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23242389 Safety of tumor necrosis factor inhibitors use for rheumatoid arthritis and ankylosing spo 2013 Mar Multiple studies of patients in Western countries with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have indicated increased risk for active tuberculosis (TB) and other infections among these individuals. It has also been consistently reported that patients receiving tumor necrosis factor (TNF) inhibitors for these conditions have higher rates of active TB and other infections than RA or AS patients not receiving these medications. These issues have been studied less extensively in the Asia and Africa-Middle East regions, and information from these regions is important because of higher rates of TB in the general population. This paper reviews studies of RA and AS patients from Asia, Africa, and the Middle East who received TNF inhibitors. A literature search was conducted using http://www.ncbi.nlm.nih.gov/pubmed to collect and report these data. The years included in the PubMed literature search ranged from January 2000 to October 2011. Additionally, information from the China Hospital Knowledge Database was used to report data from Chinese patients with RA and AS treated with TNF inhibitors. Results from these studies indicate that the risk for active TB and other infections in AS and RA patients from Asia, Africa, and the Middle East are increased in patients receiving TNF inhibitors and that the risk is higher among those treated with monoclonal antibodies versus soluble TNF receptor.
25351422 Power Doppler signal calibration between ultrasound machines by use of a capillary-flow ph 2015 Jan Ultrasound allows the detection and grading of inflammation in rheumatology. Despite these advantages of ultrasound in the management of rheumatoid patients, it is well known that there are significant machine-to-machine disagreements regarding signal quantification. In this study, we tried to calibrate the power Doppler (PD) signal of two models of ultrasound machines by using a capillary-flow phantom. After flow velocity analysis in the perfusion cartridge at various injection rates (0.1-0.5 ml/s), we measured the signal count in the perfusion cartridge at various injection rates and pulse repetition frequencies (PRFs) by using PD, perfusing an ultrasound micro-bubble contrast agent diluted with normal saline simulating human blood. By use of the data from two models of ultrasound machines, Aplio 500 (Toshiba) and Avius (Hitachi Aloka), the quantitative PD (QPD) index [the summation of the colored pixels in a 1 cm × 1 cm rectangular region of interest (ROI)] was calculated via Image J (internet free software). We found a positive correlation between the injection rate and the flow velocity. In Aplio 500 and Avius, we found negative correlations between the PRF and the QPD index when the flow velocity was constant, and a positive correlation between flow velocity and the QPD index at constant PRF. The equation for the relationship of the PRF between Aplio 500 and Avius was: y = 0.023x + 0.36 [y = PRF of Avius (kHz), x = PRF of Aplio 500 (kHz)]. Our results suggested that the signal calibration of various models of ultrasound machines is possible by adjustment of the PRF setting.
22459416 Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-an 2013 Jan OBJECTIVE: Mortality rates in patients with rheumatoid arthritis (RA) have been reported to be higher than for the general population. Fortunately, efficient therapies have reduced disease activity and may be able to diminish the excess mortality risk. This study was designed to investigate RA mortality over the last 50 years by systematic review of the literature and meta-analysis. METHODS: Data to January 2010 in the Medline, Cochrane and Embase databases were searched with the keywords "rheumatoid arthritis", "epidemiologic methods" and "mortality". Inclusion criteria were (i) longitudinal study, (ii) early RA patients, (iii) number of deaths and mean patient follow-up. Incidence mortality rates (IMR) were calculated and standardized mortality rates (SMR) were extracted when available. A meta-analysis by periods of inclusion and a Poisson regression were used to model IMR. Available SMR were computed as a meta-analysis. RESULTS: A total of 11 longitudinal studies starting from 1955 to 1995, representing 51,819 patients, met the inclusion criteria. Mean IMR was 2.7/100 person-years of follow-up (95% confidence interval [CI]: 2.2, 3.3) and ranged from 1.0 to 5.2/100 person-years. A decreasing IMR was found in the meta-analyses. Poisson regression analysis indicated a decrease in IMR of 2.3% per year (95%CI: 2.1; 2.6). SMR was available in 8 studies: the meta-SMR was 1.47 (95%CI: 1.19; 1.83) and no decrease was seen over time in the meta-regression. CONCLUSION: Mortality has decreased among RA patients over the past decades but remained higher than in the general population as assessed by the IMR and the SMR over time.
