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

ID PMID Title PublicationDate abstract
19232061 Randomized controlled trial design in rheumatoid arthritis: the past decade. 2009 Much progress has occurred over the past decade in rheumatoid arthritis trial design. Recognized challenges have led to the establishment of a clear regulatory pathway to demonstrate efficacy of a new therapeutic. The use of pure placebo beyond 12 to 16 weeks has been demonstrated to be unethical and thus background therapy and/or early rescue has become regular practice. Goals of remission and 'treating to targets' may prove more relevant to identify real-world use of new and existing therapeutics. Identification of rare adverse events associated with new therapies has resulted in intensive safety evaluation during randomized controlled trials and emphasis on postmarketing surveillance and use of registries.
19332623 Safety of etanercept in patients at high risk for mycobacterial tuberculosis infections. 2009 May OBJECTIVE: The magnitude of the risk of reactivation of tuberculosis (TB) on use of etanercept, especially in patients with positive purified protein derivative (PPD) test, has not been assessed. We evaluated the risk of developing active TB among PPD-positive patients treated with etanercept. METHODS: All patients with a positive PPD test, as defined by American Thoracic Society guidelines, who received etanercept at Cook County Hospital from 2001 to 2008 were retrospectively reviewed. The primary endpoint was the development of active TB either while receiving or after completing etanercept therapy. RESULTS: Four hundred eighty-seven patients received etanercept, of whom 84 were PPD-positive and constituted the primary cohort. The cohort was composed largely of patients who were at high risk for development of active TB: born in endemic area (80%), ethnic/racial minorities (51 Hispanic, 16 African American, and 8 Asian), and low socioeconomic status (66, 78.57%). Overall etanercept exposure was a mean of 24.6 months (range 3 to 60 mo), with 196 patient-years of etanercept exposure in PPD-positive individuals. Indications for etanercept use included rheumatoid arthritis 58 (69%), ankylosing spondylitis 11 (13%), psoriatic arthritis 13 (15.5%), juvenile inflammatory arthritis 1 (1.2%), and vasculitis 1 (1.2%). Of the 80 subjects, 74 received treatment for latent TB infection (LTBI) prior to initiating etanercept. A comprehensive review of these patients' medical records failed to reveal any active TB infection. CONCLUSION: This systematic analysis suggests that the risk of reactivation of LTBI during etanercept therapy is low in appropriately treated individuals.
20063004 Purified proteins from Leishmania amastigotes-induced delayed type hypersensitivity reacti 2010 Oct A treatment preparation composed of purified Leishmania (L) antigenic fractions (AS210) induced linear delayed type hypersensitivity (DTH) reactions over a 1-40 microg dose range, in guinea pigs. When a DBA-1 mouse collagen induced arthritis (CIA) model was used to compare AS210 treatment against: a polyvalent vaccine (AS110-1), a monovalent vaccine (AS110-2) and placebo, the AS210 treated mice had the least amount of forepaw inflammation and the lowest mean arthritis scores (MAS). When MAS for day(s) 1-40 were analyzed using one way ANOVA, statistically significant (P < 0.05) differences were seen for the following study groups: PBS versus Dexamethasone and PBS versus AS210. Subsequently, the ANOVA analysis results were corroborated by the Mann-Whitney test: analysis of the first group (P < 0.001) and analysis of the second group (P < 0.001). Comparison between dexamethasone and AS210 at different time intervals by Mann-Whitney test were as follows: day 0-day 5 both treatments had equal values (P = 1.00), from day-7 to 20 AS210 treatment had lower MAS values than dexamethasone (P = 0.037), and from day-21 to 30, AS210 MAS were similar to dexamethasone values (P = 0.319). No statistical difference was observed between AS110-1, AS110-2, and placebo groups.
