The stability of meropenem in the presence of renal dehydropeptidase I (DHP-I) varied extremely with the animal source of the enzyme. Meropenem, compared with imipenem, was rather easily hydrolyzed by DHP-Is from mice, rabbits, and monkeys, while it showed a higher resistance to guinea pig and beagle dog DHP-Is. In addition, meropenem was four times more resistant than imipenem to human DHP-I. The 1 beta-methyl substituent on carbapenems, i.e., meropenem and 1 beta-methyl imipenem, made them considerably more resistant to mouse and swine DHP-Is than the 1-unsubstituted derivatives are.

A series of new carbapenemcompounds,which have a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl group at C-5' position as C-2side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compoundswere investigated, and the structure-activity relationships were discussed. In this series, SM-7338; (l i?,5*S,61S)-2-[(35,55')-5-dimethylaminocarbonylpyrrolidin-3-ylthio]-6-[(i?)-l-hydroxyethyl]l-methylcarbapen-2-em-3-carboxylic acid (5a) was the most interesting compound.

We have been developing monolithic active pixel sensors series, named "XRPIX," based on the silicon-on-insulator (SOI) pixel technology, for future X-ray astronomical satellites. The XRPIX series offers high coincidence time resolution (∼1 µs), superior readout time (∼10 µs), and a wide energy range (0.5-40 keV). In the previous study, we successfully demonstrated X-ray detection by event-driven readout of XRPIX2b. We here report recent improvements in spectroscopic performance. We successfully increased the gain and reduced the readout noise in XRPIX2b by decreasing the parasitic capacitance of the sense-node originated in the buried p-well (BPW). On the other hand, we found significant tail structures in the spectral response due to the loss of the charge collection efficiency when a small BPW is employed. Thus, we increased the gain in XRPIX3b by introducing in-pixel charge sensitive amplifiers instead of having even smaller BPW. We finally achieved the readout noise of 35 e − (rms) and the energy resolution of 320 eV (FWHM) at 6 keV without significant loss of the charge collection efficiency.

The neurotoxicity of meropenemwas muchlower than that of both imipenemand panipenem after intraventricular administration to mice. To clarify the majorstructural features responsible for the induction of convulsions by carbapenemantibiotics, the structure-activity relationship on convulsant activity was investigated in iV-acetyl-2-pyrroline and cyclopentene derivatives which correspond to the 5-membered ring containing the C-2 side chain of carbapenem antibiotics. Among these derivatives, compoundswith strong basicity in the side chain showed convulsant activity similar to that of the parent carbapenem compounds. In addition to the strength of the basicity of the amino group, the distance from the carboxyl to the amino group and steric crowding around the amino group also appeared to play an important role in the induction of convulsions. The results of gammaaminobutyric acid (GABAA) receptor binding assays indicated that the induction of convulsions was caused predominantly by the inhibition of GABAA-mediatedinhibitory transmission. However, the in vivo convulsant activity of some of these compoundsdid not correlate with their in vitro inhibitory effect on GABAA receptor binding.

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