23374912 Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis. 2013 Feb 4 Rheumatoid arthritis (RA) is a systemic inflammatory disease resulting from an autoimmune response to self-antigens, leading to inflammation of synovial tissue of joints and subsequent cartilage and bone erosion. Current disease-modifying anti-rheumatic drugs and biologic inhibitors of TNF, IL-6, T cells and B cells block inflammation nonspecifically, which may lead to adverse effects, including infection. They do not generally induce long-term drug-free remission or restoration of immune tolerance to self-antigens, and lifelong treatment is usual. The development of antigen-specific strategies in RA has so far been limited by insufficient knowledge of autoantigens, of the autoimmune pathogenesis of RA and of the mechanisms of immune tolerance in man. Effective tolerance-inducing antigen-specific immunotherapeutic strategies hold promise of greater specificity, of lower toxicity and of a longer-term solution for controlling or even preventing RA. This paper reviews current understanding of autoantigens and their relationship to immunopathogenesis of RA, and emerging therapeutics that aim to leverage normal tolerance mechanisms for implementation of antigen-specific therapy in RA.
22801953 Risk factors associated with the occurrence of hip fracture in Japanese patients with rheu 2013 Apr Risk factors associated with the occurrence of hip fracture in Japanese patients with rheumatoid arthritis (RA) were evaluated in a prospective, observational cohort study. Physical disability, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) appear to be associated with the occurrence of hip fracture. INTRODUCTION: This study seeks to evaluate the association between potential risk factors and the occurrence of hip fractures in Japanese RA patients. METHODS: A total of 9,720 patients (82.1% female; mean age, 55.7 years) with RA were enrolled in a prospective observational study from 2000 to 2010. Self-reported hip fractures were verified using patient medical records. Cox proportional hazards models were used to analyze independent contributions of various risk factors to hip fracture occurrence. RESULTS: During a mean follow-up of 5.2 years, 152 patients reported 152 hip fractures. Among these patients, 97 hip fractures in 97 patients (15 males, 82 females) were verified with medical records. Japanese version of the Health Assessment Questionnaire (J-HAQ) disability score [per 1 score, hazard ratio (HR), 2.64; 95% confidence interval (CI), 1.94-3.58], age (per 10 years; HR, 1.53; 95% CI, 1.25-1.87), history of TKR (HR, 3.75; 95% CI, 1.57-8.96), and BMI (per 1 kg/m2, HR, 0.92; 95% CI, 0.86-0.99) were significantly associated with hip fractures. Among the scores on the eight domains of the J-HAQ, J-HAQ (arising) (HR, 1.74; 95% CI, 1.28-2.36) and J-HAQ (hygiene) (HR, 1.58; 95% CI, 1.11-2.24) were significantly correlated with the occurrence of hip fracture. CONCLUSIONS: High J-HAQ disability score, advanced age, history of TKR, and low BMI appear to be associated with the occurrence of hip fractures in Japanese RA patients. Among the eight domains of the J-HAQ, arising and hygiene disabilities appear to be correlated with the occurrence of hip fractures in this patient population.
25194756 Dysregulated Fc receptor function in active rheumatoid arthritis. 2014 Nov Given the critical role of Fc gamma receptors (FcγR) as primary targets for autoantibody-mediated effects an important issue is how the FcγR pathway is affected in autoimmune disorders. Here we investigated the FcγR function in monocytes from rheumatoid arthritis (RA) patients in relation to immunoglobulin levels and disease activity. Peripheral blood was obtained from 30 RA patients with clinical acute joint synovitis (active RA), 28 RA patients with no clinical signs of acute joint synovitis (non-active RA) and 34 healthy controls. Prior the functional studies the monocytes were characterized of their FcγRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcγR function was assessed by binding of human IgG1 and IgG3 immune complexes (IC) and TNF secretion in vitro. IgG anti-citrullinated peptide antibodies (ACPA) were analyzed in the plasma. We found that monocytes from active RA patients had increased levels of FcγRI, II and cell surface IgG concurrently with impaired FcγR function. This was evident by reduced IgG1-IC binding and decreased TNF secretion in response to IgG3-IC. In contrast, monocytes from non-active RA patients displayed a normal FcγR function and had increased FcγRIIb expression together with elevated FcγRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcγRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcγR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcγR function controlling effect is suggested by the increased inhibitory FcγRIIb in non-active RA.
