Effects Of Rheumatoid Arthritis Research Articles

Association Between Adiponectin and Clinical Manifestations in Rheumatoid Arthritis.

Adiponectin (APN) belongs to adipokines. Previous studies showed contradictory results that have both proinflammatory and anti-inflammatory effects in rheumatoid arthritis (RA). We set out to detect the levels of APN and the correlations between APN and the clinical manifestations in RA patients. Sera of 60 newly diagnosed patients with RA and 29 age- and gender-matched healthy subjects were collected. Clinical parameters, including C-reactive protein (CRP), erythrocyte sedimentation rate, rheumatoid factor (RF), antibodies to cyclic citrullinated peptide, disease activity score 28, and bone erosion conditions, were collected. The serum levels of total APN and high-molecular-weight APN (HMW-APN) were detected by enzyme-linked immunosorbent assay. As a result, total APN and HMW-APN levels were all lower in patients with RA compared with healthy controls. The levels of APN and HMW-APN were all positively correlated with CRP levels. There was also positive correlation between HMW-APN levels and RF levels. Moreover, patients with higher disease activities had higher HMW-APN levels; patients with more severe synovial thickening had higher APN and HMW-APN levels. Therefore, APN, especially HMW-APN, may play a regulatory role in RA.

Patient with rheumatoid arthritis with deep vein thrombosis presenting as a calf strain: a case report

BackgroundPatients with rheumatoid arthritis experience various comorbidities, including cardiovascular disease. More data and awareness exist regarding the adverse effects of rheumatoid arthritis affecting the arterial side of the cardiovascular system, such as stroke or myocardial infarction, than regarding adverse venous complications, such as deep vein thrombosis and pulmonary embolism. Rheumatoid arthritis affects more women than men, and the risk of venous thromboembolism in rheumatoid arthritis tends to increase with age; therefore, the presentation in this case report of deep vein thrombosis in a nonsmoking, young, fit man with rheumatoid arthritis is rare. This patient was sent away from a minor injuries unit with a diagnosis of a calf strain. Further assessment at an accident and emergency department later in the day confirmed deep vein thrombosis via ultrasonography. This case report underlines the need for vigilance because deep vein thrombosis is a risk factor in rheumatoid arthritis, even in young, male, and physically fit individuals.Case presentationA nonsmoking 39-year-old Caucasian man with a 2-year history of rheumatoid arthritis presented for assessment at a private physiotherapy clinic with a 4-week history of right-sided posterior calf pain that had developed following exercise at a gym. The patient therefore believed his symptoms were due to a calf strain. Findings at physiotherapy assessment suggested that the actual cause of the patient’s symptoms were as a result of deep vein thrombosis. The patient was directed to a local minor injuries unit with a referral letter from the author outlining this diagnosis. Following clinical assessment at the minor injuries unit, the patient was told that there was no likelihood of deep vein thrombosis, and his diagnosis was a calf strain. The patient harbored concerns at this point and decided to seek further medical opinion at a nearby accident and emergency department, where deep vein thrombosis was diagnosed using ultrasonography, and the patient was commenced on anticoagulants.ConclusionsVenous thromboembolism risk in rheumatoid arthritis is stated as being less recognized as an arterial complication. This is borne out by this patient’s clinical journey, wherein his youth, fitness, athletic appearance, and onset of symptoms during exercise were said to suggest a diagnosis of a calf strain at a minor injuries unit. Ultrasonography at a different accident and emergency unit later that day ultimately was used to diagnose deep vein thrombosis.