20232616 Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid ar 2010 Mar OBJECTIVE: To review efficacy studies of antioxidant and antiinflammatory dietary supplements used to manage osteoarthritis (OA) and rheumatoid arthritis (RA) and make conclusions about their place in therapy. Glucosamine, chondroitin, and methyl sulfonyl methane were excluded. DATA SOURCES: A literature search was conducted using MEDLINE (1996 through January 2009), EMBASE, Cochrane Library, Natural Medicines Comprehensive Database, and Natural Standard, with bibliographic review of relevant articles. Cited studies from before our search range were included if they represented the only published human data available. Search words included "antioxidant," "antiinflammatory," "cat's claw," "ginger," "fish oil," "omega-3," "turmeric," "vitamin E," "vitamin C," "Baikal skullcap," "barberry," "Chinese goldthread," "green tea," "Indian holy basil," "hu zhang,""oregano," and"rosemary." STUDY SELECTION AND DATA EXTRACTION: Efficacy studies published in English were included provided they evaluated the dietary supplements in patients with OA or RA. DATA SYNTHESIS: Our search strategy yielded 16 clinical studies (11 randomized, placebo-controlled clinical trials, three crossover trials, one case-controlled study, and one open-label study) in addition to one meta-analysis and one review article. CONCLUSIONS: Three studies support cat's claw alone or in combination for OA, and two studies support omega-3 fatty acids for the treatment of RA. We cannot recommend use of vitamin E alone; vitamins A, C, and E in combination; ginger; turmeric; or Zyflamend (New Chapter, Brattleboro, Vermont) for the treatment of OA or RA or omega-3 fatty acids for OA. Whether any of these supplements can be effectively and safely recommended to reduce nonsteroidal antiinflammatory drug or steroid usage is unclear and requires more high-quality research.
19124524 Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheuma 2009 Dec OBJECTIVES: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. METHODS: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (approximately 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. RESULTS: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. CONCLUSIONS: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.
21179283 A comparison of three different guidelines for osteoporosis treatment in patients with rhe 2010 Dec BACKGROUND/AIMS: Osteoporotic fractures are an important comorbidity with rheumatoid arthritis (RA). We determined the overall fracture risk as assessed by the World Health Organization (WHO)'s FRAX® tool in Korean patients with seropositive RA. Additionally, we compared treatment eligibility according to the criteria of the Korean Health Insurance Review Agency (HIRA), FRAX, and the National Osteoporosis Foundation (NOF). METHODS: Postmenopausal women and men ≥ 50 years of age with seropositive RA were recruited from one rheumatism center in Korea. The FRAX score was estimated using the Japanese model. Patients were classified as eligible for treatment using the HIRA, NOF, and FRAX thresholds for intervention. RESULTS: The study of 234 patients included 40 men (17%). The mean age was 60 ± 9 years, and 121 (52%) patients had osteoporosis according to the WHO criteria. The overall median 10-year fracture risk was 13% for major osteoporotic fractures and 3.5% for hip fractures. HIRA guidelines identified 130 patients (56%) eligible for treatment, FRAX included 126 patients (54%), and 151 patients (65%) were included according to NOF guidelines. Older patients with a greater number of risk factors were included by FRAX compared to HIRA. The overall concordance between HIRA and FRAX, expressed as the kappa index, was 0.67, but was as low as 0.44 when limited to patients ≥ 60 years of age. CONCLUSIONS: One-half of the patients had osteoporosis requiring treatment. RA patients have a high risk of fracture, and the adoption of a risk-scoring system should be considered.
19562563 Total elbow arthroplasty in rheumatoid arthritis: a population-based study from the Finnis 2009 Aug BACKGROUND AND PURPOSE: Although total elbow arthroplasty (TEA) is a recognized procedure for the treatment of the painful arthritic elbow, the choice of implant is still obscure. We evaluated the survival of different TEA designs and factors associated with survival using data from a nationwide arthroplasty register. METHODS: 1,457 primary TEAs for rheumatoid elbow destruction were performed during 1982 to 2006 in one hospital specialized in the treatment of rheumatoid arthritis (n = 776) and in 19 other hospitals (n = 681). The mean age of the patients was 59 years and 87% of the TEAs were performed in women. We selected different contemporary TEA designs, each used in more than 40 operations including the Souter-Strathclyde (n = 912), i.B.P./Kudo (n = 218), Coonrad-Morrey (n = 164), and NESimplavit/Norway (n = 63) to assess their individual survival rates. Kaplan-Meier analysis and the Cox regression model were used for survival analysis. RESULTS: The most frequent reason for revision was aseptic loosening (47%). We found no differences in survival rates between different TEA designs. We did, however, find a 1.5-fold (95% CI: 1.1-2.1) elevated risk of revision in unspecialized hospitals as compared to the one hospital specialized in treatment of rheumatoid arthritis. In the Souter-Strathclyde subgroup, there was a reduced risk of revision (RR 0.6, p = 0.001) in TEAs implanted over 1994-2006 as compared to those implanted earlier (1982-1993). The 10-year survivorship for the whole TEA cohort was 83% (95% CI: 81-86), which agrees with earlier reports. INTERPRETATION: The influence of implant choice on the survival of TEA is minor compared to hip and knee arthroplasties. Inferior survival rates of the TEAs performed in the unspecialized hospitals demonstrates the importance of proper indications, surgical technique, and postoperative follow-up, and endorses the need for centralization of these operations at specialized units.
