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ID PMID Title PublicationDate abstract
26213210 Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a n 2015 Nov OBJECTIVE: Synovial fluid pH is decreased in patients with rheumatoid arthritis (RA); however, the underlying mechanisms are unclear. We undertook this study to examine the mechanism by which synovial fluid pH is regulated and to explore the possibility of a therapeutic strategy by manipulating this mechanism. METHODS: We determined the pH and lactate concentration in synovial fluid from 16 RA patients. Cultured synovial fibroblasts (SFs) from the inflamed joints of 9 RA patients (RASFs) were examined for the expression of ion transporters that regulate intracellular and extracellular pH. The ion transporter up-regulated in RASF lines was then suppressed in RASFs by small interfering RNA (siRNA), and the effect of transfection on viability and proliferation was investigated. Finally, we examined the therapeutic effect of electrotransfer of monocarboxylate transporter 4 (MCT4)-specific siRNA into the articular synovium of mice with collagen-induced arthritis (CIA). RESULTS: Synovial fluid pH correlated inversely with both the Disease Activity Score in 28 joints using the C-reactive protein level and the synovial fluid lactate levels. RASFs exhibited up-regulated transcription of MCT4 messenger RNA. MCT4 exported intracellular lactate into the extracellular space. RASFs had significantly higher MCT4 protein levels than did SFs from patients with osteoarthritis. Knockdown of MCT4 induced intrinsic apoptosis of RASFs, thereby inhibiting their proliferation. Moreover, electrotransfer of MCT4-specific siRNA into the articular synovium of mice with CIA significantly reduced the severity of arthritis. CONCLUSION: RA activity correlated with decreased synovial fluid pH. This may be due to increased MCT4 expression in RASFs. Silencing MCT4 induced apoptosis in RASFs and reduced the severity of CIA, suggesting that MCT4 is a potential therapeutic target for inflammatory arthritis.
27271301 Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell Damage in Early Rheum 2016 Oct The effects of co-administration of dry olive leaf extract (DOLE) with standard methotrexate (MTX) therapy on the parameters of cell damage and inflammation in patients with early and long-term rheumatoid arthritis (RA) were evaluated at baseline, 3 and 6 weeks. Patients were assigned to groups: the early phase RA group on MTX monotherapy (E MTX), and the two RA groups that received co-treatment with DOLE and MTX: early (E MTX + DOLE) and long-term phase patients (L-t MTX+ DOLE). Baseline values indicated increased parameters of cell damage and disruption of redox balance in all groups. After three weeks the E MTX + DOLE group maintained high catalase activity, exhibited decrease of lipid peroxidation and protein damage indicators-thiols and nitrites, while levels of DNA damage and pro-inflammatory interleukin-6 were significantly reduced. In E MTX group catalase activity remained unaltered while significant lipid peroxidation and DNA damage reductions were seen only after six weeks. L-t MTX + DOLE group showed only modest alterations of cell damage parameters during six weeks. Combined administration of DOLE with MTX contributes to faster reduction of cell damage, restores oxidative balance and improves interleukin-6 suppression during high disease activity in early phase RA, but not in long term patients. Copyright © 2016 John Wiley & Sons, Ltd.
26259617 Efficacy and safety results from a Phase 3, randomized, placebo-controlled trial of subcut 2016 Nov AIM: The efficacy and safety of golimumab + methotrexate (MTX) were evaluated in Chinese patients with active rheumatoid arthritis (RA) despite MTX therapy. METHODS: Chinese patients (n = 264) were randomly assigned (1 : 1) to receive subcutaneous injections of placebo + MTX with crossover to golimumab 50 mg + MTX at week 24 (Group 1) or to golimumab 50 mg + MTX (Group 2) every 4 weeks. Group 1 patients with inadequate response entered blinded early escape to golimumab 50 mg + MTX at week 16. At least a 20% improvement in the American College of Rheumatology (ACR20) criteria at week 14 was the primary endpoint. Other assessments included the 28-joint count Disease Activity Score using C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI) through week 52. Adverse events (AEs) were monitored through week 56. RESULTS: ACR20 response at week 14 was significantly higher in Group 2 (40.9% [54/132]) compared with Group 1 (15.9% [21/132]; P < 0.001). Greater proportions of patients in Group 2 compared with Group 1 had a DAS28-CRP response at week 14 (65.2% vs. 30.3%, P < 0.001) or ACR20 response at week 24 (42.4% vs. 15.9%, P < 0.001), and Group 2 had a significantly greater change in HAQ-DI at week 24 (-0.26 vs. 0.15, P < 0.001). After week 24, the proportion of patients achieving ACR20 in Group 1 approached that in Group 2. Through week 16, 23.5% of Group 1 and 26.7% of Group 2 patients reported AEs. Among golimumab + MTX-treated patients, 50.2% and 4.2% had ≥ 1 AE or serious AE, respectively, through week 56. No unexpected safety signals were observed. CONCLUSION: Among MTX-experienced Chinese patients with active RA, a significantly greater proportion of patients receiving golimumab + MTX had improvements in the signs and symptoms of RA compared with MTX monotherapy. Safety findings were consistent with previous studies of golimumab in patients with RA.
