ABSTRACT
OBJECTIVE: To investigate platelet and leukocyte activation and interaction in patients with rheumatoid arthritis (RA) and the effect of methotrexate (MTX) or anti-tumor necrosis factor-a (TNF-a) treatment on these variables. METHODS: Four-color flow cytometry analysis was performed for quantitative measurement of platelet (P-selectin, PAC-1) and leukocyte (CD11b, CD64) activation markers and estimation of percentage of leukocyte-platelet complexes in whole blood in 20 patients with RA before and after 6 weeks of therapy and in 20 controls. In addition, measures of soluble P-selectin (sP-selectin), beta-thromboglobulin, fibrinogen, prothrombin fragment 1+2, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), and TNF-a and tender and swollen joint counts were carried out. RESULTS: Before therapy, PAC-1 binding, expression of CD11b and CD64 on monocytes and neutrophils, circulating levels of monocyte (CD11b+ or CD64+)-platelet complexes, monocyte-PAC-1+ platelet complexes, CRP, ESR, IL-6, TNF-a, fibrinogen, D-dimer and sP-selectin were significantly higher in RA patients compared to controls. The anti-TNF-a therapy significantly reduced levels of monocyte-PAC-1+ platelet complexes, sP-selectin, CRP, ESR, IL-6, TNF-a, fibrinogen, and D-dimer and tender and swollen joint counts. CD64 expression on monocytes was significantly decreased by MTX therapy. PAC-1 binding was not inhibited by MTX or anti-TNF-a. CONCLUSION: Increased platelet and leukocyte activation and increased formation of leukocyte-platelet complexes in patients with RA suggest a status of simultaneous activation of the immune and hemostatic systems.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Blood Platelets/metabolism , Monocytes/physiology , Neutrophils/physiology , P-Selectin/metabolism , Receptors, IgG/metabolism , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Biomarkers/analysis , Blood Platelets/drug effects , Case-Control Studies , Female , Flow Cytometry , Humans , Infliximab , Integrins , Male , Methotrexate/therapeutic use , Middle Aged , Probability , Prognosis , Receptors, IgG/analysis , Reference Values , Sensitivity and Specificity , Severity of Illness Index , Statistics, NonparametricABSTRACT
This work concerned a technique for a health monitoring system based on the generation and sensing of Lamb waves in composite structures by thin surface-bonded piezoceramic transducers. The objective was to develop transducers that are adapted for the damage detection in orthotropic composites. The key problem with the investigated Lamb waves was to select a mode to be sensitive to the damage. A hybrid modeling technique was therefore used to conceive transducers that were adapted to achieve such a feature. This modeling technique enabled studying the influence of the transducer characteristics on the Lamb waves propagating in orthotropic plates. It was demonstrated that a Lamb mode could be generated dominantly to other modes by using a multi-element transducer. The effectiveness of this technique was successfully verified experimentally on composite plates. It was shown that the dominant Lamb mode, obtained by use of dual-element transducers, was an appropriate mode for successfully detecting a damage in composites.
