INVESTIGATION OF CYTOKINE PROFILE IN PATIENTS WITH REACTIVE ARTHRITIS

Abstract. Pathogenesis of reactive arthritis (ReA) is not clear yet. Several trials suggest that increased production of proinflammatory cytokines is responsible for development of arthritis in ReA, while other studies report that Th1 cytokine response in ReA is impaired in favor of Th2 response. The aim of our study was to investigate serum levels of cytokines IL-1β, IL-4, IL-6, TNFα, IFNγ and IL-1Ra in the patients with ReA of different etiology, as compared with infection-related arthritis. The results of our study had demonstrated that serum levels of IL-1β and TNFα in the patients with ReA were significantly higher, whereas IL-1Ra, IL-4, IL-6 proved to be significantly lower than in healthy controls. Serum levels of IL-6 were significantly higher in patients with chronic ReA, as compared to the cases of acute and recurrent ReA. No significant differences in cytokine profiles were found between the patients with ReA, and the persons with infection-related arthritis. The data obtained are, generally, suggestive for proinflammatory Th1 cytokine profile in ReA patients studied, this confirming the mostly assumed pathogenetic hypothesis for reactive arthritis where an underlying cytokine imbalance is suggested. (Med. Immunol., 2008, vol. 10, N 2-3, pp 167-172)

EXPRESSION OF mRNAS FOR CHEMOKINES AND CHEMOKINE RECEPTORS IN THE SKIN FROM PATIENTS WITH PSORIASIS

Abstract. Some issues in etiology and pathogenesis of psoriasis are poorly studied. Therefore, a search for new potential markers is actual for diagnostics of psoriasis in less clear cases. In this study, an attempt was undertaken to evaluate contribution of some chemokines and appropriate receptors into pathogenesis of psoriasis. The main group consisted of the patients with psoriatic arthritis (n = 20) and psoriasis vulgaris (n = 9). A group of comparison consisted of patients with sclerodermia (n = 4), and a control group was represented by healthy persons (n = 9). The specimens were taken from visually normal and affected skin areas from psoriatic patients obtained by punch biopsy. Expression of the following chemokines was performed: CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/eotaxin, CCL24/eotaxin-2, CXCL8/IL-8 and their receptors (CCR1, CCR3, CCR5, CXCR1, CXCR2). In cases with PASI values < 10, an increased expression of the following genes was revealed for CCL11/eotaxin (p = 0.03), CXCR1 (р = 0.008), CXCR2 (р = 0.0006) in virtually intact skin and affected skin areas, as well as increased gene expression of CCL24/eotaxin 2 (p = 0.009), CCL5/RANTES (p = 0.05) in visually normal skin.With PASI values of 10 to 20, an increased gene expression was found for CCL11/eotaxin (p = 0.005), CCL24/eotaxin 2 (p = 0.02), CCL5/RANTES (p = 0.01), CXCR1 (р = 0.0009), CXCR2 (р = 0.002) in skin biopsies from visually healthy and affected skin, as well as increased expression CXCL8 (IL-8) (p = 0.005) in visually normal skin. In cases with PASI > 20, an increased expression of CCL11/eotaxin (p = 0.001), CCL24/eotaxin 2 (p = 0.001), CCL3/MIP-1α (р = 0.02), CXCR1 (p = 0.0001), CXCR2 (p = 0.001) was detected in visually healthy skin samples and affected skin of the patients, as well as higher expression of CCL4/MIP-1β (р = 0.03) in affected skin areas. A reverse correlation was revealed between expression of chemokines, i.e., CCL24/eotaxin 2 (r = –0,94, p = 0.005), CCL3/MIP-1α (r = –0,94, p = 0.005), CCL4/MIP-1β (r = –0,85, p = 0.03) and their receptors: ССR5 (r = –0,79, p = 0.005) and CXCR2 (r = –0,94, p = 0.005) in visually normal skin of the patients with psoriasis and PASI values < 10.A direct correlation was found between expression of mRNAs for CCL11/eotaxin (r = 0.69, p = 0.04) in visually healthy skin from psoriatic patients, and CCR5 (r = 0.82, p = 0.006) in affected skin of the patients with psoriasis and PASI values of 10 to 20. In the group of patients with PASI values over 20, no correlations were detectable. These data allow us of concluding aboutan important contribution of chemokine system to pathogenesis of psoriasis. (Med. Immunol., vol. 10, N 4-5, pp 337-346)

