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ID PMID Title PublicationDate abstract
28774451 Interventions and Therapy in Rheumatology. 2017 Sep Patients affected by rheumatic conditions frequently present with spine degeneration and vertebral compression fractures, mainly related to the long-term therapies with glucocorticosteroids. A mini-invasive approach provided by interventional radiology techniques, especially vertebroplasty, plays a relevant role in the pain management of these patients; vertebroplasty represents the symptomatic treatment of fracture pain, so patients must always be included in a specific therapeutic workup of the rheumatic condition. This article describes patient selection criteria, technique, and outcomes of vertebroplasty in patients affected by rheumatic disease and secondary osteoporosis caused by glucocorticosteroids.
28335610 Rheumatoid Forefoot Reconstruction in the Nonrheumatoid Patient. 2017 Jun BACKGROUND: Recurrent pain and deformity following forefoot surgery can cause significant patient disability. In patients with rheumatoid arthritis, first metatarsophalangeal (MTP) joint arthrodesis with lesser metatarsal head resections-termed the rheumatoid forefoot reconstruction-has been shown to be a reliable operation for pain relief and deformity correction. Limited data, however, have been published on outcomes of the same forefoot reconstruction operation in the nonrheumatoid patient. Here, we describe our experience with this procedure in patients without rheumatoid disease, hypothesizing improved clinical and radiographic outcomes following surgery. METHODS: Following chart review and reviewing billing codes, we retrospectively identified patients without a diagnosis of rheumatoid arthritis who underwent first MTP arthrodesis with lesser metatarsal head resections. Phone surveys were conducted to assess clinical outcomes including pain and patient satisfaction. Preoperative and postoperative radiographs were reviewed for 1, 2 intermetatarsal angle (IMA), hallux valgus angle (HVA), second MTP angle (MTP-2), and lesser MTP alignment (in both sagittal and axial planes). Postoperative radiographs were assessed for radiographic union. We identified 14 nonrheumatoid patients (16 feet) who underwent forefoot reconstruction. Of those, 13 patients (15 feet) were successfully contacted via follow-up phone survey at an average of 44.3 months postoperatively (range: 20-76 months). RESULTS: Mean postoperative satisfaction scores were 9.0 (out of 10). No patients required reoperation at final phone follow-up. Pain scores significantly decreased from 6.2 preoperatively to 1.9 postoperatively ( P <.001). Radiographic parameters (1,2 IMA, HVA, MTP-2, and lesser MTP alignment in the sagittal plane) improved with surgery ( P <.05), and all 16 feet achieved union of the first MTP arthrodesis. CONCLUSION: With decreased pain, high satisfaction rates, and improved radiographic parameters, first MTP arthrodesis coupled with lesser metatarsal head resection was a viable option for nonrheumatoid patients who failed prior attempts at forefoot reconstruction or have chronic forefoot pain with deformity. LEVEL OF EVIDENCE: Level IV, retrospective case series.
27186644 Effect of tumor necrosis factor-α inhibitors on ambulatory 24-h blood pressure. 2017 Feb Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly being used in inflammatory rheumatic diseases (IRD). The risk of cardiovascular disease is elevated in patients with IRD and TNF-α inhibitors reduce this risk. We assessed whether the beneficial effect of TNF-α inhibitors on cardiovascular risk is mediated by blood pressure reduction. We measured blood pressure levels with 24-h ambulatory blood pressure measurements device in patients with IRD before and 3 months after treatment with TNF-α inhibitors. The study population consisted of 15 subjects (6 men; mean age 45.9 ± 14.1 years). Most patients had either rheumatoid arthritis or psoriatic arthritis and adalimumab was the most common TNF-α inhibitor used. Mean 24-h systolic and diastolic blood pressure levels remained the same after treatment (121 ± 12/66 ± 7 before and 123 ± 11/67 ± 10 mm Hg after; p = 0.88 and 0.66, respectively). The study demonstrates that TNF-α inhibitors have no effect on blood pressure levels.
