C3 glomerulopathy and current dilemmas

C3 glomerulopathy (C3G) is a recently identified disease entity caused by dysregulation of the alternative complement pathway, and dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory detection of complement dysregulation is still uncommon in practice, “dominant C3 deposition by two orders greater than that of immunoglobulins in the glomeruli by immunofluorescence”, as stated in the consensus report, defines C3G. However, this morphological definition possibly includes the cases with glomerular diseases of different mechanisms such as post-infectious glomerulonephritis. In addition, the differential diagnosis between DDD and C3GN is often difficult because the distinction between these two diseases is based solely on electron microscopic features. Recent molecular and genetic advances provide information to characterize C3G. Some C3G cases are found with genetic abnormalities in complement regulatory factors, but majority of cases seem to be associated with acquired factors that dysregulate the alternative complement pathway. Because clinical courses and prognoses among glomerular diseases with dominant C3 deposition differ, further understanding the background mechanism, particularly complement dysregulation in C3G, is needed. This may resolve current dilemmas in practice and shed light on novel targeted therapies to remedy the dysregulated alternative complement pathway in C3G

Impact of an unusually large warm-core eddy on distributions of nutrients and phytoplankton in the southwestern Canada Basin during late summer/early fall 2010

http://www.godac.jamstec.go.jp/darwin/cruise/mirai/mr04-05/

4-META MMAレジンで接着した矯正用ブラケットの再接着時における圧縮剪断荷重について

The purpose of this study was to determine the difference of the shear bond strength between new and rebonded brackets with a chairside cleaning method proposed by the authors. A preliminary study was carried out to examine the optimal cleaning time for both 4-META MMA resin (Superbond, Sun Medical, Kyoto, Japan) and Bis-GMA resin (Concise, 3M, Monrovia, California, USA) using acetone or chloroform. The 4-META MMA resin was completely removed by acetone (13 min.) and by chloroform (8 min.), while the Bis-GMA resin was not removed by either. The resin remnant on the bracket base was stained with alcohol-based ink and analyzed quantitatively under a microscope attached to a CCD camera and a computer analyzer. Stainless steel brackets with foil mesh base designs were bonded to twenty extracted human premolars with the 4-META MMA resin. All specimens were stored in water at 37℃ for 24 hours, and thermocycled 120 times from 4℃ to 60℃ before shear bond strength testing. Specimens were stressed to bond failure using an Autograph AG-5000D testing machine (Shimadzu, Kyoto, Japan). The bases of the debonded brackets were inspected for resin according to an adaptation of the adhesive remnant index (ARI) system. After recording of the shear bond strengths, the brackets were cleaned and rebonded to the same teeth and tested once more. The results revealed that the rebonding of the brackets even twice following the original bonding had no significant effect on the bond strength value. The capacity for rebonding of the same bracket by an easy and fast cleaning method is an advantage of the 4-META MMA resin over the Bis-GMA resin

Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells

<p>Abstract</p> <p>Background</p> <p>Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis.</p> <p>Methods</p> <p>Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet), one of the predominant K₂vitamins present in the testis, for 5 weeks. <it>In vivo </it>testosterone levels of the rats' plasma and testes were measured by enzyme-linked immunosorbent assay, and <it>in vitro </it>testosterone levels of testis-derived tumor cells (I-10 cells) maintained in Ham's F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 μM) at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis.</p> <p>Results</p> <p>Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K₁, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of γ-glutamylcarboxylation.</p> <p>Conclusions</p> <p>MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders.</p