CLINICAL EFFICACY OF THE DRUG STRUCTUM IN OSTEOARTHRITIS THERAPY (results of multicenlral clinical study in Russia)

Objective. Study of the efficacy and tolerability of Structum in pts with gonarthritis and coxarthritis during 6 months therapy. Material. Open multicentral study included off -patients of both sexes with osteoarthritis (ОЛ) of knee and hip joints with obvious pain syndrome - pain in walking 30 mm and more on visual analog scale, functional Lesquene index more or equal to 4 and less or equal toll, regular NSAIDs taking for 30 days for the last 3 months, radiological I-II-III OA stage according Kellgren-Lawrence and consent of the patient for the study. Total number of pts included was 555 and 192 out of them were experimental group and 363 - controls. Pts from experimental group had Structum - three capsules in the morning and 3 capsules in the evening during meals (one capsule - 250 mg) for 3 weeks, then 2 capsules in the morning and 2 in the evening for 21 weeks. Clinical examination of pts was done after the third and sixth month of the treatment. Results. During Structum therapy reliable lessening of pain syndrome in knee and hip joints, improvement of articular function, decrease of NSAIDs dosage or their full cancellation were demonstrated. It was noticed that the assessment of clinical Structum efficacy and tolerability bu physician and patient coincided. Conclusion. Structum (chondroitin sulfate) is a new effective drug for treatment of osteoarthritis of knee and hip joints with high clinical efficacy and good tolerabilit

Once-yearly zoledronic acid and days of disability, bed rest, and back pain: Randomized, controlled HORIZON Pivotal Fracture Trial

The objective of this study was to determine the effect of once-yearly zoledronic acid on the number of days of back pain and the number of days of disability (ie, limited activity and bed rest) owing to back pain or fracture in postmenopausal women with osteoporosis. This was a multicenter, randomized, double-blind, placebo-controlled trial in 240 clinical centers in 27 countries. Participants included 7736 postmenopausal women with osteoporosis. Patients were randomized to receive either a single 15-minute intravenous infusion of zoledronic acid (5 mg) or placebo at baseline, 12 months, and 24 months. The main outcome measures were self-reported number of days with back pain and the number of days of limited activity and bed rest owing to back pain or a fracture, and this was assessed every 3 months over a 3-year period. Our results show that although the incidence of back pain was high in both randomized groups, women randomized to zoledronic acid experienced, on average, 18 fewer days of back pain compared with placebo over the course of the trial (p = .0092). The back pain among women randomized to zoledronic acid versus placebo resulted in 11 fewer days of limited activity (p = .0017). In Cox proportional-hazards models, women randomized to zoledronic acid were about 6% less likely to experience 7 or more days of back pain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.90–0.99] or limited activity owing to back pain (RR = 0.94, 95% CI 0.87–1.00). Women randomized to zoledronic acid were significantly less likely to experience 7 or more bed-rest days owing to a fracture (RR = 0.58, 95% CI 0.47–0.72) and 7 or more limited-activity days owing to a fracture (RR = 0.67, 95% CI 0.58–0.78). Reductions in back pain with zoledronic acid were independent of incident fracture. Our conclusion is that in women with postmenopausal osteoporosis, a once-yearly infusion with zoledronic acid over a 3-year period significantly reduced the number of days that patients reported back pain, limited activity owing to back pain, and limited activity and bed rest owing to a fracture

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength