‐3 and generated 200 models for each template with different modeling protocols. The quality of the models was evaluated with different tools. The results of these evaluations were used to calculate a rank‐by‐rank consensus score. The top models of this were used to compile an ensemble of PfGSK‐3 models that reflect the flexibility of the ATP‐binding site and that will be used for the structure‐based design of potential ATP‐binding site inhibitors of PfGSK‐3.
Autoimmune regulator controls T cell help for pathogenetic autoantibody production in collagen‐induced arthritis
Authors: Campbell Ian K. , Kinkel Sarah A. , Drake Sarah F. , Nieuwenhuijze Annemarie Van , Hubert François‐Xavier , Tarlinton David M. , Heath William R. , Scott Hamish S. , Wicks Ian P. 
Published: May 2009

AbstractObjectiveAutoimmune regulator (Aire) promotes the ectopic expression of tissue‐restricted antigens in medullary thymic epithelial cells (mTECs), leading to negative selection of autoreactive T cells. This study was undertaken to determine whether loss of central tolerance renders Aire‐deficient (Aire−/−) mice more susceptible to the induction of autoimmune arthritis.MethodsMedullary TECs were isolated from Aire−/− and wild‐type C57BL/6 mice for gene expression analysis. Collagen‐induced arthritis (CIA) was elicited by injection of chick type II collagen (CII) in adjuvant. Cellular and humoral immune responses to CII were evaluated. Chimeric mice were created by reconstituting lymphocyte‐deficient mice with either Aire−/− or wild‐type CD4 T cells and wild‐type B cells.ResultsWild‐type, but not Aire−/−, mTECs expressed the CII gene Col2a1. Aire−/− mice developed more rapid and severe CIA, showing elevated serum anti‐CII IgG levels, with earlier switching to arthritogenic IgG subclasses. No evidence was found of enhanced T cell responsiveness to CII in Aire−/− mice; however, Aire−/− CD4 T cells were more efficient at stimulating wild‐type B cells to produce anti‐CII IgG following immunization of chimeric mice with CII.ConclusionOur findings indicate that Aire‐dependent expression of CII occurs in mTECs, implying that there is central tolerance to self antigens found in articular cartilage. Reduced central tolerance to CII in Aire−/− mice manifests as increased CD4 T cell help to B cells for cross‐reactive autoantibody production and enhanced CIA. Aire and central tolerance help prevent cross‐reactive autoimmune responses to CII initiated by environmental stimuli and limit spontaneous autoimmunity.
Relationships between the fibromyalgia impact questionnaire, tender point count, and muscle strength in female patients with fibromyalgia: A cohort study
Authors: Henriksen Marius , Lund Hans , Christensen Robin , Jespersen Anders , Dreyer Lene , Bennett Robert M. , Danneskiold‐SamsØe Bente , Bliddal Henning 
Published: May 2009

AbstractObjectiveTo test the hypothesis that fibromyalgia (FM) patients with reduced lower extremity strength are more symptomatic and tender than FM patients with normal muscle strength.MethodsA total of 840 FM patients and 122 healthy subjects were evaluated between 1998 and 2005. All of the patients completed version 1 of the Fibromyalgia Impact Questionnaire (FIQ) and were assessed for tender points and knee muscle strength. All subjects underwent bilateral isokinetic knee muscle strength testing in flexion and extension. Normative knee muscle strength values were calculated from the healthy subjects, and the FM cohort was divided in 2 groups: 1) patients with normal muscle strength and 2) patients with low muscle strength (2 SDs below normal). The clinical characteristics of these 2 groups were compared.ResultsSignificantly reduced knee muscle strength was found in 52% of the patients. There were no clinically significant differences between patients with low versus normal muscle strength. There were no clinically significant correlations between total FIQ score, tender point count, and muscle strength. Only 4.6% of the FIQ scores and 5.1% of the tender point counts were explained by muscle strength.ConclusionSignificantly reduced knee muscle strength was found in more than half of the patients. Patients with subnormal muscle strength were not more symptomatic or tender than patients with normal muscle strength. There were no clinically significant correlations between FIQ, tender point count, and muscle strength; therefore, reduced knee muscle strength appears to be a common objective abnormality in FM that is independent of measurements of disease activity. The implication of this finding in regard to the clinical assessment of FM needs further study.
Is adiposity an under‐recognized risk factor for tendinopathy? A systematic review
Authors: Gaida James E. , Ashe Maureen C. , Bass Shona L. , Cook Jill L. 
Published: May 2009

