Following intragastrical injection of melatonin or one of its derivatives daily for 1 week, CP was given ABT-263 purchase intraperitoneally, i.p., as a single dose of 25 mg/kg BW. Pyridazin-4-yl thiadiazoloindole

derivative 8, diaminothiophen-5-yi thiadiazoloindole derivative 4a and melatonin were significantly able to reduce the number of micronucleated polychromatic erythrocytes (MnPCEs) in the bone marrow cells induced by CP (P < 0.0001, P < 0.001, P < 0.01, respectively). However, reduction of MN formation in the bone marrow cells was not significant when thiadiazoloindole derivative 2 was administered (P = 0. 14). Examination of the protective effect of see more melatonin and its derivatives on the levels of DNA, RNA and protein as well as enzyme activities showed that compound 8 had the ability to inhibit the clastogenic effect of CP in several organs of male mice. These findings suggest that compounds 4a, 8 and melatonin were able to reduce the mutagenicity effect of CP in male mice. The ability of compounds 4a, 8 and melatonin to reduce CP-related genotoxicity is possibly attributed to their antioxidant activity. (c) 2007 Elsevier Masson SAS. All rights reserved.”
“We determined the characteristic features of synovial tissues

of rheumatoid arthritis (RA) patients treated by TNF inhibitors in order to delineate their mechanism of action. Synovial tissues were obtained during the joint surgical operations from 12 RA patients who had been treated with TNF inhibitors in addition to disease modifying antirheumatic drugs (DMARDs)

for at least 5 months (5-25 months) (RA-TNFinh), and from 12 RA patients who had been treated with DMARDs alone (RA-DMARD), and were check details evaluated under light microscopy. There were no significant differences in disease duration, serum CRP levels, DAS28, Steinbrocker’s stages on X-ray and treatment regimen except for TNF inhibitors between RA-TNFinh and RA-DMARD. The most prominent changes in the synovium from RA-TNFinh were discoid fibrosis in the subliming layers of the synovium with degeneration and detachment of synoviocytes and marked decrease in vasculatures. There was no significant difference in these synovial features between RA patients with infliximab and those with etanercept. Interestingly, appearance of osteoclasts was observed in RA-TNFinh (3 out of 12 patients) and in RA-DMARD (1 out of 12 patients). These results indicate that not only infliximab, but etanercept might have direct actions on synovial cells in the deep lining layers of the synovium, leading to the discoid fibrosis thereof. Moreover, the data confirm that the deep lining or sublining layers of the synovium are the most important portions that steer the disease process of RA synovitis.