28438745 Management of chronic pain using complementary and integrative medicine. 2017 Apr 24 Complementary and integrative medicine (CIM) encompasses both Western-style medicine and complementary health approaches as a new combined approach to treat a variety of clinical conditions. Chronic pain is the leading indication for use of CIM, and about 33% of adults and 12% of children in the US have used it in this context. Although advances have been made in treatments for chronic pain, it remains inadequately controlled for many people. Adverse effects and complications of analgesic drugs, such as addiction, kidney failure, and gastrointestinal bleeding, also limit their use. CIM offers a multimodality treatment approach that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. This review focuses on the use of CIM in three conditions with a high incidence of chronic pain: back pain, neck pain, and rheumatoid arthritis. It summarizes research on the mechanisms of action and clinical studies on the efficacy of commonly used CIM modalities such as acupuncture, mind-body system, dietary interventions and fasting, and herbal medicine and nutrients.
27405509 Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with 2017 Mar OBJECTIVE: To investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: In 13 310 patients with RA observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure. RESULTS: 37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/cumulative glucocorticoids and non-steroidal anti-inflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2-0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-α inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment. CONCLUSIONS: The incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation.
28244282 Descriptive Epidemiology of Patients Undergoing Total Hip Arthroplasty in Korea with Focus 2017 Apr We analyzed the causes leading to total hip arthroplasty (THA), aimed to clarify the incidence of femoroacetabular impingement (FAI) among the causes, and compared the incidence in Korea with those in other countries. From January 2000 to December 2014, 1,206 hips of 818 patients who underwent primary THA at our institute were reviewed retrospectively in terms of radiographs and electronic charts. The radiographs and radiographic parameters were reviewed and measured by 2 of the authors, who are orthopedic surgeons. Patients were categorized in terms of the causes leading to THA as primary osteoarthritis (OA), rheumatoid arthritis (RA), posttraumatic arthritis, post infectious arthritis, avascular necrosis (AVN) of the femoral head, fracture of the femoral head or neck, ankylosing spondylitis (AS), developmental dysplasia of the hip (DDH), Legg-Calvé-Perthes disease (LCPD), FAI, and others. There were 32 patients (3.91%) in the primary OA group, 41 (5.01%) in the RA group, 84 (10.27%) in the posttraumatic arthritis group, 39 (4.77%) in the post infectious arthritis group, 365 (44.62%) in the AVN group, 39 (4.77%) in the fracture group, 21 (2.57%) in the AS group, 52 (6.36%) in the DDH group, 71 (8.68%) in the LCPD group, 52 (6.36%) in the FAI group, and 22 (2.69%) in the 'other' group. The causes leading to THA in Korea differ from those in Western countries. FAI could be causes of severe secondary OA that requires THA in Korea, therefore symptomatic FAI should not be neglected.
28391006 Capillary blood collected on volumetric absorptive microsampling (VAMS) device for monitor 2017 Jun 5 A novel technique for collection of capillary blood, termed volumetric absorptive microsampling (VAMS), has been recently cleared by the FDA for collection of human blood. VAMS absorbs a fixed volume of blood (10μl) and overcomes area bias and homogeneity issues associated with dried blood spot (DBS). This study is the application of VAMS for therapeutic drug monitoring (TDM) in human capillary blood. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow for analysis of VAMS sample was developed and validated. Concentration of hydroxychloroquine (HCQ) and its metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), in capillary blood on VAMS sampler were compared to those in venous blood in rheumatoid arthritis patients. Feasibility of capillary blood collected on both VAMS and DBS card were evaluated on patients. Stability of dried capillary blood on VAMS was also examined. Our results established that VAMS is a simple and accurate sampling technique that delivers the benefits of DBS sampling while overcoming the issues associated with hematocrit and homogeneity. It requires a small blood volume, simplifies sample logistics management, and may allow sample collection in the patient's home setting.