Pulp stem cells with hepatocyte growth factor overexpression exhibit dual effects in rheumatoid arthritis

BackgroundTo investigate the therapeutic effect of human dental pulp stem cells (DPSCs) transfected with adenovirus expressing hepatocyte growth factor (HGF) in a mouse model of collagen-induced arthritis (CIA).MethodsDPSCs were modified with Ad-HGF to produce HGF-overexpressing DPSCs, DPSCs-HGF. In experimental mouse CIA model, DPSCs-HGF and DPSCs-Null (modified with Ad-Null) were engrafted via intravenously after disease onset, which was determined by the presence of joint swelling. The therapeutic effects on joints were evaluated at 49 days after collagen injection by histopathological analysis and microcomputed tomography imaging. The inflammatory cytokines were analyzed both in sera and joints via MILLIPLEX kit and immunohistochemical staining, respectively, and the regulatory T cells (Tregs) were analyzed in peripheral blood by using flow cytometry. Furthermore, primary fibroblast-like synoviocytes were isolated, colony formation analysis and FACS were performed to evaluate the effect of HGF on the proliferation and cell cycle of FLSs. Western blot assay was carried out to clarify the signal pathway of HGF-cMet.ResultsWe found that without HGF modification, DPSC transfusion was helpful in controlling autoimmune status, local synovitis, and bone erosion after intravenous administration. However, HGF-modified DPSCs have dual role in rheumatoid arthritis (RA). In the early phase, HGF overexpression inhibited RA progression by its immunosuppressive effects, while in the late phase, HGF promoted synovitis by activating fibroblast-like synoviocytes to produce pathogenic IL-6, accelerating cell proliferation and inducing apoptosis resistance via phosphorylating the c-Met/Akt pathway. The overall effect of HGF modification attenuated the therapeutic effect of DPSCs.ConclusionsOur study provides a comprehensive evaluation of the therapeutic effect of DPSCs in the mouse model and a primary answer to the divergence of whether HGF is harmful or helpful in RA.

Transcutaneous auricular stimulation of the vagus nerve for erosive hand osteoarthritis an open label pilot study

Purpose: Beyond classical effect on vegetative functions, the activation of the vagus nerve inhibits inflammation and reduces the pain signal. Recently, vagus nerve stimulation (VNS) using implantable cervical devices have demonstrated an analgesic and anti-inflammatory therapeutic effect in rheumatoid arthritis. However, the use of such implantable device is limited by the need of cervical surgery and subsequent potential side effects. Besides implantable devices, VNS can also be performed using transcutaneous VNS (tVNS) of the ascendant auricular branch of the vagus nerve that selectively innervates the cutaneous zone of cymba conchae.

Resveratrol Reduces Cartilage Matrix Degradation and Affects Chondrocyte Apoptosis in Rats with Traumatic Arthritis

Objective: Resveratrol (Resv) is a polyphenolic compound with anti-inflammatory, anti-oxidant, and other pharmacological effects in rheumatoid arthritis (RA). However, whether Resv has protective and therapeutic effects in post-traumatic arthritis (PTA) remains poorly understood. We explored the function of Resv in the treatment of PTA and reducing chondrocyte matrix degradation and chondrocyte apoptosis in PTA rats. Methods: The PTA rat model was established and divided into sham group and Resv gavage group. MMP-13 and Hyp contents in the joint cavity fluid were tested by ELISA. MMP-13 and COL2A1 protein expressions in the articular cartilage tissue were detected by Western blot. Mankin score was measured. The chondrocytes cultured in vitro and divided into control group, IL-1β group, and IL-1β + Resv group. Flow cytometry was adopted to detect cell apoptosis. Results: MMP-13 and Hyp contents were significantly increased, MMP-13 protein expression was significantly upregulated, COL2A1 protein expression was significantly reduced, while Mankin score was increased in PTA group in comparison to those in normal rats. Resv treatment significantly reduced MMP-13 protein expression and elevated COL2A1 protein level in cartilage tissue, decreased MMP-13 and Hyp contents in joint cavity fluid, and reduced Mankin score. After the treatment of IL-1β, the level of MMP-13 protein was significantly elevated, with decreased COL2A1 protein level in chondrocytes, and enhanced chondrocytes apoptosis. Resv intervention significantly inhibited MMP-13 protein and increased COL2A1 level in chondrocytes, and attenuated cell apoptosis. Conclusion: Resv inhibits MMP-13 expression, attenuates chondrocyte matrix degradation and apoptosis, indicating it plays a therapeutic value in treating PTA.