AbstractObjectiveTendon injuries have been reported to occur more frequently in individuals with increased adiposity. Treatment also appears to have poorer outcomes among these individuals. Our objective was to examine the extent and consistency of associations between adiposity and tendinopathy.MethodsA systematic review of observational studies was conducted. Eight electronic databases were searched (Allied and Complementary Medicine, Biological Abstracts, CINAHL, Current Contents, EMBase, Medline, SPORTDiscus, and Web of Science) and citation tracking was performed on included reports. Studies were included if they compared adiposity between subjects with and without tendon injury or examined adiposity as a predictor of conservative treatment success.ResultsFour longitudinal cohorts, 14 cross‐sectional studies, 8 case–control studies, and 2 interventional studies (28 in total) met the inclusion criteria, providing a total of 19,949 individuals. Forty‐two subpopulations were identified, 18 of which showed elevated adiposity to be associated with tendon injury (43%). Sensitivity analyses indicated a clustering of positive findings among studies that included clinical patients (81% positive) and among case–control studies (77% positive).ConclusionElevated adiposity is frequently associated with tendon injury. Published reports suggest that elevated adiposity is a risk factor for tendon injury, although this association appears to vary depending on aspects of study design and measurement. Adiposity is of particular interest in tendon research because, unlike a number of other reported risk factors for tendon injury, it is somewhat preventable and modifiable. Further research is required to determine if reducing adiposity will reduce the risk of tendon injury or improve the results of treatment.
Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus
Authors: Bachen Elizabeth A. , Chesney Margaret A. , Criswell Lindsey A. 
Published: May 2009

AbstractObjectiveTo examine the lifetime prevalence of mood and anxiety disorders in patients with systemic lupus erythematosus (SLE). Demographic and disease‐related variables were examined for association with lifetime major depressive disorder (MDD) and the presence of any mood or anxiety disorder.MethodsThree hundred twenty‐six white women with SLE completed the Composite International Diagnostic Interview and the Systemic Lupus Activity Questionnaire, a self‐report measure of SLE disease activity. The binomial test was used to compare the prevalence of psychiatric diagnoses in patients with SLE with a population sample of white women.ResultsSixty‐five percent of the participants received a lifetime mood or anxiety diagnosis. MDD (47%), specific phobia (24%), panic disorder (16%), obsessive‐compulsive disorder (9%), and bipolar I disorder (6%) were more common among patients with SLE than among other white women (P = 0.00009 for specific phobia; for all other values P = 0.00001). Although most patients with histories of mood disorders reported their psychiatric symptoms to a medical provider, a substantial number of patients with anxiety disorders did not. Self‐reported disease activity was associated with a lifetime history of MDD (P = 0.001) and presence of a mood or anxiety disorder (P = 0.001), after controlling for demographic and clinical characteristics.ConclusionSeveral mood and anxiety disorders were more common in women with SLE compared with the general population, and disease activity may contribute to this higher risk. Brief self‐report questionnaires may help providers identify patients with these conditions, particularly when patients are reluctant to disclose their symptoms.
Time course and nature of brain atrophy in the MRL mouse model of central nervous system lupus
Authors: Sled John G. , Spring Shoshana , van Eede Matthijs , Lerch Jason P. , Ullal Sangeeta , Sakic Boris 
Published: May 2009