25433349 Quality of life in patients with chronic diseases. 2014 OBJECTIVES: A quality of life assessment is of great importance for patients with chronic diseases, because problems caused by specific diseases impact specific areas of their lives. The goal of this work was to determine, in which areas select diseases (rheumatoid arthritis, Crohn's disease, ischemic disease of the lower extremities and chronic obstructive pulmonary disease) affect patients' quality of life. METHODS: The Czech version of the WHOQOL-100 instrument and specific standardized questionnaires for individual diseases: EuroQol, EQ-5D-5L, IBDQ, PAQ were used to assess quality of life. This paper presents the results of the WHOQOL-100 questionnaire. In total, 5 research samples were put together. The first sample consisted of 200 respondents with rheumatoid arthritis (RA); the second sample included 100 respondents with inflammatory bowel disease (IBD); the third sample was comprised of 404 respondents with ischemic disease of the lower extremities (IDLE); the fourth sample consisted of 449 respondents with chronic obstructive pulmonary disease (COPD); and the fifth sample was represented by 1,456 healthy respondents. The acquired data were then statistically analyzed. A statistical data analysis was performed in two steps. In the first step descriptive statistical analyses were performed in the SASD program (absolute and relative frequencies of respondents' answers, median values and variability characteristics). In the second step differences in means of the subjectively-perceived quality of life in patients with individual diseases and in control group were tested using the Mann-Whitney U test and the non-parametric Wilcoxon pair test. These analyses were computed in the SPSS (Statistical Package for the Social Sciences) program. RESULTS: The results show that a statistically significant difference in average domain score values was found between the healthy population and patients diagnosed with RA in the domains of "physical health", "level of independence", "environment", and "spirituality/religion/personal beliefs". A statistically significant difference was found in all domains for patients with IDLE and COPD. A statistically significant difference was found in four domains for patients with IBD, namely those of "physical health", "level of independence", "social relationships" and "spirituality/religion/personal beliefs". CONCLUSION: All therapeutic and nursing interventions that can contribute to improving QoL in poorly performing domains should be utilized.
24989895 Novel application of multi-stimuli network inference to synovial fibroblasts of rheumatoid 2014 Jul 3 BACKGROUND: Network inference of gene expression data is an important challenge in systems biology. Novel algorithms may provide more detailed gene regulatory networks (GRN) for complex, chronic inflammatory diseases such as rheumatoid arthritis (RA), in which activated synovial fibroblasts (SFBs) play a major role. Since the detailed mechanisms underlying this activation are still unclear, simultaneous investigation of multi-stimuli activation of SFBs offers the possibility to elucidate the regulatory effects of multiple mediators and to gain new insights into disease pathogenesis. METHODS: A GRN was therefore inferred from RA-SFBs treated with 4 different stimuli (IL-1 β, TNF- α, TGF- β, and PDGF-D). Data from time series microarray experiments (0, 1, 2, 4, 12 h; Affymetrix HG-U133 Plus 2.0) were batch-corrected applying 'ComBat', analyzed for differentially expressed genes over time with 'Limma', and used for the inference of a robust GRN with NetGenerator V2.0, a heuristic ordinary differential equation-based method with soft integration of prior knowledge. RESULTS: Using all genes differentially expressed over time in RA-SFBs for any stimulus, and selecting the genes belonging to the most significant gene ontology (GO) term, i.e., 'cartilage development', a dynamic, robust, moderately complex multi-stimuli GRN was generated with 24 genes and 57 edges in total, 31 of which were gene-to-gene edges. Prior literature-based knowledge derived from Pathway Studio or manual searches was reflected in the final network by 25/57 confirmed edges (44%). The model contained known network motifs crucial for dynamic cellular behavior, e.g., cross-talk among pathways, positive feed-back loops, and positive feed-forward motifs (including suppression of the transcriptional repressor OSR2 by all 4 stimuli. CONCLUSION: A multi-stimuli GRN highly concordant with literature data was successfully generated by network inference from the gene expression of stimulated RA-SFBs. The GRN showed high reliability, since 10 predicted edges were independently validated by literature findings post network inference. The selected GO term 'cartilage development' contained a number of differentiation markers, growth factors, and transcription factors with potential relevance for RA. Finally, the model provided new insight into the response of RA-SFBs to multiple stimuli implicated in the pathogenesis of RA, in particular to the 'novel' potent growth factor PDGF-D.
