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ID PMID Title PublicationDate abstract
26761790 Endothelial Dysfunction in Rheumatoid Arthritis: Mechanistic Insights and Correlation with 2016 OBJECTIVES: To determine mechanisms involved in endothelial dysfunction (ED) during the course of arthritis and to investigate the link between cytokines, chemokines and osteoprotegerin. APPROACH AND RESULTS: Experiments were conducted on aortic rings at day 4 (preclinical), day 11 (onset of disease), day 33 (acute disease) and day 90 (chronic disease) after adjuvant-induced arthritis (AIA) in Lewis rats. At day 4, the unique vascular abnormality was a reduced norepinephrine-induced constriction. At day 11, endothelial function assessed by the relaxation to acetylcholine was normal despite increased cyclo-oxygenase-2 activity (COX-2) and overproduction of superoxide anions that was compensated by increased nitric oxide synthase (NOS) activity. At day 33, ED apparition coincides with the normalization of NOS activity. At day 90, ED was only observed in rats with a persisting imbalance between endothelial NOS and COX-2 pathways and higher plasma levels of IL-1β and TNFα. Plasma levels of IL-1β, TNFα and MIP-1α negatively correlated with Ach-induced relaxation throughout the course of AIA. CONCLUSIONS: Our data identified increased endothelial NOS activity as an important compensatory response that opposes the ED in the early arthritis. Thereafter, a cross-talk between endothelial COX-2/NOS pathways appears as an important element for the occurrence of ED. Our results encourage determining the clinical value of IL-1β, TNFα and MIP-1α as biomarkers of ED in RA.
26555552 Disease activity, obesity, functional disability, and depression in patients with rheumato 2016 Sep OBJECTIVES: This study aims to estimate the impact of disease activity, obesity, functional disability, and depression on lipid status, glycoregulation, and risk for coronary heart disease (CHD) in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 36 patients with RA (30 women and 6 men, mean age 54.9 years, mean disease duration 7.9 years) were included in this study. We estimated the impact of age, body mass index, disease activity [assessed by DAS28 index and C-reactive protein (CRP) value], functional ability (estimated using the HAQ disability index), and depression [assessed using the Beck Depression Inventory (BDI)] on glycoregulation, lipid status, and risk for CHD in our patients. Glycoregulation was assessed by measuring insulin resistance, insulin, and glucose in blood. Lipids tested in blood included total cholesterol, HDL and LDL cholesterol, and triglycerides (TG). The 10-year risk for CHD was estimated using the Framingham risk score. RESULTS: Of 36 patients, 11 (30.6 %) fulfilled the criteria for metabolic syndrome (MS). Ten of 11 patients (90.1 %) with MS have a 10-year risk for CHD greater than 10 % compared to only 3 of 25 patients (12 %) without MS (p = 0.0001). Patients with high disease activity had lower HDL values than patients with mild or moderate disease activity (1.4 vs. 1.7 mmol/l, p = 0.04). Significant correlations were observed between CRP level and insulinemia (ρ = 0.57, p = 0.003), as well as CRP level and the HOMA index (ρ = 0.59, p = 0.002). The body mass index (BMI) correlated significantly with total cholesterol (r = 0.46, p = 0.02), LDL (ρ = 0.41, p = 0.04), and TG (ρ = 0.65, p < 0.001) in blood. The HAQ-DI did not correlate either with parameters of glycoregulation or lipid status. There was a significant positive correlation between BDI and BMI (ρ = 0.60, p < 0.001). CONCULSION: Active RA is independently associated with decreased HDL cholesterol and increased insulin resistance. Obesity was found to be an independent risk factor for increased total cholesterol, LDL cholesterol, and TG. Depressed patients with RA tend to be overweight or obese and, therefore, have an unfavorable lipid profile.