27734232 Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background met 2017 Jan Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis investigated the effect of methotrexate (MTX) dose on the efficacy of tofacitinib in patients with RA. ORAL Scan (NCT00847613) was a 2-year, randomized, Phase 3 trial evaluating tofacitinib in MTX-inadequate responder (IR) patients with RA. Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo, with low (≤12.5 mg/week), moderate (>12.5 to <17.5 mg/week), or high (≥17.5 mg/week) stable background MTX. Efficacy endpoints (at months 3 and 6) included American College of Rheumatology (ACR) 20/50/70 response rates, and mean change from baseline in Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints (DAS28)-4(erythrocyte sedimentation rate [ESR]), Health Assessment Questionnaire-Disability Index (HAQ-DI), and modified Total Sharp score. 797 patients were treated with tofacitinib 5 mg BID (N = 321), tofacitinib 10 mg BID (N = 316), or placebo (N = 160); 242, 333, and 222 patients received low, moderate, and high MTX doses, respectively. At months 3 and 6, ACR20/50/70 response rates were greater for both tofacitinib doses vs placebo across all MTX doses. At month 3, mean changes from baseline in CDAI and HAQ-DI were significantly greater for both tofacitinib doses vs placebo, irrespective of MTX category; improvements were maintained at month 6. Both tofacitinib doses demonstrated improvements in DAS28-4(ESR), and less structural progression vs placebo, across MTX doses at month 6. Tofacitinib plus MTX showed greater clinical and radiographic efficacy than placebo in MTX-IR patients with RA, regardless of MTX dose.
28546563 Microbiota in T-cell homeostasis and inflammatory diseases. 2017 May 26 The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation. In particular, commensal microbiota is necessary in the development, induction and function of T cells to maintain host immune homeostasis. Alterations in the compositional diversity and abundance levels of microbiota, known as dysbiosis, can trigger several types of autoimmune and inflammatory diseases through the imbalance of T-cell subpopulations, such as Th1, Th2, Th17 and Treg cells. Recently, emerging evidence has identified that dysbiosis is involved in the progression of rheumatoid arthritis, type 1 and 2 diabetic mellitus, and asthma, together with dysregulated T-cell subpopulations. In this review, we will focus on understanding the complicated microbiota-T-cell axis between homeostatic and pathogenic conditions and elucidate important insights for the development of novel targets for disease therapy.
28199970 Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arth 2017 Mar 28 Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. To date, many studies explored the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs6920220, rs2230926, and rs5029937 polymorphisms and the risk of rheumatoid arthritis (RA), but with contradictory results. We therefore conducted a comprehensive meta-analysis to address the associations. We searched in the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Stata 11.0 software. A total of 21 case-control studies for these three single nucleotide polymorphisms (SNPs) were included in this meta-analysis. Meta-analysis indicated that TNFAIP3 gene rs6920220, rs2230926, and rs5029937 polymorphisms were associated with the increased risk of RA. Stratification analysis of ethnicity found that rs6920220 and rs5029937 polymorphisms increased the risk of RA among Caucasians, while rs2230926 polymorphism increased the risk of RA among Asians. In summary, this meta-analysis confirms that TNFAIP3 gene polymorphisms may play important roles in the pathogenesis of RA.
28462539 Correlation of Functional Ability of the Hand with Upper Limb Function and Quality of Life 2017 Mar BACKGROUND / OBJECTIVES: Rheumatoid arthritis (RA) is associated with significant pain and deformities, where individuals continue to perform activities with reduced abilities. Fatigue and functional disability ensues with the progressive nature of the disease. The study was designed to observe the correlation between the Functional Ability of the Hand with Upper Limb function and Quality of Life in patients with Rheumatoid Arthritis. METHODS: 75 patients diagnosed with RA who were classified in Class I, II, III as per the revised criteria for Classification of Functional Status as given by the American College of Rheumatology were asked to perform the Grip Ability Test to calculate the Hand function. They were then asked to grade their Upper limb function on the Disabilities of Arm, Shoulder and Hand Questionnaire and Quality of Life on the Health Assessment Questionnaire- Disability Index. The scores were analyzed and statistical analysis was done using the Spearmann Rho Correlation. RESULTS: A total of 75 patients (68 females, 7 males) were included. The mean age of the patients was 41.10 years, with the range being from 19 to 55 years. The Hand function, upper limb function and Quality of life was affected in varying degrees amongst the patients. CONCLUSIONS: We concluded that, there is a moderate positive correlation between the functional ability of the hand and upper limb function, a moderate positive correlation between the functional ability of the hand and quality of life and a strong positive correlation between the upper limb function and quality of life. Thus we need to incorporate newer techniques and approaches to assessment and treatment for enhancing functioning of the upper extremity, thus reducing disability.