25758228 Staphylococcus aureus sepsis in rheumatoid arthritis. 2015 Sep Patients with rheumatoid arthritis (RA) are at increased risk of infection. In this study, we determined the risk of and risk factors for Staphyococcus aureus (S. aureus) sepsis in RA. We assembled a retrospective nested case-control subset of RA patients with S. aureus sepsis from the Barnes-Jewish Hospital Medical Informatics database, confirmed the diagnoses, and collected data electronically and by chart review. We used multivariate logistic regression to identify independent risk factors for S. aureus sepsis, with risk expressed as odds ratios (ORs). We extracted data on the length of hospitalization and 30-day and 1-year mortality from the Medical Informatics database for all cases and controls. There were 48 confirmed S. aureus sepsis cases and 232 confirmed controls in the RA cohort. In multivariate analysis, indwelling central venous catheter (OR 15.97; 95 % CI 5.09-50.10; p < 0.01) and congestive heart failure (OR 2.89; 95 % CI 1.26-6.63; p = 0.01) were independently associated with risk of S. aureus sepsis, while treatment with disease-modifying anti-rheumatic drugs (DMARDs), both biologic and non-biologic, was not. S. aureus sepsis was associated with increased 30-day and 1-year mortality (OR 7.37; 95 % CI 2.86-19.0; p < 0.01 for 30-day and OR 5.24; 95 % CI 2.51-10.94; p < 0.01 for 1-year mortality) and longer hospitalization (p < 0.01). Treatment with biologic DMARDs was not associated with longer hospitalization (p = 0.89). Indwelling central venous catheters and congestive heart failure increased the risk of S. aureus sepsis in this observational cohort of patients with RA. Treatment with biologic and non-biologic DMARDs did not increase this risk.
27214046 Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy 2016 Nov OBJECTIVE: To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX). METHODS: Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearson's correlation coefficient. RESULTS: After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP (<2.6) had the lowest mean 5-joint and 3-joint composite synovial vascularity scores. The 5-joint and 3-joint scores were strongly correlated (ρ > 0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physician's global assessment, patient's global assessment of pain, and disease duration (ρ < 0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of ≥1. CONCLUSION: PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved.
27369643 Immunogenicity of tocilizumab in patients with rheumatoid arthritis. 2017 Jan OBJECTIVE: The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls. METHODS: Anti-drug antibodies (ADAs) to TCZ and serum TCZ trough levels in RA patients were assessed at different times by ELISA. Frequencies of naive anti-TCZ CD4+ precursors were studied in healthy controls. RESULTS: In total, 91 samples from 40 RA patients were analyzed: 21 patients within the first 6 months after treatment initiation and 19 during follow-up after a mean TCZ treatment duration of 21±13 months. None of the 91 samples showed persistent ADAs to TCZ. Only 3 RA patients showed transient and low titers of anti-TCZ ADAs. Serum TCZ trough levels were associated with neither patient characteristics (gender, body mass index) nor disease activity and were identical for patients with and without co-treatment with methotrexate. Three of 9 healthy donors showed preexisting TZC-specific CD4+ T cells at a low level. CONCLUSION: Serum TCZ trough levels were not affected by patient characteristics. The occurrence of ADAs to TCZ was a rare event. Because healthy donors show the same frequency of naive TCZ-specific and infliximab-specific CD4+ T cell precursors, the low prevalence of ADAs to TCZ might result from interleukin-6 blockade.