AbstractObjectiveSimilar to patients with systemic lupus erythematosus, autoimmune MRL/lpr mice spontaneously develop behavioral deficits and pathologic changes in the brain. Given that the disease‐associated brain atrophy in this model is not well understood, the present study was undertaken to determine the time course of morphometric changes in major brain structures of autoimmune MRL/lpr mice.MethodsComputerized planimetry and high‐resolution magnetic resonance imaging (MRI) were used to compare the areas and volumes of brain structures in cohorts of mice that differ in severity of lupus‐like disease.ResultsA thinner cerebral cortex and smaller cerebellum were observed in the MRL/lpr substrain, even before severe autoimmunity developed. With progression of the disease, the brain area of coronal sections became smaller and the growth of the hippocampus was retarded, which likely contributed to the increase in the ventricle area:brain area ratio. MRI revealed reduced volume across different brain regions, with the structures in the vicinity of the ventricular system particularly affected. The superior colliculus, periaqueductal gray matter, pons, and midbrain were among the regions most affected, whereas the volumes of the parietal‐temporal lobe, parts of the cerebellum, and lateral ventricles in autoimmune MRL/lpr mice were comparable with values in congenic controls.ConclusionThese results suggest that morphologic alterations in the brains of MRL/lpr mice are a consequence of several factors, including spontaneous development of lupus‐like disease. A periventricular pattern of parenchymal damage is consistent with the cerebrospinal fluid neurotoxicity, limbic system pathologic features, and deficits in emotional reactivity previously documented in this model.
Large‐scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand
Authors: Evangelou Evangelos , Chapman Kay , Meulenbelt Ingrid , Karassa Fotini B. , Loughlin John , Carr Andrew , Doherty Michael , Doherty Sally , Gómez‐Reino Juan J. , Gonzalez Antonio , Halldorsson Bjarni V. , Hauksson Valdimar B. , Hofman Albert , Hart Deborah J. , Ikegawa Shiro , Ingvarsson Thorvaldur , Jiang Qing , Jonsdottir Ingileif , Jonsson Helgi , Kerkhof Hanneke J. M. , Kloppenburg Margreet , Lane Nancy E. , Li Jia , Lories Rik J. , van Meurs Joyce B. J. , Näkki Annu , Nevitt Michael C. , Rodriguez‐Lopez Julio , Shi Dongquan , Slagboom P. Eline , Stefansson Kari , Tsezou Aspasia , Wallis Gillian A. , Watson Christopher M. , Spector Tim D. , Uitterlinden Andre G. , Valdes Ana M. , Ioannidis John P. A. 
Published: May 2009

AbstractObjectiveGDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large‐scale meta‐analysis of individual‐level data.MethodsFourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex‐specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed‐effects and random‐effects models for allele‐based effects, and also for haplotype effects for FRZB.ResultsA significant random‐effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09–1.22]) (P = 9.4 × 10−7), with no significant between‐study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between‐study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P = 0.016]) or absent (for OA of the hand [P = 0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P = 0.019).ConclusionEvidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.
Risks of rheumatic diseases in first‐ and second‐generation immigrants in Sweden: A nationwide followup study
Authors: Li Xinjun , Sundquist Jan , Sundquist Kristina 
Published: May 2009

AbstractObjectiveTo examine whether there is an association between country of birth in first‐generation immigrants and first hospitalization for a rheumatic disease, and to study whether any such association remains in second‐generation immigrants.MethodsIn this followup study, the Swedish MigMed database at the Karolinska Institute in Stockholm was used to identify all primary hospital diagnoses of rheumatic diseases in first‐ and second‐generation immigrants in Sweden between January 1, 1964 and December 31, 2004. Incidence ratios, standardized with regard to age, geographic region, and socioeconomic status, were estimated by sex in first‐ and second‐generation immigrants.ResultsFirst‐generation immigrants from Iraq had a higher risk of rheumatoid arthritis than did subjects in the native‐born Swede reference group, and the risk of systemic lupus erythematosus was increased in immigrants from Iraq and Africa; these raised risks persisted in the second generation. The lower risk of rheumatoid arthritis in some first‐generation immigrants disappeared in the second generation. In groups of second‐generation immigrants, the risk of ankylosing spondylitis was similar to the risk in the corresponding parental groups. Polish‐born immigrants and second‐generation Yugoslavs and Russians showed a significantly increased risk of systemic sclerosis. The raised risk of systemic sclerosis did not persist in the second generation, but was clustered in groups involved in certain blue collar occupations.ConclusionCountry of birth affected the risk of rheumatic disease. These findings indicate that both genetic and environmental factors are involved in the etiology of specific rheumatic diseases.
Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree
Authors: Saulsbury Frank T. , Wouters Carine H. , Martin Tammy M. , Austin Carrie R. , Doyle Trudy M. , Goodwin Kelly A. , Rosé Carlos D. 
Published: May 2009

