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ID PMID Title PublicationDate abstract
30766044 Arthritis, Infectious Tenosynovitis, and Tendon Rupture in a Patient With Rheumatoid Arthr 2015 Feb Multiple comorbidities, advanced age, tobacco use, and alcohol abuse made a proper diagnosis difficult in a patient with polyarticular septic arthritis, infectious tenosynovitis, and ruptures in the tendons of both thumbs.
26637956 Suppressive effect of Sanmiao formula on experimental gouty arthritis by inhibiting cartil 2016 Jan Sanmiao formula (SM) is a compound prescription, which has been used in traditional Chinese medicine since the Ming Dynasty for gouty and rheumatoid arthritis treatments. However, no evidence has been unfolded to show the relationship between SM and gouty arthritis (GA), particularly inhibiting cartilage matrix degradation. In the present study, we undertook a characterization of anti-GA activity of SM using an in vivo rat model induced by potassium oxonate and cold bath together with in vitro studies with chondrocytes for further molecular characterization. Potassium oxonate and cold bath rats were treated with SM at doses of 7.2g/kg per day for 5days. SM treatments significantly suppressed the swelling rate and the severe pathologic changes in the joints of the animals in gout model. Inflammatory factors count by ELISA analysis, SM exhibited inhibition on IL-1β and TNF-α. Moreover, histological analysis of the joints and SM-serum substantially interfered with the MSU-induced expression of glycosaminoglycans (GAG), up-regulated the content of proteoglycan. Importantly, SM interfered with GA-augmented expression of matrix metalloproteinases (MMPs) -3 and aggrecanases (ADAMTS)-4, which are considered to be key enzymes in cartilage matrix degradation, and simultaneously augmented GA-reduced tissue inhibitors of metalloproteinases (TIMPs) -1 and -3 expression in the joints and chondrocytes. Therefore, SM is looking forward to be a potential novel agent that could prevent cartilage matrix degradation effectively in gouty arthritis, and this provides a new target for development of new medicines.
27245733 Psoriatic arthritis: An assessment of clinical, biochemical and radiological features in a 2016 May 5 BACKGROUND: Although psoriatic arthritis (PsA) is a well-documented clinical entity, epidemiological, clinical and radiological studies of South African (SA) patients are scarce. OBJECTIVES: To assess clinical, biochemical and radiological features in a single-centre SA cohort. METHODS: We conducted a prospective assessment of the clinical, biochemical and radiological features of 384 consecutive patients with PsA seen at the rheumatology clinic at Prince Mshiyeni Memorial Hospital, Durban, SA, between January 2007 and December 2013. Patients were assessed at enrolment and 6 months after enrolment. They were classified into five groups as described by Moll and Wright, being entered into the group that best described the clinical manifestations. Clinicopathological characteristics recorded at enrolment were age at the time of examination, racial background, personal and family medical history, age and symptoms at the onset of PsA, pattern of joint involvement, joint pain, and the relationship between joint pain and the onset of PsA. RESULTS: Of the patients, 59.1% had a polyarticular presentation indistinguishable from rheumatoid arthritis, 19.0% had distal interphalangeal involvement, 9.1% had spondyloarthropathy, 11.9% had oligoarthritis and 0.9% had arthritis mutilans. The epidemiological trends (male/female ratio 1.45:1, mean age at onset of arthritis 50.2 (standard deviation 11.8) years, female preponderance in the polyarticular group and male preponderance in the spondyloarthropathy and oligoarticular groups) were similar to trends published elsewhere. A notable characteristic of our cohort was the complete absence of black South Africans with PsA. CONCLUSIONS: The complete absence of black South Africans with PsA is interesting. We anticipate that our findings will prompt genetic studies to isolate both protective and susceptibility genes for further elucidating PsA.
26058550 Clinical trial development for biosimilars. 2015 Jun OBJECTIVES: Discuss issues regarding clinical trial design for the development of biosimilars in the European Union and the United States, with special focus on monoclonal antibodies used in the treatment of inflammatory diseases. METHODS: A search of the Internet as well as PubMed was conducted through June 2014 for information related to the clinical development of biosimilars using the keywords biosimilar, rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and ankylosing spondylitis. The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) websites were searched for biosimilar guidelines. RESULTS: The EMA began issuing draft guidelines for the development of biosimilars almost a decade ago and has approved numerous biosimilars. The US FDA has issued draft guidances providing stepwise considerations for the nonclinical and clinical development of biosimilars but has yet to approve a biosimilar under this pathway. CONCLUSIONS: Clinical trials aim to resolve uncertainties that may remain following nonclinical development regarding the similarity of the proposed biosimilar with the reference product. Pharmacokinetic and pharmacodynamic studies form the backbone of early clinical development and serve to inform phase 3 clinical development. Factors to be considered in clinical development include study population, design, end points, sample size, duration, and analytical methods.