28880689 Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumato 2018 May OBJECTIVE: To search for signs and symptoms before serious infection (SI) occurs in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients. METHODS: Individual case safety reports, including structured (age, sex, adverse event [AE]) and unstructured (clinical narratives) data, were analyzed by automated text mining from a Japanese post-marketing AE-reporting database (16 April 2008-10 April 2015) assuming the following: treated in Japan; TCZ RA treatment; ≥1 SI; unable to exclude causality between TCZ and SIs. RESULTS: The database included 7653 RA patients; 1221 reports met four criteria, encompassing 1591 SIs. Frequent SIs were pneumonia (15.9%), cellulitis (9.9%), and sepsis (5.0%). Reports for 782 patients included SI onset date; 60.7% of patients had signs/symptoms ≤28 days before SI diagnosis, 32.7% had signs/symptoms with date unidentified, 1.7% were asymptomatic, and 4.9% had unknown signs/symptoms. The most frequent signs/symptoms were for skin (swelling and pain) and respiratory (cough and pyrexia) infections. Among 68 patients who had normal laboratory results for C-reactive protein, body temperature, and white blood cell count, 94.1% had signs or symptoms of infection. CONCLUSION: This study identified prodromal signs and symptoms of SIs in RA patients receiving TCZ. Data mining clinical narratives from post-marketing AE databases may be beneficial in characterizing SIs.
28395950 Prevalence of metabolic syndrome in Algerian rheumatoid arthritis patients. Correlation wi 2017 Nov BACKGROUND: There is evidence that rheumatoid arthritis (RA) patients have an over-risk of cardiovascular disease. This may be mainly due to an increase in the prevalence of metabolic syndrome (MetS). The prevalence of MetS among adults in Algeria is 19.1%. OBJECTIVES: The aim of the study was to evaluate the prevalence of MetS among RA patients in Algeria. Another aim was to evaluate the relationship between MetS, inflammation biomarkers and disease scores. METHODS: The study was performed on a cohort of 249 patients meeting the ACR/EULAR criteria for RA, followed in 11 Algerian centers. The diagnosis of MetS was based on the NCEP/ATP III (MetS+ if ≥3/5) definition. Prevalence of MetS was calculated, and patients were divided in two groups (MetS+ and MetS-). Comparison between the groups was performed using a t-test. RESULTS: Among the 249 RA patients, 213 were females and 36 males of a mean age of 50.1±14.5years and a mean disease duration of 8.4±7.8years. The overall prevalence of MetS was 13.9% (CI95%: 9.5-20.1%); it was 14.3% in males and 13.8% in females. The ESR level was significantly higher in MetS+ patients than in MetS- patients (p=0.036). CONCLUSION: In this multicenter study, unlike most studies on RA patients, the prevalence of MetS was as not higher in Algerian RA patients (13.9%) than in the Algerian general population (19.1%). Only ESR levels correlate with the presence of MetS, this may be due to the modest cohort size and needs to be confirmed.
