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ID PMID Title PublicationDate abstract
23548052 A pilot study of yoga as self-care for arthritis in minority communities. 2013 Apr 2 BACKGROUND: While arthritis is the most common cause of disability, non-Hispanic blacks and Hispanics experience worse arthritis impact despite having the same or lower prevalence of arthritis compared to non-Hispanic whites. People with arthritis who exercise regularly have less pain, more energy, and improved sleep, yet arthritis is one of the most common reasons for limiting physical activity. Mind-body interventions, such as yoga, that teach stress management along with physical activity may be well suited for investigation in both osteoarthritis and rheumatoid arthritis. Yoga users are predominantly white, female, and college educated. There are few studies that examine yoga in minority populations; none address arthritis. This paper presents a study protocol examining the feasibility and acceptability of providing yoga to an urban, minority population with arthritis. METHODS/DESIGN: In this ongoing pilot study, a convenience sample of 20 minority adults diagnosed with either osteoarthritis or rheumatoid arthritis undergo an 8-week program of yoga classes. It is believed that by attending yoga classes designed for patients with arthritis, with racially concordant instructors; acceptability of yoga as an adjunct to standard arthritis treatment and self-care will be enhanced. Self-care is defined as adopting behaviors that improve physical and mental well-being. This concept is quantified through collecting patient-reported outcome measures related to spiritual growth, health responsibility, interpersonal relations, and stress management. Additional measures collected during this study include: physical function, anxiety/depression, fatigue, sleep disturbance, social roles, and pain; as well as baseline demographic and clinical data. Field notes, quantitative and qualitative data regarding feasibility and acceptability are also collected. Acceptability is determined by response/retention rates, positive qualitative data, and continuing yoga practice after three months. DISCUSSION: There are a number of challenges in recruiting and retaining participants from a community clinic serving minority populations. Adopting behaviors that improve well-being and quality of life include those that integrate mental health (mind) and physical health (body). Few studies have examined offering integrative modalities to this population. This pilot was undertaken to quantify measures of feasibility and acceptability that will be useful when evaluating future plans for expanding the study of yoga in urban, minority populations with arthritis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01617421.
25187413 Novel benzenediamine derivative FC99 ameliorates zymosan-induced arthritis by inhibiting R 2014 Oct Increased IL-17-producing helper T (Th17) cells have been observed in patients with rheumatoid arthritis (RA). The retinoic-acid-related orphan nuclear receptor (RORγt) is the master regulator of Th17 cells. Our previous research showed that FC99 possesses anti-inflammation activity. However, to date the effects of FC99 on RORγt expression in Th17 cell differentiation have not been investigated yet. In the present study, we found that FC99 significantly attenuated arthritis-like symptoms, i.e., suppressing the development of paw edema in zymosan-induced arthritis (ZIA) mice. H&E staining showed that the infiltration of inflammatory cells in ankle synovial tissues was significantly suppressed. FC99 also reduced the mRNA levels of pro-inflammatory cytokines in ankle synovial tissues as shown by Q-PCR analysis. The protein levels of the pro-inflammatory cytokines in sera were also suppressed after FC99 treatment. Moreover, FC99 decreased the RORγt mRNA level in spleen tissues. Th17 cell percentage was significantly decreased in spleens and draining lymph nodes (dLNs). The mRNA and protein levels of IL-17A and IL-23 were reduced after FC99 treatment in ZIA mice. Furthermore, in vitro experiments showed that FC99 inhibited the expression of IL-6 in LPS-induced RAW264.7 cells and BMDCs. Moreover, FC99 significantly inhibited the RORγt expression in PMA-induced CD4(+) T cells and LPS-induced RAW264.7 cells. These data indicate that FC99 improves arthritis-like pathological symptoms in vivo and in vitro, which might be related to the inhibition of RORγt expression in Th17 cells. Our findings suggest that FC99 may be a potential therapeutic candidate for the treatment of RA and other inflammatory disorders.