Telmisartan alone or in combination with etanercept improves anemia associated with rheumatoid arthritis in rats: a possible role of anti-inflammatory and reno-protective effects.

There are conflicting data regarding angiotensin receptor blockers (ARBs) induced anemia and its beneficial anti-inflammatory effect in rheumatoid arthritis. The aim of the present study was to investigate the effect of telmisartan administration either alone or in combination with etanercept on anemia of chronic inflammatory diseases in a model of rheumatoid arthritis in rats. Rheumatoid arthritis (RA) was induced by Freund's Complete Adjuvant (FCA; 1mg/0.1ml paraffin oil), injected subcutaneously on days 0, 30 and 40. Rats with RA received dimethyl sulfoxide (DMSO), etanercept (0.3mg/kg 3 times/week; sc), telmisartan (1.5mg/kg/day; orally) or combination of etanercept and telmisartan. Arthritis parameters (footpad circumference change and paw volume change), erythrocyte indices (hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin level changes), iron profile (serum iron and serum ferritin), serum levels of erythropoietin (EPO), hepcidin, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were evaluated, along with measuring serum urea and creatinine levels. All treated groups showed improvement of the measured parameters in comparison to RA-control subgroup. Telmisartan either alone or in combination with etanercept significantly improved arthritis and erythrocyte indices. Telmisartan showed significant increase in EPO and decrease in hepcidin compared to etanercept. Combination group showed significant improvement in serum iron, ferritin, EPO, hepcidin, TNF-α, IL-6, urea and creatinine, compared to etanercept. Telmisartan either alone or in combination, but not etanercept alone, significantly decreased creatinine level. Telmisartan improved anemia and arthritis parameters and showed anti-inflammatory and reno-protective effects, in a rat model of rheumatoid arthritis.

<p>Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study</p>

BackgroundThe traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA.Methods64 RA patients aged 18–64 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 × 107 cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy.Results1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05).ConclusionUC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.

Effect of rheumatoid arthritis and age on metacarpal bone shaft geometry and density: A longitudinal pQCT study in postmenopausal women

ObjectiveThis study aimed to elucidate the effects of changes in the geometry and density of the metacarpal bone of patients with rheumatoid arthritis (RA). MethodsThis prospective study included consecutive postmenopausal RA patients who met the American College of Rheumatology Criteria and healthy controls (HC). Peripheral quantitative computed tomography scans at 50% of the total metacarpal shaft (third metacarpal bone) were obtained at baseline and follow-ups. Use of bisphosphonates (BP), glucocorticoids (GC), biologics, and disease-modifying anti-rheumatic drugs (DMARD) was monitored (baseline to follow-up). Total cross-sectional area (CSA), cortical-transitional zone and compact zone CSA, cortical volumetric bone mineral density, and compact cortex porosity were measured. A linear mixed-effects model was used to determine significant differences in the rate of change in the RA and control groups and in RA patient subgroups. ResultsThirty-nine RA patients and 42 consecutive postmenopausal HC were followed for 63 months. RA and HC depicted a time-dependent increase of medullary CSA (+0.41 mm2/year, P < 0.0001), while total CSA remained stable (P = 0.2). RA status was associated with a loss of cortical bone mineral density (interaction: −3.08 mg/mm3; P = 0.014). In RA subgroup analysis, GC use ≥5 mg/day was positively correlated with a fourfold increase of medullary CSA (0.67 mm2/year P = 0.009), which resulted in a three- to fourfold loss of cortical density (−6.6 mg/mm3/year; P = 0.002) and cortical CSA (−0.57 mm2/year, P = 0.004). Patients with high disease activity and high GC dose at baseline demonstrated an increase in the total CSA (0.29 mm2/y; P = 0.049) and a loss of cortical BMD (−5.73 mg/mm3/y; P = 0.05) despite good clinical response. ConclusionIncrease in medullary metacarpal CSA and thinning of the cortical CSA are physiological and time dependent. RA status is associated with loss in cortical density. Even upon biological therapy, low glucocorticoid dose affects metacarpal bone shaft geometry and density over time.

