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ID PMID Title PublicationDate abstract
27393379 Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis. 2016 Oct Recombinant SjCystatin (rSjCystatin), a recombinant protein of Schistosoma japonicum cystatin, has been reported to have an effect on immunoregulation mediated by IL-10 induction. Rheumatoid arthritis (RA) is a common autoimmune inflammatory arthropathy, and recombinant immune-modulating drugs for RA treatment are under development. We aimed to study the putative immune regulation of rSjCystatin and its prophylactic/therapeutic effects on murine collagen-induced arthritis (CIA). CIA was induced in DBA/1 mice by inoculation with bovine collagen II (CII). rSjCystatin was administered prior or post development of CIA. The severity of CIA was assessed using established clinical and histopathological scoring systems. The incidence was also determined. The CII-specific antibodies in sera and cytokines in splenocyte culture supernatants were measured by ELISA. Th1/Th2/Th17 cells and Tregs development in splenocytes were monitored by flow cytometry. The inflammatory mediators in the diseased joint were semiquantitated by qPCR. Prophylactic injection of rSjCystatin attenuated paw clinical scores, incidence, and histopathology scores of joints in CIA mice. The arthritis-alleviative effects were closely associated with the augmentation of IL-4, IL-10, and collagen-specific IgG1, and with the distinct reduction of IFN-γ, collagen-specific IgG2a, and the marked decrease of proinflammatory cytokines IL-6, IL-17, and TNF-α and RANKL. The data indicate that rSjCystatin may prevent cartilage destruction and inflammation of joints in CIA mice. The effects are related to the inhibitory modulation of Th1 and Th17 and upregulation of Tregs and Th2 via a shift of cytokines profiling from Th1 to Th2 response.
26829271 Comparison of the efficacy of prednisone and cyclosporine for treatment of dogs with prima 2016 Feb 15 OBJECTIVE: To compare efficacy between cyclosporine and prednisone for treatment of primary immune-mediated polyarthritis (IMPA) in dogs. DESIGN: Randomized controlled clinical trial. ANIMALS: 20 client-owned dogs with primary IMPA. PROCEDURES: Dogs were randomly assigned to receive prednisone (starting at 1 mg/kg [0.45 mg/lb], PO, q 12 h; n = 10) or cyclosporine (5 mg/kg [2.3 mg/lb], PO, q 12 h; 10) for 90 days. Cyclosporine-treated dogs also received carprofen, tramadol, or both for the first 7 days for analgesia. Data collection, physical examination, and cytologic analysis of synovial fluid samples were performed on days 0, 14, 45, and 90. Trough whole blood cyclosporine concentrations were determined on days 7 to 17 for cyclosporine-treated dogs. Treatment failure was defined as lack of clinical improvement by day 14, lack of cytologic improvement by day 45, or need to change treatment because of adverse effects. RESULTS: Treatment was successful for 7 prednisone-treated dogs and 7 cyclosporine-treated dogs. Absence of synovial fluid cytologic abnormalities on day 45 was identified for 5 prednisone-treated dogs and 8 cyclosporine-treated dogs. Prednisone-treated dogs were more likely to develop polyuria, polydipsia, and polyphagia than were cyclosporine-treated dogs. Opportunistic infections (ie, demodicosis or Erysipelothrix bacteremia) were identified in 2 cyclosporine-treated dogs and 0 prednisone-treated dogs, and diarrhea developed in 1 cyclosporine-treated dog, requiring treatment discontinuation. CONCLUSIONS AND CLINICAL RELEVANCE: Although the number of dogs evaluated was small, limiting generalizability, results of this study suggested that cyclosporine offers promise as a suitable alternative to prednisone for treatment of IMPA in dogs.
