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ID PMID Title PublicationDate abstract
31030445 [Association of polymorphisms of miR-146a rs2910164 locus with clinical features of rheuma 2019 May 10 OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of microRNA-146a (miR-146a) with clinical features of rheumatoid arthritis (RA). METHODS: In 126 patients with RA and 102 matched healthy controls, SNPs of miR-146a rs2910164 locus were determined with a high-resolution melting method. The association of such polymorphisms with disease activity score in 28 joints (DAS28) and clinical features of RA was assessed. RESULTS: The distribution of SNPs of miR-146a rs2910164 among RA patients did not differ from that of the control group. No significant association was found between miR-146a rs2910164 polymorphism with DAS28. However, RA patients with a GG genotype had a greater chance to develop extra-articular manifestations (P<0.01). CONCLUSION: Polymorphisms of miR-146a rs2910164 locus is not an independent risk factor for RA, though its GG genotype may be associated with extra-articular manifestations of RA.
31292399 Glucocorticoid-sensitive Paroxysmal Atrial Fibrillation, Sick Sinus Syndrome, and Mitral R 2019 Nov 1 An 80-year-old woman with rheumatoid arthritis presented with chest pain. Clinical examination revealed new-onset paroxysmal atrial fibrillation with symptomatic sinus pauses and worsening mitral regurgitation, which were both resistant to conventional therapies. Based on her skin lesions, an increase in pleural and pericardial effusion, possible myocardial involvement, and a positive finding for immune complex testing, rheumatoid vasculitis was diagnosed. Subsequent glucocorticoid therapy suppressed systemic inflammation, resulting in structural, functional, and electrical reverse remodeling of the left atrium with complete remission of atrial arrhythmias and also an improvement of mitral regurgitation. This case highlights the importance of evaluating the underlying disease activity in a case of de novo paroxysmal atrial fibrillation associated with systemic autoimmune disease.
31117158 Headache and vision changes in an elderly man with rheumatoid arthritis. 2019 Jul We present a case of an elderly, immunosuppressed patient with rheumatoid arthritis who was not appropriately vaccinated, and subsequently developed herpes zoster ophthalmicus, which initially presented similar to giant cell arteritis. Evidence-based vaccinations are integral in decreasing the incidence of preventable diseases and promoting optimal health at the individual and population level. Although the patient ultimately did not suffer any long-term adverse sequelae, this case highlights the importance of vaccination in the rheumatology setting, and to consider both inflammatory and infectious causes of headache and vision changes in the elderly.
31177446 Dichotomy of Local Th1- and Systemic Th2/Th3-Dependent Types of Immune Response in Rheumat 2019 May Biomarkers of activity of rheumatoid arthritis were analyzed in the blood serum and synovial fluid of affected joints in 84 patients. Significant differences between the serum and synovial fluid levels were revealed for 10 of 17 analyzed biomarkers; the levels of IgM and proinflammatory cytokines TNFα, IL-1β, IFNγ, and IL-6 were higher in the synovial fluid. The concentration of IL-10 in the synovial fluid was also elevated. In the peripheral blood, the content of antinuclear antibodies, circulating immune complexes, and cytokines IL-4 and TGF-β was elevated. These findings attest to the development of local Th1 type immune response in affected joints paralleled by compensatory elevation of immunosuppressive cytokine IL-10 and systemic Th2/Th3 type immune response (judging from peripheral blood parameters) in patients with rheumatoid arthritis.
29409929 Cysteine cathepsins in extracellular matrix remodeling: Extracellular matrix degradation a 2019 Jan Cysteine cathepsins have been for a long time considered to execute mainly nonspecific bulk proteolysis in the endolysosomal system. However, this view has been changing profoundly over the last decade as cathepsins were found in the cytoplasm, nucleus and in the extracellular milieu. Cathepsins are currently gaining increased attention largely because of their extracellular roles associated with disease development and progression. While kept under tight control under physiological conditions, their dysregulated and elevated activity in the extracellular milieu are distinctive hallmarks of numerous diseases such as various cancers, inflammatory disorders, rheumatoid arthritis, bone disorders and heart diseases. In this review, we discuss cysteine cathepsins with a major focus on their extracellular roles and extracellular proteolytic targets beyond degradation of the extracellular matrix. We further highlight the perspectives of cathepsin research and novel avenues in cathepsin-based diagnostic and therapeutic applications.
