Evolving Acceptance and Use of RWE for Regulatory Decision Making on the Benefit/Risk Assessment of a Drug in Japan.

There is growing interest in the utilization of real-world data (RWD) and real-world evidence (RWE) for regulatory purposes. However, there are challenges in the practical utilization of RWD to provide RWE as a basis for regulatory decision making. This article presents the regulatory initiatives in Japan and efforts taken to promote the utilization of RWD/RWE for regulatory decision making at the pre- and postapproval stages of a drug.

Establishment of the MID-NET medical information database network as a reliable and valuable database for drug safety assessments in Japan.

Purpose: To establish a new medical information database network (designated MID-NET ) to provide real-world data for drug safety assessments in Japan.

Methods: This network was designed and developed by the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency in collaboration with 23 hospitals from 10 healthcare organizations across Japan. MID-NET is a distributed and closed network system that connects all collaborative organizations through a central data center.

4-Hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded by cathepsin G.

Degradation of oxidized or oxidatively modified proteins is an essential part of the antioxidant defenses of cells. 4-Hydroxy-2-nonenal (HNE), a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. It has been reported that HNE-modified proteins are degraded by the ubiquitin-proteasome pathway or, in some cases, by the lysosomal pathway.

Degradation of glyceraldehyde-3-phosphate dehydrogenase triggered by 4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal.

Lipid peroxidation products such as 4-hydroxy-2-nonenal (HNE) may be responsible for various pathophysiological events under oxidative stress, since they injure cellular components such as proteins and DNA. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is a key enzyme of glycolysis and has been reported to be a multifunctional enzyme, is one of the enzymes inhibited by HNE. Previous studies showed that GAPDH is degraded when incubated with acetylleucine chloromethyl ketone (ALCK), resulting in the liberation of a 23-kDa fragment.

Improved determination of bovine glutaminyl cyclase activity using precolumn derivatization and reversed-phase high-performance liquid chromatography with ultraviolet detection.

A sensitive, rapid and reproducible assay for the determination of glutaminyl cyclase activity is reported. This method is based on the monitoring of the absorption of l-pyroglutamic acid beta-naphthylamide at 235 nm, enzymatically formed from the substrate l-glutaminyl-beta-naphthylamide, after separation by high-performance liquid chromatography using a C-18 reversed-phase column by isocratic elution. The detection limit of this method is at a level as low as 0.

Conformational change of glyceraldehyde-3-phosphate dehydrogenase induced by acetylleucine chloromethyl ketone is followed by unique enzymatic degradation.

We have previously reported that acetylleucine chloromethyl ketone (ALCK), an inhibitor of acylpeptidehydrolase, induces the inhibition and degradation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the U937 cell extract. In the present study, the process of ALCK-induced GAPDH degradation was investigated. A kinetic study revealed that GAPDH was irreversibly inhibited by ALCK.

Anterograde axonal transport of endopeptidase 24.15 in rat sciatic nerves.

Axonal transport of endopeptidase 24.15 (EP24.15), a putative neuropeptide degrading-enzyme, was examined in the proximal, middle, and distal segments of rat sciatic nerves using a double ligation technique.

Degradation of glyceraldehyde-3-phosphate dehydrogenase induced by acetylleucine chloromethyl ketone in U937 cells.

We examined whether any changes were induced in cellular proteins by an inhibitor of acylpeptide hydrolase (ACPH) (EC 3.4.19.