27523005 Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder Presenting as Pr 2016 Primary bone lymphoma (PBL) is a rare disorder. We herein present a case of other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) presenting as PBL. A 63-year-old woman was diagnosed with rheumatoid arthritis and had been treated with methotrexate for seven years. Two months before admission, she suffered from pain in the limbs. Magnetic resonance imaging revealed multiple irregular lesions in the bones of the limbs, which showed an uptake of (18)F-FDG on positron emission tomography. A biopsy of the right radius revealed diffuse large B-cell lymphoma, leading to the diagnosis of OIIA-LPD. She received rituximab-containing regimens resulting in a complete response.
26704133 Serum Levels of IL-6 and TNF-α May Correlate with Activity and Severity of Rheumatoid Art 2015 Dec 24 BACKGROUND We aimed to investigate the association of rheumatoid arthritis (RA) with interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) through a meta-analysis. MATERIAL AND METHODS The case-control studies that investigated the association between RA and serum levels of IL-6 and TNF-α were retrieved strictly according to the inclusion and exclusion criteria. The statistical analysis was performed using STATA statistical software (Version 12.0, Stata Corporation, College Station, TX, USA). RESULTS Fourteen studies were enrolled in our meta-analysis, with a total of 890 patients with RA and 441 healthy people as the controls. The results of this meta-analysis revealed that the serum IL-6 and TNF-α levels of RA patients were significantly higher than in the controls, and this difference was statistically significant (IL-6: SMD=2.40, 95% CI=1.57~3.24, P<0.001; TNF-α: SMD=1.93, 95% CI=1.23~2.64, P<0.001). According to ethnic subgroup analysis, the serum IL-6 and TNF-α levels of RA patients were also significantly higher compared with the controls in Asians and Caucasians (IL-6: Asians: SMD=3.64, 95% CI=2.16~5.12, P<0.001; Caucasians: SMD=0.75, 95% CI=0.47~1.02, P<0.001; TNF-α: Asians: SMD=2.74, 95%CI=1.58~3.91, P<0.001; Caucasians: SMD=0.81, 95% CI=0.50~1.11, P<0.001). CONCLUSIONS IL-6 and TNF-α may play crucial roles in the activity and severity of RA.
26344809 Control treatments in biologics trials of rheumatoid arthritis were often not deemed accep 2016 Jan OBJECTIVES: Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage patients. The objectives of the study were to compare (1) willingness to include vs. (2) willingness to prescribe control treatment among physicians randomized to assess, respectively, either (1) enrollment in a trial or (2) appropriateness of control treatment in a care context for the same fictional patient. STUDY DESIGN AND SETTING: Physicians were authors of articles about rheumatoid arthritis (RA), involved in RA patient care, and used to enrolling patients in trials. The outcomes were willingness to give control treatment: trial enrollment or control-treatment appropriateness in care context. We derived three case vignettes of fictional standard eligible patients for each of 30 RCTs assessing biologics in RA. Physicians were randomly allocated to the "trial" or "care" arm. For each of the 90 fictional patients, physicians assigned to the trial arm were asked if they would enroll the patient in the RCT the patient was derived from. For the same 90 fictional patients, physicians assigned to the care arm were asked if the control treatment of the RCT was appropriate in a context of usual care. RESULTS: Of the 1,779 physicians invited to participate, 151 were randomized. Half of the fictional patients {41/90; 45% [95% confidence interval (CI): 37%, 53%]} would be enrolled in the RCT although the control-arm treatment of the RCT was not considered appropriate for them in the context of care. This rate differed by type of comparator [55% for non-head-to-head RCTs vs. 6% for head-to-head RCTs; adjusted odds ratio (aOR), 23.9 (95% CI: 5.5, 92.7)] and duration of trial control treatment [56% for ≤24 weeks and 15% for >24 weeks; aOR, 10.7 (95% CI: 2.8, 63.9)] but not patient RA activity [aOR, 2.5 (95% CI: 1.0, 6.6)]. The limitation of this study was that physicians gave their opinion on fictional patients with only RA. CONCLUSIONS: Control treatments in RCTs of biologics in RA are often deemed not acceptable in the context of usual care, especially those for non-head-to-head RCTs. These findings raise ethical concerns and challenge the choice of the comparator in RCTs.
