227 resultados para 3899
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Introduction: Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMPs), play key roles in osteoarthritis (OA) development. The aim of the present study was to investigate if cross-talk between subchondral bone osteoblasts (SBOs) and articular cartilage chondrocytes (ACCs) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13, and also to test the possible involvement of mitogen activated protein kinase (MAPK) signaling pathway during this process. Methods: ACCs and SBOs were isolated from normal and OA patients. An in vitro co-culture model was developed to study the regulation of ADAMTS and MMPs under normal and OA joint cross-talk conditions. MAPK-ERK inhibitor, PD98059 was applied to delineate the involvement of specific pathway during this interaction process. Results: Indirect co-culture of OA SBOs with normal ACCs resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3 and MMP-9 in ACCs, whereas co-culture of OA ACCs led to increased MMP-1 and MMP-2 expression in normal SBOs. The upregulation of ADAMTS and MMPs under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway and the addition of the MAPK-ERK inhibitor, PD98059, reversed the overexpression of ADAMTS and MMPs in co-cultures. Conclusion: In summary, we believe, these results add to the evidence that in human OA, altered bi-directional signals transmitted between SBOs and ACCs significantly impacts the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMPs. Furthermore, we have demonstrated for the first time that this altered cross-talk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.
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Objective. The Effective Consumer Scale (EC-17) comprises 17 items measuring the main skills and behaviors people need to effectively manage their healthcare. We tested the responsiveness of the EC-17. Methods. Participants, in 2 waves of a 6-week Arthritis Self-Management Program (ASMP) from Arthritis Ireland, received a questionnaire at the first and last week of the weekly ASMP. The questionnaire included the EC-17 and 10 other measures for arthritis. Deficits, mean change, and standard deviations were calculated at baseline and Week 6. The EC-17 scores were compared to the Arthritis Self-Efficacy (ASE) and Patient Activation Measure (PAM) scales. Results were presented at OMERACT 9. Results. There is some overlap between the EC-17 and the ASE and PAM; however, most items of greatest deficit in the EC-17 are not covered by those scales. In 327 participants representing both intervention waves (2006 and 2007), the EC-17 was more efficient than the ASE but less efficient than the PAM for detecting improvements after the ASMP, and was moderately correlated with the PAM. Conclusion. The EC-17 appears to measure different skills and attributes than the ASE and PAM. Discussions with participants at OMERACT 9 agreed that it is worthwhile to measure the skills and attributes of an effective consumer, and supported the development of an intervention (such as proposed online decision aids) that would include education in the categories in the EC-17.
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This good practice report, commissioned by the ALTC, provides a summative evaluation of useful outcomes and good practices from ALTC projects and fellowships on curriculum renewal. The report contains: -a summative evaluation of the good practices and key outcomes for teaching and learning from completed ALTC projects and fellowships -a literature review of the good practices and key outcomes for teaching and learning from national and international research -the proposed outcomes and resources for teaching and learning which will be produced by current incomplete ALTC projects and fellowships -identifies areas in which further work or development are appropriate.
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Objective. Unconfirmed reports describe association of ankylosing spondylitis (AS) with several candidate genes including ANKH. Cellular export of inorganic pyrophosphate is regulated by the ANK protein, and mutant mice (ank/ank), which have a premature stop codon in the 3′ end of the ank gene, develop severe ankylosis. We tested the association between single-nucleotide polymorphisms (SNP) in these genes and susceptibility to AS in a population of patients with AS. We investigated the role of these genes in terms of functional (BASFI) and metrological (BASMI) measures, and the association with radiological severity (mSASSS). Methods. Our study was conducted on 355 patients with AS and 95 ethnically matched healthy controls. AS was defined according to the modified New York criteria. Four SNP in ANKH (rs27356, rs26307, rs25957, and rs28006) were genotyped. Association analysis was performed using Cochrane-Armitage and linear regression tests for dichotomous and quantitative variables. Analyses of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASFI, and mSASSS were controlled for sex and disease duration. Results. None of the 4 markers showed significant single-locus disease associations (p > 0.05), suggesting that ANKH was not a major determinant of AS susceptibility in our population. No association was observed between these SNP and age at symptom onset, BASDAI, BASFI, BASMI, or mSASSS. Conclusion. These results confirm data in white Europeans that ANKH is probably not a major determinant of susceptibility to AS. ANKH polymorphisms do not markedly influence AS disease severity, as measured by BASMI and mSASSS. The Journal of Rheumatology
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The International Genetics of Ankylosing Spondylitis (IGAS) meeting was held in Houston, Texas, July 25, 2009. Sixteen investigators from Asia, Australia, Europe, and North and South America presented the status of their respective cohorts of patients with ankylosing spondylitis (AS). They also reviewed a proposal to examine their patients by single-nucleotide polymorphism (SNP) genotyping on an Illumina Infinium microarray SNP genotyping chip in a case-control cohort exceeding 12,000 samples. This chip will type 200,000 SNP selected from the most strongly associated variants identified in genome-wide association studies of inflammatory diseases, including inflammatory bowel disease, psoriasis, and ankylosing spondylitis.
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A joint meeting was held in July 2009 in Houston, Texas, of members of the Spondyloarthritis Research and Therapy Network (SPARTAN), founded in 2003 to promote research, education, and treatment of ankylosing spondylitis (AS) and related forms of spondyloarthritis (SpA), and members of International Genetics of AS (IGAS), founded in 2003 to encourage and coordinate studies internationally in the genetics of AS. The general topic was the genetic basis of SpA, with presentations on the future of human genetic studies; microbes, SpA, and innate immunity; susceptibility of AS to the major histocompatibility complex (MHC) and non-MHC; and individual discussions of the genetics of psoriasis and psoriatic arthritis, uveitis, inflammatory bowel disease, and enteropathic arthritis. Summaries of those discussions are presented.
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