Identification and quantification of selected inflammatory genes modulated by leflunomide and prednisone treatment in early rheumatoid arthritis patients

OBJECTIVES: The present study evaluates the effects of combined leflunomide (LEF) and low dose of prednisone therapy, on selected inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) of early rheumatoid arthritis (ERA) patients by gene microarray analysis and quantitative real time-polymerase chain reaction (qRT-PCR). METHODS: Ten ERA patients (mean age 53±10 years) were assigned as untreated (group 1) or pre-treated (group 2) with prednisone (5 mg/day for 3 months) after informed consent and ethics committee approval. Five sex- and age-matched healthy subjects were used as controls (CNT). RNA was extracted by PBMCs, amplified, labelled and hybridised on inflammation DualChip microarray. The expression ratio of 282 inflammatory genes between CNT and ERA patients, before (T0) and after 12 weeks (T1) of combined therapy was detected. qRT-PCR was performed on 7 selected inflammatory RA-related genes (STAT4, MAPK9, HIF1A, MIF, STAT6, NFKB1, TNFRSF1B). RESULTS: At T0, microarray analysis showed 34 altered genes in both ERA groups when compared to CNT (vs. CNT). Seven RA-related genes, investigated in further details, were found up-regulated in group 1 and down-regulated or unchanged in group 2 vs. CNT. At T1, combined therapy induced the down-regulation of these genes in both groups vs. CNT as also confirmed by qRT-PCR performed on selected genes. CONCLUSIONS: Untreated ERA patients seem characterised by up-regulation of specific genes involved both in the resistance/inhibition to apoptosis and in the stimulation of pro-inflammatory cytokine production by immune inflammatory cells. Combined LEF and low dose of prednisone therapy seems to play synergistic effects on down-regulation of these genes

The unilateral contact buckling problem of continuous beams in the presence of initial geometric imperfections: An analytical approach based on the theory of elastic stability

An analytical method for the treatment of the elastic buckling problem of continuous beams with intermediate unilateral constraints is presented, which is based on the fundamental theory of elastic stability. The study focuses on the unilateral contact buckling problem of beams in the presence of initial geometric imperfections. The mathematical Euler approach, based on the fundamental solution of the boundary value problem of the buckling of continuous beams, is appropriately modified in order to take into account the unilateral contact conditions. Furthermore, in order the obtained analytical solutions to be applicable for practical design cases, the actual strength of the cross-section of the beam under combined compression and bending is considered. The implementation of the proposed method is demonstrated through a characteristic example. (C) 2011 Elsevier Ltd. All rights reserved