23990050 Mesenchymal stromal cells versus betamethasone can dampen disease activity in the collagen 2014 Aug The objective of this study was to compare between the effects of mesenchymal stem cell (MSC) and betamethasone in the treatment of rheumatoid arthritis. Sixty male albino mice were divided equally into 2 models. They are MSC model, group 1: saline control group, group 2: collagen-induced arthritis (CIA), group 3: induced arthritis mice that received intravenous injection of MSCs. Betamethasone model, group 1: phosphate buffer saline, group 2: CIA, group 3: induced arthritis mice that received intraperitoneal injection of betamethasone. Mice arthritis models were assessed by clinical paw edema and X-rays, at the proper time of sacrefaction, tissues were collected and examined using real-time PCR, and synovial tissue was examined for interleukin-10, tumor necrosis factor α, cartilage oligomeric matrix protein and matrix metalloproteinase 3. While serum levels of rheumatoid factor and C-reactive protein were detected by enzyme-linked immunosorbent assay kits. Also blood erythrocyte sedimentation rate was detected. Histopathological, paw edema and PCR results showed improvement in the groups that received MSC compared with the diseased group and the groups which received betamethasone. MSC significantly enhanced the effect of collagen-induced arthritis treatment, which is superior to betamethasone treatment, likely through the modulation of the expression of various cytokines.
23834772 Muscle wasting associated with pathologic change is a risk factor for the exacerbation of 2013 Jul 9 BACKGROUND: Not only joint destruction but also muscle wasting due to rheumatoid cachexia has been problem in terms of quality of life of patients with rheumatoid arthritis (RA). In the present study, we performed histopathological examination and assessed relationships between characteristic parameters relating to muscle and joint swelling in a collagen-induced arthritis (CIA) model using cynomolgus monkeys (CMs). METHODS: Female CMs were used and CIA was induced by twice immunizations using bovine type II collagen with Freund's complete adjuvant. Arthritis level was evaluated from the degree of swelling at the peripheral joints of the fore and hind limbs. Food consumption, body weight, and serum biochemical parameters were measured sequentially. Five or 6 animals per time point were sacrificed at 2, 3, 5 and 9 weeks after the first immunization to obtain quadriceps femoris specimens for histopathology. Pimonidazole hydrochloride was intravenously administered to determine tissue hypoxia in skeletal muscle. RESULTS: Gradual joint swelling was observed and the maximum arthritis score was noted at Week 5. In histopathology, necrosis of muscle fiber in the quadriceps femoris was observed only at Week 2 and the most significant findings such as degeneration, atrophy, and regeneration of muscle fiber were mainly observed at Week 5. Food consumption was decreased up to Week 4 but recovered thereafter. Body weight decreased up to Week 5 and did not completely recover thereafter. A biphasic increase in serum cortisol was also observed at Weeks 2 and 5. Histopathology showed that muscle lesions were mainly composed of degeneration and atrophy of the muscle fibers, and ATPase staining revealed that the changes were more pronounced in type II muscle fiber than type I muscle fiber. In the pimonidazole experiment, mosaic pattern in skeletal muscle was demonstrated in the intact animal, but not the CIA animal. Increased arthritis score was accompanied by a decrease in serum creatinine, a marker that reflects muscle mass. CONCLUSIONS: Muscle wasting might exacerbate joint swelling in a collagen-induced arthritis model of cynomolgus monkeys.
23821428 Rheumatoid atlantoaxial instability treated by anterior transarticular C1-C2 fixation. Cas 2013 May The authors present a case that demonstrates the usefulness of anterior transarticular screw fixation in the treatment of instability due to rheumatoid arthritis. The surgical technique of this infrequently used procedure is presented. A 35-year-old female patient with medical history significant for rheumatoid arthritis complained of persistent headache and upper neck pain. Examination revealed a decreased range of cervical rotational motion. Magnetic resonance imaging of the cervical spine revealed anterior displacement of C1, destruction of the left lateral atlantoaxial articulation and bony erosion of the C2 vertebral body below the base of the odontoid. Dynamic radiographs showed increased C1-C2 mobility. The authors used a right anterolateral approach to the cervical spine to perform fixation of lateral atlantoaxial articulations by means of titanium cannulated compressive screws. On 4-month follow-up examination, successful C1-C2 stabilization was documented. Despite restriction of neck rotation, the patient reported satisfactory improvement and re-turned to work.
