- 著者
- Chie Sakanaka Ryoko Ihara Akiko Kishi Kenji Kirihara Gaku Oguri Mihoko Shibuya Kazushi Suzuki Keiko Ueda Yumi Umeda-Kameyama Mitsutaka Yakabe Tomohiro Haga Hidenori Yamasue
- 出版者
- Japanese Pharmacological Society
- 雑誌
- 日本薬理学会年会要旨集 (ISSN:24354953)
- 巻号頁・発行日
- pp.OR6-3, 2018 (Released:2020-09-10)
- 被引用文献数
- 3 4
Background:Autism spectrum disorder (ASD) is a neurodevelopmental disorder, mainly exhibit problems in social communication/interaction behaviors. ASD is shown to affect one out of 100 individuals, however, the cause and the established treatments on the core symptoms of ASD are unavailable. Recently, peptide hormone Oxytocin showed some promises in treating ASD core symptoms, and various clinical studies are currently underway. The objective of this study is to evaluate the safety and pharmacokinetics of new formulation of intra-nasal Oxytocin in healthy Japanese male.Methods:In this double-blind, randomized, placebo-controlled Phase1 study, 5 cohorts of eight subjects received a single dose of intranasal TTA-121 at dose levels of 5, 10, 30, 100 and 200 U/ml or placebo and 3 cohorts of eight subjects received 30, 100 and 200 U/ml or placebo at repeated doses for 9 days. Safety assessments were conducted throughout the study.Results:Regarding safety, no serious adverse events were reported and no clinically significant findings were observed throughout the study. A linear relationship between plasma concentration of Oxytocin and administered dose of TTA-121 (5 to 200 U/ml) was observed. There was no drug accumulation after multiple doses of intra-nasal Oxytocin.Conclusions:TTA-121 was well tolerated and safe in Japanese healthy male subjects after administration of multiple doses up to 200U/ml, BID for 9 days.Trial Registration:UMIN000025922
- 著者
- Shoji Fukushima Tatsuya Kasai Yumi Umeda Makoto Ohnishi Toshiaki Sasaki Michiharu Matsumoto
- 出版者
- (公社)日本産業衛生学会
- 雑誌
- Journal of Occupational Health (ISSN:13419145)
- 巻号頁・発行日
- pp.17-0102-RA, (Released:2017-10-18)
- 被引用文献数
- 55
Objectives: This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. Methods: MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. Results: Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. Conclusions: Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.