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61.
Kazuhide Iwasaki Yusuke Kitsugi Kanami Ikeda Takahiro Yoshikawa Shinya Hosaka Shotaro Uehara Yasuhiro Uno Masahiro Utoh Hiroshi Yamazaki 《Biopharmaceutics & drug disposition》2016,37(6):379-383
Cynomolgus monkeys are used frequently in preclinical studies for new drug development due to their evolutionary closeness to humans. An antiretroviral drug, efavirenz, is a typical probe substrate for human cytochrome P450 (P450) 2B6, but is mainly metabolized by cynomolgus monkey P450 2C9. In this study, plasma concentrations of efavirenz were assessed in six cynomolgus monkeys genotyped for P450 2C9 c.334 A > C (I112L) (three wild‐type, one heterozygote and two homozygotes) by high performance liquid chromatography with tandem mass spectrometry. After intravenous administration at a dose of 1.0 mg/kg, biphasic plasma elimination curves of efavirenz were seen in these cynomolgus monkeys. The mean plasma concentration of the primary metabolite 8‐hydroxyefavirenz (1 h after treatment, with hydrolysis by β‐glucuronidase) in the wild‐type group was significantly higher (4.0‐fold) than the combined heterozygous and homozygous group mean. The area under the plasma concentration–time curve value of efavirenz in the homozygous group after oral administration at a dose of 2.0 mg/kg was significantly higher (2.0‐fold) than the combined wild‐type and heterozygous group. These results collectively indicated that P450 2C9 c.334 A > C (I112L) variation was associated with efavirenz metabolic clearance in vivo. Cynomolgus P450 2C9 polymorphism might account for interindividual variations of efavirenz metabolism in cynomolgus monkeys. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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Mori K Kawano M Fuchino H Ooi T Satake M Agatsuma Y Kusumi T Sekita S 《Journal of natural products》2008,71(1):18-21
A methanol extract of the wood of Cordia fragrantissima, collected in Burma (Myanmar), was found to exhibit significant activity against Leishmania major. Bioassay-guided fractionation of this extract using several chromatographic techniques afforded three new compounds (1-3) and five known compounds (4-8). The structures of the new compounds were revealed on the basis of spectroscopic data interpretation and by X-ray crystallographic analysis. Interestingly, the new compounds, despite the presence of asymmetric carbons, were found to be racemates. The activities of the isolates from C. fragrantissima and several derivatives were evaluated against the promastigote forms of Leishmania major, L. panamensis, and L. guyanensis. 相似文献
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The fate of callosal neurons after callosotomy is yet unclear although this has become a common surgical procedure for intractable generalized epilepsies. Using retrograde neuronal labeling with two fluorescent dyes, we demonstrated that callosal neurons in the parietal cortex of the adult rat survive up to 20 weeks after callosotomy. Our data suggest that these neurons possess numerous ipsilateral axon collaterals with indispensable functions in the ipsilateral hemisphere. 相似文献
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Shin-ichi Kubo Mamoru Ogata Osamu Kitamura Ryouichi Tsuda Yoshiyuki Orihara Wataru Hirose Hideki Matsumoto Ichiro Nakasono 《International journal of legal medicine》1994,106(6):281-284
Summary Using immunohistochemical staining, the histological changes and the presence of neuropeptides (enkephalin and VIP) in the carotid body have been investigated in medico-legal autopsy cases, especially asphyxia cases. Only in cases of manual and/or ligature strangulation cases that sustained a force near the carotid body, were the chief cells mainly lightly stained, indicating that they had been active cells. Furthermore, these cells and their nuclei were enlarged in comparison to the chief carotid body cells in other autopsy groups. It was thus felt that these changes had resulted from the force that had directly affected the carotid body. Based on these findings, it was concluded that immunohistochemical investigation of the carotid body offers a useful possibility for diagnosing manual asphyxia, especially in autopsy cases involving strangulation. 相似文献
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Two high saponin-producing cell lines were selected from the original callus induced in 1967 and maintained in good state. For saponin production and growth in two cell lines, the comparison of static and suspension cultures, static cultures in the dark or in the light and rotary or reciprocal shaking cultures were made in detail. It was shown that the growth in rotary shaking cultures were 1.8 times higher than in reciprocal cultures, while the saponin production was almost the same, and the most effective hormonal condition was the combination of indole-3-butyric acid with kinetin. The saponin content per fresh weight was almost the same as that of the crude drug, whereas that per dry weight was 4 times higher. 相似文献