19753838 [Financial cost of early rheumatoid arthritis in the first year of medical attention: thre 2009 Mar INTRODUCTION: In Colombia, the cost burden of chronic diseases is not well known, either globally or in localized areas of the health system. Rheumatoid arthritis is one of most common chronic diseases, and represents a high cost for the health system. OBJECTIVE: The direct medical costs were estimated for rheumatoid arthritis patients in the in the first year of diagnosis at a level 3 university hospital in Colombia. MATERIALS AND METHODS: Three therapy settings for early rheumatoid arthritis patients were established in the first year of diagnosis according to national and international guidelines. Each setting included treatment with disease-modifying anti-rheumatic drugs or biologic therapy based on disease severity as measured by Disease Activity Score 28. All direct medical costs were included: specialized medical care, diagnostic tests and drugs. Cost information was obtained from the Central Military Hospital finance department in Bogotá and the national manual of drug prices based on the "Farmaprecios" 2007 guide, a reference in general use by health institutions. Results. The average of cost of medical care in patients with mild, moderate and severe disease was US $1689, $1805 and $23,441 respectively. The recommended retail prices of the medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the charges levied by several major health institutions were compared, substantial increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs represented 86% of total cost, laboratory costs were 10% and medical attention was only 4%. CONCLUSIONS: Drugs costs were the principal component of the total direct medical cost, and it increased 40 times when a biological therapy is used. Complete economic evaluation studies are necesary to estimate the viability and clinical relevance of biological therapy for early rheumatoid arthritis.
19811562 Lack of association between elevated mean red cell volume and haematological toxicity in p 2010 Aug AIMS: It has been suggested that elevated mean red cell volume (MCV) may be a predictor of haematological toxicity in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). We wished to identify whether there was an association between MCV, red cell folate and haematological toxicity in patients on MTX monotherapy for the long-term management of RA. METHODS: Evidence of haematological toxicity was sought by note review of patients recruited in a cross-sectional study of MTX monotherapy in RA. Retrospective data included MCVs from before MTX initiation and after 3 and 6 months of treatment. Data were collected prospectively every 6 months for up to 2 years after enrolment. Any record of cytopenia or the development of haematological malignancy was recorded from commencement of MTX until the present day. Red cell folate concentrations were tested on enrolment to the study. RESULTS: A total of 165 patients was included, 74.5% female, median disease duration 7 years (range 3 months-57 years). The median duration of MTX treatment was 74.9 months (range 10-241 months) giving 1030.2 patient-years of MTX exposure. Twenty-four patients (14.5%) had a MCV > 98 fL on study entry. Evidence of haematological abnormality was found in six patients (3.6%); chronic lymphocytic leukaemia (1), persistent lymphocytosis (1), persistent monocytosis (1) and neutropenia (3). There was no association between red cell folate or MCV and haematological toxicity. CONCLUSION: Neutropenia and pancytopenia are rare side-effects of MTX therapy in this cohort. Elevated MCV or low mean red cell folate does not appear to be associated with haematological malignancy or toxicity in this cohort of patients on long-term MTX therapy.
20102615 RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis. 2010 INTRODUCTION: We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40. METHODS: Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses. RESULTS: Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells. CONCLUSIONS: These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.