26230728 The Additive Value of Femoral Ultrasound for Subclinical Atherosclerosis Assessment in a S 2015 BACKGROUND: Presence of femoral atheromatic plaques, an emerging cardiovascular disease (CVD) biomarker additional to carotid plaques, is poorly investigated in conditions associating with accelerated atherosclerosis such as Rheumatoid Arthritis (RA), Human Immunodeficiency Virus (HIV) infection and Type 2 Diabetes Mellitus (T2DM). OBJECTIVE/METHODS: To assess the frequency of femoral/carotid subclinical atheromatosis phenotypes in RA, HIV and T2DM and search for each disease-specific probability of either femoral and/or carotid subclinical atheromatosis, we examined by ultrasound a single-center cohort of CVD-free individuals comprised of consecutive non-diabetic patients with RA (n=226) and HIV (n=133), T2DM patients (n=109) and non-diabetic individuals with suspected/known hypertension (n=494) who served as reference group. RESULTS: Subclinical atheromatosis--defined as local plaque presence in at least on arterial bed--was diagnosed in 50% of the overall population. Among them, femoral plaques only were found in 25% of either RA or HIV patients, as well as in 16% of T2DM patients and 35% of reference subjects. After adjusting for all classical CVD risk factors, RA and HIV patients had comparable probability to reference group of having femoral plaques, but higher probability (1.75; 1.17-2.63 (odds ratio; 95% confidence intervals), 2.04; 1.14-3.64, respectively) of having carotid plaques, whereas T2DM patients had higher probability to have femoral and carotid plaques, albeit, due to their pronounced dyslipidemic profile. CONCLUSION: RA and HIV accelerate predominantly carotid than femoral. A "two windows" carotid/femoral, rather than carotid alone ultrasound, screening improves substantially subclinical atheromatosis detection in patients at high CVD risk.
27765724 Systemic delivery of small interfering RNA targeting nuclear factor κB in mice with colla 2016 Dec 30 This study aimed to build an innovative system to deliver a systemic small interfering RNA (siRNA) treatment for rheumatoid arthritis. We combined arginine-histidine-cysteine based oligopeptide-modified polymer micelles with siRNA targeting the nuclear factor κB subunit, RelA (siRelA). This is a key molecule in the control of inflammation. We tested the cellular uptake of siRNA and its effects on inflammatory cytokine levels in vitro using synoviocytes, and siRNA distribution and therapeutic effects in vivo in mice with collagen-induced arthritis (CIA). These studies showed that arginine-histidine based oligopeptide modified micelles produced effective cellular siRNA uptake and suppressed inflammatory cytokine levels in synoviocytes. In vivo, these micelles produced marked accumulation of siRNAs in arthritic paws in CIA mice, with much less accumulation in healthy mice. The siRelA-polymer micelle complexes also produced more effective suppression of RelA mRNA expression and inflammatory cytokine levels in the arthritic paws of CIA mice and reduced their clinical symptom scores and paw thickness.
28743353 Which is the best cutoff of body mass index to identify obesity in female patients with rh 2017 Jul INTRODUCTION: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. OBJECTIVE: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. PATIENTS AND METHOD: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. RESULTS: Eighty two patients were included, mean age 55±10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value≥25kg/m(2) was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86cm. CONCLUSION: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25kg/m(2) and WC cutoff point of 86cm were the most appropriate to detect obesity.
26377953 Indirect costs of absenteeism due to rheumatoid arthritis, psoriasis, multiple sclerosis, 2016 INTRODUCTION: The aim of this study is to assess the indirect costs of six major autoimmune diseases including seropositive rheumatoid arthritis, other types of rheumatoid arthritis, psoriasis, multiple sclerosis, Type 1 diabetes, and ulcerative colitis. METHODS: Relevant data for 2012 on sick leave and short- and long-term work disabilities were obtained from the Social Insurance Institution in Poland. Indirect costs were estimated using the human capital approach based on gross domestic product per capita, gross value added per worker, and gross income per worker in Poland in 2012 and expressed in euro. RESULTS: We recorded data on the total number of 45,500 patients. The total indirect costs were EUR 146,862,569; 353,683,508; and 108,154,271, calculated using gross domestic product, gross value added, and gross income, respectively. CONCLUSIONS: Considering only data on absenteeism collected by the Social Insurance Institution in Poland, we can conclude that the selected autoimmune diseases are associated with great indirect costs.