26713272 Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch und 2015 Nov Triptolide (TP), a major active component of Tripterygium wilfordii Hook.F. (TWHF), is used to treat rheumatoid arthritis (RA). However, it has a narrow therapeutic window due to its serious toxicities. To increase the therapeutic index, a new triptolide-loaded transdermal delivery system, named triptolide-loaded liposome hydrogel patch (TP-LHP), has been developed. In this paper, we used a micro-needle array to deliver TP-LHP to promote transdermal absorption and evaluated this treatment on the pharmacokinetics and pharmacodynamics of TP-LHP in a rat model of collagen-induced arthritis (CIA). The pharmacokinetic results showed that transdermal delivery of microneedle TP-LHP yielded plasma drug levels which fit a one-compartment open model. The relationship equation between plasma concentration and time was C=303.59×(e(-0.064t) -e(-0.287t) ). The results of pharmacodynamic study demonstrated that TP-LHP treatment mitigated the degree of joint swelling and suppressed the expressions of fetal liver kinase-1, fetal liver tyrosine kinase-4 and hypoxia-inducible factor-1α in synovium. Other indicators were also reduced by TP-LHP, including hyperfunction of immune, interleukin-1β and interleukin-6 levels in serum. The therapeutic mechanism of TP-LHP might be regulation of the balance between Th1 and Th2, as well as inhibition of the expression and biological effects of vascular endothelial growth factor.
26207886 Interferon regulatory factor 5 in human autoimmunity and murine models of autoimmune disea 2016 Jan Interferon regulatory factor 5 (IRF5) has been demonstrated as a key transcription factor of the immune system, playing important roles in modulating inflammatory immune responses in numerous cell types including dendritic cells, macrophages, and B cells. As well as driving the expression of type I interferon in antiviral responses, IRF5 is also crucial for driving macrophages toward a proinflammatory phenotype by regulating cytokine and chemokine expression and modulating B-cell maturity and antibody production. This review highlights the functional importance of IRF5 in a disease setting, by discussing polymorphic mutations at the human Irf5 locus that lead to susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. In concordance with this, we also discuss lessons in IRF5 functionality learned from murine in vivo models of autoimmune disease and inflammation and hypothesize that modulation of IRF5 activity and expression could provide potential therapeutic benefits in the clinic.
25985972 The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Ou 2016 Jun OBJECTIVE: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. METHODS: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. RESULTS: 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. CONCLUSIONS: In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.
28450796 Ellagic acid alleviates adjuvant induced arthritis by modulation of pro- and anti-inflamma 2016 Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology, but it is now clear that pro-inflammatory cytokines play a central role in its pathogenesis. Ellagic acid (EA) has a variety of biological activities including anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of the present study was to evaluate the potential effect of ellagic acid on the prevention and/or treatment of adjuvant induced arthritis (AIA) model in mice. Ellagic acid treatment was started one week before AIA induction and continued for three weeks after induction of AIA. Ellagic acid treatment significantly (p < 0.01) inhibited foot paw oedematous swelling and attenuated AIA-associated pathology. Ellagic acid significantly (p < 0.01) reduced serum levels of pro-inflammatory cytokines: interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin 17 (IL-17). However, serum levels of IL-10 and interferon γ (IFN-γ) significantly increased (p < 0.01 and p < 0.05, respectively), while serum level of transforming growth factor β (TGF-β) did not significantly alter with EA treatment. In conclusion, these results suggest that EA attenuated AIA-associated pathology in the mouse model by downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines.
30641009 [Effect of Qingluo Tongbi Compound on Osteoclast Differentiation-related mIRNA Expressions 2016 Oct Objective To observe the effect of Qingluo Tongbi Compound (QTC) on osteoclast dif- ferentiation-related miRNA expressions in adjuvant induced arthritis (AIA) rats, and to study its mecha- nism for treating rheumatoid arthritis (RA). Methods The synovial fibroblasts and monocytes of peripher- al blood from AIA rats were co-cultured to induce osteoclast-like cells. Differently expressed miRNAs in the late stage osteoclasts differentiation were detected by miRCURYâ„¢ Array. Real-time quantitative PCR (RT- PCR) was applied to verify the reliability of miRNA array. QTC drug-containing sera and blank sera were prepared and added to the co-cultured system. The osteoclasts were randomly divided into three groups, the blank group, the blank serum group, and the QTC group. RT-PCR was applied to detect the effect of QTC on related differentially expressed miRNAs. Bioinformatics software was applied to analyze related differentially expressed miRNAs. Results miRNA array results showed that as compared with the monocytes group, there were 211 miRNAs differentially expressed in osteoclast-like cell differentiation, including 88 up-regulated miRNAs and 123 down-regulated miRNAs. Results of RT-PCR were consistent with results of the array. RT-PCR showed that the expression level of miR-140-5p was obviously up-regulated after the intervention of QTC. Results of bioinformatics analyses showed that the target gene of miR-140-5p was sig- nificantly enriched in signaling pathways such as the regulation of actin cytoskeleton, Ras signaling path- ways, cAMP signaling pathways, and Rap1 signaling pathways. Conclusions There were various dysregulated expressions of miRNAs in the anaphase of osteoclast-like cells differentiation. QTC participated the regulation of osteoclast differentiation by effecting the expression of miR-140-5p.