20015916 Cardiac autonomic profile in rheumatoid arthritis and systemic lupus erythematosus. 2010 Mar Neurological involvement is a well-documented issue in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, little is known about the involvement of the autonomic nervous system. This study was conducted to investigate autonomic nervous system dysfunction in patients with RA and SLE. Twenty-six RA patients, 38 SLE patients and 40 healthy controls were recruited from our in- and out-patient departments. Heart rate variability (HRV) parameters (the power of the high- [HF] and low-frequency [LF] band of haemodynamic time series, the ratio between low- and high-frequency components [LF/HF ratio], the power spectral density), baroreflex sensitivity (BRS) and beat-to-beat blood pressures were assessed by a novel non-invasive haemodynamic monitoring tool (Task Force Monitor [TFM], CNSystems Medizintechnik GmbH, Graz, Austria). Autonomic nervous system dysfunction was determined according to classical Ewing autonomic test battery. Furthermore, we implemented a secondary autonomic test score by modifying the Ewing test battery with additional criteria. Both the classical and modified Ewing test batteries have revealed that the frequencies of autonomic neuropathy were significantly higher in patient groups compared with controls (p < 0.001). Evaluation by TFM revealed that deterioration of sophisticated autonomic parameters (such as HRV and BRS) were more pronounced in the patient groups compared with controls. There was a significant association between BRS and Ewing test scores and abnormal BRS results were more frequent in patients with autonomic dysfunction according to Ewing test batteries. No relation was found between autonomic neuropathy and disease duration, disease activity and autoantibody positivity. Consequently, we believe that further large-scale studies investigating cardiovascular autonomic neuropathy in rheumatic diseases should be carried out to verify our findings and manifest clinical consequences beyond these results.
19565551 Targeted ultrasound of the fifth metatarsophalangeal joint in an early inflammatory arthri 2009 Jul 15 OBJECTIVE: To determine whether targeted ultrasonographic (US) imaging of the fifth metatarsophalangeal (MTP) joint, compared with radiographs, could aid in the early diagnosis of rheumatoid arthritis (RA) by identifying erosions sooner in early inflammatory arthritis. Radiographic erosion in RA is a late indication of poor prognosis. The earlier detection of erosion may facilitate the timely initiation of disease-modifying antirheumatic drug therapy, particularly in patients with undifferentiated synovitis. METHODS: Patients presenting with synovitis for the first time were invited to participate. Each patient underwent laboratory tests, radiographs of the hands and feet, and US imaging of both fifth MTP joints. RESULTS: Thirty patients (22 women) took part in the study. Seventeen patients (57%) had RA, and 13 (43%) had undifferentiated arthritis (UA). The mean +/- SD time taken to scan both fifth MTP joints was 10.9 +/- 4.4 minutes. Ten patients (33%) had US evidence of synovitis associated with a positive power Doppler (PD) signal (P = 0.04). Seven patients (23%) had radiographic erosions of the fifth MTP joint, and 17 patients (57%) had US evidence of fifth MTP joint erosions (P = 0.01). A positive PD signal at the fifth MTP joint was seen in 9 of 17 patients with RA and 1 of 13 patients with UA (P = 0.02). Patients with a definite diagnosis of RA were more likely to have fifth MTP joint erosions (11 [65%] of 17) compared with UA (6 [46%] of 13). CONCLUSION: Targeted US is a rapid and useful tool in detecting erosive disease in early inflammatory arthritis. It gives a better indication of disease severity and prognosis compared with routinely available laboratory tests, even in the absence of a definite diagnosis.
20939210 [Abnormal cervicovaginal cytology in women with rheumatoid arthritis]. 2010 Feb BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of infections and cancer. A link between RA and abnormal cervicovaginal cytology has rarely been reported. OBJECTIVE: The aim of this study was to review cervicovaginal cytology results in women with RA and compare them with a control population. Sexual behavior also was investigated. MATERIAL AND METHOD: Cervicovaginal cytology results of 95 women with RA were compared to those of a control population of 1,719 women attending at the same hospital and followed until June 2009. Records of RA patients were reviewed to obtain clinical data, particularly sexual behavior. RESULTS: Of 95 RA patients, 13/95 had an abnormal cervicovaginal cytology result, compared with 120/1,719 controls. Twelve/13 had squamous intraepithelial lesions (SIL), compared with 27/120 controls. There was no significant difference in sexual partners between women with RA and controls. Women with RA without abnormal cervicovaginal cytology had less sexual partners than those with RA and abnormal cytology. Two women with RA and abnormal cervicovaginal cytology had a history of condylomata and herpes genital. Three/13 women with RA developed abnormal cervicovaginal cytology after 12 to 36 months initiating their illness. None from them had ever received immunosuppressants. CONCLUSIONS: Women with RA have an increased prevalence of abnormal cervical cytology, compared with a control population. It may be related to chronic inflammatory disease and sexual behavior.
