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Biomedical subjects

D Mitrovic

Publications and source records attributed to D Mitrovic.

62 records · Page 4Linked to original sources

Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients.

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.

Adjuvants, Immunologic↗

[Systemic mixed connective tissue disease--Sharp's syndrome].

Sharp's syndrome is a systemic mixed connective tissue disease that is defined with specific ribonucleoprotein antibody (U1RNP). The key diagnostic criterion is positive antinuclear antibodies in stain form. The disease is primarily localized on joints, muscles and skin; however, there are not widely used diagnostic criteria. There are USA, Mexican and Japanese diagnostic criteria. A 18-year-old male who fulfilled Sharp's diagnostic criteria is presented in the paper. In this patient the disease was manifested in pleura and pericardium. We wish to point out the importance of immunologic approach to the aetiology of pleural and pericardial inflammatory effusions in young patients, as well as the therapeutical dilemmas in the treatment of the disease.

Adolescent↗

[Effect of oxaceprol on the synthesis and degradation in vitro of proteoglycans and proteins by calf articular cartilage explants].

The authors have studied in organ culture, the effects of oxaceprol-structural analogue of hydroxyproline, on the proteoglycan and protein synthesis and degradation by calf articular chondrocytes. A stimulation of the incorporation of 35SO4, which indicate proteoglycan synthesis, was shown. The effect was observed at concentrations 10(-6) M to 10(-9) M, i.e. at 170 ng to 170 pg of the oxaceprol per ml of culture media, respectively. However, no significant effect was seen at concentrations 10(-4) M (17 micrograms/ml) to 10(-8) M (1.7 ng/ml) on the protein and proteoglycan catabolism. These results support those reported by Kalbhen and Kalbert and are favouring the use of this drug in order to stimulate reparative processes of articular cartilage in osteoarthritis and aging.

Animals↗

Use of enzymatically isolated chondrocytes for short term metabolic studies.

Chondrocytes isolated from calf articular cartilage by pretreatment with various enzymes prior to collagenase digestion were examined to determine the effect of enzymatic exposure on cell viability and to establish optimal conditions whereby freshly isolated cells could be used for short term metabolic studies. Pre-collagenase exposure to proteolytic enzymes for short intervals has no effect on cell viability. Trypsin pre-treatment appeared to increase the efficiency of cell isolation. Proteoglycan and RNA synthetic activity was influenced by the conditions of incubation (i.e., cell suspension vs. cell pellet: with or without a 24 hour "rest" period; and differential pre-collagenase enzyme exposure). The data suggest that the experimental conditions of incubation and the enzymes used in isolation of the cells, materially alter the freshly isolated chondrocyte's "pattern" of metabolic activity in short term culture studies.

Animals↗