Is Virtual Reality Effective in Orthopedic Rehabilitation? A Systematic Review and Meta-Analysis

Virtual reality (VR) is an interactive technology that allows customized treatment and may help in delivering effective person-centered rehabilitation. The purpose of this review was to systematically review and critically appraise the controlled clinical trials that investigated VR effectiveness in orthopedic rehabilitation. Pubmed, CINAHL, Embase, PEDro, REHABDATA, and Sage publications were searched up to September 2018. In addition, manual searching and snowballing using Scopus and Web of Science were done. Two reviewers screened studies for eligibility first by title and abstract and then full text. Articles were categorized into general or region-specific (upper limbs, lower limbs, and spine) orthopedic disorders. Study quality was assessed using the Evaluation Guidelines for Rating the Quality of an Intervention Study scoring. Meta-analysis quantified VR effectiveness, compared with no treatment, in back pain. Nineteen studies were included in the quality assessment. The majority of the studies were of moderate quality. Fourteen studies showed that VR did not differ compared with exercises. Compared with the no-treatment control, 5 studies favored VR and 3 other studies showed no differences. For low back pain, the meta-analysis revealed no significant difference between VR and no-treatment control (n=116; standardized mean difference=-0.21; 95% confidence interval=-0.58 to 0.15). Limitations included heterogeneity in interventions and the outcome measures of reviewed studies. Only articles in English were included. The evidence of VR effectiveness is promising in chronic neck pain and shoulder impingement syndrome. VR and exercises have similar effects in rheumatoid arthritis, knee arthritis, ankle instability, and post-anterior cruciate reconstruction. For fibromyalgia and back pain, as well as after knee arthroplasty, the evidence of VR effectiveness compared with exercise is absent or inconclusive.

Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumatoid arthritis but not psoriatic arthritis

Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA.Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy.Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes.Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations.Clinicaltrials.gov NCT01078090, NCT01077258, NCT01111240

Ca2+ signalling plays a role in celastrol-mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats.

Background and PurposeCelastrol exhibits anti‐arthritic effects in rheumatoid arthritis (RA), but the role of celastrol‐mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol‐induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant‐induced arthritis (AIA) in rats.Experimental ApproachWe used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast‐like synoviocytes (RAFLS), mechanisms of Ca2+‐mediated autophagy were analysed by histological, immunohistochemical and flow cytometric techniques. Anti‐arthritic effects of celastrol, autophagy induction, and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes, using siRNA methods to study calmodulin, calpains, and calcineurin.Key ResultsCelastrol inhibited SERCA to induce autophagy‐dependent cytotoxicity in RASFs/RAFLS via Ca2+/calmodulin‐dependent kinase kinase‐β–AMP‐activated protein kinase–mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory‐ and autoimmunity‐associated genes down‐regulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca2+ in celastrol‐regulated gene expression.Conclusion and ImplicationsCelastrol triggered Ca2+ signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium‐dependent/‐binding proteins facilitating the exploitation of anti‐arthritic drugs based on manipulation of Ca2+ signalling.

Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naïve patients with rheumatoid arthritis

ObjectivesTo compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). MethodsPatients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan–Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. Results6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41–3.83) for TNFi-combo, 4.14 (3.77–4.62) for TNFi-mono, 2.98 (2.76–3.34) for TCZ-combo and 3.63 years (3.34–5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52–0.69) and TCZ-combo (0.66, 95% CI 0.54–0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. ConclusionIn routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.