19027090 Anti-TNFalpha therapy in a cohort of rheumatoid arthritis patients: clinical outcomes. 2009 Jan OBJECTIVE: To assess the effectiveness of anti-TNFalpha agents by analysing the principal clinical outcomes in patients with active rheumatoid arthritis (RA). METHODS: 1010 patients who received no clinical benefit from previous treatment with methotrexate and/or other DMARDs, were subsequently treated with one or more of the anti-TNFalpha agents. RESULTS: After the first six months of anti-TNFalpha therapy, 29% of the patients showed a good and 47% a moderate European League Against Rheumatism (EULAR) response, and this positive result was maintained after two years of follow-up. Their median Disease Activity Score based on the erythrocyte sedimentation rate and the evaluation of 28 joints (DAS28) decreased from 5.94 at baseline to 4 after six months (p<0.001; Delta 1.94), and further significant responses were also observed after 12, 18 and 24 months; their median 36-month DAS28 score reflected mild disease activity. The median Health Assessment Questionnaire (HAQ) score fell from 1.34 at baseline to 1 after six months of therapy (Delta 0.34; p<0.05), and a further significant reduction was observed during the second and third year of follow up. CONCLUSIONS: Especially when combined with DMARDs, anti-TNFalpha drugs can induce a good clinical response regardless of the particular molecule used, whereas their combination with steroids does not seem to improve disease outcomes at any time during follow-up.
18477739 Breast feeding, but not use of oral contraceptives, is associated with a reduced risk of r 2009 Apr OBJECTIVE: To determine whether breast feeding or the use of oral contraceptives (OCs) affects the future risk of rheumatoid arthritis (RA) in a community-based prospective cohort. METHODS: A community-based health survey (18 326 women) was linked to regional and national registers, and incident cases of RA were identified. All women with a diagnosis of RA after inclusion in the health survey (n = 136) and four female controls for every case, who were alive and free from RA when the index person was given a diagnosis of RA, were included in a case-control study. Data on lifestyle factors at baseline were derived from a self-administered questionnaire. Potential predictors were examined in logistic regression models. RESULTS: 136 women with incident RA were compared with 544 age-matched controls. A longer history of breast feeding was associated with a reduced risk of RA (OR 0.46 (95% CI 0.24 to 0.91) for women who had breast fed for >/=13 months and OR 0.74 (95% CI 0.45 to 1.20) for those who had breast fed for 1-12 months, compared with those who had never breast fed). The protective effect of longer breast feeding remained significant after adjustment for smoking and level of education in multivariate models, and point estimates were protective also when the analyses were restricted to parous women. Neither parity nor OC use had any significant effect on the risk of RA. CONCLUSION: In this study, long-term breast feeding, but not OC use, was associated with a significant reduction in the risk of RA.
20820842 Insulin-like growth factor binding protein-related protein 1 is expressed in rheumatoid sy 2011 Feb Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a secretory protein that shares a structural similarity with IGFBP. Studies have shown that IGFBP-rP1 synergistically increases fibroblast growth with insulin and stimulates angiogenesis in tumor tissues. In this report, we examined the expression and function of IGFBP-rP1 in rheumatoid arthritis (RA). IGFBP-rP1 expression in synovial tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, and immunohistochemical analysis. In vitro, IGFBP-rP1 expression was examined in synovial fibroblasts established from rheumatoid synovium (RASFs) by RT-PCR, Western blot, and immunostaining. The effect of IGFBP-rP1 small interfering RNA (siRNA) on RASF proliferation was assessed by alamarBlue assay. IGFBP-rP1 mRNA was detected by RT-PCR in all synovial tissues from RA and OA patients. In immunohistochemical analysis, IGFBP-rP1 was mainly expressed in synovial cells in the lining layers and endothelial cells in the sublining layers of RA synovium. In vitro, constitutive expression of IGFBP-rP1 in RASFs was detected by RT-PCR, Western blot, and immunostaining. Treatment with IGFBP-rP1 siRNA induced a 26% decrease in RASF growth compared to control siRNA. A similar extent of growth-suppressive effect by IGFBP-rP1 siRNA was also observed when RASF proliferation was induced by TNF-α. Collectively, these data suggest that IGFBP-rP1 may regulate synovial fibroblast proliferation in RA.