26486791 Prevention of Stroke in Rheumatoid Arthritis. 2015 Dec The risk of cerebrovascular disease is increased among rheumatoid arthritis (RA) patients and remains an underserved area of medical need. Only a minor proportion of RA patients achieve suitable stroke prevention. Classical cardiovascular risk factors appear to be under-diagnosed and undertreated among patients with RA. Reducing the inflammatory burden is also necessary to lower the cardiovascular risk. An adequate control of disease activity and cerebrovascular risk assessment using national guidelines should be recommended for all patients with RA. For patients with a documented history of cerebrovascular or cardiovascular risk factors, smoking cessation and corticosteroids and non-steroidal anti-inflammatory drugs at the lowest dose possible are crucial. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor, and their results interpreted to appropriately direct clinical care. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers are preferred treatment options. Biologic and non-biologic disease-modifying anti-rheumatic drugs should be initiated early to mitigate the necessity of symptom control drugs and to achieve early alleviation of the inflammatory state. Early control can improve vascular compliance, decrease atherosclerosis, improve overall lipid and metabolic profiles, and reduce the incidence of heart disease that may lead to atrial fibrillation. In patients with significant cervical spine involvement, early intervention and improved disease control are necessary and may prevent further mechanical vascular injury.
25462582 Zinc and its role in immunity and inflammation. 2015 Apr Zinc (Zn) nutritional importance has been known for a long time, but in the last decades its importance in immune modulation has arisen. This review aims at describing the mechanisms involved in the regulation of Zn homeostasis and their effects on the immune response focusing on those which are implicated in the physiopathology of rheumatoid arthritis. Zn functions as a modulator of the immune response through its availability, which is tightly regulated by several transporters and regulators. When this mechanism is disturbed, Zn availability is reduced, altering survival, proliferation and differentiation of the cells of different organs and systems and, in particular, cells of the immune system. Zn deficiency affects cells involved in both innate and adaptive immunity at the survival, proliferation and maturation levels. These cells include monocytes, polymorphonuclear-, natural killer-, T-, and B-cells. T cell functions and the balance between the different T helper cell subsets are particularly susceptible to changes in Zn status. While acute Zn deficiency causes a decrease in innate and adaptive immunity, chronic deficiency increases inflammation. During chronic deficiency, the production of pro-inflammatory cytokines increases, influencing the outcome of a large number of inflammatory diseases, including rheumatoid arthritis.
26289226 Key findings from studies of methotrexate tapering and withdrawal in rheumatoid arthritis. 2015 Methotrexate is the dominant initial drug in the management of rheumatoid arthritis (RA). Despite its widespread use, methotrexate is associated with a number of adverse effects. Tapering its dose to the minimal amount required to maintain RA remission is, therefore, an important clinical goal. While the complete withdrawal of disease-modifying anti-rheumatic drugs is associated with a definite risk of a disease flare, it is unclear as to what the risk is specific to methotrexate withdrawal and whether this can be minimized by gradual dose reduction (termed 'tapering'). This review examines studies of methotrexate tapering and withdrawal on RA outcomes. It covers three scenarios: tapering/withdrawing methotrexate monotherapy; tapering/withdrawing methotrexate as part of a 'step-down' combination disease-modifying anti-rheumatic drug regimen; and tapering/withdrawing methotrexate when it is being co-prescribed with biologic agents.
26162632 Improvement in patient-reported outcomes after rituximab in rheumatoid arthritis patients: 2015 Dec OBJECTIVE: Patient-reported outcomes (PROs) reflect treatment efficacy from the patients' perspective. The objective was to assess PROs improvement with rituximab in rheumatoid arthritis. METHODS: Patients with long-standing rheumatoid arthritis received rituximab 1000mg twice at 2 weeks interval, and were assessed over 6 months. PROs including physical PROs (pain, functional assessment, physical quality of life) and mental or mixed aspects (fatigue, sleep and mental quality of life) were assessed. Standardized response means were calculated. Early improvement in PROs was used to predict EULAR response at 6 months. RESULTS: For the 175 patients (mean age 54.6±10.6 years, mean disease duration 12.9±9.3 years), the plateau of efficacy of rituximab on PROs was reached at week 12, and the effect was more prominent on physical PROs (e.g., pain standardized response means -0.75 [95% confidence interval -0.91; -0.60]), than on sleep (-0.43; [-0.56; -0.29]). It was not possible to accurately predict 6-month EULAR response by early improvement in PROs. CONCLUSION: Rituximab was effective on PROs with an early effect. PROs reflecting physical aspects were more modulated by this biologic than other PROs (fatigue, sleep or mental quality of life). Links between sleep difficulties, fatigue and RA should be further studied.
