Rheumatoid Arthritis: Mitrovic D

Afonso V, Champy R, Mitrovic D, Collin P, Lomri A. · INSERM U606, IFR-139, Paris 7 University, Lariboisière Teaching Hospital, 2 rue Ambroise Paré, 75475 Paris Cedex 10, France. · Joint Bone Spine. · Pubmed #17590367 No free full text.

Abstract: Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. The superoxide anion O(2)(-) is the main ROS. Increased ROS production leads to tissue damage associated with inflammation. Superoxide dismutases (SODs) convert superoxide to hydrogen peroxide, which is then removed by glutathione peroxidase or catalase. Thus, SODs prevent the formation of highly aggressive ROS, such as peroxynitrite or the hydroxyl radical. Experimental models involving SOD knockout or overexpression are beginning to shed light on the pathophysiological role of SOD in humans. Although the antiinflammatory effects of exogenous native SOD (orgotein) are modest, synthetic SOD mimetics hold considerable promise for modulating the inflammatory response. In this review, we discuss new knowledge about the role of the superoxide anion and its derivates as mediators of inflammation and the role of SODs and SOD mimetics as antioxidant treatments in joint diseases such as rheumatoid arthritis, osteoarthritis, and crystal-induced arthropathies.

Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, Pavlica L, Stefanovic D. · Department of Rheumatology, Military Medical Academy, Belgrade, Yugoslavia. · Clin Exp Rheumatol. · Pubmed #10464556 No free full text.

Abstract: OBJECTIVE: Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis. METHODS: We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium. RESULTS: After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed. CONCLUSION: These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.