AbstractPediatric granulomatous arthritis (PGA) has been associated with 12 different substitutions in the NOD2 gene thus far. We report a case of PGA in a 6‐year‐old girl with the NOD2 E383K gene substitution. Genotype analysis of the patient's family members revealed that her affected paternal aunt, as well as her asymptomatic father and 3 younger siblings, were heterozygous for the E383K substitution. The patient's mother did not have a NOD2 mutation. This is the first report of a pedigree in which 4 asymptomatic members carry the E383K substitution in NOD2, as well as the first observation of an asymptomatic carrier state for any of the NOD2 “Blau mutations.”
Anaerobic‐to‐aerobic power ratio in children with juvenile idiopathic arthritis
Authors: van Brussel Marco , van Doren Lieke , Timmons Brian W. , Obeid Joyce , van der Net Janjaap , Helders Paul J. M. , Takken Tim 
Published: May 2009

AbstractObjectiveTo examine the anaerobic‐to‐aerobic power ratio in children with juvenile idiopathic arthritis (JIA) compared with healthy peers.MethodsSixty‐two patients with JIA (mean ± SD age 11.9 ± 2.1 years, range 7.2–15.9 years) with varying severity of disease and 50 healthy children (mean ± SD age 12.1 ± 2.1, range 8.4–15.9 years) participated in this study. Anaerobic power was measured using the Wingate Anaerobic Exercise Test. Aerobic power was measured using a cardiopulmonary exercise test. The power ratio was calculated as the ratio between the anaerobic mechanical power and aerobic mechanical power in watts.ResultsMean ± SD anaerobic‐to‐aerobic power ratio and peak anaerobic‐to‐aerobic ratios in children with JIA were 1.98 ± 0.51 and 3.28 ± 1.15, respectively. Compared with healthy children these differences were not statistically significant (P = 0.52 and P = 0.99, respectively). The differences in these ratios were not statistically significant when corrected for age, height, and body mass. Statistical analyses showed no significant difference between disease‐onset types of JIA for mean anaerobic‐to‐aerobic power ratio and peak anaerobic‐to‐aerobic ratio, respectively. Furthermore, there was no significant difference in the development of the power ratios between children with JIA and healthy controls, or between girls and boys.ConclusionThis cross‐sectional study suggests that the development of the anaerobic‐to‐aerobic power ratio is not statistically different in children with JIA compared with healthy peers. Exercise training of the anaerobic capacity through interval training, along with aerobic exercise training, seems warranted in the exercise therapy programs of children with JIA.
Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: A single center study of a cohort of 71 subjects
Authors: Colina Matteo , Govoni Marcello , Orzincolo Carlo , Trotta Francesco 
Published: May 2009

AbstractObjectiveTo assess the basic features and outcomes of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.MethodsWe identified all patients seen in our unit between 1990 and 2008 diagnosed according to the proposed inclusion criteria with SAPHO syndrome, who had a followup of at least 2 years.ResultsSeventy‐one patients (48 women, 23 men) with SAPHO syndrome were identified. The median disease duration at the end of followup was 10 years (interquartile range [IQR] 7–15 years), and the median followup duration was 11 years (IQR 6–11.5 years). Six patients were diagnosed with Crohn's disease. Fourteen patients had never had cutaneous involvement, but 8 patients presented >1 skin manifestation. Nine patients (13%) presented a limited (<6 months) monophasic disease course, 25 cases (35%) had a relapsing–remitting course, and 37 patients (52%) had an acute painful phase with a prolonged course lasting >6 months. A total of 4% of the patients were HLA–B27 positive. Female sex (odds ratio [OR] 7.2, 95% confidence interval [95% CI] 2.2–22.9) and the presence at onset of anterior chest wall (ACW) involvement (OR 5.7, 95% CI 1.8–18.1), peripheral synovitis (P = 0.0036), skin involvement (OR 10.3, 95% CI 3.4–31.1), and high values of acute‐phase reactants (OR 7.7, 95% CI 2.7–22) were correlated with a chronic disease course and involvement of new osteoarticular sites.ConclusionA chronic course is the more common evolution of SAPHO syndrome. Female sex, elevated erythrocyte sedimentation rate and C‐reactive protein values, ACW involvement, peripheral synovitis, and skin involvement at the onset seem to be associated with a chronic course.