25796462 A disintegrin and metalloprotease-10 is correlated with disease activity and mediates mono 2015 Sep A disintegrin and metalloproteases (ADAMs) are a family of proteins that have been reported to be involved in several inflammatory conditions. We examined the secretion of ADAM-10 in biological fluids from patients with rheumatoid arthritis (RA) and the role it plays in monocyte migration. ADAM-10 levels were measured using enzyme-linked immunosorbent assays and immunofluorescence. To examine the role of ADAM-10 in RA synovial fluids (SFs), we studied THP-1 (human acute monocyte leukemia cell line) and monocyte chemotaxis. To determine whether ADAM-10 plays a role in cell proliferation in the RA synovium, we assayed the proliferation of ADAM-10 small interfering RNA (siRNA)-transfected RA fibroblast-like synoviocytes (FLSs). The ADAM-10 level in RA serum was significantly higher than that in normal serum and was correlated with a disease activity score of 28. ADAM-10-depleted RA SFs showed a decrease in THP-1 and monocyte migratory activity compared with that of sham-depleted controls. ADAM-10 siRNA inhibited monocyte adhesion to RA FLSs. Finally, blocking ADAM-10 secretion in RA FLSs resulted in decreased production of fractalkine/CX3CL1 and vascular endothelial cell growth factor. These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method of decreasing inflammation and potentially treating other inflammatory diseases.
25854489 Patient reported outcomes in rheumatoid arthritis clinical trials. 2015 Apr Patient reported outcomes (PRO) are at the core of assessing RA treatment response with patient assessments of global health or disease activity, pain, and physical function included in the calculation of American College of Rheumatology (ACR) responses. Progress has been made in assessing PROs that include additional patient-valued aspects of disease in recent RA randomized clinical trials (RCTs), particularly fatigue. Importantly, the National Institute of Health (NIH)--Patient Reported Outcomes Measurement Information System (PROMIS) development of psychometrically advanced generic health measures that span the range of symptoms potentially affected in RA, with high precision across the entire range of a symptom are undergoing additional study in RA and other rheumatologic diseases to establish their construct validity, responsiveness, and clinically meaningful cutoffs. PRO measures that are currently used and widely available can provide important perspectives not captured in composite clinical response criteria with the potential of better informing treatment decisions in clinical practice.
30695331 [Biologics-Induced Kidney Injury -with Special Attention to Anti-Rheumatic Drugs -]. 2016 Jun A variety of anti-rheumatic drugs including biologics are currently used to treat rheumatoid arthritis (RA). These drugs, as well as RA itself, can cause kidney injury. RA may trigger mesangial proliferative glomeru- lonephritis (MesPGN), membranous nephropathy (N), thin basement membrane disease, and renal amyloi- dosis. As for anti-rheumatic drugs, non-steroidal anti-inflammatory drugs (NSAID) increase serum Cr lev- els due to a reduction of glomerular circulation, particularly in the presence of dehydration. Among disease- modifying anti-rheumatic drugs (DMARD), methotrexate as an anchor drug for RA rarely causes tubular ob- struction as a result of its crystallization, and bucillamine occasionally elicits IN. Calcineurin inhibitors induce vasoconstriction of the afferent arteries. Recently developed anti-rheumatic drugs, biologics, include biological inhibitors of TNF-a, IL6, and CD80/26. These can generally induce the remission of RA, while they have been reported to albeit uncom- monly trigger autoimmune renal disorders (AIRD). A recent meta-analysis identified a total of 29 cases with biologics-induced AIRD, 62% of who manifested AIRD within 12 months after treatment with biologics. AIRD cases were classified into 3 different groups: isolated autoimmune renal disorders (IARD, n =13), glo- merulonephritis with systemic vasculitis (GNSV, n= 12), and glomerulonephritis with lupus-like syndrome (GNLS, n=4). The IARD cases had 4 MesPGN, 4 MN, and 2 crescentic GN, while the GNSV cases had 8 crescentic GN and 3 purpura GN, and the GNLS cases had all MesPGN. To detect these renal disorders early in RA patients, urinalysis and serum Cr measurement should be peri- odically performed. New urinary biomarkers (L-FABP and Ngal) may be more sensitive for kidney injury. Notably, in RA patients receiving biologics, ANA, anti-dsDNA, and ANCA should also be tested at the base- line and regular intervals. [Review].
26121915 Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as 2015 Sep In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune-mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5-1.0 × 10(6) cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M-CSF as controls. Tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M-CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.
