Effect of first-pass metabolism on enantioselective pharmacokinetics after oral administration of (+)-, (-)- and racemic homochlorcyclizine to rats

The enantioselective relationship between the pharmacokinetics and hepatic metabolism of homochlorcyclizine hydrochloride (HCZ) was investigated using rats. There were no significant differences in blood concentrations between the three forms after intravenous administration (5 mg/kg) of (+)-, (-)- and racemic HCZ. On the other hand, there were significant differences in the pharmacokinetics between (-)- and (+)-HCZ and between (-)- and racemic HCZ after oral administration (50 mg/kg) of these three forms. The Cmax and AUC0-infinity of (-)-HCZ were lower than those of (+)-isomer and racemate, and its CLo was clearly higher than the others. The (+)-isomer and racemate showed no significant differences in their pharmacokinetic parameters. At a lower dose (10 mg/kg), however, no enantiomeric differences were found in the pharmacokinetic parameters of (+)- and (-)-HCZ. Also examined was the cytochrome p-450-dependent-oxidative metabolism of (+)-, (-)- and racemic HCZ in vitro using rat liver 9000 x g supernatant fraction. The in vitro metabolism of (-)-HCZ was extremely fast, compared with those of the (+)-isomer and the racemate. The Vmax in vitro showed a good correlation with the CLo in vivo after oral administration (50 mg/kg) of all three forms of HCZ. In vitro study of enantiomeric inhibition of the metabolism showed that (+)-HCZ was a competitive inhibitor of (-)-HCZ metabolism, with a Ki of 6.96 microM. (-)-HCZ was also a competitive inhibitor of (+)-HCZ metabolism, with a Ki of 20.4 microM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extremely small-chirp electroabsorption-modulator integrated distributed feedback laser diode with a shallow quantum-well absorption layer

We have developed an extremely small-chirp electroabsorption modulator integrated with a distributed feedback laser diode (EAM-DFB-LD) with a novel shallow quantum-well (QW) absorption layer. By using a shallow QW absorption layer, the estimated lifetime of the photogenerated holes and thus the estimated concentration of the holes generated by optical absorption has been reduced to 9% of that for a conventional QW. It was experimentally confirmed that the excess chirp due to the pileup of carriers has been reduced to 10% of that for a conventional QW, and this result is consistent with the estimates. The shallow QW EAM-DFB-LD has shown a chirp parameter |/spl alpha/| less than 0.7 over the entire range of the EAM reverse bias voltage of 0-3 V. Finally, successful 10-Gb/s return to zero transmission has been confirmed through both positive dispersion (+425 ps/nm) and negative dispersion (-425 ps/nm).     

Propagation and radiation field characteristics of nanometer electromagnetic waves in x‐ray dielectric waveguides with random media

X‐rays in the nanometer electromagnetic region are useful for nanospace fabrication, information and high‐energy transmission and control techniques of angstrom‐size structures in biomedical sciences and technology. In this paper, the electromagnetic fields in X‐ray gradient fiber with random refractive index media are studied. Statistical mode conversion of beam propagation, beam broadening, and beam center are investigated by the stochastic process theory of electromagnetic fields. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 139(3): 53–61, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.10002/eej.1160     

Correction of count-loss effect in neutron correlation methods that employ single neutron counting system for subcriticality measurement

It is well known that the count-loss effect produces serious problems for the neutron correlation methods that employ a single neutron counting system, e.g. the variance-to-mean and the auto-correlation methods, since it deteriorates the information extracted from the subcritical reactor system. New formulae of the variance-to-mean and auto-correlation methods were hence obtained on the basis of a rigorous theoretical approach for treating the count-loss process. It is expected that the present formulae work better than conventional ones for determination of the neutron decay constant.     

Dynamic Mechanical Properties and Adhesive Joint Strengths of Emulsion Polymers Produced by Power Feed Technique. III. Adhesive Joint Strengths of Grafted Power Feed Copolymer

Power feed copolymers were synthesized using styrene and n-butyl acrylate through non-uniform feeding emulsion polymerization. Poly(vinyl alcohol) (PVA) was used as a protective colloid, onto which vinyl monomers were grafted. Power feed copolymer had a very broad glass transition temperature compared with random copolymer, even if grafting and/or crosslinking were introduced to the system. This tendency was almost the same as the non-grafted power feed copolymer where only low molecular weight surfactant was used.

Adhesive joint strengths of power feed copolymers were evaluated compared with random copolymers. In the case of usual linear power feed copolymer, the adhesive joint strengths were not higher than those of random copolymer, which was considered to be due to the lower film strengths of the power feed copolymer. Power feed copolymer having grafting showed slightly higher adhesive joint strengths over a wide range of temperatures than random copolymer. When crosslinking was introduced to the system, power feed copolymer showed much higher adhesive joint strengths over a wide temperature range.     

Damping capacity improvement of machine structures by close packing with balls

This paper deals with an experimental investigation on damping characteristics of structures packed with balls. The structures for testing are square pipes packed with glass balls. The effects of impulse magnitude, square pipe dimensions, ball size and excitation directions on damping characteristics are investigated. The experiments show that the damping characteristics are markedly affected by the ball size, and the damping capacity is improved by the ball packing. It is also shown that the damping capacity is affected by the packing arrangements, packing ratio and repulsion coefficient. Dramatic improvement in damping capacity is achieved by leaving only a small space between the packed balls and the inner surface of the square pipe. This fact is confirmed experimentally.     

Combined effects of work hardening and precipitation strengthening on the cyclic stability of TiNiPdCu-based high-temperature shape memory alloys

The combined effects of work hardening and precipitation strengthening were employed to improve the cyclic stability of TiNiPdCu-based high-temperature shape memory alloys. Annealing after cold deformation resulted in the formation of nano-scale TiPdCu and Ti₂Pd precipitates, stable at high temperatures in Ti₅₀Ni_25?xPd₂₅Cu_x alloys. The nano-scale precipitates were also observed to retard recovery/recrystallization processes at higher temperatures. It was found that the combined effects of work hardening and precipitation strengthening remarkably enhanced the high-temperature stability of the Ti₅₀Ni₂₀Pd₂₅Cu₅ alloy and increased its maximum working temperature range while keeping the transformation temperatures and recovery strains at sufficiently high levels. Precipitation strengthening helped to greatly improve the high-temperature cyclic stability of the alloy. Creep tests at 673 K under 500 MPa confirmed that the better high-temperature cyclic stability of the precipitate-containing alloy was mainly due to its higher creep resistance.     

Microformability of optical glasses for precision molding

We investigated macroscopic and microscopic deformation of optical glasses K-PSK100 and K-PG375 for precision molding. The materials are characterized by a low glass transition temperature T_g; T_g is 663 K for PSK100 and 616 K for PG375. The materials exhibit Newtonian viscous flow above T_g. We studied the temperature dependence of the normal viscosity and evaluated the microformability by the geometrical transferability of a V-grooved die shape to the material. The dies were made of (1 0 0)Si and the width of the V-groove W_g was 0.1–2.0 μm. After die-forming, we measured the transferred shape of the material with AFM and analyzed the curvature r of the tip of the deformed specimen and the formed and filled area to the V-groove R_f. As a result, we found that the materials exhibit superior microformability due to the homogeneity on a nanometer scale and will be applied to micro- or nano-forming and thus contribute to mass production of micro/nano-devices.