Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
26686423 Network-assisted analysis of primary Sjögren's syndrome GWAS data in Han Chinese. 2015 Dec 21 Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder. So far, genetic research in pSS has lagged far behind and the underlying biological mechanism is unclear. Further exploring existing genome-wide association study (GWAS) data is urgently expected to uncover disease-related gene combination patterns. Herein, we conducted a network-based analysis by integrating pSS GWAS in Han Chinese with a protein-protein interactions network to identify pSS candidate genes. After module detection and evaluation, 8 dense modules covering 40 genes were obtained for further functional annotation. Additional 31 MHC genes with significant gene-level P-values (sigMHC-gene) were also remained. The combined module genes and sigMHC-genes, a total of 71 genes, were denoted as pSS candidate genes. Of these pSS candidates, 14 genes had been reported to be associated with any of pSS, RA, and SLE, including STAT4, GTF2I, HLA-DPB1, HLA-DRB1, PTTG1, HLA-DQB1, MBL2, TAP2, CFLAR, NFKBIE, HLA-DRA, APOM, HLA-DQA2 and NOTCH4. This is the first report of the network-assisted analysis for pSS GWAS data to explore combined gene patterns associated with pSS. Our study suggests that network-assisted analysis is a useful approach to gaining further insights into the biology of associated genes and providing important clues for future research into pSS etiology.
26368934 Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstr 2015 OBJECTIVE: The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS). METHODS: We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. RESULTS: We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study. CONCLUSION: This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.
27030337 [Coexistence of pulmonary sarcoidosis and primary Sjögren's syndrome]. 2016 The paper describes a case of a rare coexistence of primary Sjögren's syndrome (PSS) and sarcoidosis in a 41-year-old female with histologically verified lung and locomotor system diseases and keratoconjunctivitis sicca. PSS was diagnosed based on the 2012 ACR classification criteria, in the framework of which serological, histological, and gland function tests and instrumental diagnostic methods were performed. The diagnosis of sarcoidosis was based on clinical, radiographic, and histological findings.
26973276 Aortic Stenosis in a Patient With Sjogren's Syndrome. 2016 Sjogren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and the eyes. Systemic involvement in SS is well known, however, obvious cardiac manifestations, particularly significant valve disorders, are extremely rare and only three cases of significant valve disease associated with SS that required surgical intervention have been previously described. We report a case of aortic stenosis (AS) associated with SS in an elderly patient. The diagnosis of primary SS had been made based on clinical features, positive ocular signs, and positive serologic findings. Echocardiography showed severe calcification, elevated mean pressure gradient (57 mmHg), and a small orifice area (0.45 cm(2)) of the aortic valve. At surgery, severe calcification of the aortic cusps and the annulus was the mechanism of AS, and the aortic valve was replaced with a bioprosthetic valve. Valve pathology showed nodular calcification and hyaline degeneration, but lymphocyte infiltration was not evident. The etiologic relation of SS to the valve lesions is not clear pathologically in this case, however, chronic inflammation related to immunologic reactions in SS could have some effect on exacerbation for degeneration of the valve tissue.
26591173 Primary Sjögren's Syndrome Presenting as Flaccid Quadriparesis. 2015 Apr Primary Sjögren's syndrome is an autoimmune disease presenting classically as keratoconjunctivitis sicca. Renal involvement in Sjögrens's syndrome is less common, and the initial presentation with renal complications without any sicca symptoms is extremely rare. The renal involvement may present with symptoms arising from interstitial nephritis, mainly distal renal tubular acidosis.
26302236 Inter-grader Agreement of the Ocular Staining Score in the Sjögren's International Clinic 2015 Dec PURPOSE: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists. DESIGN: Reliability analysis within a prospective, observational, multicenter cohort study. METHODS: Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining. RESULTS: Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90). CONCLUSIONS: Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.
