Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25182154 Inhibition mechanism of Qingluo Tongbi Granule () on osteoclast differentiation induced by 2015 Apr OBJECTIVE: To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (, QTG) on osteoclast differentiation in rheumatoid arthritis in rats. METHODS: Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic (AIA) rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 (TRAF6/MAPK/NFATc1) pathways was examined. RESULTS: The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase (TRAP) staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 and decreased the percentage of cells with nuclear NFATc1 in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity (P<0.01 and P<0.05, respectively). After the addition of MAPK inhibitors, the NFATc1 expression showed no significant difference compared with the control group (P>0.05). CONCLUSIONS: Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATc1 pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.
23289865 Update on biologicals for treatment of juvenile idiopathic arthritis. 2013 Mar INTRODUCTION: The development of biologics has markedly changed the treatment of JIA. Complete control of the disease and remission has today become the main goal of treatment preventing long-term damage and disability. AREAS COVERED: This review gives an overview of the current treatment options using biologics in JIA. The biologic drugs are discussed on the basis of recent clinical trials. EXPERT OPINION: While JIA is a group of heterogeneous diseases, differences in their biology turned out to influence treatment success with different biologics. TNF inhibitors emerged to be the most commonly used biologics for the treatment of JIA. First they were successful for the treatment of rheumatoid factor positive and negative polyarticular JIA. TNF inhibitors have also been studied in patients with enthesitis-related arthritis, psoriatic arthritis, and extended olioarthritis, and approval of at least etanercept is expected. Second-line biologics are abatacept and tocilizumab. For systemic onset JIA, tocilizumab, and the IL-1 inhibitors anakinra and canakinumab have been successfully studied. In the treatment of JIA, biologics have emerged as potent drugs to control the disease. New advancements will be crucial for further improvement of treatment options in JIA.
24862114 Relative motion splint: active motion after extensor tendon injury and repair. 2014 Jun The relative motion splint was initially developed to facilitate postoperative rehabilitation after repair of extensor tendon injuries at the dorsum of the hand and forearm. It has subsequently been used for rehabilitation of sagittal band injuries and after repair of closed attrition extensor tendon ruptures in rheumatoid arthritis. This is much less awkward than other braces and can readily be worn during normal past-time and work activities. This so-called immediate controlled active motion splinting protocol has also more recently been applied to both operative and nonsurgical rehabilitation for boutonniere deformity.
24579323 [Novel uses of rituximab]. 2013 Dec Since its approved by HAS in 1998, the use of rituximab increases every year. Marketed in France under the name MabThera, rituximab is used primarily in the treatment of B-cell malignancies including follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia and corresponding to the three main indications for treatment. However, given its action on B cells, rituximab also proves to be effective in rheumatoid arthritis. By extension as anti-B-cell, rituximab is actually used in other autoimmune diseases: in autoimmune cytopenias as idiopathic thrombocytopenic purpura and hemolytic anemia, in vasculitis, or multiple sclerosis, it is also used in organ transplantation as kidney in prophylaxy to rejection and treatment of EBV-mediated complications.
24282510 Pharmacokinetics of drugs in cachectic patients: a systematic review. 2013 Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid arthritis. It leads to changes in body structure and function that may influence the pharmacokinetics of drugs. Changes in gut function and decreased subcutaneous tissue may influence the absorption of orally and transdermally applied drugs. Altered body composition and plasma protein concentration may affect drug distribution. Changes in the expression and function of metabolic enzymes could influence the metabolism of drugs, and their renal excretion could be affected by possible reduction in kidney function. Because no general guidelines exist for drug dose adjustments in cachectic patients, we conducted a systematic search to identify articles that investigated the pharmacokinetics of drugs in cachectic patients.
24003301 Microscopic Colitis is Associated with Several Concomitant Diseases. 2013 Microscopic colitis (MC) is a disease with intestinal mucosal inflammation causing diarrhea, affecting predominantly middle-aged women. The etiology is unknown, but increased prevalence of autoimmune diseases in these patients has been described, although not compared with controls or adjusted for confounding factors. The aim of this study was to examine the prevalence of common diseases in patients with MC and controls from the general population. Hypertension, rheumatoid arthritis, asthma or bronchitis, ischemia, and diabetes mellitus were more prevalent in patients than in controls. The prevalence of gastric ulcer and cancer did not differ between the groups. Besides corticosteroids, many patients were also being treated with proton pump inhibitors, antidepressant drugs, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, statins, thyroid hormones, and beta-blockers. More patients than controls were former or current smokers (72.5% versus 57.7%). Thus, MC patients have an increased prevalence of several diseases, not only of autoimmune origin.