28885321 Bone fracture risk in patients with rheumatoid arthritis: A meta-analysis. 2017 Sep BACKGROUND: Patients with rheumatoid arthritis (RA) are predisposed to osteoporotic fracture. The present study aims to determine the association between rheumatoid arthritis (RA) and bone fracture risk, and in relation to gender and site-specific fractures. METHODS: Studies related to bone fracture in patients with RA were searched from databases including PubMed, EMBASE, and OVID from inception through April 2016. The quality of the studies was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed with Stata13.1 software. The results were reported based on risk ratio (RR) and 95% confidence interval (95% CI) using a random effects model. RESULTS: The meta-analysis of 13 studies showed a significant higher risk of bone fracture in patients with RA than in patients without RA (RR = 2.25, 95% CI [1.76-2.87]). Subgroup analyses showed that both female and male patients with RA had increased risk of fracture when compared with female and male patients without RA (female: RR = 1.99, 95% CI [1.58-2.50]; male: RR = 1.87, 95% CI [1.48-2.37]). Another subgroup analysis of site-specific fracture also showed that RA is positively correlated with the incidence of vertebral fracture (RR = 2.93, 95% CI [2.25-3.83]) or hip fracture (RR = 2.41, 95% CI [1.83-3.17]). CONCLUSION: RA is a risk factor for bone fracture in both men and women, with comparable risks of fractures at the vertebral and hip.
28524434 Unaffected reaction level in tuberculin skin test by long-term therapy with tumor necrosis 2017 May AIM: The tuberculin skin test (TST) is used to diagnose tuberculosis; however, the influence of tumor necrosis factor (TNF) inhibitors on the test is unclear. This study investigated whether therapy with TNF inhibitors suppresses the TST reaction due to immunosuppression or whether the TST reaction increases due to reactivation of latent Mycobacterium tuberculosis infection. METHOD: Ninety-one patients with rheumatoid arthritis receiving TNF inhibitors (40 using infliximab and 51 using etanercept) were studied. The TST was performed before starting TNF inhibitors (T1) and more than 1 year after starting them (T2). RESULTS: At T1, the reaction was negative in 45 patients, weakly positive in 21 patients, moderately positive in 18 patients and strongly positive in seven patients, while the numbers at T2 were 44, 20, 16 and 11, respectively. There were no significant differences of the TST reaction between T1 and T2 in all patients (P = 0.657), patients using infliximab (P = 0.462) or patients using etanercept (P = 1.00). No patients with a strongly positive TST reaction at T1 became negative at T2. However, two patients who were negative at T1 became strongly positive at T2. Although they had no signs of M. tuberculosis infection, isoniazid prophylaxis was given. CONCLUSION: The TST reaction was not suppressed after more than 1 year of therapy with TNF inhibitors. Patients in whom the TST reaction changes from negative to strongly positive may need appropriate prophylaxis.
28375829 Incidence and clinical characteristics of hepatitis B virus reactivation in HBsAg-negative 2017 Sep OBJECTIVES: To analyse the incidence, clinical characteristics, and prognosis of patients with rheumatoid arthritis (RA) and hepatitis B virus (HBV) surface antigen negative/core antibody positive serostatus (HBsAg-/HBcAb+), who underwent rituximab therapy and developed HBV reactivation. METHODS: Medical records of RA patients with different HBV serostatus who received rituximab from January 2000 through January 2015 were reviewed. Case notes of four HBsAg-/HBcAb+ patients with RA who had HBV reactivation during treatment with rituximab were excerpted and summarised. We also searched the Medline (PubMed) database to identify published reports of other HBsAg-/HBcAb+ RA patients who likewise developed HBV reactivation during rituximab treatment. RESULTS: The study cohort comprised 54 RA patients who received rituximab, of whom 44 (81.5%) were HBsAg-/HBcAb+ whilst receiving rituximab. Four HBsAg-/HBcAb+ patients had HBV reactivations during rituximab therapy; thus, the incidence of HBV reactivation in the HBsAg-/HBcAb+ group was 9.1%. The literature search discovered another three cases, making a total of at least seven known rituximab-treated HBsAg-/HBcAb+ RA patients who have developed HBV reactivation. The mean duration from the first rituximab infusion to HBV reactivation was 25.4±4.6 months; no fatalities occurred. CONCLUSIONS: Approximately 9% of Taiwanese RA patients with HBsAg-/HBcAb+ serostatus had HBV reactivation around 2 years after starting regular rituximab therapy; they all had a relatively good prognosis.