25781583 Nebulized isotonic saline improves voice production in Sjögren's syndrome. 2015 Oct OBJECTIVE: This study examined the effects of a topical vocal fold hydration treatment on voice production over time. STUDY DESIGN: Prospective, longitudinal, within-subjects A (baseline), B (treatment), A (withdrawal/reversal), B (treatment) experimental design. METHODS: Eight individuals with primary Sjögren's syndrome (SS), an autoimmune disease causing laryngeal dryness, completed an 8-week A-B-A-B experiment. Participants performed twice-daily audio recordings of connected speech and sustained vowels and then rated vocal effort, mouth dryness, and throat dryness. Two-week treatment phases introduced twice-daily 9-mL doses of nebulized isotonic saline (0.9% Na(+)Cl(-)). Voice handicap and patient-based measures of SS disease severity were collected before and after each 2-week phase. Connected speech and sustained vowels were analyzed using the Cepstral Spectral Index of Dysphonia (CSID). Acoustic and patient-based ratings during each baseline and treatment phase were analyzed and compared. RESULTS: Baseline CSID and patient-based ratings were in the mild-to-moderate range. CSID measures of voice severity improved by approximately 20% with nebulized saline treatment and worsened during treatment withdrawal. Posttreatment CSID values fell within the normal-to-mild range. Similar patterns were observed in patient-based ratings of vocal effort and dryness. CSID values and patient-based ratings correlated significantly (P < .05). CONCLUSION: Nebulized isotonic saline improves voice production based on acoustic and patient-based ratings of voice severity. Future work should optimize topical vocal fold hydration treatment formulations, dose, and delivery methodologies for various patient populations. This study lays the groundwork for future topical vocal fold hydration treatment development to manage and possibly prevent dehydration-related voice disorders. LEVEL OF EVIDENCE: 2b.
27731553 Clinical Spectrum of Chikungunya in Bikaner (North Western India) in 2006 and Follow up of 2016 Mar OBJECTIVE: To find out clinical and laboratory profile of patients of chikungunya outbreak in 2006 in Bikaner (North-West Rajasthan) and follow up of chikungunya patients for 5 years. METHODS: Study was conducted among 50 chikungunya patients. For this study the inclusion criteria was clinical presentation consistent with chikungunya virus infection (e.g. abrupt onset of fever and/or polyarthralgia) and laboratory confirmation of chikungunya virus infection by IgM-capture ELISA. All patients were subjected for thorough clinical and general physical examination, investigations like CBC, ESR, CRP, rheumatoid factor, ECG, LFT, RFT, anti-CCP antibody were done in all patients and their follow up was done for 5 years. RESULTS: Among the 50 patients of chikungunya arthritis 34 (68%) patients developed persistent arthritis. Among the patients with persistent arthritis 70.58% were shown positive for anti-ccp antibody. CRP (95.24%) and ESR level were raised (68%) in patient with persistent arthralgia. Level of CRP and ESR was proportionally related to number of partially recovered joints, higher the CRP positivity and raised ESR levels severe were the persistent arthralgias. CONCLUSIONS: Our study shows that chikungunya patients who had persistent arthralgia on 5 year follow up mimicked rheumatological disorder like rheumatoid arthritis in 70.58%. Therefore DMARD can be effective.
27183113 The Expression of BTLA Was Increased and the Expression of HVEM and LIGHT Were Decreased i 2016 BACKGROUND: Currently, the pathogenesis of rheumatoid arthritis (RA) is not clearly understood. The LIGHT/HVEM/BTLA co-signaling pathway may be involved in the pathogenesis of RA, although reports on the expression levels of LIGHT, HVEM and BTLA in T lymphocytes from RA patients are limited. METHOD: In this study, we recruited 30 healthy controls and 21 RA patients. Clinical characteristics were collected for RA patients. The levels of LIGHT, HVEM and BTLA expressed on the surface of circulating T cells of RA patients and healthy controls were measured by flow cytometry. RESULT: The percentages of CD3+, CD4+ and CD8+ T lymphocytes that expressed BTLA from RA patients were all higher than those of the controls (all p < 0.05), while the percentages of CD3+, CD4+ and CD8+ T lymphocytes that expressed HVEM and LIGHT were all lower than those of the controls (all p < 0.05). The rheumatoid factor and the percentage of HVEM+CD4+ T lymphocytes showed a statistically significant negative correlation in RA patients (r = -0.453, p = 0.039), as did the swollen joint count and the percentage of BTLA+CD8+ T lymphocytes (r = -0.501, p = 0.021). CONCLUSION: Here, we provide the first report on the increased expression of BTLA in T lymphocytes and on the decreased expression of HVEM and LIGHT in RA patients. BTLA, HVEM and LIGHT might be involved in the pathogenesis of RA and have the potential to be new clinically useful characteristics of RA.