25914745 The efficiency of biologic therapy in a group of patients with rheumatoid arthritis. 2015 Jan OBJECTIVES: The following study aims to evaluate the monotherapy with biologic agents: Infliximab (IFX), Etanercept (ETA), Adalimumab (ADA) and Rituximab (RTX) in patients diagnosed with rheumatoid arthritis (RA). METHODS: To achieve these objectives, the database of "Dr. I. Cantacuzino" Clinical Hospital, Department of Internal Medicine and Rheumatology, was used. The study was retrospective and descriptive, covering 168 patients with RA, followed for 12 months, from January 2012 to January 2013. Admission criteria for the study were the following: patients diagnosed with RA according to ACR 1987/ EULAR 2010 criteria, disease activity score (DAS 28)> 5.1, positive inflammation tests, presence of RA refractory to classic remitting treatment administered at least 6 months prior to the initiation of biological therapy, on patients treated with RTX. They were considered non-responders after 6 months of treatment with anti tumor necrosis factor alpha (anti-TNF) and decided to switch agents with anti CD-20. RESULTS: Comparing values between any two points in time (baseline - 6 months -12 months) for any type of therapy, there were significant decreases in the values of erythrocyte sedimentation rate (ESR), reactive C protein (CRP) and disease activity score (DAS 28). There were no significant differences between therapies regarding ESR at 6 months (p = 0.070, ANOVA) and 12 months (p = 0.375, Kruskal-Wallis), significant differences were regarding CRP at 6 and 12 months (p = 0.000, Kruskal-Wallis) and DAS 28 at 6 months (p = 0.000, Kruskal- Wallis) and 12 months (p = 0.018, Kruskal-Wallis). CONCLUSION: All 4 therapies have proven efficient, prognostic markers decreasing gradually at 6 and 12 months.
24684408 Tocilizumab is clinically, functionally, and radiographically effective and safe either wi 2015 Jan OBJECTIVES: To explore the effectiveness and safety of tocilizumab (TCZ) with or without methotrexate (MTX) in active rheumatoid arthritis (RA) patients showing inadequate responses to DMARDs and/or TNF inhibitors in clinical practice. METHODS: We observed consecutive 115 RA patients initiating TCZ treatment in Keio University Hospital, dividing them into two groups with (TCZ + MTX group) or without MTX (TCZ group), and evaluated clinical, functional and structural outcomes besides safety at week 52. RESULTS: Overall mean age, RA duration, and DAS28-ESR were 55.4, 8.4 years, and 5.0, respectively. Proportions of the prior use of TNF inhibitors and concomitant MTX were 45.5% and 57.4%, respectively. Mean dose of concomitant MTX was 8.4 mg/week. Baseline characteristics were comparable between the groups. TCZ improved disease activity measured by DAS28-ESR to 2.1 at week 52 overall, without significant difference between the groups. Clinical (DAS28-ESR < 2.6), functional (HAQ-DI ≤ 0.5), and structural (ΔTSS ≤ 0.5) remission rates in the TCZ group and the TCZ + MTX group were 79.1%/63.8% (P = 0.10), 62.8%/54.4% (P = 0.40), and 70.0%/53.8% (P = 0.61), respectively. Retention rates were 81.0% in the TCZ + MTX group and 88.5% in the TCZ group (P = 0.47). The rate of serious adverse events was comparable between the groups. CONCLUSIONS: TCZ was clinically, functionally, and radiographically effective and safe either with or without low-dose MTX.
27450196 Inhibition of furin results in increased growth, invasiveness and cytokine production of s 2017 Jul OBJECTIVES: Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes. METHODS: In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated. RESULTS: The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1β and tumor necrosis factor-α secretion of synoviocytes. CONCLUSIONS: Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis.