The roles of synovial hyperplasia, angiogenesis and osteoclastogenesis in the protective effect of apigenin on collagen-induced arthritis

Apigenin (API) is a plant flavone that is known to exert a protective effect in rheumatoid arthritis (RA), which is a chronic autoimmune disease. However, the molecular mechanism for API's protective effect against RA is still unclear. Here, a collagen-induced arthritis (CIA) mouse model was used to assess the protective effect of API on RA. Histomorphological studies, immunohistochemistry, RT-PCR, and western blot were conducted to elucidate the roles of synovial hyperplasia, angiogenesis, and osteoclastogenesis in the protective effect of API on RA. Fibroblast-like synoviocytes (FLSs) were isolated to measure the effect of API on FLS proliferation and apoptosis. API exhibited a significant protective effect in CIA mice in a dose- and time-dependent manner. An increase in apoptosis and decrease in proliferation were observed after the API treatment in FLSs, suggesting that API might inhibit synovial hyperplasia. Moreover, CIA angiogenesis was repressed by API via down-regulation of VEGF and VEGFR. Furthermore, API regulated the osteoclastogenesis-associated RANKL/RANK/OPG system in CIA mice. Therefore, API inhibits CIA by repressing synovial hyperplasia, angiogenesis, and osteoclastogenesis. This suggested that API might be a putative low toxicity candidate drug for RA treatment.

Influence of different supplementation on platelet aggregation in patients with rheumatoid arthritis.

Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been reported to reduce platelet aggregation. Our aim was to prospectively assess the potential influence of different supplementation omega-3 PUFA on the antiplatelet effects in rheumatoid arthritis (RA) patients. The study included 60 patients with RA at the Department of Rheumatology, Clinical Center Kragujevac. Patients were divided into three groups depending on who used concentrated fish oil only or concentrated fish oil in combination with evening primrose oil or control group without supplementation in a period of 3months. Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test, aranchidonic acid-induced aggregation (ASPI) test, thrombin receptor-activating peptide (TRAP) test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP representing the degree of inhibition of platelet aggregation compared to the basal value. The platelet function analysis in whole blood was performed 18-24h before starting supplementation and after 90days. Considerations were taken in the representation of demographic, clinical characteristics, and laboratory parameters between the groups. Patients who used concentrated fish oil only had a significantly lower value of the ratio of ADP/TRAP (0.68 ± 0.20) compared to patients without supplementation (0.83 ± 0.12; p = 0.008), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. Co-administration of supplementation-concentrated fish oil may reduce platelet aggregation in adults with RA. • Omega-3 PUFAs are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases.. • In this paper, we report on anti-aggregation effects n-3 PUFAs and ɤ-linolenic acid in RA. • The risk of cardiovascular morbidity and mortality is increased in RA, and dietary supplementation of n-3 PUFA may have preventive potential for the cardiovascular management in rheumatoid arthritis.

A Population-level Analysis of the Differing Effects of Rheumatoid Arthritis and Spondyloarthritis on Peripartum Outcomes.

The effects of rheumatoid arthritis (RA) and spondyloarthritis (SpA) on maternal and neonatal outcomes at a population level have not previously been well compared. A contemporary pregnancy cohort of 312,081 women and corresponding birth events was assembled for the province of Alberta from the random selection of 1 live birth event per woman. We identified 3 groups: (1) no inflammatory arthritis (no IA, n = 308,989), (2) RA (n = 631), and (3) SpA (n = 2461). We compared maternal and neonatal outcomes, comorbid conditions, and medication use among the 3 groups. Multivariable logistic regression models evaluated the independent association between RA and SpA, relative to no IA, and the outcomes of small for gestation age (SGA) and hypertensive disorders during pregnancy. Pregnant women with RA were significantly more likely to have preterm delivery (13.5%), cesarean delivery (33.9%), hypertensive disorders in pregnancy (10.5%), and SGA babies (15.6%), compared to pregnant women with either SpA or no IA. Nonsteroidal antiinflammatory drugs and corticosteroid use were significantly higher in pregnant women with RA compared to the other groups. Women with RA were significantly more likely to have an SGA baby (OR 1.51, 95% CI 1.21-1.88; p < 0.01), and hypertensive disorder in pregnancy (OR 1.51, 95% CI 1.16-1.97; p < 0.01), compared to women with no IA, while no difference was found between women with SpA and those with no IA. Women with RA have a higher risk of worse maternal and neonatal outcomes, whereas the risk of these events is similar between women with and without SpA.