23611654 Fibroblasts and synovial immunity. 2013 Aug Rheumatoid arthritis (RA) synovium is characterised not only by increases in number and activity of lymphocytes and macrophages, but also of resident mesenchymal cells known as fibroblast-like synoviocytes (FLS). Originally thought of as passive structural cells, research over two decades has demonstrated the capacity for autonomous contributions of FLS to RA inflammation as effector cells producing cytokines and other pro-inflammatory mediators. More recently, as understanding of RA as a genuine autoimmune disease characterised by immunity to citrullinated proteins has grown, so the potential involvement of FLS in even proximal aspects of initiation and maintenance of abnormal adaptive immune responses has come to light. In this review we take a step-by-step approach to the role of FLS, considering their contribution to the phenomena, as currently understood, in RA pathogenesis. It can be concluded that significant evidence favours a broad role for FLS in synovial immunity, as well as inflammation.
23557513 Biologic therapy for autoimmune diseases: an update. 2013 Apr 4 Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying anti-rheumatic drugs and other immunosuppressive medications. However, the current drawbacks of biologic therapies, including the inconvenience of intravenous administration, the high costs of these drugs, and the adverse events associated with them, prevent their wide use as first-line medications. This review provides an update of the recent literature on the new biologic therapies available. The review concentrates on nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab, abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, or vasculitis.
25248975 Bounds on sufficient-cause interaction. 2014 Nov A common goal of epidemiologic research is to study how two exposures interact in causing a binary outcome. Sufficient-cause interaction is a special type of mechanistic interaction, which requires that two events (e.g. specific exposure levels from two risk factors) are necessary in order for the outcome to occur. Recently, tests have been derived to establish the presence of sufficient-cause interactions, for categorical exposures with at most three levels. In this paper we derive prevalence bounds, i.e. lower and upper bounds on the prevalence of subjects for which sufficient-cause interaction is present. The derived bounds hold for categorical exposures with arbitrary many levels. We apply the bounds to data from a study of gene-gene interaction in the development of Rheumatoid Arthritis. We provide an R-program to estimate the bounds from real data .
27631019 Many Roles of CCL20: Emphasis on Breast Cancer. 2014 Mar CCL20 or MIP3α is a small ~8 kDa protein primarily expressed in the liver, colon, prostate, cervix, and skin. The cellular receptor for CCL20 is CCR6. CCl20 unlike many other cytokines only binds CCR6, making the CCL20/CCR6 pathway an attractive drug target. Since the initial discovery of CCL20 in the early 1990's, there has been an increase in the evidence implicating the chemokine and its receptor in a number of diseases, including rheumatoid arthritis and human immunodeficiency virus infection. CCL20 has also been linked to malignancies such as ovarian, colorectal and pancreatic cancers. CCL20 can also attract tumor-promoting immune-suppressive cells to the tumor microenvironment, which may contribute to the immune evasive potential of the tumor and tumor progression.
25856975 [Clinical analysis of nontuberculous mycobacterial infection complicated by pleurisy]. 2014 Dec OBJECTIVE: There are few reports describing pleurisy caused by nontuberculous pulmonary mycobacteriosis; in addition, there are few reports describing the frequency of cases. METHOD: We retrospectively studied 116 consecutive cases of nontuberculous mycobacteriosis occurring between January 2009 and January 2014. RESULT: Of these, 7 patients (6.0%) were diagnosed with pleuritis caused by nontuberculous pulmonary mycobacteriosis. One patient each had a history of ulcerative colitis, rheumatoid arthritis treated with steroids, and retinitis pigmentosa. Pleural effusion was examined in all 7 cases. In addition, nontuberculous mycobacteria were cultured from pleural effusion in 4 of the 7 cases; all were cases of Mycobacterium avium complex infection. The mean adenosine deaminase level in pleural effusion was 86 U/mL, and in 5 out of 7 cases, the adenosine deaminase level was greater than 50 U/mL. Pneumothorax occurred with pleuritis in 5 cases. Pleuritis was treated with NTM therapy in 5 cases, and pleural effusion decreased or cleared completely in all cases. CONCLUSION: To reveal pleurisy accompanied by nontuberculous mycobacteriosis, further consideration is needed.