31362993 Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with 2019 Nov BACKGROUND: In SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response. METHODS: Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised. RESULTS: Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26. CONCLUSION: Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.
31124139 Ca(2+) signalling plays a role in celastrol-mediated suppression of synovial fibroblasts o 2019 Aug BACKGROUND AND PURPOSE: Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca(2+) mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca(2+) signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. EXPERIMENTAL APPROACH: We used computational docking, Ca(2+) dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca(2+) -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 RESULTS: Celastrol inhibited SERCA to induce autophagy-dependent cytotoxicity in RASFs/RAFLS via Ca(2+) /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 Ca(2+) in celastrol-regulated gene expression. CONCLUSION AND IMPLICATIONS: Celastrol triggered Ca(2+) 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 Ca(2+) signalling.
30713716 Predicting adherence to therapy in rheumatoid arthritis, psoriatic arthritis or ankylosing 2019 OBJECTIVE: This analysis explored the association of treatment adherence with beliefs about medication, patient demographic and disease characteristics and medication types in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) to develop adherence prediction models. METHODS: The population was a subset from ALIGN, a multicountry, cross-sectional, self-administered survey study in adult patients (n=7328) with six immune-mediated inflammatory diseases who were routinely receiving systemic therapy. Instruments included Beliefs about Medicines Questionnaire (BMQ) and 4-item Morisky Medication Adherence Scale (MMAS-4(©)), which was used to define adherence. RESULTS: A total of 3390 rheumatological patients were analysed (RA, n=1943; PsA, n=635; AS, n=812). Based on the strongest significant associations, the adherence prediction models included type of treatment, age, race (RA and AS) or disease duration (PsA) and medication beliefs (RA and PsA, BMQ-General Harm score; AS, BMQ-Specific Concerns score). The models had cross-validated areas under the receiver operating characteristic curve of 0.637 (RA), 0.641 (PsA) and 0.724 (AS). Predicted probabilities of full adherence (MMAS-4(©)=4) ranged from 5% to 96%. Adherence was highest for tumour necrosis factor inhibitors versus other treatments, older patients and those with low treatment harm beliefs or concerns. Adherence was higher in white patients with RA and AS and in patients with PsA with duration of disease <9 years. CONCLUSIONS: For the first time, simple medication adherence prediction models for patients with RA, PsA and AS are available, which may help identify patients at high risk of non-adherence to systemic therapies. TRIAL REGISTRATION NUMBER: ACTRN12612000977875.
30488094 [Depression as comorbidity of rheumatoid arthritis]. 2019 Apr Depressive disorders are among the most common comorbidities in patients not only with rheumatoid arthritis (RA) but also with other forms of inflammatory rheumatic diseases. The prevalence of a depressive disorder in RA is estimated to be between 9.5% and 41.5% depending on the study and with women being more affected. After adjusting for sex, age and other parameters the risk of depression in RA was significantly elevated with an odds ratio of 1.63 (95% CI, 1.43-1.87) compared to the general population. In RA the risk of developing a depressive disorder is highest in the first 5 years and depression is a better predictor of work disability than disease activity and response to treatment. Depression in RA is associated with more pain, fatigue and impaired quality of life, whereby the association between depression and RA is bidirectional. Therefore, the risk to develop a depression is increased with impaired function as measured by the health assessment questionnaire (HAQ) and there is evidence that increased disease activity increases the risk for depression in RA. In addition, a depressive disorder also affects the subjective severity of patient-reported outcomes (PRO), such as tender joints and the global patient assessment with respect to disease activity and thus exhibiting a direct influence on the DAS28. Finally, it could be shown that depression unfavorably influences the response to therapy, the rate of remission is lower and the mortality is increased in RA patients. Taken together, this indicates that it is necessary to detect a depression in patients with RA as early as possible in order to initiate appropriate treatment of depression in such cases.
32598760 [New directions of pharmacotherapy of immune - inflammatory rheumatic diseases]. 2019 Aug 15 Deciphering immunopathogenesis, expanding the scope of diagnostics and developing new methods for treating human autoimmune diseases are among the priority areas of XXI century medicine. Particularly widely autoimmune pathology is presented in immunoinflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, systemic vasculitis associated with the synthesis of antineutrophilic cytoplasmic antibodies, Sjogren's syndrome, idiopathic inflammatory myopathies and other other types of others. Deciphering the pathogenesis mechanisms of IIRD created the prerequisites for improving pharmacotherapy, which in the future should lead to a dramatic improvement in the prognosis for these diseases. The review discusses new approaches to IIRD pharmacotherapy associated with the inhibition of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, IL-17, IL-23, and the prospects for using Janus kinase inhibitors, depending on the prevailing pathogenesis mechanisms - autoimmunity or autoinflammation.