27336451 Imaging in Foot and Ankle Arthritis. 2016 Apr The foot and ankle are commonly involved in a range of arthritides that affect the joints, bones, and soft tissues. Accurate plain film interpretation can often aid the diagnosis and monitor disease progression and treatment response. Ultrasound and MRI afford superior depiction of the soft tissues, and advances over recent years have centered on early detection of synovitis, enabling earlier diagnosis and treatment. Advantages and disadvantages of the imaging techniques of radiography, multidetector computed tomography, ultrasound, and MRI are discussed, as is optimization of these modalities for the assessment of the anatomically complex joints of the foot and ankle. Diagnostic features enabling differentiation between rheumatoid arthritis, seronegative spondyloarthropathies, osteoarthritis, gout, crystal deposition disease, pigmented villonodular synovitis, Charcot arthropathy, septic arthritis, synovial osteochondromatosis, hemophilia, and reflex sympathetic dystrophy are also reviewed.
26002449 US Guided Treat-to-Target Approach in Early RA: Implications for Uncoupling of Disease Act 2015 OBJECTIVE: To assess the relationship between disease activity, measured by DAS28, and radiographic progression, using X-Ray and US as tools to evaluate structural joint damage and residual inflammation, in early RA patients. METHODS: Changes from baseline to week 52 in clinical variables and measures of radiographic progression were compared between early RA patients who received anti-TNF biologic therapy (192 patients), and those who received synthetic DMARD therapy (288 patients). Patients were stratified into: in remission, low (LDA), moderate (MDA) and high (HDA) disease activity at 52-weeks of treatment according to DAS-28 score. Radiographic progression was assessed both at baseline and at 52-weeks using modified Total Sharp Score (mTSS). In addition, US scores for number of erosions, synovial hypertrophy and vascularity were recorded. RESULTS: Whilst there was no significant radiologic progression in the patients who achieved remission, whether treated with synthetic DMARD or biologic therapy; on the other hand, there was a steady increase of joint damage in those who did not achieve remission, mainly in those treated with synthetic DMARD and in favor of the biologic therapy. On comparing the MSS scores at 52-weeks, the biologic therapy cohort who showed LDA (DAS-28: 2.6-3.1), MDA (DAS-28 score > 3.2-5.1) and HDA (>5.1) had significantly (p< 0.001) less number of erosions and joint space narrowing (P< 0.001) as well as US-GS and US-PD scores in comparison to the synthetic DMARD therapy cohort. X-Ray and US parameters showed a discriminating value regarding joint damage particularly in the patients who did not achieve remission, with US parameter showing accurate 95% CI estimate. CONCLUSION: Using US as a sensitive tool for joint affection assessment, the combination of biologic and DMARDs therapies retards joint damage, independently of its effects on disease activity, contrasting synthetic DMARDs monotherapy.
27843372 Wissler-Fanconi syndrome and related diagnoses: a case report. 2016 INTRODUCTION: Wissler-Fanconi syndrome is a rare rheumatic syndrome that was first described during the 1940s in Europe. Since then, many papers have been written that cover all aspects of this syndrome, most of which are in French and German language, with only a very few in English (none of them recent). We report here a case that fulfils the criteria for Wissler-Fanconi syndrome. Under the more general descriptive umbrella of Wissler-Fanconi syndrome, our patient also fulfils the Modified Jones criteria, and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis, and was interpreted by other internists and another rheumatologist as fulfilling the Yamaguchi criteria for adult onset Still's disease. CASE PRESENTATION: A middle-aged female presented to the emergency department with shortness of breath and chest pain associated with fever, polyarthritis, and had a chronic polymorphic rash on the back and lower extremities. Blood analysis showed highly elevated inflammatory markers and rheumatoid factor. After ruling out other possible deferential diagnoses and reviewing the medical literature, the patient was diagnosed with Wissler-Fanconi syndrome. A combination of nonsteroidal anti-inflammatory drugs and steroids achieved complete remission. CONCLUSION: This case report highlights the important differential diagnosis that may be included under the nomenclature of Wissler-Fanconi syndrome (subsepsis hyperergica). Features of Wissler-Fanconi syndrome can be found in a differential diagnosis that includes true sepsis, acute rheumatic fever, rheumatoid arthritis, and adult onset Still's disease.