Investigation of Efficacy Enhancing and Toxicity Reducing Mechanism of Combination of Aconiti Lateralis Radix Praeparata and Paeoniae Radix Alba in Adjuvant-Induced Arthritis Rats by Metabolomics.

Combination of Aconiti Lateralis Radix Praeparata (FZ) and Paeoniae Radix Alba (BS) shows a significant effect in rheumatoid arthritis (RA). This study aimed to investigate the efficacy enhancing and toxicity reducing mechanism of combination of them in adjuvant-induced arthritis (AIA) rats by metabolomics. Rats were randomly divided into seven groups, including A (healthy control), B (model control), C1 (therapy group), C2 (efficacy enhancing group), D1 (toxicity group), and D2 (toxicity reducing group), and dexamethasone group was used as positive control. The plasma biochemical indexes showed that therapeutic dose of lipid-soluble alkaloids of FZ could significantly inhibit the concentrations of IL-1β, TNF-α, and IFN-γ in AIA rats, and combination with total glucosides of peony could further reduce the concentration of IL-1β. Then, UPLC-LTQ/Orbitrap MS with untargeted metabolomics was performed to identify the possible metabolites and pathways. Through multivariate data analysis of therapeutic dose groups (A vs. B vs. C1 vs. C2) and multivariate data analysis of toxic dose groups (A vs. B vs. D1 vs. D2), 10 and 7 biomarkers were identified based on biomarker analysis, respectively. After inducing AIA model, the plasma contents of spermidine, vanillylmandelic acid, catechol, and linoleate were increased significantly, and the contents of citric acid, L-tyrosine, L-phenylalanine, leucine, L-tryptophan, and uridine 5'-monophosphate (UMP) were decreased significantly. High dose of lipid-soluble alkaloids of FZ could increase the plasma contents of L-lysine, L-arginine, and deoxycholic acid, while the plasma contents of UMP, carnitine, N-formylanthranilic acid, and adenosine were decreased significantly. The pathway analysis indicated that therapeutic dose of lipid-soluble alkaloids of FZ could regulate energy and amino acid metabolic disorders in AIA rats. However, toxic dose could cause bile acid, fat, amino acid, and energy metabolic disorders. And combination with total glucosides of peony could enhance the therapeutic effects and attenuate the toxicity induced by lipid-soluble alkaloids of FZ.

Melatonin attenuates TNF-α and IL-1β expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis.

The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1β production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1β production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.

The effect of rheumatoid arthritis on patient-reported outcomes following knee and hip replacement: evidence from routinely collected data.

ObjectivesTo compare outcomes of total knee replacement (TKR) and total hip replacement (THR) for individuals with RA and OA.MethodsWe performed a cohort study using routinely collected data. Oxford Knee Score, Oxford Hip Score, and EuroQol 5-dimension 3-level (EQ-5D-3L) questionnaires were collected before and 6 months after surgery. Multivariable regressions were used to estimate the association between diagnosis and post-operative scores after controlling for pre-operative scores and patient characteristics.ResultsStudy cohorts included 2070 OA and 142 RA patients for TKR and 2030 OA and 98 RA patients for THR. Following TKR, the median Oxford Knee Score was 37 [interquartile range (IQR) 29–43] for OA and 36 (27–42) for RA while the median EQ-5D-3L was 0.76 (0.69–1.00) and 0.69 (0.52–0.85), respectively. After THR, the Oxford Hip Score was 42 (IQR 36–46) for OA and 39 (30–44) for RA while the EQ-5D-3L was 0.85 (0.69–1.00) and 0.69 (0.52–1.00), respectively. The estimated effect of RA, relative to OA, on post-operative scores was −0.05 (95% CI −1.57, 1.48) for the Oxford Knee Score, −0.09 (−0.13, −0.06) for the EQ-5D-3L following TKR, −1.35 (−2.93, −0.22) for the Oxford Hip Score, and −0.08 (−0.12, −0.03) for the EQ-5D-3L following THR.ConclusionTKR and THR led to substantial improvements in joint-specific scores and overall quality of life. While diagnosis had no clinically meaningful effect on joint-specific outcomes, improvements in general quality of life were somewhat less for those with RA, which is likely due to the systemic and multijoint nature of rheumatoid disease.