31347977 Health Care Effect of Disease-Modifying Antirheumatic Drug Use on Patients with Rheumatoid 2019 Aug BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are recommended as the standard of care for patients with rheumatoid arthritis (RA) due to their ability to reduce pain and disability; however, DMARD use is low in some subgroups of the RA population. OBJECTIVE: To identify characteristics associated with DMARD use in the overall cohort of patients with RA and newly diagnosed RA patients. METHODS: This retrospective observational study used claims from a large national health plan. Use of DMARDs was measured according to the Healthcare Effectiveness Data and Information Set (HEDIS) as the proportion of patients with RA receiving DMARDs. Following HEDIS measure technical specifications, we identified patients aged 18-89 years with continuous enrollment during 2014 (measurement year) with ≥ 2 claims for RA outpatient visits and/or discharges on different dates between January and November 2014. Additionally, we identified a subset of patients newly diagnosed with RA in 2014 based on absence of any claims for RA or DMARDs in 2013. Descriptive analyses and bivariate associations were used to compare demographic and clinical characteristics of patients with RA with or without DMARD use in 2014. Health care resource utilization (HCRU) and costs were compared in 2014 for patients enrolled in Medicare Advantage Prescription Drug (MAPD) plans during both 2014 and 2015. Regression models were used to evaluate patient and provider characteristics associated with DMARD use in 2014 and the effect on HCRU and costs. RESULTS: Among the 33,880 patients identified with RA in 2014, most patients received a DMARD (75.2%); 29.4% of patients newly diagnosed with RA had been treated with DMARDs in 2014. Patients with DMARD use, on average, were younger (aged 67 years ± 10.7 vs. 69 years ± 10.7) and healthier (Deyo-Charlson Comorbidity Index [DCCI] 2.4 ± 1.9 vs. 2.6 ± 2.1) and included a greater proportion of women (75.9% vs. 71.0%) than those with no DMARD use (P < 0.0001). Use of DMARDs (P < 0.0001) was associated with 14.5% fewer hospitalizations and 18.0% fewer emergency department visits. Although total costs increased by 15.0% with use of DMARDs, when the cost of DMARDs was excluded, the total cost decreased by 13.7% (P < 0.0001). Female gender (32.2%), higher claims-based index for RA severity score (47.0%), higher RxRisk-V score (26.7%), visit to a rheumatologist (34.3%), and use of glucocorticoids (17.7%) increased the odds of DMARD use (P < 0.0001). Use of certain classes of medication, such as nonsteroidal anti-inflammatory drugs (12.3%), opioids (19.5%), antidepressants (20.0%), muscle relaxants (12.5%), and anticonvulsants (15.5%), were associated with lower use of DMARDs (P < 0.0001). CONCLUSIONS: We found significant differences in demographic and clinical characteristics between patients with and without DMARD use, which can potentially inform treatment decisions regarding DMARD use as deemed necessary by the provider. Future research should investigate the reasons for lack of treatment. DISCLOSURES: This study was supported by funding from Eli Lilly to Humana as a collaborative research project involving employees of both companies. Boytsov, Saverno, Zhang, and Gaich are employees of Eli Lilly. Nair, Bhattacharya, Abbott, and Dixon are employees of Humana, which received funding from Eli Lilly to complete this research.
30771056 Regulatory effects of paeoniflorin-6'-O-benzene sulfonate (CP-25) on dendritic cells matur 2019 Oct Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease. Dendritic cells (DCs) are one of the most powerful antigen-presenting cells, and they play an important role in RA pathogenesis. Prostaglandin E2 (PGE2) is a potent lipid mediator that can regulate the maturation and activation of DCs, but the molecular mechanisms have not been elucidated. In this study, both in vitro and in an RA rat model, we investigated the mechanisms involved by focusing on PGE2-mediated signaling and using a novel anti-inflammatory compound, paeoniflorin-6'-O-benzene sulfonate (CP-25). PGE2 combined with tumor necrosis factor-α promoted DC maturation and activation through EP4-cAMP signaling. Treatment with CP-25 increased the endocytic capacity of DCs induced by PGE2. CP-25 inhibited the potency of DCs induced by the EP4 receptor agonist, CAY10598, to stimulate allogeneic T cells. Consistent with these findings, the CAY10598-induced upregulation of DC surface activation markers and production of IL-23 was significantly inhibited by CP-25 in a concentration-dependent manner. In vivo administration of CP-25 alleviated adjuvant arthritis (AA) in rats through inhibition of DC maturation and activation. Our results indicate that PGE2-EP4-cAMP signal hyperfunction can lead to abnormal activation of DC functions, which correlates with the course of disease in AA rats and provides a possible treatment target. The inhibition of DC maturation and activation by CP-25 interference of the PGE2-EP4 pathway may significantly contribute to the immunoregulatory profile of CP-25 when used to treat RA and other immune cell-mediated disorders.