26842423 The Prevalence of Atherosclerosis in Those with Inflammatory Connective Tissue Disease by 2016 Feb 4 Systemic inflammation promotes cardiovascular disease. Inflammatory connective tissue diseases (CTD) like lupus and rheumatoid arthritis associate with cardiovascular risk, but it is unknown whether particular groups of patients have enhanced propensity for atherosclerotic cardiovascular disease (ASCVD) associated with their CTD. Analysis of aggregate health record data at a large U.S. academic center identified CTD and ASCVD status for 287,467 African American and white adults. ASCVD prevalence in those with CTD was 29.7% for African Americans and 14.7% for white patients with prevalence ratios, compared to those without CTD, of 3.1 and 1.8, respectively. When different types of CTD were analyzed individually (rheumatoid arthritis; lupus; scleroderma; Sjögren Syndrome; dermatomyositis/polymyositis; unspecified/mixed CTD; other inflammatory arthropathy), increased ASCVD rates were found in nearly all subsets, always with higher prevalence ratios in African Americans. The prevalence ratio of ASCVD was particularly high in young African Americans. Furthermore, individuals lacking traditional cardiovascular risk factors had more ASCVD if they had CTD (prevalence ratio 2.9). Multivariate analysis confirmed a positive interaction between CTD and African-American race and a negative interaction between CTD and age. The factors driving the observed disproportionate CTD-associated ASCVD in African Americans, young adults, and those without traditional risk factors warrant further study.
25861406 Test-retest reliability and convergent validity of a computer based hand function test pro 2015 OBJECTIVES: A computer based hand function assessment tool has been developed to provide a standardized method for quantifying task performance during manipulations of common objects/tools/utensils with diverse physical properties and grip/grasp requirements for handling. The study objectives were to determine test-retest reliability and convergent validity of the test protocol in people with arthritis. METHODS: Three different object manipulation tasks were evaluated twice in forty people with rheumatoid arthritis (RA) or hand osteoarthritis (HOA). Each object was instrumented with a motion sensor and moved in concert with a computer generated visual target. Self-reported joint pain and stiffness levels were recorded before and after each task. Task performance was determined by comparing the object movement with the computer target motion. This was correlated with grip strength, nine hole peg test, Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, and the Health Assessment Questionnaire (HAQ) scores. RESULTS: The test protocol indicated moderate to high test-retest reliability of performance measures for three manipulation tasks, intraclass correlation coefficients (ICCs) ranging between 0.5 to 0.84, p<0.05. Strength of association between task performance measures with self- reported activity/participation composite scores was low to moderate (Spearman rho <0.7). Low correlations (Spearman rho < 0.4) were observed between task performance measures and grip strength; and between three objects' performance measures. Significant reduction in pain and joint stiffness (p<0.05) was observed after performing each task. CONCLUSION: The study presents initial evidence on the test retest reliability and convergent validity of a computer based hand function assessment protocol in people with rheumatoid arthritis or hand osteoarthritis. The novel tool objectively measures overall task performance during a variety of object manipulation tasks done by tracking a computer based visual target. This allows an innovative method of assessing performance than considering the time taken to complete a task or relying on subjective measures of self-reports on a limited range of objects and tasks covered. In addition, joint pain and stiffness levels before and after a manipulation task are tracked, which is lacking in other hand outcome measures. Performance measures during a broad range of object manipulation tasks relate to many activities relevant to life role participation. Therefore, task performance evaluation of common objects, utensils, or tools would be more valuable to gauge the difficulties encountered in daily life by people with arthritis. Future studies should consider a few revisions of the present protocol and evaluate a number of different objects targeting strength, fine, and gross dexterity based tasks for a broader application of the tool in arthritis populations.
27027815 Treat-to-target as an approach in inflammatory arthritis. 2016 May PURPOSE OF REVIEW: Treat-to-target (T2T) is a new paradigm in the treatment of rheumatoid arthritis (RA). This review is timely, because the evidence is compelling and the world's major organizations have included it in their management recommendations. RECENT FINDINGS: T2T involves regular disease activity monitoring, ideally using the most recently described composite measures and remission criteria. The findings in the literature fully support previous notions on prevention of damage, maintenance of physical function and reduction of comorbidity risks using this strategy in early RA and have expanded these insights to established RA, elderly patients and work capacity. T2T has now even been advocated for psoriatic arthritis and is suggested of value also for ankylosing spondylitis and systemic lupus erythematosus. SUMMARY: This paradigm is independent of the availability of particular drugs, as the strategy in itself will maximize the benefit for the patient, irrespective of specific medications. Adhering to this strategy in clinical practice will optimize the outcomes in patients with RA.