25456434 Evaluation of the efficacy and safety of different Tripterygium preparations on collagen-i 2014 Dec 2 ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium preparations (TPs), a traditional Chinese Medicines extracted from Tripterygium wilfordii Hook f., are widely used for treatment of rheumatoid arthritis (RA). However, TPs from different Pharmaceutical factory have different efficacy and side effects for RA treatment. AIM OF THE STUDY: The purpose of the current study is to evaluate the efficacy and safety of four TPs from different Pharmaceutical factory in china on the treatment of collagen-induced arthritis (CIA) rats and provide a theoretical and experimental basis for the individualized use of TPs. MATERIALS AND METHODS: The model of wistar rats of CIA was made, and the rats were perfused a stomach with four TPs for 3 weeks continuously. Then arthritis severity was determined by visual examination of the paws and histopathologic changes of joint, liver, kidney and testis were determined by hematoxylin-eosin (H&E) staining. The expression of inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) in the joint was analyzed by real-time PCR, and the count and motion parameters (sperm motility and progressive sperm) of sperm in cauda epididymis were assessed with computer-assisted sperm analysis (CASA) system. Routine blood tests were conducted using automated hematology analyzer, and the aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, creatinine (Cr), and blood urea nitrogen (BUN) in serum of CIA rats were measured using a UniCel DxC 880i autoanalyzer. RESULTS: All of tested TPs could reduce inflammatory score, histopathological arthritis severity and joint׳s inflammatory cytokines (IL-1β, TNF-α, IL-17 and IL-6) expression in CIA rats, however, TP-D showed stronger inhibitory effect for inflammatory score compared with other three TPs in vivo. All of tested TPs did not show hepatotoxicity and nephrotoxicity and also had little effect for the concentration of hemoglobin (Hb) and the count of white blood cell (WBC). Analysis of red blood cell (RBC) number showed that TP-C and TP-D could reverse lower RBC number in untreated CIA rats to normal level. Interestingly, the results showed TPs named TP-C and TP-D could decrease platelet (PLT) number which significantly increases in untreated CIA rats. Reproductive toxicity, the main side effect of TPs, assay showed that the sperm quality (density, viability, and motility) in four of TPs-treated CIA rats were decreased significantly, consistently with spermatogenic cell density reduced. However parallel analysis showed that in four TPs-treated rats, the number of sperm, motile sperm and progressive sperm were highest in TP-D group, in contrast, were lowest in TP-C group. CONCLUSIONS: These findings suggested that four TPs showed significantly therapeutic effect on ameliorating inflammation of CIA rats, with no obvious hepatotoxicity and nephrotoxicity in vivo. TP-D showed advantages with its higher efficacy and less reproductive toxicity as well as increasing RBC number, decreasing PLT number in CIA treatment. Thus, in the development of individualized treatment plan for RA patients, TP-D might be considered preferentially.
24273397 Pharmaceutical approval update. 2013 Sep Afatinib (Gilotrif) for non-small-cell lung cancer; golimumab (Simponi Aria) for moderate-to-severe active rheumatoid arthritis; and levomilnacipran (Fetzima) extended release for major depressive disorder.