31515874 Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics predicti 2020 Jan Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5-1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug-likeness properties will be further studied and developed. Therefore, the herbal compounds with anti-RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti-inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-RA drug discovery.
30892152 Circulating Insulin-like Growth Factor-1 Levels in Patients with Rheumatoid Arthritis: A M 2019 BACKGROUND AND OBJECTIVES: Insulin-like growth factor-1 (IGF-1) levels have been investigated in rheumatoid arthritis (RA), however, produced inconsistent results. The purpose of this meta-analysis was to derive a more precise conclusion about serum/plasma IGF-1 levels in RA patients. METHODS: PubMed, Embase and the Cochrane Library databases were searched up to December 2018 in English, and the studies comparing serum/plasma IGF-1 levels between RA group and healthy control group were what we are interested in. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of the included studies. The heterogeneity test was performed by the Cochrane Q statistic and I2 -statistic. The publication bias was evaluated by the funnel plot and Egger's test. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the fixed-effects or random-effects model. RESULTS: A total of eleven articles with 334 cases and 261 controls were finally included. Compared with the healthy group, the RA group had lower circulating IGF-1 levels (pooled SMD= -0.936, 95% CI= -1.382 to -0.489, p<0.001). The subgroup analysis showed that RA patients from Asia (SMD= -0.645, 95% CI= -1.063 to -0.228, p= 0.002) and Europe (SMD= -1.131, 95% CI= -1.767 to -0.495, p<0.001) had lower circulating IGF-1 levels, no significant difference in plasma/serum IGF-1 levels was observed in RA patients from America. Sensitivity analysis indicated the stability and credibility of the overall effect sizes. CONCLUSION: Patients with RA have lower circulating IGF-1 level than healthy controls, particularly for patients from Asia and Europe. Further studies are necessary to elucidate the role of IGF-1 in the pathological process of RA.
28286938 N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation an 2019 Jan BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4+ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14+ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4+ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSION: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.
31802648 Profiles of resources and body image in health and illness: A comparative study among fema 2020 Jan BACKGROUND: The aim of this study was to examine whether or not profiles of resources (i.e., a multifaceted picture that simultaneously includes different types of resources), as described by the conservation of resources (COR) theory, and profiles of body image (i.e., a multidimensional picture that simultaneously includes different aspects of body image) differ between females that represent two clinical samples (rheumatoid arthritis [RA]; breast cancer [BC]) and a healthy control group. METHOD: The sample comprised 328 females, including 141 women with RA, 102 with a BC diagnosis, and 85 healthy women as a control group, and was collected from the general population. To measure the level of COR resources in each participant, we used the COR evaluation questionnaire (COR-E). Participants' body image was assessed with the aid of the Multidimensional Body-Self Relations Questionnaire (MBSRQ). RESULTS: A discriminant analysis revealed that females from the clinical groups differed with respect to their profiles of some resources and body image when compared to those of the healthy control group. In addition, we found differences in body image evaluations between women with RA and women with BC. CONCLUSIONS: Women with RA or BC differ substantially with respect to their subjectively assessed resources and body image when compared to women with no chronic diseases. Therefore, psychological counselling designed for females with RA or BC should be employed to help them restore the aspects altered by their respective illnesses.