25747479 CD47-dependent regulation of H₂S biosynthesis and signaling in T cells. 2015 Pharmacological concentrations of H2S donors inhibit some T cell functions by inhibiting mitochondrial function, but evidence is also emerging that H2S at physiological concentrations produced via chemical sources and endogenously is a positive physiological mediator of T cell function. Expression of the H2S biosynthetic enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) is induced in response to T cell receptor signaling. Inhibiting the induction of these enzymes limits T cell activation and proliferation, which can be overcome by exposure to exogenous H2S at submicromolar concentrations. Exogenous H2S at physiological concentrations increases the ability of T cells to form an immunological synapse by altering cytoskeletal actin dynamics and increasing the reorientation of the microtubule-organizing center. Downstream, H2S enhances T cell receptor-dependent induction of CD69, CD25, and Interleukin-2 (IL-2) gene expression. The T cell stimulatory activity of H2S is enhanced under hypoxic conditions that limit its oxidative metabolism by mitochondrial and nonenzymatic processes. Studies of the receptor CD47 have revealed the first endogenous inhibitory signaling pathway that regulates H2S signaling in T cells. Binding of the secreted protein thrombospondin-1 to CD47 elicits signals that block the stimulatory activity of exogenous H2S on T cell activation and limit the induction of CSE and CBS gene expression. CD47 signaling thereby inhibits T cell receptor-mediated T cell activation.
26467595 Previous history of tuberculosis is associated with rheumatoid arthritis. 2015 Nov BACKGROUND: Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To explore the association between previous tuberculosis (TB) and RA. METHODS: We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. RESULTS: Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. CONCLUSION: TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.
26970913 Lymphatic endothelial cells efferent to inflamed joints produce iNOS and inhibit lymphatic 2016 Mar 12 BACKGROUND: In this study, we sought to determine the cellular source of inducible nitric oxide synthase (iNOS) induced in lymphatic endothelial cells (LECs) in response to tumor necrosis factor (TNF), the effects of iNOS on lymphatic smooth muscle cell (LSMC) function and on the development of arthritis in TNF-transgenic (TNF-Tg) mice, and whether iNOS inhibitors improve lymphatic function and reduce joint destruction in inflammatory erosive arthritis. METHODS: We used quantitative polymerase chain reactions, immunohistochemistry, histology, and near-infrared imaging to examine (1) iNOS expression in podoplanin + LECs and lymphatic vessels from wild-type (WT) and TNF-Tg mice, (2) iNOS induction by TNF in WT LECs, (3) the effects of iNOS inhibitors on expression of functional muscle genes in LSMCs, and (4) the effects of iNOS inhibitors on lymphatic vessel contraction and drainage, as well as the severity of arthritis, in TNF-Tg mice. RESULTS: LECs from TNF-Tg mice had eight fold higher iNOS messenger RNA levels than WT cells, and iNOS expression was confirmed immunohistochemically in podoplanin + LECs in lymphatic vessels from inflamed joints. TNF (0.1 ng/ml) increased iNOS levels 40-fold in LECs. LSMCs cocultured with LECs pretreated with TNF had reduced expression of functional muscle genes. This reduction was prevented by ferulic acid, which blocked nitric oxide production. Local injection of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide into inflamed paws of TNF-Tg mice resulted in recovery of lymphatic vessel contractions and drainage. Treatment of TNF-Tg mice with ferulic acid reduced synovial inflammation as well as cartilage and bone erosion, and it also restored lymphatic contraction and drainage. CONCLUSIONS: iNOS is produced primarily by LECs in lymphatic vessel efferent from inflamed joints of TNF-Tg mice in response to TNF and inhibits LSMC contraction and lymph drainage. Ferulic acid represents a potential new therapy to restore lymphatic function and thus improve inflammatory arthritis by inhibiting local production of nitric oxide by LSMCs.
26398753 Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry. 2015 Jul OBJECTIVE: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA). METHODS: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry. RESULTS: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure. CONCLUSIONS: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.