27141810 Near-infrared fluorescence imaging with indocyanine green-lactosomes in a mouse model of r 2016 Nov OBJECTIVES: The early diagnosis and treatment of rheumatoid arthritis (RA) is important to reduce joint destruction. Many of the current imaging techniques have disadvantages, such as the need for contrast agents and interpretation by specialists. Fluorescence imaging is an emerging technique that overcomes some of these problems. The aim of this study was to determine whether near-infrared (NIR) fluorescence imaging of indocyanine green (ICG)-lactosomes can detect joint inflammation in a mouse model of RA. METHODS: Control and arthritic SKG/Jcl mice were injected with ICG alone or ICG-lactosomes and examined by NIR fluorescence imaging. Arthritis severity was assessed macroscopically and histopathologically. RESULTS: ICG fluorescence was detected in the liver soon after injection and then decreased over the next several hours. ICG was not detected in the joints of control or arthritic mice. In contrast, ICG-lactosomes remained in mice for at least 48 h and accumulated specifically at inflamed joints. ICG-lactosome fluorescence was higher in arthritic versus normal joints at all times examined and was maximal at 24 h after injection. CONCLUSIONS: NIR fluorescence imaging of ICG-lactosomes detects arthritic joints in a mouse model of RA. ICG-lactosomes may preferentially localize to inflamed joints via enhanced permeability and retention.
27316486 Cardiac involvement in rheumatoid arthritis: A cross-sectional study in Iran. 2016 May BACKGROUND: Cardiovascular disease is one of the extra-articular manifestations of rheumatoid arthritis (RA) that is the most common cause of death in these patients. So we decided to evaluate RA patients in terms of history, clinical examination, electrocardiography, and echocardiography to determine the prevalence of types of cardiac involvements in these patients. METHODS: 100 consecutive patients, diagnosed with RA, referred to rheumatology clinic in Razi referral hospital of Rasht, Iran, were enrolled. Complete physical examination of the joints was performed in all subjects to evaluate the remission of disease. Signs and symptoms of possible cardiac involvement were evaluated in patients by taking history and erythrocyte sedimentation rate test; moreover, an expert cardiologist performed complete cardiovascular examination in all participants. Then, all subjects were referred to a same center for electrocardiography and echocardiography. Finally, analysis was performed by using chi-square and t tests. RESULTS: 23 (23%) males and 77 (77%) females were included in this study. Tachycardia, dyspnea, and chest pain were the most cardiac signs and symptoms of patients. 32 subjects had abnormal findings in electrocardiogram. The most abnormal findings in patient's ECG were ST interval and T wave changes. Abnormal findings in echocardiography were observed in 74 participants. Pericardial involvement and ventricular dysfunction were the most abnormal findings in patient's echocardiography. We found a significant relation between duration of RA disease and abnormal echocardiography findings (p<0.05). CONCLUSION: This study indicates the high prevalence of cardiac involvement in RA patients.
25900189 Multicentric reticulohistiocytosis: a critical review. 2015 Jun The literature reports approximately 300 cases of multicentric reticulohistiocytosis (MRH) worldwide, mostly women of Caucasian origin. MRH manifests as a symmetric erosive polyarthritis mimicking rheumatoid arthritis with the subsequent appearance of typical papulonodular skin lesions. The disease may rapidly progress towards mutilans arthritis in the majority of cases, but it generally remits spontaneously in 10 years. The only diagnostic hallmark for MRH is the observation at histology of numerous histiocytes and multinucleated giant cells and ground glass eosinophilic cytoplasm. Despite its rarity, clinical and pathogenetic challenging features characterize the condition. First, the differential diagnosis with other forms of arthritis and the frequent coexistence of neoplasms or autoimmune diseases warrant a careful evaluation of suspected cases. Second, data from isolated MRH cases are consistent in supporting a role for monocyte/macrophage cells and for an enhanced osteoclastic activity in the affected tissues. Third, beside anti-inflammatory treatments, promising reports suggest that biologics targeting TNF-alpha and bisphosphonates may prove beneficial in MRH. Based on these observations, we are convinced that our understanding of this rare condition may prove beneficial in mechanistic advancement for other more prevalent inflammatory conditions such as arthritidies and other bone diseases.
