Inhibition of gastric H+,K+-ATPase by new dihydropyrazole derivative KYY-008.

The gastric proton pump (H+,K+-ATPase) responsible for the H+ secretion of gastric acid is an essential therapeutic target for acid-related diseases. H+,K+-ATPase belongs to a P2-type ATPase family. Here, we examined the effects of a newly synthesized dihydropyrazole derivative KYY-008 on the H+,K+-ATPase. KYY-008 concentration-dependently inhibited the enzyme activity of the ATPase in the membrane fractions prepared from isolated hog gastric mucosa and from human kidney HEK293 cells in which gastric H+,K+-ATPase is exogenously expressed. The IC50 values in these samples were 3.4 µM and 3.7 µM, respectively. In addition, KYY-008 significantly inhibited the H+,K+-ATPase-derived H+ uptake into the tightly sealed vesicles prepared from the hog gastric mucosa. In contrast, KYY-008 has no effect on the activities of other P2-type ATPases such as Na+,K+-ATPase and Ca2+-ATPase. KYY-008 did not change the ionic currents of voltage-dependent Ca2+ channels, that were potential targets for some dihydropyrazole derivatives. Together, we discovered a new dihydropyrazole derivative which acts as a selective inhibitor of gastric H+,K+-ATPase.

Bandwidth enhancement of graded index plastic optical fiber by control of differential mode attenuation.

We propose a novel method of graded index plastic optical fiber (GI POF) to enhance bandwidth. Recently, it has been reported that perfluorinated GI POF with a double cladding structure had much higher bandwidth than theoretical value. The result of analysis of this fiber indicates that the high-bandwidth property is obtained because higher order modes are attenuated at a core and cladding polymer boundary. In addition, it does not induce large increment of attenuation of lower order modes and bending loss. Then, by adopting the rod-in-tube method, we control differential mode attenuation of PMMA based GI POF, and it is proved that bandwidth of GI POF can be enhanced by utilizing scattering of the core and cladding polymer boundary.