26556652 Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome 2016 Feb AIM: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA. PATIENTS & METHODS: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals. RESULTS: Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T lymphocytes, 113 sites in B lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease. CONCLUSION: Treatment-naive early RA patients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA.
27916091 [Tryptase inhibits cell apoptosis through upregulating PAR-2 and Rho kinase in rheumatoid 2016 Dec Objective To investigate the regulatory effects of tryptase on protease-activated receptors 2 (PAR-2), Rho signal pathway and apoptosis of MH7A rheumatoid arthritis synovial fibroblasts. Methods In MH7A cells, the expression of PAR-2 was measured by flow cytometry; cell apoptosis was examined by annexin V- FITC/PI staining combined with flow cytometry; the expression of Rho kinase was detected by Pull-down assay and Western botting. Results Tryptase upregulated the expression of PAR-2 in MH7A cells, and suppressed Fas-mediated apoptosis of MH7A cells in a dose-dependent manner. Meanwhile, PAR-2 inhibitor, FSLLRY-NH2 significantly reduced anti-apoptotic effects of tryptase in MH7A cells, which was related with the increase of activated Rho kinase expression. Conclusion Tryptase plays a role in resistance to the apoptosis of MH7A cells through raising PAR-2 and activating Rho kinase.
26502635 Non-Biologic Nanodelivery Therapies for Rheumatoid Arthritis. 2015 Oct Rheumatoid arthritis is a common chronic inflammatory disease characterized by progressive bone and cartilage destruction causing severe functional limitations, increased morbidity and mortality rate, which results in a strong negative socioeconomic impact. Current therapies only slow the progression of the disease and try to enhance quality of life. Furthermore, such therapies present several drawbacks due to the adverse effects caused by the lack of selectively of the drugs and frequent and long-term dosing that lead to patient non-compliance. Drug delivery systems based on nanocarriers represent a promising approach to overcome the current therapeutic limitations because they can selectively carry drugs to inflamed synovium allowing for improved drug efficacy, thereby reducing the biodistribution of anti-rheumatic drugs. Additionally, controlled drug release can lead to the reduction of drug dosages. The increasing interest and confidence that nanocarriers can revolutionize the treatment of rheumatoid arthritis has led to an increased number of investigations in this field. In this context, the present review focuses on drug delivery system strategies for non-biological drugs developed for the treatment of rheumatoid arthritis.
27763638 1, 25-dihydroxy-vitamin D3 with tumor necrosis factor-alpha protects against rheumatoid ar 2016 Oct 20 Impaired apoptosis of fibroblast-like synoviocytes (FLSs) causes synovial hyperplasia, facilitating destruction of cartilage and bone in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α, a dominant inflammatory mediator in RA pathogenesis, promotes progression of RA symptoms. Prevalence of 1, 25-dihydroxy-vitamin D(3) (hereafter termed VD) deficiency is 30-63% in patients with RA. Whether VD leads to apoptosis or enhances TNF-α-mediated apoptosis in FLSs to ameliorate RA is unclear. To determine this, 10-week-old CYP27B1-deficient (CYP27B1(-/-)) mice with collagen-induced arthritis (CIA) were intraperitoneally treated with 1 μg/kg VD every other day for 9 weeks. RA phenotypes were compared between vehicle-treated CYP27B1(-/-) and wild-type CIA mice. Human rheumatoid FLS-MH7A cells were treated with Dulbecco's modified Eagle's medium (DMEM) without fetal bovine serum (FBS) for 24 h, then with different concentrations of VD and TNF-α, human vitamin D receptor (VDR) siRNA or the p53 pro-apoptotic inhibitor pifithrin-α. Apoptosis and p53 pro-apoptotic signaling were analyzed. The 19-week-old vehicle-treated CYP27B1(-/-) CIA mice had increased cumulative arthritis scores and levels of serous rheumatoid factors and C-reactive protein. They had exacerbated articular cartilage and bone destruction, joint space narrowing, joint stiffness, deformity and dysfunction, synovitis and TNF-α secretion, FLS hyperplasia with increased proliferation and decreased apoptosis compared to CIA mice. These RA phenotypes that were aggravated in CIA mice by CYP27B1 deficiency were largely rescued by VD treatment. In vitro, VD with TNF-α treatment upregulated p53 acetylation-mediated apoptosis in MH7A cells by promoting Sirt1 translocation from the nucleus to the cytoplasm. These findings indicated that VD with TNF-α protected against RA by promoting apoptosis of FLSs. The results indicated that clinical administration of VD could be a specific therapy to promote FLS apoptosis and prevent RA progression.