Transdermal delivery of fluvastatin sodium via tailored spanlastic nanovesicles: mitigated Freund's adjuvant-induced rheumatoid arthritis in rats through suppressing p38 MAPK signaling pathway

The current study aimed to encapsulate fluvastatin sodium (FVS), a member of the statins family possessing pleiotropic effects in rheumatoid arthritis (RA), into spanlastic nanovesicles (SNVs) for transdermal delivery. This novel delivery could surmount FVS associated oral encumbrances such as apparent first-pass effect, poor bioavailability and short elimination half-life, hence, accomplishing platform for management of RA. To consummate this objective, FVS-loaded SNVs were elaborated by thin film hydration method, utilizing either Span 60 or Span 80, together with Tween 80 or Brij 35 as an edge activator according to full factorial design (24). Applying Design-Expert® software, the influence of formulation variables on SNVs physicochemical properties and the optimized formulation selection were explored. Additionally, the pharmacokinetic studies were scrutinized in rats. Furthermore, in Freund's adjuvant-induced arthritis, rheumatoid markers, TNF-α, IL-10, p38 MAPK, and antioxidant parameters were measured. The optimum SNVs were nano-scaled spherical vesicles (201.54 ± 9.16 nm), having reasonable entrapment efficiency (71.28 ± 2.05%), appropriate release over 8 h (89.45 ± 3.64%) and adequate permeation characteristics across the skin (402.55 ± 27.48 µg/cm2). The pharmacokinetic study disclosed ameliorated bioavailability of the optimum SNVs gel by 2.79- and 4.59-fold as compared to the oral solution as well as the traditional gel, respectively. Moreover, it elicited a significant suppression of p38 MAPK expression and also significant improvement of all other measured biomarkers. Concisely, the foregoing findings proposed that SNVs can be auspicious for augmenting FVS transdermal delivery for management of RA.

The effects of rheumatoid arthritis on Cypriot recreational athletes

Introduction: Recreational athletes may be hindered by systemic pathologies that appear as sport related injury, however on closer inspection they are later diagnosed with Rheumatoid Arthritis (RA). The aims of this study endeavour to investigate the effects of RA on recreational athletes in the Cypriot population, more specifically physical ability, mental perceptions, behavioural choices and the use of alternative therapeutic modalities of treatment. Methods: Six recreational athletes (3 males and 3 females, mean ± SD 41.33 ± 15.85 years) diagnosed with RA were selected for this study. All participants were of Cypriot nationality and were involved in physical activity of 5+ hours per week. Participants were required to undergo a Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and a semi-structured reflective interview. Results: The data collected from both the interview and the MDHAQ are directly related to the participant’s current state (present time evaluation) of disease. Participants in this study had a mean score of 3.04 resulting in a moderate severity rating on the MDHAQ. Seven prominent reoccurring themes were present amongst the six participants. Discussion: Themes indicate an overlap in patient phenomenon and perspective. The detailed insights may possibly aid the future development and research into the effects of RA on patient well-being, a more optimal treatment and care plan for therapy and support. Conclusion: Recreational athletes suffering from RA may be limited in daily physical activity and participation in recreational activity. The purpose of this study intended to draw themes between RA, physical activity limitations and recreational athlete perspectives.