25337995 Rheumatoid arthritis increases the risk of nontuberculosis mycobacterial disease and activ 2014 BACKGROUND: Few studies have examined the association of rheumatoid arthritis (RA) with nontuberculosis mycobacterium (NTM) disease and pulmonary tuberculosis (PTB). METHODS: We identified 29 131 patients with RA from the catastrophic illness registry who were diagnosed from 1998-2008; 116 524 patients without RA from inpatient data files were randomly frequency matched according to sex, age, and index year and used as a comparison group. Both groups were followed-up until the end of 2010 to measure the incidence of NTM disease and active PTB. We analyzed the risk of NTM disease and active PTB using the Cox proportional hazards regression models, controlling for sex, age, and Charlson comorbidity index (CCI). RESULTS: The incidence of NTM disease was 4.22 times greater in the RA group than in the non-RA group (1.91 vs 0.45 per 10,000 person-years). The incidence of PTB was 2.99 times greater in the RA group than in the non-RA group (25.3 vs 8.46 per 10,000 person-years). After adjusting for age, sex, and CCI, the adjusted hazard ratios (HRs) of NTM disease and active PTB for the RA group were 4.17 (95% CI = 2.61-6.65) and 2.87 (95% CI = 2.55-3.23), respectively, compared with the non-RA group. In the first 2 years of follow-up, the RA group yielded corresponding adjusted HRs of 4.98 and 3.39 compared with the non-RA group. The follow-up time-specific RA group to the non-RA group HR of both the NTM disease and active PTB varied. CONCLUSION: This study can serve as a reference for clinical physicians to increase awareness regarding the detection of NTM disease and active PTB in RA patients among the any stage of the clinical course even without CCI.
25160475 Accuracy of the second metatarsal as a landmark for the extramedullary tibial cutting guid 2014 Dec PURPOSE: The purpose of this study was to evaluate the accuracy of the second metatarsal (MT2) as a landmark for proximal tibial cutting in total knee arthroplasty (TKA). It was hypothesized that the accuracy of the MT2 is not high, especially in rheumatoid arthritis (RA) patients whose foot joints are apt to be involved. METHODS: Computer simulation studies on 48 RA knees and 45 osteoarthritis (OA) knees were performed. The deviations from the mechanical axis (MA) of the tibia when the guide rod was pointed toward the base of the MT2 or the distal part of the MT2 were measured. RESULTS: The mean deviation from MA was 0.8° ± 2.1° valgus (range 8.1°-6.3° valgus) and 1.2° ± 2.9° valgus (range 11.6°-7.9° valgus) at the base of the MT2, and at the distal part of the MT2, respectively. The outlier rate when using the base of the MT2 was lower than when using the distal part of the MT2 (12.9 vs 32.3%, p = 0.0032). The outlier rate was equivalent in OA and RA patients (n.s.). However, foot involvement in RA patients demonstrated a trend toward significance (base of MT2 p = 0.078, distal part of MT2 p = 0.068). CONCLUSIONS: The major clinical relevance was to raise caution about using the MT2. Surgeons should aim toward the base of the MT2, but avoid using it in RA patients with foot involvement. The accuracy of the MT2 is not high and it should be used only to supplement other landmarks. LEVEL OF EVIDENCE: II.
22993229 The structural basis of MRI bone erosions: an assessment by microCT. 2013 Aug OBJECTIVE: To determine whether erosions appearing in MRI in patients with rheumatoid arthritis (RA) represent true erosions. METHODS: 50 RA patients received 1.5 T MRI and microCT (μCT) of the dominant hand. Erosion counts were assessed in coronal T1 weighted MRI sections and in coronal as well as axial μCT sections of the metacarpophalangeal (MCP) joints II-IV. Extent of erosions was assessed by RA MRI Score (RAMRIS) erosion score (MRI) and by three-dimensional assessment of erosion volume (μCT). RESULTS: 111 of the 600 evaluated joint regions showed erosions in the MRI and 137 in the μCT. In only 28 regions false negative lesions (μCT positive, MRI negative) were found, all of which were very small lesions with a volume of less than 10 mm(3). Only two results were false-positive (μCT negative, MRI positive). RAMRIS erosion scores were strongly correlated to erosion volumes in the μCT (Pearson's r=0.514, p<0.001). Mean RAMRIS erosion scores were below 1 with erosion volumes up to 1.5 mm(3), below 2 with erosion volumes up to 20 mm(3) and over 2 with volumes of more than 20 mm(3). DISCUSSION: MRI erosions are generally based on true cortical breaks as shown by μCT. MRI is sensitive to detect bone erosions and only very small lesions escape detection. Moreover, RAMRIS erosion scores are closely linked to the absolute size of bone erosions in the μCT.
