著者

Yu Inoue Seiji Hasegawa Yuichi Hasebe Mika Kawagishi-Hotta Ryosuke Okuno Takaaki Yamada Hiroaki Adachi Katsuma Miyachi Yoshie Ishii Kazumitsu Sugiura Hirohiko Akamatsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1403-1412, 2021-10-01 (Released:2021-10-01)

参考文献数

29

被引用文献数

6

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Currently, human-skin derived cell culture is a basic technique essential for dermatological research, cellular engineering research, drug development, and cosmetic development. But the number of donors is limited, and primary cell function reduces through cell passage. In particular, since adult stem cells are present in a small amount in living tissues, it has been difficult to obtain a large amount of stem cells and to stably culture them. In this study, skin derived cells were isolated from the epidermis, dermis, and adipose tissue collected from single donor, and immortalization was induced through gene transfer. Subsequently, cell lines that could be used as stem cell models were selected using the differentiation potential and the expression of stem cell markers as indices, and it was confirmed that these could be stably cultured. The immortalized cell lines established in this study have the potential to be applied not only to basic dermatological research but also to a wide range of fields such as drug screening and cell engineering.

著者

Tassadit Belabbas Takaaki Yamada Yuichi Tsuchiya Kimitaka Suetsugu Nobuaki Egashira Ichiro Ieiri

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.7, pp.646-651, 2021-07-01 (Released:2021-07-01)

参考文献数

17

被引用文献数

2

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With the aim of studying the pharmacokinetics of letermovir, which is a newly developed antiviral agent for human cytomegalovirus, a rapid and simple ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS) method was developed and validated for the quantification of letermovir in human plasma. Separation was performed in reverse phase mode using an ACQUITY UPLC BEH C18 column (130 Å, 1.7 µm, 2.1 × 50 mm) at a flow rate of 0.3 mL/min, 10 mM ammonium acetate–0.1% formic acid solution as mobile phase A, and acetonitrile as mobile phase B with a gradient elution. The method was validated over a linear range of 10–1000 ng/mL with a coefficient of determination (R2) >0.99 using weighted linear regression analysis. The intra- and inter-assay accuracy (nominal%) and precision (relative standard deviation%) were within ±15 and ≤15%, respectively. The specificity, recovery, matrix effect, stability, and dilution integrity of this method were also within acceptable limits. This method could be useful in studying the pharmacokinetics and pharmacodynamics, as well as performing the therapeutic drug monitoring of letermovir.

著者

Yu Inoue Seiji Hasegawa Takaaki Yamada Yasushi Date Hiroshi Mizutani Satoru Nakata Kayoko Matsunaga Hirohiko Akamatsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.11, pp.1722-1730, 2013-11-01 (Released:2013-11-01)

参考文献数

27

被引用文献数

17 32

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Hydroquinone (HQ) is a chemical compound that inhibits the functions of melanocytes and has long been known for its skin-whitening effect. According to previous studies, the Tyrosinase (Tyr) activity inhibitory effect and melanocyte-specific cell toxicity are known depigmenting mechanisms; however, details of the underlying mechanisms are unknown. Arbutin (Arb) is also known for its Tyr activity inhibitory effect and is commonly used as a skin-whitening agent. However, the detailed depigmenting mechanism of Arb is also not yet fully understood. Few studies have attempted to elucidate the effects of HQ and Arb on undifferentiated melanocytes. In this study, we examined the effects of HQ and Arb throughout each stage of differentiation of melanocytes using a mouse embryonic stem cell (ESC) culture system to induce melanocytes. The results showed that HQ in particular downregulated the early stage of differentiation, in which neural crest cells were generated, and the late stage of differentiation, in which melanogenesis became active. On the other hand, Arb had no effect on the differentiation of melanocytes, and only suppressed melanogenesis by specifically suppressing elevations in Tyr expression in the late stage of differentiation.