27848057 The additional benefit of ultrasonography to 2010 ACR/EULAR classification criteria when d 2017 Feb The aim of this study was to assess the benefit of ultrasonography (US) contributing to 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria in diagnosing rheumatoid arthritis (RA), when anti-citrullinated protein (CCP) antibody and radiographic erosions are absent. Ninety-four patients suffering from arthritis of at least one joint in hands, symptom duration of less than 2 years, normal radiographs at baseline, and negative anti-CCP had 22 joint US assessments and were followed prospectively for at least 12 months. Sensitivity and specificity for final RA diagnosis based on 1987 RA criteria were determined for ultrasound variables. Logistic regression models were then fitted to evaluate predictive ability over and above the 2010 ACR/EULAR classification criteria. Twenty-nine of them were classified as RA patients and 65 had alternative diagnoses. There were significantly more joints with synovial hypertrophy, synovitis, and bone erosion detected by US in RA patients. The gray-scale (GS) variables positively correlated with acute phase reactants. The area under curve (AUC) values of GS and power Doppler (PD) were comparable, higher than bone erosion. However, regression analysis demonstrated that only PD involvement of joints, especially wrists, provided independently predictive data, with improved AUC values from 0.738 to 0.872 combined with 2010 ACR/EULAR classification criteria. PD scanning of hand joints, especially wrists, may provide independently assistance to 2010 ACR/EULAR criteria in the early diagnosis of RA in those patients who are negative for anti-CCP antibody.
26394271 Varicella-zoster virus infection in rheumatoid arthritis patients in the anti-tumour necro 2015 Nov Patients with rheumatoid arthritis are increasingly being treated with different drugs (both non-biologic and biologic disease-modifying anti-rheumatic drugs - DMARDs) that may have immunomodulatory, cytotoxic, or immunosuppressive effects; in particular, anti-tumour necrosis factor (TNF) agents are raising major concern as regards safety issues. An increased risk of infections has been extensively reported during anti-TNF treatment, owing to the primary role of TNF in host defense and immune responses. Although in clinical practice cases of reactivation of varicella zoster virus (VZV) infections during therapy with TNF inhibitors commonly occur, the knowledge on this topic deriving from randomised clinical trials is limited. In this narrative review we focus on the pathophysiology of VZV infection and the role of TNF, and report the available data about VZV outbreaks recorded on Registries of rheumatic patients treated with anti-TNF agents. Finally, we discuss screening strategies and promising preventive measures against VZV infection.
26628596 Summary Findings of a Systematic Literature Review of the Ultrasound Assessment of Bone Er 2016 Jan OBJECTIVE: Bone erosions in rheumatoid arthritis (RA) have been studied in an increasing amount of research. Both earlier and present classification criteria of RA contain erosions as a significant classification component. Ultrasound (US) can detect bone changes in accessible surfaces. Therefore, the study group performed a systematic literature review of assessment of RA bone erosions with US. METHODS: A systematic search of PubMed and Embase was performed. Data on the definitions of RA bone erosions, their size, scoring, relation to synovitis, comparators, and elements of the OMERACT (Outcome Measures in Rheumatology Clinical Trials) filter were collected and analyzed. RESULTS: The selection process identified 58 original research papers. The assessed joints were most frequently metacarpophalangeal (MCP; 41 papers), proximal interphalangeal (19 papers), and metatarsophalangeal joints (MTP; 18 papers). The OMERACT definition of RA bone erosion on US was used most often (17 papers). Second and fifth MCP and fifth MTP were recommended as target joints. Conventional radiography was the most frequently used comparator (27 papers), then magnetic resonance imaging (17 papers) and computed tomography (5 papers). Reliability of assessment was presented in 20 papers and sensitivity to change in 11 papers. CONCLUSION: This paper presents results of a systematic literature review of bone erosion assessment in RA with US. The survey suggests that US can be a helpful adjunct to the existing methods of imaging bone erosions in RA. It analyzes definitions, scoring systems, used comparators, and elements of the OMERACT filter. It also presents recommendations for a future research agenda based on the results of the review.
