461 research outputs found

    Future therapeutic targets in rheumatoid arthritis?

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    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

    Fatty Acid Binding Protein 1 Is Related with Development of Aspirin-Exacerbated Respiratory Disease

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    BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA). METHODOLOGY/PRINCIPAL FINDINGS: Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS). Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1) in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots) or down-regulated in the nasal polyps of patients with AERD (n = 5) compared to those with ATA (n = 8). LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045). FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps. CONCLUSIONS/SIGNIFICANCE: Our results indicate that alterations in 15 proteins, including FABP1, may be related to the development of AERD

    Social participation reduces depressive symptoms among older adults: An 18-year longitudinal analysis in Taiwan

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    <p>Abstract</p> <p>Background</p> <p>Relatively little empirical attention has focused on the association between social participation and depressive symptoms amongst older adults in Asian nations, where persons over the age of 65 represent a rapidly growing segment of the population. This study explores the dynamic relationship between participation in social activities and trajectories of depressive symptomatology among older Taiwanese adults surveyed over 18 years.</p> <p>Methods</p> <p>Data are from a nationally representative sample of 1,388 adults aged 60-64 first surveyed in 1989 and followed over an 18-year time period for a total of six waves. Individual involvement in social activities was categorized into continuous participation, ceased participation before age 70, initiating participation in older adulthood, never participated, and dropped out before age 70. Two domains of depressive symptoms--negative affect and lack of positive affect--were measured using a 10-item version of the Center for Epidemiologic Studies-Depression Scale.</p> <p>Results</p> <p>Analyses using growth curve modeling showed that continuously participating or initiating participation in social activities later life is significantly associated with fewer depressive symptoms among older Taiwanese adults, even after controlling for the confounding effects of aging, individual demographic differences, and health status.</p> <p>Conclusions</p> <p>These findings suggest that maintaining or initiating social participation in later life benefits the mental health of older adults. Facilitating social activities among older adults is a promising direction for programs intended to promote mental health and successful aging among older adults in Taiwan.</p

    FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

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    A single nucleotide polymorphism in the gene for FGFR4 (−Arg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P=0.023 and AJCC, P=0.046), presence of microulceration (P=0.009), tumour vascularity (P=0.001), metastases (P=0.025), number of primary tumours (P=0.022), overall survival (P=0.047) and disease-free survival (P=0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P=0.004) and by Breslow in mm (P=0.02)) and the tumour subtype nodular melanoma (P=0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma

    Efficacies of the new Paclitaxel-eluting Coroflex Please™ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please™ and Taxus™ (ECO-PLEASANT) trial: study rationale and design

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    <p>Abstract</p> <p>Background</p> <p>Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1<sup>st </sup>generation paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner.</p> <p>Methods</p> <p>In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.</p> <p>Discussion</p> <p>The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number, NCT00699543.</p
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