26712749 Adiponectin Induces Oncostatin M Expression in Osteoblasts through the PI3K/Akt Signaling 2015 Dec 25 Rheumatoid arthritis (RA), a common autoimmune disorder, is associated with a chronic inflammatory response and unbalanced bone metabolism within the articular microenvironment. Adiponectin, an adipokine secreted by adipocytes, is involved in multiple functions, including lipid metabolism and pro-inflammatory activity. However, the mechanism of adiponectin performance within arthritic inflammation remains unclear. In this study, we observed the effect of adiponectin on the expression of oncostatin M (OSM), a pro-inflammatory cytokine, in human osteoblastic cells. Pretreatment of cells with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB reduced the adiponectin-induced OSM expression in osteoblasts. Stimulation of the cells with adiponectin increased phosphorylation of PI3K, Akt, and p65. Adiponectin treatment of osteoblasts increased OSM-luciferase activity and p65 binding to NF-κB on the OSM promoter. Our results indicate that adiponectin increased OSM expression via the PI3K, Akt, and NF-κB signaling pathways in osteoblastic cells, suggesting that adiponectin is a novel target for arthritis treatment.
25125695 FHL2 regulates the resolution of tissue damage in chronic inflammatory arthritis. 2015 Dec OBJECTIVE: We analysed the role of the adaptor molecule four-and-a-half Lin11, Isl-1 & Mec-3 (LIM) domain protein 2 (FHL2) in the activation of fibroblast-like synoviocytes in human rheumatoid arthritis (RA) and tumour necrosis factor α (TNFα)-dependent animal models of the disease. METHODS: Synovial tissues of patients with RA and osteoarthritis (OA) as well as hind paw sections from arthritic human TNFα transgenic (hTNFtg) mice and synovial fibroblasts from these were analysed. The effects of cytokines on the expression of FHL2 and disease-relevant matrixmetalloproteases (MMPs) were determined. Analyses of human tissue specimens from patients treated with anti-TNFα as well as anti-TNFα treatment of hTNFtg mice were performed to substantiate the TNFα effects on FHL2 levels. FHL2(-/-) mice and hTNFtg mice (with constitutive or inducible transgene expression) were crossbred to generate TNFα overexpressing FHL2-deficient animals. Signalling pathways were analysed in cells from these mice and in human cells after knock down of FHL2 by western blot. RESULTS: FHL2 levels were higher in RA than in OA and in hTNFtg than in wild-type mice. Surprisingly, while transforming growth factor (TGF)β-induced FHL2 expression, TNFα suppressed FHL2. In vivo, anti-TNFα treatment led to higher FHL2 levels both in RA patients and hTNFtg mice. The loss of FHL2 increased joint destruction in hTNFtg mice, which was accompanied by elevated MMP-13. In vitro, TNFα-mediated MMP-13 was significantly higher in FHL2(-/-) cells and after knock down of FHL2, which was caused by prolonged p38 MAPK activation. CONCLUSIONS: These data suggest that FHL2 serves as a protective factor and that, rather than promoting the pathology, the upregulation of FHL2 in RA occurs in frame of a regenerative attempt.
27571073 Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rat 2016 Aug 26 To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.
26440401 A novel coumarin derivative, 8-methoxy chromen-2-one alleviates collagen induced arthritis 2015 Dec Ruta graveolens (Rue) is a well-known medicinal plant having anti-inflammatory and other healing properties. This contains many active phytochemicals such as coumarins which possess anti-inflammatory and anti-cancer activities. The present study was carried out to evaluate the therapeutic potential of a newly isolated coumarin derivative from rue plant, 8-methoxy-chromen-2-one (MCO) in the collagen induced arthritic (CIA) rat model. MCO showed inhibition of cytokines and NF-κB in LPS stimulated J774 cells which prompted its possible use in animal. In CIA, arthritic index and arthritic score reduced markedly within 15days of MCO treatment at doses of 2mg and 20mg per kg body weight. Alleviation of joint damage in CIA animals on treatment with MCO was evident from radiographic and histological data. Behavioral studies by open field tests also showed convalescence in the MCO treated CIA rats. Further, escalated plasma levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and also nitric oxide reduced significantly with the treatment. All these results indicate the therapeutic efficacy of MCO and its possible use as an anti-arthritic drug.
25205184 Biological agents in psoriatic arthritis. 2015 Jan Anti-tumor necrosis factors (TNFs) are effective drugs for the treatment of psoriatic arthritis (PsA) regarding reduction of pain and inflammation, enthesitis, dactylitis, as well as psoriatic skin and nail disease. Moreover, radiographic progression in PsA is decelerated. The efficacy of anti-TNFs seems to be independent of synthetic disease-modifying anti-rheumatic drugs, suggesting only a minor role of combination therapy in PsA. Anti-TNFs are generally well tolerated in patients with PsA. Adverse events are similar to those reported in patients with rheumatoid arthritis. Ustekinumab, a recently approved IL-12/IL-23-antibody is another promising biological agent in the treatment of PsA.