25760299 Interleukin-6 in rheumatoid arthritis - from the laboratory to the bedside. 2015 Rheumatoid arthritis (RA) is a common and debilitating disease. Expanded therapeutic options, targeting pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-6 (IL-6), have revolutionised RA treatment. To date, efficacy data shows superiority of IL-6 inhibition over placebo, conventional disease modifying anti-rheumatic drugs such as methotrexate, and TNF inhibition. Moreover, while demonstrating some key differences in the safety profile compared with TNF inhibition (e.g. hyperlipidemia and neutropenia), these safety concerns have not, at least to date, been found to cause clinically significant adverse outcomes. Other safety parameters, such as infection and malignancy rates have been found to be comparable between IL-6 and TNF inhibition. This review explores the biology and clinical applications of IL-6 inhibition in the management of RA.
27311175 [Genetic risk factors for rheumatoid arthritis]. 2016 Jun Rheumatoid arthritis (RA), the most common autoimmune diseases, is a systemic, chronic inflammatory disease, which is primarily involves the joints affecting up to 1% of the population. RA is believed to be a complex, multifarious disease that is influenced by both genetic and environmental factors. Disease susceptibility has been estimated to have a genetic component of 60% by data from twin studies. To date, more than 100 RA susceptibility loci, including HLA-DRB1, have been identified by genome-wide association studies (GWAS) and GWAS meta-analyses. Through a big data approach using large amounts of comprehensive biologic data included GWAS, we identified important information, such as susceptible genes, pathways and cell types that contribute to RA pathogenesis.
25832554 Effects of Concomitant Methotrexate on Large Joint Replacement in Patients With Rheumatoid 2015 Oct OBJECTIVE: To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. METHODS: A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias. RESULTS: Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6-8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P < 0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20-0.65). Additionally, propensity score-matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032). CONCLUSION: Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.
27919207 Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifyin 2017 Sep OBJECTIVE: To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. METHODS: This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. RESULTS: Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. CONCLUSION: Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.
25803089 Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stres 2015 Jun BACKGROUND: Rheumatoid arthritis is an inflammatory autoimmune disorder. Withania somnifera Dunal (Solanaceae) (WS), is a common medicinal plant used in traditional systems of medicine for the treatment of arthritis, and is an ingredient of anti-arthritic polyherbal formulations such as Habb-e-Asgand® and Arthritin™. In the present study, we evaluated the antioxidant and anti-arthritic activity of aqueous extract of WS root (WSAq) in collagen-induced arthritic (CIA) rats. METHODS: CIA rats were treated by using three doses of WSAq (100, 200, 300 mg/kg b. wt., orally) and methotrexate (MTX, 0.25 mg/kg b. wt. i.p.) as a standard reference drug for 20 days. The anti-arthritic effect was assayed by measuring the arthritic index, autoantibodies such as rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (a-CCP), anti-nuclear antibody (ANA), anti-collagen type II antibody (a-CII) and inflammatory marker like C-reactive protein (CRP). The oxidative stress parameters were also measured. RESULTS: Treatment with WSAq resulted in a dose-dependent reduction in arthritic index, autoantibodies and CRP (p < 0.05) with maximum effect at dose of 300 mg/kg b. wt. and the results were comparable to that of MTX-treated rats. Similarly, oxidative stress in CIA rats was ameliorated by treatment with different doses of WSAq, as evidenced by a decrease in lipid peroxidation and glutathione-S-transferase activity and an increase in the glutathione content and ferric-reducing ability of plasma (p < 0.05). CONCLUSIONS: The results showed that WSAq exhibited antioxidant and anti-arthritic activity and reduced inflammation in CIA rats and suggests the potential use of this plant in the treatment of arthritis.
27520507 Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation 2016 Nov 1 Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of high-density lipoprotein (HDL) has been observed. Although the actual players are unknown, anti-HDLs were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA. Therefore, we aimed to evaluate whether the presence of antibodies against PON1 may be involved in this scenario. IgG anti-PON1 antibodies were quantified by ELISA in serum samples from 212 RA patients, 175 healthy controls (HC) and 54 subjects with traditional CV risk factors (CVR). A subgroup of 13 RA patients was prospectively followed upon tumour necrosis factor-α  (TNFα) blockade. Serum PON1 activity, nitric oxide (NO) and total antioxidant capacity (TAC) were measured. Interferon-γ (IFNγ), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule (sICAM) and TNFα serum levels were assessed by immunoassays. PON1 rs662 (Q > R) status was studied by reverse transcription (RT)-PCR. IgG anti-PON1 antibodies are increased in RA patients compared with HC (P<0.0001) and CVR subjects (P<0.001), even after correcting for total IgG levels. Although no associations with lipid profile were found, a positive correlation with Health Assessment Questionnaire (HAQ) was observed (r=0.215, P=0.004). Anti-PON1 antibodies were associated with PON1 activity, NO and TAC, a rs662-mediated gene-dosage effect being found. Similarly, anti-PON1 antibodies were associated with sICAM serum levels in univariate and multivariate models. Finally, these antibodies were not affected by TNFα blockade. Anti-PON1 antibodies can be responsible for PON1 impairment in RA patients, with a potential impact on biomarkers of oxidative status and endothelial activation. A gene-environment interaction of rs662 variants is supported.