30712718 The effectiveness of Mindfulness-Based Cognitive Therapy on the illness perception and Psy 2019 Feb This study was conducted to evaluate the Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) on the Illness Perception (IP) and Psychological Symptoms (PS) for Patients in primary care with an active symptom of Rheumatoid Arthritis (RA). The present design is a clinical trial that uses the pre-test and post-test design with a control group. MBCT as an evidence-based psychotherapeutic intervention and Mindfulness-Based Intervention (MBI), is an 8-week course developed for patients with relapsing depression that integrates mindfulness meditation practices and cognitive therapy. This semi-experimental study was conducted using a pretest-posttest and control group. Diagnostic criteria for the diagnosis of patients with RA were all patients with RA who visited the clinic of Jam Rheumatology Centers and met other inclusion criteria in Mashhad in the spring of 2018. Therefore, 28 patients were randomly selected from the diagnostic group. They were randomly assigned to an experimental group and a control group (14 individuals in each group) and then were post-tested after two months. The data were collected using the revised Illness Perception Questionnaire (IPQ-R) and Depression Anxiety Stress Scales (DASS-21 scores) which were completed by the participants. The data were analyzed using repeated measures MANOVA. The results showed that there was a significant difference between the mean scores of pre-test (before MBI) and post-test (after MBI) in the experimental group compared to the control group, and MBCT had a significant effect on the perception of the disease and the psychological syndrome in the experimental group compared to the control group. Therefore, it can be concluded that MBCT is effective on IP and psychological syndrome and can be used as an MBI method to reduce the illness perceptions in people with RA. The future researches with longer pursuing period's efficacy continuation are suggested.
30596535 Quercetin, a Plant Polyphenol, Has Potential for the Prevention of Bone Destruction in Rhe 2019 Feb We investigated the immune-regulatory function of quercetin, in interleukin (IL)-17-produced osteoclastogenesis in rheumatoid arthritis (RA). RA fibroblasts-like synoviocytes (RA-FLS) were stimulated with IL-17, and the mRNA expression and secretion of receptor activator of nuclear factor kappa-B ligand (RANKL) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. CD14(+) monocytes (osteoclast precursors) were stimulated with IL-17, RANKL, with/without quercetin, and tartrate-resistant acid phosphatase activity was evaluated to assess osteoclast differentiation. Osteoclast differentiation was investigated after coculturing IL-17-stimulated RA-FLS and Th17 cells with monocytes. CD4(+) T cells were cocultured with quercetin under Th17-inducing conditions, and their differentiation to Th17 cells and Treg cells was determined by flow cytometry analysis. We found that IL-17 stimulated RA-FLS to produce RANKL and quercetin decreased the IL-17-induced RANKL protein levels. Quercetin decreased the IL-17-produced activation of mammalian target of rapamycin, extracellular signal-regulated kinase and inhibitor of kappa B-alpha. When monocytes were stimulated with IL-17, macrophage colony-stimulating factor or RANKL, mature osteoclasts were formed, and quercetin decreased this osteoclastogenesis. When monocytes were cultured with IL-17-prestimulated RA-FLS or Th17 cells, osteoclasts were produced, and quercetin decreased this osteoclast differentiation. In Th17-differentiation conditions, quercetin suppressed Th17 cell and the production of IL-17, but quercetin did not affect Treg cells. Quercetin inhibits IL-17-stimulated RANKL production in RA-FLS and IL-17-stimulated osteoclast formation. Quercetin reduces Th17 differentiation. Quercetin could be an additional therapeutic option for bone destructive processes in RA.
31653636 Atypical presentation of rheumatoid arthritis: a case of massive bilateral pleural effusio 2019 Oct 25 Rheumatoid arthritis (RA) is a common connective tissue disorder affecting the synovial joints. In patients with RA, involvement of the lungs occurs in 30%-40% of cases while pleural effusions occur in only 3%-5%. However, the majority of RA-associated pleural effusions are small, unilateral and asymptomatic. We present a case of massive bilateral pleural effusions in a patient with established rheumatoid pneumoconiosis (Caplan syndrome). Interestingly, the pleural effusion occurred following recent treatment for minimal change disease and atrial fibrillation.
31154348 Methotrexate and doxycycline interaction: a rare cause of pancytopenia. 2019 May 31 Methotrexate (MTX) was originally formulated as one of the first antitumour drugs due to its ability to alter folate metabolism, which renders it to be an antiproliferative agent. Classically, the higher dosage is administered via parenteral route, in a cyclical fashion, to achieve antitumour effects. Patients on high doses of MTX are prone to develop rare complications of myelosuppression and pancytopenia, in a dose-dependent fashion, secondary to altered folate metabolism. (1) Herein, we present a unique case of rheumatoid arthritis presented with pancytopenia due to low-dose MTX and doxycycline drug interaction. We also report the successful management of pancytopenia and oral ulcers with combination therapy of leucovorin and granulocyte colony-stimulating factor.