28499744 Does prednisone use or disease activity in pregnant women with rheumatoid arthritis influe 2017 Aug Glucocorticoids are given during pregnancy when rheumatoid arthritis (RA) is too active. It could lead to increased risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) in the offspring. Elevated RA disease activity during pregnancy is associated with low birth weight and rapid post-natal growth. Both can negatively influence the body composition later in life. This study shows that prednisone use or RA disease activity in pregnant women with RA had no influence on the body composition of prepubertal offspring. Furthermore, no components of the metabolic syndrome (MetS) were present in the children, which minimalize the change on CVD or T2DM later in life. This reassuring conclusion might lead to a different therapeutic view when glucocorticoid treatment during pregnancy is inevitable.
28388293 Long-term safety and effectiveness of adalimumab for the treatment of Japanese patients wi 2018 Jan OBJECTIVES: To determine the safety and effectiveness of and identify associated factors in long-term adalimumab (ADA) treatment of Japanese patients with rheumatoid arthritis (RA). METHODS: Of 7740 patients participating in the all-case postmarketing surveillance study, 552 were enrolled in the present study and observed for 3 years. The safety and effectiveness of ADA were analyzed in 509 and 430 patients, respectively. RESULTS: Adverse drug reactions (ADRs) were reported in 34.2% of patients (23.3/100 person-years [PYs]); serious ADRs (SADRs) were reported in 10.6% (5.9/100 PYs). The most common ADRs and SADRs were infection (16.5%) and serious infection (6.1%), respectively. Seven patients (1.4%) developed malignancies. Multivariate analysis revealed that the risk factors for SADRs were age ≥65 years and respiratory disorder at baseline. The proportion of patients who achieved remission (28-joint count Disease Activity Score based on four erythrocyte sedimentation rates <2.6) increased from 3.3% at baseline to 49.2% at 36 months. Significant predictors of failure to achieve remission were female sex, age ≥65 years, blood disorders and advanced structural change at baseline. CONCLUSIONS: Overall, no unknown safety issues were noted during the 3-year treatment with ADA in Japanese patients with RA.
28288820 Resveratrol inhibits BK-induced COX-2 transcription by suppressing acetylation of AP-1 and 2017 May 15 Bradykinin (BK) induces inflammation in rheumatoid arthritis (RA). Resveratrol is a potent activator of Sirt1 which could modulate inflammation through deacetylating histones of transcription factors. Here, we investigated the mechanisms underlying BK-induced COX-2 expression which is modulated by resveratrol/Sirt1 in human rheumatoid arthritis synovial fibroblasts (RASFs). We found that BK-induced COX-2 protein and mRNA expression associated with PGE(2) synthesis, and promoter activity was mediated through B2R receptors, which were attenuated by selective B2R antagonist Hoe140 or transfection with B2R siRNA. BK-induced responses were mediated through PKCμ, MAPKs, AP-1 and NF-κB which were inhibited by their respective inhibitors or siRNAs. Up-regulation of Sirt1 by resveratrol suppressed the BK-induced COX-2/PGE(2) production through inhibiting the interaction of AP-1 and NF-κB with COX-2 promoter in RASFs. BK-induced COX-2/PGE(2) expression is mediated through a B2R-PKCμ-dependent MAPKs, AP-1, and NF-κB cascade. Resveratrol inhibited the phosphorylation and acetylation of p65, c-Jun, and Fos and reduced the binding to the COX-2 promoter, thereby attenuated the COX-2 expression. Therefore, resveratrol may be a promising therapeutic intervention for treatment of inflammatory arthritis.
28930753 Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kin 2017 BACKGROUND/AIMS: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. METHODS: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund's adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. RESULTS: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. CONCLUSION: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.