Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation

High Speed Turn-on Gate Driving for 4.5kV IEGT without Increase in PiN Diode Recovery Current

4.5 kV IEGT turn-on loss reduction is experimentally and numerically achieved by employing the proposed simple two step gate drive method without affecting PiN diode reverse recovery performance. It was found that 14% of turn-on loss is reduced only by the simple method. This study determines, for the first time, the optimum gate driving in the two step gate drive which can reduce IEGT turn-on loss maximally without affecting PiN diode reverse recovery performance by TCAD simulation. The method is simple yet effective for reducing switching loss of high voltage IEGT.2013 25th International Symposium on Power Semiconductor Devices & IC\u27s (ISPSD), May 26-30, 2013, Ishikawa Ongakudo, Kanazawa. Japan

High Speed Turn-on Gate Driving for 4.5kV IEGT without Increase in PiN Diode Recovery Current

2013 25th International Symposium on Power Semiconductor Devices & IC's (ISPSD), May 26-30, 2013, Ishikawa Ongakudo, Kanazawa. Japan.4.5 kV IEGT turn-on loss reduction is experimentally and numerically achieved by employing the proposed simple two step gate drive method without affecting PiN diode reverse recovery performance. It was found that 14% of turn-on loss is reduced only by the simple method. This study determines, for the first time, the optimum gate driving in the two step gate drive which can reduce IEGT turn-on loss maximally without affecting PiN diode reverse recovery performance by TCAD simulation. The method is simple yet effective for reducing switching loss of high voltage IEGT

Role of fibroblast growth factor 8 (FGF8) in animal models of osteoarthritis

10.1186/ar2474Arthritis Research and Therapy104R9

Bipolar localization of putative photoreceptor protein for phototaxis in thermophilic cyanobacterium Synechococcus elongatus

Funding Information: This work was supported in part by Grants-in-Aid for scientific research from the Ministry of Education, Science, Sports and Culture, Japan (no. 11640653 to K.M.).We identified an open reading frame from a database of the entire genome of Synechococcus elongatus, the product of which was very similar to pixJ1, which was proposed as photoreceptor gene for phototaxis in Synechocystis sp. PCC6803 [Yoshihara et al. (2000) Plant Cell Physiol. 41: 1299]. The mRNA of S. elongatus pixJ (SepixJ) was expressed in vivo as a part of the product of an operon. SePixJ was detected exclusively in the membrane fraction after cell fractionation. Immunogold labeling of SePixJ in ultra-thin sections indicated that it existed only in both ends of the rod-shaped cell; probably bound with the cytoplasmic membrane.publishersversionPeer reviewe

Surface Active Buffered Hydrogen Fluoride Having Excellent Wettability for ULSI Processing

application/pdf学術論文 (Article)1460269 bytesjournal articl

Coronary angioscopic findings 9 months after everolimus-eluting stent implantation compared with sirolimus-eluting stents

AbstractObjectivesWe assessed angioscopic findings after everolimus-eluting stents (EES) implantation, compared with sirolimus-eluting stents (SES).BackgroundCoronary angioscopy (CAS) provides an opportunity to assess neointimal coverage over stent struts, thrombus, and plaque color by direct visualization. CAS is a useful tool for evaluating stent struts after drug-eluting stent implantation. Angioscopic findings after EES implantation have not been reported before.MethodsWe performed CAS in 23 patients who were treated with EES and 41 patients with SES. CAS was performed 8.5 months after stent implantation. We assessed neointimal coverage, thrombus, and plaque color. We classified neointimal coverage in 4 grades: grade 0=struts were completely exposed; grade 1=struts were visible with dull light reflexion; grade 2=there was no light reflexion from slightly visible struts; grade 3=struts were completely covered.ResultsThere was no significant difference in minimum, maximum, dominant grade of neointimal coverage, and heterogeneity index between EES and SES. Thrombus was less frequently observed in EES than SES (4% vs 29%, p=0.02). When we divided study patients into acute coronary syndrome (ACS) or stable angina pectoris (SAP), there was a tendency toward less thrombus in EES than SES, in both ACS and SAP. Maximum color grade of the plaques was less advanced in EES than SES (p<0.01). Yellow plaques of grade 2 or 3 were less frequent in EES than SES (35% vs 76%, p<0.01).ConclusionsThis study suggested that EES were associated with lower risk of thrombus formation than SES