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ABSTRACT:A novel and convenient method was established for the prediction of in vivo metabolic clearance in human liver. The present method applied the in vitro-in vivo extrapolation paradigm previously established in rats to the in vitro data obtained from cryopreserved human hepatocytes. Predicted hepatic availability and clearance were compared with the reported oral bioavailability and plasma clearance in humans for 14 clinically used drugs (naloxone, buspirone, verapamil, lidocaine, imipramine, metoprolol, timolol, antipyrine, diazepam, quinidine, caffeine, propranolol, diclofenac, and phenacetin). A large interindividual variation was observed in the intrinsic metabolic clearance among separate cryopreserved preparations from different subjects. The prediction generally resulted in a marked underestimation when the biologically based scaling (cells/kg) from pooled preparation of two selected lots, which were 3-to 4-fold larger than the biologically based scaling factor. These data suggested that the calibration of inherent interindividual variation of metabolic activities among different cryopreserved preparations of human hepatocytes to obtain the empirical scaling factor, which is applicable only to the preparation used, was an essential step for more reliable and quantitative prediction of in vivo metabolic activity in humans.Hepatic clearance for the metabolism of compounds kinetically consists of two major determinants: intrinsic (metabolic) clearance of the unbound compound and unbound fraction of compound in the blood (or plasma when corrected by the blood-to-plasma partition). Generally, the intrinsic clearance for the unbound compound is measured in vitro by the incubation of isolated hepatocytes or subcellular fractions such as S-9 and microsomes in the protein-free medium. The in vitro metabolic parameters thus obtained are extrapolated by using anatomical parameters such as cell numbers and protein content in the intact liver for the prediction of in vivo metabolic activity (Houston and Carlile, 1997;Iwatsubo et al., 1997;Obach, 1999). Separate experiments necessarily are further carried out to measure the unbound fraction in the plasma. Many technical problems including adsorption of compounds to the apparatus during the equilibrium dialysis and ultra-filtration often hamper the accuracy of the evaluated values (Bertilsson et al., 1979;Desoye, 1988). To improve the accuracy and avoid complexity for predicting in vivo metabolic clearance from in vitro experiments, we have recently developed a novel and convenient in vitro method for predicting in vivo metabolic clearance by using freshly isolated rat hepatocytes suspended in rat serum (Shibata et al., 2000). Oral bioavailability and hepatic clearance for 16 widely used compounds were well predicted directly from the in vitro metabolic clearance values obtained from a single incubation without separate evaluation of unbound fraction in the plasma. The purposes of the present study were to 1) determine whether the same methodology was applicable ...

There has been an increasing interest in the application of terahertz (THz) waves to broadband wireless communications. In particular, use of frequencies above 275 GHz is one of the strong concerns among radio scientists and engineers, because these frequency bands have not yet been allocated at specific active services, and there is a possibility to employ extremely large bandwidths for ultra-broadband wireless communications. Introduction of photonics technologies for signal generation, modulation and detection is effective not only to enhance the bandwidth and/or the data rate, but also to combine fiber-optic (wired) and wireless networks. This paper reviews recent progress in THz wireless communications using telecom-based photonics technologies towards 100 Gbit/s.

Hydrothermally synthesized BaTiO3 powders with nanoscale-sized particles were densified by microwave sintering. A sintered sample of the nanopowder fabricated by hydrothermal synthesis has a high piezoelectric constant d33 due to fabrication by microwave sintering. The maximum value of the piezoelectric constant d33 of a specimen fabricated by microwave sintering was approximately 350 pC/N for a small grain size of 2.1 µm. Detailed microstructures of the samples were observed by transmission electron microscopy (TEM) and scanning electron microscopy/electron backscattered diffraction analysis/orientation imaging microscopy (SEM/EBSD/OIM). The size of ferroelectric domains in the samples showing superior piezoelectric properties was less than 50 nm. SEM/EBSD/OIM observations revealed that the fraction of random boundaries was higher by approximately 10% in microwave sintered samples than in conventionally sintered ones. It is suggested that the small size of domain and the higher fraction of random boundaries might be responsible for the excellent piezoelectric properties of small grains, which can partially be attributed to domain size.

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