25597313 Role of p53 in systemic autoimmune diseases. 2014 The tumor suppressor p53 has been shown to play a central role in tumor suppression by inducing apoptosis, cell cycle arrest, senescence, and DNA repair. In addition, recent observations indicate that the dysfunction of p53 is associated with the development of autoimmune diseases. In this review, we discuss the importance of p53 in various human and murine autoimmune diseases. We also discuss the role of p53 in controlling the balance between Th17 cells and Tregs, the alteration of which is shown to be involved in the development of autoimmunity. It is postulated that the selective restoration of p53 function in T cells could be applicable to the treatment of systemic autoimmune diseases.
24930647 Characteristics of tuberculosis in patients with rheumatoid arthritis: a retrospective sin 2014 OBJECTIVE: The objective of this study was to assess the characteristics of hospitalized patients suffering from tuberculosis with rheumatoid arthritis (RA), focusing specifically on those treated without anti-tumor necrosis factor (TNF) therapy. METHODS: We conducted a retrospective review to assess the characteristics of 1,022 hospitalized Japanese patients suffering from tuberculosis with and without RA between 2002 and 2011. RESULTS: Compared with the 995 non-RA patients with tuberculosis, the 24 RA patients with tuberculosis treated without anti-TNF therapy were older and predominantly female. They less frequently had a history of smoking, with a higher rate of underlying respiratory diseases, an impaired performance status and side effects. The three RA patients receiving anti-TNF therapy had extrapulmonary tuberculosis; however, the rate of extrapulmonary tuberculosis in the other RA patients treated without anti-TNF therapy did not differ from that observed in the non-RA patients. Five patients died during hospitalization. The in-hospital mortality of the RA patients did not differ significantly from that of the non-RA patients. Independent factors contributing to in-hospital mortality did not include RA. CONCLUSION: In this study, the RA patients treated without anti-TNF therapy did not differ from the non-RA patients in terms of the rate of extrapulmonary tuberculosis or bilateral pulmonary lesions, although they did exhibit a higher frequency of side effects of antituberculosis treatment. RA was not found to be an independent factor contributing to in-hospital mortality.
24431391 Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoi 2015 May OBJECTIVES: The success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium. METHODS: Synovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4(+) and FcRL4(-) B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR. RESULTS: RANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4- B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA. CONCLUSIONS: We have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug.
24205134 The risk of metabolic syndrome in patients with rheumatoid arthritis: a meta-analysis of o 2013 BACKGROUND: Observational studies suggest an association between the incidence of rheumatoid arthritis (RA) and the prevalence of metabolic syndrome (MetS). However, the relationship between RA and MetS is controversial and research in this area is currently lacking. OBJECTIVE: The aim of this study was to assess whether the prevalence of MetS was higher in a group of RA patients compared to subjects without RA. DESIGN: A PubMed database search was conducted during April 2013 to identify observational studies of RA and risk of MetS. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments, and the method used to control for potential confounding factors. A random-effects model was used for the risk estimates. RESULTS: Our meta-analysis of four cross-sectional controlled studies plus eight case-control studies involving a total of 2283 cases and 4403 controls identified a significant association between RA and risk of MetS, with an overall OR of 1.24 (95% CI, 1.03-1.50). CONCLUSION: This meta-analysis provides further evidence supporting patients with RA have a higher prevalence of MetS than subjects without RA. In addition, the geographic region of the population and the criteria used for MetS diagnosis could influence the association. However, these observations would need to be evaluated using prospective, randomized studies.
22565655 Strengthening exercises to improve hand strength and functionality in rheumatoid arthritis 2013 Mar Rheumatoid arthritis (RA) is a systemic inflammatory and chronic disease of joints, which may result in irreversible deformities. To evaluate the effects of an exercise programme aimed at improving the hand strength in individuals with hand deformities resulting from RA and to analyse the impact these exercises have on functionality. Twenty women with RA hand deformities participated in the study. They were randomly divided into two groups as follows: Group 1 (n = 13) had women participating in the exercise programme aimed at improving handgrip (HS) and pinch strengths (PS) as well as the motor coordination of the hand; Group 2 (n = 7) had women with RA who received no treatment for their hands (control). The treatment programme for hands consisted of 20 sessions, twice a week and at-home exercises. Both groups were submitted to Health Assessment Questionnaire (HAQ) and evaluation of HS and PS by means of dynamometry. Re-evaluations were performed after 10 and 20 sessions in Group 1 and after 2 months in Group 2. After 20 sessions of physiotherapy, Group 1 had a significant gain in HS and PS (p < 0.05) in addition to the improvement of functionality as assessed by HAQ (p = 0.016). For Group 2, no difference was found between the variables analysed (p > 0.05). The strengthening exercises for individuals with RA hand deformity are beneficial to improve handgrip and pinch strengths as well as functionality.