19234364 The efficacy and mechanism action of RvCSd, a new herbal agent, on immune suppression and 2009 Feb The aim of the present study is to investigate the potential therapeutic action of RvCSd, an oriental herbal mixture, in an experimental model of rheumatoid arthritis (RA). DBA/1J mice were immunized with type II collagen. After a second collagen immunization, mice were treated with RvCSd or methotrexate (MTX) orally once a day for 35 days, and the incidence, clinical score, and joint histopathology were evaluated. The inflammatory response cytokines and cartilage protection effect were determined by measuring the levels in the joints and sera. The Th1/Th2-mediated auto-reactive response was evaluated by determining the proliferative response and cytokines of drained spleen cells stimulated with type II collagen. RvCSd treatment significantly reduced the incidence and severity of CIA, markedly abrogating joint swelling, synovial hyperplasia, and cartilage destruction. RvCSd significantly inhibited the production of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6, IL-2, interferon (IFN)-gamma, and matrix metalloproteinases (MMP)-1 and up-regulated anti-inflammatory cytokines IL-4, IL-10, and metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, RvCSd has therapeutic effects exerted through inhibition of inflammatory and Th1 responses, regulation of MMP/TIMP, and induction of regulatory T cells in CIA; these effects make RvCSd an outstanding candidate for use as an immune suppressive and cartilage protective medicine in RA patients.
19319875 Degradation of high-molar-mass hyaluronan by ascorbate plus cupric ions: effects of D-peni 2009 Mar Pro- and anti-oxidative effects of an anti-rheumatoid drug, D-penicillamine (D-PN), on the kinetics of high-molar-mass hyaluronan (HA) degradation were monitored using the method of rotational viscometry. The degradation of the dissolved HA macromolecules was attained by applying the Weissberger's system comprising ascorbic acid plus cupric ions. Electron paramagnetic resonance (EPR) spectroscopy was used to identify the generated free radicals. The results obtained indicate that the initial anti-oxidative action of D-PN is followed by induction of pro-oxidative conditions due to the generation of reactive free radicals. It is speculated, however, that the latter situation may be considered as an advantageous property of D-PN. Hydroxyl radicals formed in this way may participate in decomposition of proteinases, which are believed to be responsible for the destruction of joint cartilage under rheumatoid arthritic conditions.
20001767 Expression of IL-10 family cytokines in rheumatoid arthritis: elevated levels of IL-19 in 2010 Mar OBJECTIVES: Interleukin (IL)-10 functions as an anti-inflammatory cytokine in rheumatoid arthritis (RA). New IL-10 family cytokines IL-19, IL-20, IL-22, IL-24, and IL-26 have recently been discovered. Information concerning the expression and function of these cytokines in autoimmune diseases is currently limited. The aim of this study was to investigate their expression in RA. METHODS: mRNA levels of the cytokines were studied using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs), purified T cells, and monocytes/macrophages from RA patients and healthy volunteers, and synovial tissues from patients with RA or osteoarthritis (OA), were examined. The expression of IL-19 protein in T cells and monocytes/macrophages was studied by flow cytometry. RESULTS: IL-10 and IL-19 mRNA levels were significantly elevated in SFMCs from patients with RA compared with PBMCs from RA patients or healthy volunteers. IL-20 and IL-22 mRNA levels were also upregulated in RA SFMCs but their level of expression was lower than that of IL-10 or IL-19. Importantly, synovial tissue IL-19 levels in RA were increased when compared with OA. IL-19 expression was upregulated in both T cells and macrophages derived from patients with RA. IL-1beta increased IL-19 levels in PBMCs, suggesting that elevated levels of IL-1 in RA joints may contribute to upregulated IL-19 expression. CONCLUSIONS: The majority of the IL-10 family cytokines are expressed in RA. IL-19 demonstrated the highest expression in rheumatoid joints, and could thus be involved in the regulation of synovial inflammation in RA.
19326186 Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a redu 2009 The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-alpha used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4-8, 12-16, and 20-24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12-16 and 20-24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12-16 and in five patients (50%) at weeks 20-24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics.