Objective Infliximab treatment results in a decrease in synovial cellularity as early as 48 hours after initiation of therapy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether infliximab induces apoptosis within the first 24 hours after infusion. Methods The percentage of apoptotic cells was determined by flow cytometry in blood drawn from 21 patients directly before, 1 hour after, and 24 hours after infliximab infusion. Synovial tissue samples obtained before, 1 hour after (n = 5), or 24 hours after (n = 5) initiation of therapy were subjected to immunohistochemistry to detect active caspase 3 and to TUNEL assay and electron microscopy to detect apoptosis. In addition, plasma levels of nucleosomes (generated during apoptosis) and C4b/c (an indicator of complement activation) were measured. Results There were no signs of apoptosis induction in peripheral blood monocytes or lymphocytes after infliximab treatment. Circulating lymphocyte counts were increased within 1 hour after infusion (P < 0.05). There was no definite evidence of apoptosis induction in the synovium, except in 1 patient 24 hours after the infliximab infusion. Consistent with these results, there was no increase in nucleosome levels nor were there signs of complement activation. Conclusion Our findings indicate that the rapid decrease in synovial cellularity observed after initiation of anti–tumor necrosis factor antibody therapy cannot be explained by apoptosis induction at the site of inflammation. It is tempting to speculate that the striking effects on synovial inflammation may be explained by other mechanisms, such as decreased migration toward the synovial compartment and reduced retention in the inflamed synovium.

Abstract. The aim of the present study was to investigate the changes in mitotic reorientation and relative differential gene expression in rat prostate epithelial cells following long-term exposure to testosterone propionate (TP). Sprague-Dawley rats were randomly divided into two groups as follows: TP group, which received 3.7 mg/kg/day TP for 30 days (n=10); and control group, in which rats were injected with olive oil (n=10). Microscopic analysis of the prostate tissue was performed by immunohistochemical analysis and hematoxylin and eosin staining. Differential gene expression analysis was performed via gene microarray, and a total of five genes (Dkk3, Ran, Fas, Tgm4 and Wnt2) were selected and their expression levels were verified using reverse transcription-polymerase chain reaction. For rats treated with TP, mitosis was significantly reoriented, becoming parallel to the basement membrane. By contrast, in the control group cells mitotic orientation remained perpendicular to the basement membrane. Genes such as Ran and Tgm4 in the androgen receptor (AR) signaling pathway and Wnt2 in the Wnt signaling pathway, were upregulated following treatment with TP. Conversely, the Dkk3 and Fas genes were downregulated following treatment with TP. In conclusion, mitotic orientation of prostate epithelial cells was altered following long-term administration of TP. Wnt and AR signaling pathways influenced cell proliferation and may have participated in the mitotic orientation change.

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