27374036 Left ventricular function in rheumatoid arthritis during anti-TNF-α treatment: a speckle 2016 Jun 22 AIM: Rheumatoid arthritis (RA) shows a high risk for cardiovascular disease, including heart failure. Although TNF-α has been implicated in the pathogenesis of myocardial remodelling, TNF-α inhibition did not show any efficacy in patients with advanced heart failure and should be contraindicated in RA with cardiac complications. We aimed to assess global left ventricular (LV) systolic function using global longitudinal strain (GLS) as a measure of myocardial deformation, in a group of RA patients before and during anti-TNF-α treatment. METHODS: 13 patients (female:male 7:6) affected by RA were prospectively followed for one year during anti TNF-α treatment. Every subject underwent echocardiography before starting anti-TNF-α drugs and after one year of treatment, to evaluate LV ejection fraction (EF), telediastolic diameter, telediastolic volume and global longitudinal strain (GLS) that was calculated using 2D speckle tracking as the mean GLS from three standard apical views (2, 3 and 4 -chambers). The patients showed a mean age of 43 years at RA onset (SD: 13) and a mean follow-up of 7.3 years (SD: 4.8). Steroid and methotrexate were used in 84.6% and 100%, respectively, in association with etanercept (6 cases), adalimumab (4 cases) and infliximab (3 cases). RESULTS: Patients globally showed a normal EF before and after one year of treatment (mean: 65% and 65.7%, respectively). GLS did not differ before or after anti-TNF-α treatment (mean: -15.8% and -16.7%, respectively). CONCLUSION: Anti-TNF-α treatment did not significantly modify myocardial contractility after 12 months.
27337798 [Value of serum matrix metalloproteinase-3 in the assessment of active disease in patients 2015 Dec 15 OBJECTIVE: To investigate the value of serum matrix metalloproteinase-3 (sMMP-3) in the assessment of active disease in patients with rheumatoid arthritis (RA). METHODS: One hundred and ninety-one RA patients were recruited from the Department of Rheumatology of Sun Yat-sen Memorial Hospital from June 2010 to June 2014. sMMP-3 level of these RA patients and 58 healthy people was tested by enzyme-linked immunosorbent assay, while clinical data was collected simultaneously. Receiver operating characteristic (ROC) curve was used for the analysis of optimal cut-off point for the evaluation of disease activity. RESULTS: There were 128 female patients and 63 male patients recruited. sMMP-3 was significantly higher in RA patients than healthy control and it was higher in patients with active disease than that in patients in remission (all P < 0.01). ROC curve analysis showed that the optimal cut-off point for diagnosing active RA was 84 μg/L with area under the curve (AUC) 0.822 in female and 168 μg/L with AUC 0.824 in male (both P < 0.01). According to the optimal cut-off points, the sensitivity of sMMP-3 + CRP combined detection was 97.2% for diagnosing active RA, which was significantly higher than that of sMMP-3 (84.7%) or C-reactive protein (CRP) (88.2%, both P < 0.05). The specificity of combined detection was 95.7%, which was significantly higher than that of sMMP-3 (68.1% , P < 0.01). And Youden's index of combined detection (0.951) was significantly higher than that of sMMP-3 (0.528) or CRP (0.754, both P < 0.05). CONCLUSION: sMMP-3 is a helpful indicator for disease activity measurement in RA patients. Combined detection of sMMP-3 and CRP can improve the accuracy of disease activity assessment.