Variability of Zaleplon 5-Oxidase Activity in Mice and Humans, and Inhibition by Raloxifene.

Background: Zaleplon (ZAL) is a sedative-hypnotic agent, which is mainly metabolized to inactive 5-oxidized zaleplon (5-oxo-ZAL) and N-des-ethylated ZAL (des-ethyl-ZAL) in mice and humans. The former reaction is considered to be catalyzed by aldehyde oxidase present in liver cytosol.

Methods: Here, we examined sex and strain differences of ZAL metabolism to 5-oxo-ZAL among four strains of mice, as well as the inter-individual variation in humans, in order to evaluate the variability of 5-oxo-ZAL-forming activity and its relationship with aldehyde oxidase activity.

Study of the usefulness of patch testing and use test to predict the safety of commercial topical drugs.

Patch testing (PT) can be used to identify allergens and irritants responsible for contact allergic and irritant dermatitis, respectively. However, the reproducibility of PT and correlation between PT and use test has not been fully evaluated. The aim of the present study was to examine the reproducibility of PT and its usefulness in assessing the safety of topical drugs.

Prediction of human metabolism of the sedative-hypnotic zaleplon using chimeric mice transplanted with human hepatocytes.

1. Human chimeric mice (h-PXB mice) having humanized liver, constructed by transplantation of human hepatocytes, were evaluated as an experimental model for predicting human drug metabolism. Metabolism of zaleplon in h-PXB mice was compared with that in rat chimeric mice (r-PXB mice) constructed by transplantation of rat hepatocytes.

Strain difference of oxidative metabolism of the sedative-hypnotic zaleplon by aldehyde oxidase and cytochrome P450 in vivo and in vitro in rats.

The in vivo and in vitro metabolism of the sedative-hypnotic agent zaleplon (ZAL) to 5-hydroxylated ZAL (5-oxo-ZAL) and N-desethylated ZAL (desethyl-ZAL) was studied in four strains of rats. Incubation of ZAL with liver microsomes afforded desethyl-ZAL via cytochrome P450-catalyzed reaction, with little strain difference. In contrast, incubation of ZAL with liver cytosol afforded 5-oxo-ZAL with marked strain differences.

Analysis of Trichophyton antigen-induced contact hypersensitivity in mouse.

Background: Trichophyton-induced superficial skin mycosis is a common infectious human disease, but the immunological mechanism against Trichophyton infection is unclear with regard to many points. Since Trichophyton cannot colonize mice, guinea pigs were used in previous experiments on Trichophyton infection. However, it is difficult to perform immunological and genetic analyses in guinea pigs.

Aldehyde oxidase-catalyzed metabolism of N1-methylnicotinamide in vivo and in vitro in chimeric mice with humanized liver.

Aldehyde oxidase-mediated oxidation of N(1)-methylnicotinamide to N(1)-methyl-2-pyridine-5-carboxamide (2-PY) and N(1)-methyl-4-pyridone-5-carboxamide (4-PY) in chimeric mice constructed by transplanting human hepatocytes into urokinase-type plasminogen activator-transgenic severe combined immunodeficient mice was examined in vivo and in vitro. The activity in liver cytosol of chimeric mice with a high replacement index was approximately 4-fold higher than that in control mice. Furthermore, the oxidation products in control mice were 2-PY and 4-PY, whereas, in chimeric mice, the major product was 2-PY, as in humans.

Ouabain-induced hypertension enhances left ventricular contractility in rats.

Chronic ouabain treatment produces hypertension acting on the central nervous system and at vascular levels. However, cardiac effects in this model of hypertension are still poorly understood. Hence, the effects of hypertension induced by chronic ouabain administration ( approximately 8 microg day(-1), s.

[Rapid detection of mycobacteria in sputa using media supplemented with culture filtrate of Gemella haemolysans].

The effect of the culture filtrate Gemella haemolysans in enhancing mycobacterial growth has been previously demonstrated. In the present studies, an attempt was made to confirm whether the addition of the filtrate into the medium would be an effective method to promote the rapid detection of mycobacteria in sputum specimens of patients. One-hundred and one sputum specimens pretreated with NaOH were inoculated with various media (Dubos, Dubos-agar, 1% Ogawa, Kudo PD, and Middlebrook 7H9) supplemented with the culture filtrate of Gemella haemolysans grown in blood-BHI or blood-HEM at the dilutions of 1/32 or 1/64.

Enhanced growth of mycobacteria by culture filtrate of Gemella haemolysans.

The culture filtrate of G. haemolysans enhanced the growth of mycobacteria. The enhancing substance seemed to be effectively produced in BHI broth supplemented with human blood.

Phototropism in Hypocotyls of Radish: IV. Flank Growth and Lateral Distribution of cis- and trans-Raphanusanins in the First Positive Phototropic Curvature.

The first positive phototropic curvature induced by a pulse of unilateral white irradiation (0.1 watt per square meter, 30 seconds) of etiolated and de-etiolated Sakurajima radish (Raphanus sativus var hortensis f. gigantissimus Makino) hypocotyls was analyzed in terms of differential growth and growth inhibitor contents of the hypocotyls.