27487156 Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical F 2016 OBJECTIVES: Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis. METHODS: Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic -AA-, linolenic, eicosapentaenoic -EPA- and docosahexaenoic -DHA-) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction in 124 RA patients and 56 healthy controls (HC). CD4+ phenotype was studied by flow cytometry. TNFα, IL-8, VEGF, GM-CSF, IFNγ, IL-17, CCL2, CXCL10, leptin and resistin serum levels were quantified by immunoassays. The effect of FA on IFNγ production by PBMC was evaluated in vitro. RESULTS: Lower levels of palmitic (p<0.0001), palmitoleic (p = 0.002), oleic (p = 0.010), arachidonic (p = 0.027), EPA (p<0.0001) and DHA (p<0.0001) were found in RA patients, some NEFA being altered at onset. Cluster analysis identified a NEFA profile (hallmarked by increased stearic and decreased EPA and DHA) overrepresented in RA patients compared to HC (p = 0.002), being associated with clinical features (RF, shared epitope and erosions), increased IFNγ expression in CD4+ T-cells (p = 0.002) and a Th1-enriched serum milieu (IFNγ, CCL2 and CXCL10, all p<0.005). In vitro assays demonstrated that imbalanced FA could underlie IFNγ production by CD4+ T-cells. Finally, changes on NEFA levels were associated with clinical response upon TNFα-blockade. CONCLUSION: An altered NEFA profile can be found in RA patients associated with clinical characteristics of aggressive disease and enhanced Th1 response. These results support the relevance of lipidomic studies in RA and provide a rationale for new therapeutic targets.
27372662 Dental treatments, tooth extractions, and osteonecrosis of the jaw in Japanese patients wi 2017 May This study aimed to evaluate dental treatments, tooth extractions, and osteonecrosis of the jaw (ONJ) in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in our cohort completed self-administered questionnaires, which included questions regarding their dental treatments, tooth extractions by dentists during the past 6 months, and past history of ONJ. The history of ONJ was validated with the patients' medical records. Logistic regression was used to determine the association of variables with dental treatments and tooth extractions during the past 6 months. Among 5695 Japanese patients with RA who responded to the questionnaires (mean age, 61.0 years; 85.6 % female), 2323 patients (40.8 %) and 378 patients (6.6 %) reported having had dental treatments and tooth extractions performed by a dentist within the past 6 months, respectively. In multivariate models, advanced age was significantly (P < 0.0001) associated with both dental treatments and tooth extractions during the prior 6-month period, and ever smoking was significantly (P = 0.023) correlated with tooth extractions during that time. Among patients who reported a history of ONJ, we confirmed five cases of ONJ with patient medical records. The prevalence of ONJ was 0.094 % among all RA patients and 0.26 % among female RA patients ≥65 years of age (n = 1888). Our data suggest that more than a few Japanese patients with RA have dental complications that require care by dentists, and that Japanese rheumatologists and dentists should cooperate to improve dental health in patients with RA.
26556105 Majoon ushba, a polyherbal compound ameliorates rheumatoid arthritis via regulating inflam 2016 Jan The present study was aimed to investigate the anti-arthritic effect of majoon ushba (MU) and its underlying mechanism in adjuvant induced arthritis (AIA) rats. Arthritis was induced by intradermal injection of complete freund's adjuvant (0.1ml) into the right hind paw of the Wistar albino rats. MU (1000mg/kg/b.wt) and methotrexate (3mg/kg/b.wt) were administered from day 11 to day 18th for 8days after adjuvant induction. We have found that MU treatment significantly increased the level of anti-inflammatory cytokine (IL-10) and inhibited the over production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and monocyte chemoattractant protein-1 (MCP-1) (ELISA) in the serum of adjuvant-induced arthritic rats. The mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), inflammatory enzymes (inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2)), MCP-1, receptor activator of nuclear factor-kB ligand (RANKL) and transcription factors (NF-кB and AP-1) (Real-Time PCR) was found significantly downregulated in the synovial tissues of MU treated arthritic rats. In addition, the protein expression of NF-кB, IL-17, COX-2, and RANKL (western blotting and immunohistochemistry analysis) was found reduced. On the other hand, osteoprotegerin (OPG), a bone remodeling marker was found to be elevated in synovial tissues of MU treated arthritic rats. Furthermore, MU treatment prevented body weight loss and reduced the joint paw edema, cell infiltration, cartilage and bone degradation as evidenced by the histopathological and radiological analysis. In conclusion, our current findings provide scientific evidence for the traditional claim of MU as an anti-arthritic drug.