24584757 Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen-induced arthri 2015 Nov OBJECTIVE: To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA). METHODS: Wistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent. RESULTS: Compared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal. CONCLUSION: Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.
23605471 Higher expression of latency-associated peptide on the surface of peripheral blood monocyt 2013 Oct Latency-associated peptide (LAP) forms small latent complexes with transforming growth factor beta 1 (TGF-β1). TGF-β-LAP complexes can be detected on the surfaces of immune cells and have been recently shown to play a role in immune regulation through TGF-β1-mediated functions. A study was undertaken to investigate the correlation of LAP expression on the surface of immune cells and presence of articular erosions in patients with rheumatoid arthritis (RA). Venous blood was obtained from patients with severe RA as well as from healthy control subjects. Surface expression of LAP on peripheral blood mononuclear cells was analyzed by flow cytometry, measured as flow cytometric intensity separately on CD14(+) and CD14(-) cells, and compared between RA patients and healthy subjects. Patients with RA demonstrated higher surface expression of LAP on both CD14(+) and CD14(-) mononuclear cells than healthy individuals. Patients with erosive RA had significantly reduced intensity of anti-LAP staining on the CD14(+) cells when compared to RA patients without erosions (p = 0.01). The intensity of anti-LAP staining on CD14(-) cells was not different between groups of RA patients. Higher expression of LAP on the surface of the cells of monocyte lineage may be protective of formation of articular erosions in RA. Further studies are needed to elaborate the mechanism of this phenomenon.
22610975 Occurrence and relative risk of stroke in incident and prevalent contemporary rheumatoid a 2013 Apr OBJECTIVE: In contrast with the wealth of data on ischaemic heart disease in rheumatoid arthritis (RA), data on stroke are scarce and contradictory. Despite the high clinical and aetiological relevance, there is no data regarding when (if ever) after RA diagnosis there is an increased risk. Our objective was to assess the risk of stroke (by subtype) in contemporary patients with RA, particularly in relation to time since RA diagnosis. METHODS: One incident RA cohort diagnosed between 1997 and 2009 (n=8077) and one nationwide prevalent RA cohort followed at Swedish rheumatology clinics between 2005 and 2009 ((n=39 065) were assembled). Each cohort member was matched to a general population comparator. Information on first-time hospitalisations for stroke up to 2009 was retrieved from the Swedish Patient Register. HR and 95% CI were estimated using Cox models. RESULTS: In prevalent unselected RA, the HR of ischaemic stroke was 1.29 (95% CI 1.18 to 1.41). In the incident RA cohort, the overall risk increase was small and non-significant (overall HR 1.11, 95% CI 0.95 to 1.30). When stratified by RA disease duration, an increased risk of ischaemic stroke was indeed detectable but only after 10 or more years since RA diagnosis (HR>10 years: 2.33, 95% CI 1.25 to 4.34). Risk of haemorrhagic stroke was increased in prevalent but not in incident RA. CONCLUSION: The magnitude of stroke risk is lower than for ischaemic heart disease in RA, and the evolvement of this risk from RA diagnosis may be slower. This suggests different driving forces behind these two RA co-morbidities and has implications for the clinical follow-up of patients with RA.
24131046 Evaluation of corneal biomechanical properties in patients with rheumatoid arthritis: a st 2014 Jun PURPOSE: To compare the corneal biomechanical properties of rheumatoid arthritis (RA) patients with those of healthy controls. METHODS: Measurements of 39 eyes of 39 RA patients (patient group) were compared with those of 55 eyes of 55 healthy controls (control group). Corneal hysteresis (CH), corneal resistance factor (CRF), intraocular pressure (IOP), and corneal-compensated IOP (IOPcc) were obtained for each subject by the ocular response analyzer (ORA). Corneal thickness (CCT) was measured by ultrasonic pachymeter. RESULTS: CH and CRF were significantly lower in the patient group than in the control group (p1 = 0.002, p2 = 0.019, respectively). The patient group had significantly higher IOPcc values than the control group (p = 0.024). There was no significant differences between the groups concerning CCT and IOP. CONCLUSIONS: RA patients had lower CH and CRF, but higher IOPcc values than healthy controls. RA should be considered when the corneal biomechanical properties measured by the ORA are used for diagnoses or therapies.