25776035 Use and Spending for Biologic Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthrit 2015 Sep OBJECTIVE: Biologic therapies have assumed an important role in treating rheumatoid arthritis (RA). We sought to investigate use, spending, and patient cost-sharing for Medicare beneficiaries using biologic drugs for RA, comparing patients exposed to minimal cost-sharing because of a Part D low-income subsidy (LIS) to those facing substantial out-of-pocket costs (OOP). METHODS: We performed a retrospective, nationwide study using 2009 Medicare claims for a 5% random sample of beneficiaries with RA who had at least 1 RA drug dispensed. We analyzed biologic drug utilization and costs across the Part B (medical benefit) and Part D (pharmacy benefit) programs by LIS status using multinomial regression. We also projected OOP costs as the Affordable Care Act (ACA) mandates closure of the Part D coverage gap by 2020. RESULTS: Among 6,932 beneficiaries, 1,812 (26.1%) received a biologic drug. LIS beneficiaries were significantly more likely to obtain Part D home-administered biologics (relative risk ratio [RRR] 2.98, 95% confidence interval [95% CI] 2.50-3.56), while non-LIS beneficiaries were less likely to receive Part D biologic agents (RRR 0.58, 95% CI 0.48-0.69). OOP costs in Part D were lower, as expected, for LIS beneficiaries ($72 versus $3,751 per year for non-LIS). Non-LIS beneficiaries had lower costs for Part B facility-administered biologic agents (range $0-$2,584) than for Part D home-administered biologic agents. ACA reforms will narrow OOP differences between Part D and B for non-LIS beneficiaries. CONCLUSION: In contrast to LIS beneficiaries who receive mostly Part D home-administered biologic DMARDs, nonsubsidized beneficiaries have significant cost-based incentives to obtain facility-administered biologic DMARDs through Part B. The ACA will result in only slightly lower costs for Part D biologic drugs for these beneficiaries.
26726982 Is There an Ideal Patellar Thickness Following Total Knee Arthroplasty? 2016 Jan Orthopedic surgeons resurface the patella during total knee arthroplasty to avoid complications such as pain, patello-femoral arthritis, and patellar maltracking and to reduce the risk for reoperation. However, many complications, such as decreased range of motion, increased fractures, and polyethylene wear, have been described with this procedure. One determinant when resurfacing a patella is the thickness of its cuts. This review aims to investigate the relationship between patellar thickness and outcome parameters such as range of motion, patient-reported outcomes, periprosthetic fractures, and reoperations.
27428186 High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthri 2016 Jul OBJECTIVES: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). METHODS: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. RESULTS: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. CONCLUSIONS: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment.