23623942 Torilin ameliorates type II collagen-induced arthritis in mouse model of rheumatoid arthri 2013 Jun Advancements in rheumatoid-arthritis-(RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential agents with relative safety and efficacy continues and natural compounds have been considered as alternatives to identify new entities. Since previous in-vivo data and our in-vitro findings showed that torilin has a strong anti-inflammatory property, we further investigated its effect against collagen-induced-arthritis-(CIA) in mice. CIA-induced DBA/1J mice were treated with torilin or methotrexate (MTX) for 5-weeks. Arthritis severity was evaluated by arthritic score and joint histopathology. Draining lymph node (dLN), joint and peripheral-blood mononuclear-cell (PBMC) counts, and activation/localization of T-/B-lymphocytes, dendritic cells (DCs) and neutrophils were examined by FACS analysis. Serum anti-type-II-collagen-(CII) antibody levels and cultured-splenocyte and serum cytokines were also evaluated. Torilin markedly reduced CIA-induced arthritic score, histopathology and leukocyte counts. Besides, torilin suppressed CIA-activated T-cells including CD3+, CD3+/CD69+, CD8+, CD4+ and CD4+/CD25+ in dLNs or joints. It also modified CD19+ or CD20+/CD23+ (B-cells), MHCII+/CD11c+ (DCs) and Gr-1+/CD11b+ (neutrophil) subpopulations. It further depressed total anti-CII-IgG, anti-CII-IgG1 and anti-CII-IgG2a antibody productions. Moreover, while IFN-γ and IL-10 were not affected, torilin suppressed CIA-induced serum TNF-α, IL-1β and IL-6 levels. Interestingly, torilin also blocked IFN-γ, IL-17 and IL-6 cytokines while it did not affect IL-10 but enhanced IL-4 in splenocytes. These results show that torilin attenuated arthritis severity, modified leukocyte activations in dLNs or joints, and restored serum and splenocyte cytokine imbalances. Torilin may have immunomodulatory and anti-inflammatory properties with the capacity to ameliorate the inflammatory response in CIA-mice.
27471707 Antigen-based immunotherapy for autoimmune disease: current status. 2015 Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease.
25353186 Simultaneous Exposure-Response Modeling of ACR20, ACR50, and ACR70 Improvement Scores in R 2014 Oct 29 The Markovian approach has been proposed to model American College of Rheumatology's (ACR) response (ACR20, ACR50, or ACR70) reported in rheumatoid arthritis clinical trials to account for the dependency of the scores over time. However, dichotomizing the composite ACR assessment discards much information. Here, we propose a new approach for modeling together the three thresholds: a continuous-time Markov exposure-response model was developed, based on data from five placebo-controlled certolizumab pegol clinical trials. This approach allows adequate prediction of individual ACR20/50/70 time-response, even for non-periodic observations. An exposure-response was established over a large range of licensed and unlicensed doses including phase II dose-ranging data. Simulations from the model (50-400 mg every other week) illustrated the range and sustainability of response (ACR20: 56-68%, ACR50: 27-42%, ACR70: 11-22% at week 24) with maximum clinical effect achieved at the recommended maintenance dose of 200 mg every other week.
24418307 Socioeconomic status. The relationship with health and autoimmune diseases. 2014 Jun Socioeconomic status (SES) is a hierarchical social classification associated with different outcomes in health and disease. The most important factors influencing SES are income, educational level, occupational class, social class, and ancestry. These factors are closely related to each other as they present certain dependent interactions. Since there is a need to improve the understanding of the concept of SES and the ways it affects health and disease, we review herein the tools currently available to evaluate SES and its relationship with health and autoimmune diseases.
26237144 Mesenchymal Stromal Cells: Updates and Therapeutic Outlook in Rheumatic Diseases. 2013 Oct 23 Multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs) are adult stem cells exhibiting functional properties that have opened the way for cell-based clinical therapies. MSCs have been reported to exhibit immunosuppressive as well as healing properties, improving angiogenesis and preventing apoptosis or fibrosis through the secretion of paracrine mediators. This review summarizes recent progress on the clinical application of stem cells therapy in some inflammatory and degenerative rheumatic diseases. To date, most of the available data have been obtained in preclinical models and clinical efficacy needs to be evaluated through controlled randomized double-blind trials.
23319022 Development of rice bodies in 2 children younger than 3 years. 2013 Jan Rice bodies are synovial fluid nodules macroscopically resembling shiny white rice beans. They have been seen in synovial fluid from several types of inflammatory arthritis including tuberculosis, pyogenic arthritis, and juvenile idiopathic arthritis and adult rheumatoid arthritis. Microscopically, they consist of amorphous material, fibrin, and collagen. We report the rare cases of 2 children younger than 3 years with multiple rice body formations in the knee joints.