27508035 Relationship between PI3K pathway and angiogenesis in CIA rat synovium. 2016 To investigate the expression of hypoxia inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) in the synovium of collagen-induced arthritis (CIA) joint, and whether the PI3K pathway regulates angiogenesis in rheumatoid arthritis or not. A randomized controlled according to the principle of the rats were divided into normal control group (10 rats) and the experimental group (40 rats). The experimental group rats were established as type II collagen plus adjuvant Freund's complete adjuvant-induced arthritis model. HIF-1α and VEGF proteins' expression in serum of CIA rats group and normal control group were detected by ELISA. Microvessel density (MVD) in synovial tissue of CIA rats group and normal control group were detected by immunohistochemistry (IHC) staining. The protein expression of PTEN, PI3K, and AKT in synovial tissue were detected by Western Blot. Compared with normal control group, toes and ankle swelling and arthritis index (AI) of CIA rat increased, and the expression of VEGF and HIF-1α proteins in peripheral serum increased, IHC showed that MVD was significantly higher than that of the control group, and the difference was statistically significant (p<0.05). Western Blot results showed that PI3K and AKT proteins expression in CIA synovial tissue of rats increased, while the expression of PTEN protein decreased. Correlation analysis showed that VEGF and HIF-1 levels in the peripheral serum of CIA rats were positively correlated with arthritis index (AI); the contents of HIF-1α and VEGF in the peripheral serum of CIA rats were positively correlated with MVD in synovium tissue. The CIA rat model regulated the expression of HIF-1α and VEGF proteins in peripheral serum by PI3K signaling pathway, and then regulated neovascularization in RA.
27402110 Economic Theory and Self-Reported Measures of Presenteeism in Musculoskeletal Disease. 2016 Aug This study had two objectives: to describe the historical development of self-reported presenteeism instruments that can be used to identify and measure presenteeism as a result of musculoskeletal disease (MSD) and to identify if, and how many of these, presenteeism instruments are underpinned by economic theory. Systematic search methods were applied to identify self-report instruments used to quantify presenteeism caused by MSD. A total of 24 self-reported presenteeism instruments were identified; 24 were designed for use in general health, and 1 was specifically designed for use in rheumatoid arthritis. One generic self-reported presenteeism instrument was explicitly reported to be underpinned by economic theory. Overtime, self-reported presenteeism instruments have become more differentiated and complex by incorporating many different contextual factors that may impact levels of presenteeism. Researchers are encouraged to further develop presenteeism instruments that are underpinned by relevant economic theory and informed by robust empirical research.
26676797 The Microbiome and Musculoskeletal Conditions of Aging: A Review of Evidence for Impact an 2016 Feb Recently, we have begun to realize that the billions of microorganisms living in symbiosis with us have an influence on disease. Evidence is mounting that the alimentary tract microbiome, in particular, influences both host metabolic potential and its innate and adaptive immune system. Inflammatory states characterize many bone and joint diseases of aging. This prompts the hypothesis that the gut microbiome could alter the inflammatory state of the individual and directly influence the development of these common and burdensome clinical problems. Because the microbiome is easily modifiable, this could have major therapeutic impact. This perspective discusses evidence to date on the role of the microbiome and the highly prevalent age-related disorders of osteoporosis, osteoarthritis, gout, rheumatoid arthritis, sarcopenia, and frailty. It also reviews data on the effects of probiotics and prebiotic interventions in animal and human models. Despite suggestive findings, research to date is not conclusive, and we identify priorities for research to substantiate and translate findings.
27824549 ACPAs Are Much More Than Diagnostic Autoantibodies. 2016 Oct 31 Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.
27762196 The National Data Bank for Rheumatic Diseases (NDB). 2016 Sep The National Data Bank for Rheumatic Diseases (NDB) is a longitudinal observational patient-driven database, founded as a non-profit research organization in 1998 by Dr. Frederick Wolfe. Patients are sent a primary questionnaire twice a year. More than 50,000 patients with more than 100 various rheumatic diseases under the care of more than 1,500 rheumatologists have completed at least one 6-month questionnaire. Many important publications concerning rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, fibromyalgia, and pharmaco-epidemiology have resulted from NDB research.