26745543 Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estro 2016 Mar In addition to the systemic inflammation present in rheumatoid arthritis (RA), decreased estradiol levels in postmenopausal RA patients further accelerate bone loss in these patients. The tissue-selective estrogen complex (TSEC), an estrogen combined with a selective estrogen receptor modulator, is a new hormone replacement therapy option. The first approved TSEC, containing conjugated estrogens and bazedoxifene (BZA), reduces menopausal symptoms and prevents osteoporosis with an improved safety profile compared with conventional hormone replacement therapy. Previous studies have shown that estrogens strongly inhibit experimental arthritis whereas BZA is mildly suppressive. In this study the antiarthritic potential of combined BZA and estradiol is explored for the first time. Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis, an experimental postmenopausal RA model, and treated with BZA, 17β-estradiol (E2), combined BZA and E2 (BZA/E2), or vehicle. BZA/E2 suppressed arthritis severity and frequency, synovitis, and joint destruction, equally efficient as E2 alone. Unwanted estrogenic proliferative effects on the endometrium were blocked by the addition of BZA, determined by collecting uterine weights. Bone mineral density was measured by peripheral quantitative computed tomography, and all treatments protected collagen-induced arthritis mice from both trabecular and cortical bone loss. Moreover, BZA/E2, but not E2 alone, inhibited preosteoclast formation and reduced serum anticollagen type II antibodies. In conclusion, a TSEC, herein combined BZA/E2, suppresses experimental arthritis and prevents associated bone loss as efficiently as E2 alone but with minimal uterine effects, highlighting the need for clinical trials that evaluate the addition of a TSEC to conventional postmenopausal RA treatment.
27300757 New Insights into the Management of Patients with Autoimmune Diseases or Inflammatory Diso 2016 Sep The treatment of autoimmune diseases remains a serious problem. Current therapies can lead to adverse effects in patients. One of the most vulnerable patient groups is pregnant women. It has been reported that different autoimmune diseases have a certain trend during pregnancy and after delivery which could be explained by maternal immune responses. Better management of pregnant women with autoimmune diseases or inflammatory disorders could be achieved by linking such alterations in immune responses and governed immune responses in different autoimmune disorders while considering various reports of autoimmune conditions during pregnancy. This study considers changing the T helper cells (Th1) and Th2 balance and suggests some new approaches for the better management of autoimmune diseases in pregnant women based on immune responses. Additionally, the possible role of Th17, alterations in some selected autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), asthma and pemphigus during pregnancy, and possible associated mechanisms are discussed.
26684633 Safety and efficacy of intra-articular anti-tumor necrosis factor α agents compared to co 2016 Jun The aim of this study was to assess safety and efficacy of ultrasonography (US)-guided intra-articular injections using tumor necrosis factor (TNF) blockers compared to corticosteroids in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients, experiencing refractory monoarthritis despite the current systemic therapy. Eighty-two patients were randomized to receive three intra-articular injections monthly of either corticosteroid or TNF blockers. Primary endpoints were the safety and an improvement greater than 20% for visual analogic scales of involved joint pain in patients injected with anti-TNFα. Further clinical, US, and magnetic resonance imaging (MRI) evaluations were considered secondary endpoints. Intra-articular TNF blockers are a safe strategy, determining a significant reduction of patient and physician reported clinical outcomes and US/MRI scores, in RA and PsA patients, when compared to intra-articular injections of corticosteroids. US guidance excluded the possibility to inject the drug in the wrong site, maximizing local effects, reducing systemic effects, and increasing the safety of the procedure. Patients with inflammatory monoarthritis could be successfully treated with US-guided intra-articular TNF blockers that are a safe and well tolerated procedure, to achieve a longstanding clinical and radiological good clinical response and/or disease remission.
26914266 Resistance Training as a Tool for Preventing and Treating Musculoskeletal Disorders. 2016 Sep The aging process is characterized by several physiological, morphological, and psychological alterations that result in a decreased functional and health status throughout the life span. Among these alterations, the loss of muscle mass and strength (sarcopenia) is receiving increased attention because of its association with innumerous age-related disorders, including (but not limited to) osteoporosis, osteoarthritis, low back pain, risk of fall, and disability. Regular participation in resistance training programs can minimize the musculoskeletal alterations that occur during aging, and may contribute to the health and well-being of the older population. Compelling evidence suggest that regular practice of resistance exercise may prevent and control the development of several musculoskeletal chronic diseases. Moreover, resistance training may also improve physical fitness, function, and independence in older people with musculoskeletal disorders, which may result in improved quality of the years lived. In summary, regular participation in resistance training programs plays an important role in aging and may be a preventive and therapeutic tool for several musculoskeletal disorders.