23390586 Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent a 2013 Feb 5 FK506 (Tacrolimus) is a potent inhibitor of calcineurin that blocks IL2 production and is widely used to prevent transplant rejection and treat autoimmunity. FK506 treatment of dendritic cells (FKDC) limits their capacity to stimulate T cell responses. FK506 does not prevent DC survival, maturation, or costimulatory molecule expression, suggesting that the limited capacity of FKDC to stimulate T cells may be due to inhibition of calcineurin signaling in the DC. Instead, we demonstrate that DC inhibit T cells by sequestering FK506 and continuously releasing the drug over several days. T cells encountering FKDC proliferate but fail to upregulate the survival factor bcl-xl and die, and IL2 restores both bcl-xl and survival. In mice, FKDC act in an antigen-specific manner to inhibit T-cell mediated autoimmune arthritis. This establishes that DCs can act as a cellular drug delivery system to target antigen specific T cells.DOI:http://dx.doi.org/10.7554/eLife.00105.001.
24965126 Recurrent pyoderma gangrenosum precipitated by breast cancer: a case report and review of 2014 Jun 25 INTRODUCTION: Pyoderma gangrenosum is a rare clinical entity of poorly understood pathogenesis, characterized by rapidly progressing skin necrosis. In around half of patients pyoderma gangrenosum is a manifestation of underlying systemic diseases, such as rheumatoid arthritis, inflammatory bowel disease or myeloproliferative disorders. There have been very few reports on the association of pyoderma gangrenosum with solid malignancies. CASE PRESENTATION: We report a case of a 68-year-old Caucasian woman in whom pyoderma gangrenosum first appeared around 30 years earlier, at the time of exacerbation of rheumatoid arthritis, and recurred as a manifestation of locally advanced breast cancer. The causative role of the neoplastic process was partly confirmed by the healing of the skin ulceration only following effective endocrine cancer therapy, whereas earlier attempts with standard anti-inflammatory therapy were unsuccessful. CONCLUSIONS: Pyoderma gangrenosum has a recurrent nature and may be reactivated by various causes within several years. Therefore, a prompt and thorough diagnosis accompanied by treatment of the underlying disease is necessary.
24148767 The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases. 2013 Oct The balance between osteoblast-dependent bone formation and osteoclast-dependent bone resorption maintains bone homeostasis. In inflammatory conditions, this balance shifts toward bone resorption, causing osteolytic bone lesions observed in rheumatoid arthritis and periodontitis. A recently discovered family of cytokine IL-17 is widely reported to mediate diverse inflammatory processes. During the last decade, novel roles for IL-17 in skeletal homeostasis have been discovered indicating the potential importance of this cytokine in bone metabolism. This review will summarize and discuss the involvement of IL-17 during bone homeostasis in both physiologic and pathologic conditions. A better understanding of the role of IL-17 in skeletal systems warrants an advance in bone biology, as well as development of therapeutic strategies against bone-lytic diseases, such as rheumatoid arthritis and periodontitis.
25509832 [Sex hormones, immune disorders, and inflammatory rheumatic diseases]. 2014 It is a well-documented fact that sex hormones are implicated in the immune response and that androgens and estrogens modulate susceptibility and progression of autoimmune rheumatic diseases. Estrogens are considered to stimulate cell proliferation and humoral immune responses while androgens exert suppressive effects on both humoral and cellular immune responses. Autoimmune diseases are common in females, especially during the generative period, the most representative of estrogen-related autoimmune diseases being systemic lupus erythematosus. Estrogens and androgens are involved in the pathogenesis of the disease; both exogenous and endogenous estrogens are strong stimulators of cytokine production and disease activity. Some physiological conditions, as well as some drugs and chronic stress, can modulate hormone levels. Low levels of gonadal androgens have been detected in body fluids of both male and female rheumatoid arthritis patients, supporting the possibility of the pathogenic role for decreased androgen levels. Views on hormone replacement therapy or hormonal contraception in rheumatic diseases have been modified and in most rheumatic diseases, including rheumatoid arthritis, hormones are not prohibited. There are still controversies regarding systemic lupus; the new standpoint being that hormonal contraception is not contraindicated in women with inactive or stable active SLE, except for those with positive antiphospholipid antibodies.