25386507 Relationship between loneliness, psychiatric disorders and physical health ? A review on t 2014 Sep Human beings are social species which require safe and secure social surroundings to survive. Satisfying social relationships are essential for mental and physical well beings. Impaired social relationship can lead to loneliness. Since the time of dawn, loneliness is perceived as a global human phenomenon. Loneliness can lead to various psychiatric disorders like depression, alcohol abuse, child abuse, sleep problems, personality disorders and Alzheimer's disease. It also leads to various physical disorders like diabetes, autoimmune disorders like rheumatoid arthritis, lupus and cardiovascular diseases like coronary heart disease, hypertension (HTN), obesity, physiological aging, cancer, poor hearing and poor health. Left untended, loneliness can have serious consequences for mental and physical health of people. Therefore it is important to intervene at the right time to prevent loneliness, so that physical and mental health of patients is maintained.
25335457 IL-6 blockade in chronic inflammatory diseases. 2015 Jan Proinflammatory cytokines are centrally involved in the pathogenesis of various rheumatic diseases. Interleukin (IL)-6 is a prototypic representative of this family. Basic research has uncovered a multitude of functions for this cytokine, such as immune regulation, hematopoiesis, inflammation, and oncogenesis (Fig. 1). In recent years, agents blocking the actions of IL-6 have been developed for the therapy of rheumatologic inflammatory diseases. While in some diseases, most notably rheumatoid arthritis, the clinical efficacy of these drugs was excellent, the results of clinical trials in other chronic inflammatory diseases were heterogeneous. In this review, we will summarize the data currently available on IL-6 blockade in chronic inflammatory diseases and will also discuss the safety issues of blocking this cytokine.
25136456 Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review. 2014 Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts.
24215409 Accelerated telomere shortening in rheumatic diseases: cause or consequence? 2013 Dec Accelerated aging of the immune system (immune aging), represented by telomere shortening, has been implicated in a variety of rheumatic diseases. Studies addressing telomere shortening in rheumatic diseases so far yielded controversial results. The current review aims to provide an overview on the role of immune aging in a plethora of immune-mediated conditions including systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis. The main question this review aims to answer is whether rheumatic diseases cause accelerated aging or that accelerated aging drives rheumatic diseases.
23216081 Are there new emerging drugs for ankylosing spondylitis or spondyloarthritis? 2013 Mar New emerging drugs in the treatment of ankylosing spondylitis (AS), and spondyloarthritis in general, should be compared to anti-TNF agents, which provided clear evidence of efficacy in these conditions. To date, other biologic agents used in rheumatoid arthritis failed to demonstrate efficacy in AS, even in anti-TNF naïve patients. Some new potential options may target cytokines such as IL-17, or molecules involved in entheseal ossification or signaling pathways, but need confirmatory evaluation.
22961090 Leflunomide: friend or foe for systemic lupus erythematosus? 2013 Feb Leflunomide is a new immunosuppressive medicine that has been effectively used in the therapy of rheumatoid arthritis and subsequently used with success in animal models and patients with systemic lupus erythematosus (SLE). However, its use has also been associated with significant and serious adverse reactions involving hematological, hepatic, immune, dermatological and respiratory systems. In the current review, we attempt to describe the two sides of this drug in the treatment of SLE.
22080212 Effects of dialysis on the pharmacokinetics of salazosulfapyridine. 2013 Feb There was no standard or report for the treatment of rheumatoid arthritis (RA) patients on hemodialysis with Salazosulfapyridine (SASP). We examined the pharmacokinetics of SASP and its metabolites in RA patient on hemodialysis. Hemodialysis was started 2 h after administration of SASP at a dose of 250 or 500 mg. Blood samples were took 8 times during the observation period. The concentration of SASP and its metabolites (SP, Ac-SP) in blood sample were measured. There was no difference for the concentration of SASP before and after hemodialysis. Results showed SASP was nondialyzable, but SP and AC-SP were dialyzable. At a dose of 500 mg, AUC0-∞ of SASP and SP were higher than healthy volunteer. Therapy with SASP for hemodialysis RA should be started at a lower dose for adverse event risk.
24656780 Gallium nitrate ameliorates type II collagen-induced arthritis in mice. 2014 May Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA.
25431725 Leprosy mimicking common rheumatologic entities: a trial for the clinician in the era of b 2014 Rheumatoid arthritis and seronegative spondyloarthritis, which make up the lion's share of cases attending a rheumatology clinic, are relatively easy to diagnose. However, when an entity of infective aetiology like leprosy known to be a great mimic of different autoimmune conditions presents with features similar to these, the possibility of it being diagnosed at the outset is very slim indeed. The ease with which the diagnosis of leprosy can be missed assumes sinister proportions as the use of disease modifying agents can have deleterious effects in these patients. In the era of increasing availability and use of biologic disease modifying agents, it is imperative not only to actively rule out the presence of leprosy but also to make it a part of the prebiologic screening of patients in whom biologics are being planned to be administered, especially in leprosy endemic areas.