26292933 [Differential diagnostic specific skin infiltrates in chronic myelomonocytic leukemia]. 2015 Sep A 72-year-old male patient presented with multiple erythematous plaques on the lower arms, lower legs and feet. The patient suffered from rheumatoid arthritis and accompanying interstitial granulomatous dermatitis under treatment with tocilizumab. Several months prior to presentation a chronic myelomonocytic leukemia (CMML) had been diagnosed. The skin biopsy showed a perivascular infiltration of medium-sized cells with positivity for CD123, CD303 and CD4 with a low proliferation activity so that a diagnosis of a CMML-associated proliferation of plasmacytoid dendritic cells was made. The differential diagnosis of specific cutaneous infiltrates in CMML is discussed.
25789178 Etanercept-induced pityriasis lichenoides chronica in a patient with rheumatoid arthritis. 2015 We present a 74-year-old female patient who developed a pityriasis lichenoides chronica (PLC) during etanercept therapy. This association is not described in the literature and might be considered in the spectrum of cutaneous adverse reactions of etanercept.
25738844 Leflunomide: an immune modulating drug that may have a role in controlling secondary infec 2015 Mar BACKGROUND: Leflunomide (LEF) is an immune modulator used most commonly for rheumatoid arthritis (RA). The mechanisms of action of LEF also include anti-microbial effects, particularly anti-viral effects. OBSERVATIONS: We present three patients with atopic dermatitis on azathioprine therapy who had multiple verrucae and in two molluscum contagiosum (MC) that were resistant to repeated conventional therapies. These patients were switched to LEF, and all the patients showed complete resolution of their verrucae and MC within 2 months of starting therapy. In addition, all three patients showed equivalent to better control of their atopic dermatitis with LEF. CONCLUSIONS: LEF has previously been reported to be a useful immune modulator for the treatment of severe atopic dermatitis. The spectrum of anti-viral effects previously seen with leflunomide did appear beneficial in these patients in clearing verrucae and MC, which had been resistant to conventional therapies while the patients were on azathioprine.
28104973 Unusual Case of an Alcoholic with Liver Injury from Sulfasalazine Use. 2016 Dec A 57-year-old male with a history of alcoholism presented to the emergency room with abdominal pain, jaundice, transaminitis, and hyperbilirubinemia. Due to the history of alcoholism, it was initially presumed that the patient had alcoholic hepatitis but further investigation revealed that he was recently started on sulfasalazine for the treatment of rheumatoid arthritis. Upon cessation of the drug, the patient's liver function tests significantly improved over a few days and eventually normalized within weeks. This case was interesting as the patient's history of alcoholism disguised the actual diagnosis. Furthermore, the late presentation of sulfasalazine-induced liver injury is uncommon as it commonly presents 2-4 weeks after initiation of therapy.
29648709 INHIBITORS OF LEUKOTRIENES SYNTHESIS: NOVEL AGENTS AND THEIR IMPLEMENTATION. 2016 Jul Leukotrienes (LTs) belong to pro-inflammatory mediators that are biosynthesized from arachidonic acid (AA), inter alia, by 5-lipoxygenase (5-LOX) enzyme in association with 5-LOX-activating protein (FLAP). An activation of LTs synthesis pathway occurs during the development and maintenance of numerous diseases such as asthma, anaphylactic shock, allergic rhinitis, psoriasis, rheumatoid arthritis, osteoporosis, as well as cardiovascular diseases, neurodegenerative diseases and certain types of cancer. The main goal of this review was to present recent advances on the new compounds influencing the LOX pathway, which are under-going clinical studies. The mechanisms of action and possible implementations of these molecules in a treatment of asthma, cancer and cardiovascular diseases are discussed.
26783460 FOXO3a Gene Polymorphism Associated with Asthma in Indian Population. 2015 Asthma is a chronic inflammatory disorder delineated by a heightened immunological response due to environmental or genetic factors. Single nucleotide polymorphism studies have shown that FOXO3a plays a pivotal role in maintaining immunoregulation. Polymorphism in FOXO3a has been linked to inflammatory diseases such as chronic obstructive pulmonary disease (COPD), Rheumatoid Arthritis, and Crohn's disease suggesting that FOXO3a may be associated with asthma. Airway inflammation in asthma is characterized by activation of T helper type 2 (Th2) T cells and Foxo family members are reported to play critical roles in the suppression of T cell activation. Thus this study was undertaken to investigate an association between single nucleotide polymorphism of the FOXO3a (rs13217795, C>T transition) gene and asthma in Indian population. To our knowledge we are the first ones reporting an association between FOXO3a and asthma.