25477254 High hopes for cannabinoid agonists in the treatment of rheumatic diseases. 2014 Dec 4 There are two well-characterised isoforms of cannabinoid receptor; CB1 and CB2 and of these CB2 is under active investigation as a potential target for treatment of the chronic pain associated with widespread and intractable joint diseases osteoarthritis and rheumatoid arthritis. The recent report by Fukuda et al (BMC Musculoskelet Disord15:275, 2014) in BMC Musculoskeletal Disorders investigates the efficacy of a selective CB2 agonist, JW133, in both in vitro and in vivo models of rheumatoid arthritis and provides encouraging data. The report shows that JW133 inhibits expression of the CCL2 cytokine, osteoclastogenesis and reduces histological indicators of joint degeneration. Each of these could potentially contribute to beneficial analgesic effects in a therapeutic context.
24783297 Biotechnologically produced drugs as second-line therapy for rheumatoid arthritis: Executi 2005 The aims of the present investigation were: ■. to assess the benefit of treatment with biotechnologically produced drugs compared with each other. ■. to assess the benefit of treatment with biotechnologically produced drugs compared with treatment with non-biotechnologically produced drugs, as well as ■. to assess the benefit of treatment with biotechnologically produced drugs compared with treatment without therapy extension (with or without placebo control); in each case as second-line therapy in patients with RA. The assessment was based on patient-relevant outcomes. In this context, “treatment extension” is understood as continued therapy initiated as a supplementation to existing therapy. For the present commission, for biotechnologically produced drugs (biologic disease modifying anti-rheumatic drugs, bDMARDs), second-line therapy, i.e. therapy after failure of previous treatment, was to be distinguished from first-line therapy, i.e. therapy in treatment-naive patients. In the present benefit assessment, the definition of second-line therapy therefore covered the use of biotechnologically produced drugs in persons who had been pretreated with at least one disease-modifying antirheumatic drug, also including biotechnologically produced ones.
25526913 Bi-specific antibodies with high antigen-binding affinity identified by flow cytometry. 2015 Feb Using conventional approaches, the antigen-binding affinity of a novel format of bi-specific antibody (BsAb) cannot be determined until purified BsAb is obtained. Here, we show that new lipoprotein A (NlpA)-based bacteria display technology, combined with flow cytometry (FCM), can be used to detect antigen-binding affinity of BsAbs, in the absence of expression and purification work. Two formats of BsAb, scFv2-CH/CL and Diabody-CH/CL, specific for human interleukin 1β (hIL-1β) and human interleukin 17A (hIL-17A), were constructed and displayed in Escherichia coli using NlpA-based bacteria display technology. Conversion of these cells to spheroplasts, and their incubation with fluorescently conjugated antigens resulted in the selective labeling of spheroplasts expressing BsAb; enabling their antigen-binding affinity to be analyzed with FCM. The association and dissociation of BsAbs for binding to hIL-1β and hIL-17A were analyzed using FCM-based assays. The results showed that antigen-binding affinity of Diabody-CH/CL was significantly higher than that of scFv2-CH/CL. To confirm these results of FCM-based assays, BsAbs were expressed, purified and subjected to relative affinity measurements, in vitro and in vivo bioactivity analysis. The results showed that Diabody-CH/CL had greater relative affinities for both antigens, resulting in better blocking bioactivities on cellular level and effects on alleviating joint inflammation, and cartilage destruction and bone damage in collagen induced arthritis (CIA) mice model. These results indicate that BsAbs with good antigen-binding affinity can be identified by FCM-based assays without expression and purification work, and the indentified BsAb can serve as a lead compound for further drug development.