- 著者
- Hidekazu Nishimura Mutsuo Yamaya
- 出版者
- Tohoku University Medical Press
- 雑誌
- The Tohoku Journal of Experimental Medicine (ISSN:00408727)
- 巻号頁・発行日
- vol.237, no.1, pp.45-50, 2015 (Released:2015-09-03)
- 参考文献数
- 30
- 被引用文献数
- 11 22
Ebola virus disease (EVD) has been a great concern worldwide because of its high mortality. EVD usually manifests with fever, diarrhea and vomiting, as well as disseminated intravascular coagulation (DIC). To date, there is neither a licensed Ebola vaccine nor a promising therapeutic agent, although clinical trials are ongoing. For replication inside the cell, Ebola virus (EBOV) must undergo the proteolytic processing of its surface glycoprotein in the endosome by proteases including cathepsin B (CatB), followed by the fusion of the viral membrane and host endosome. Thus, the proteases have been considered as potential targets for drugs against EVD. However, no protease inhibitor has been presented as effective clinical drug against it. A synthetic serine protease inhibitor, nafamostat mesilate (NM), reduced the release of CatB from the rat pancreas. Furthermore, it has anticoagulant activities, such as inhibition of the factor VIIa complex, and has been used for treating DIC in Japan. Thus, NM could be considered as a drug candidate for the treatment of DIC induced by EBOV infection, as well as for the possible CatB-related antiviral action. Moreover, the drug has a history of large-scale production and clinical use, and the issues of safety and logistics might have been cleared. We advocate in vitro and in vivo experiments using active EBOV to examine the activities of NM against the infection and the DIC induced by the infection. In addition, we suggest trials for comparison among anti-DIC drugs including the NM in EVD patients, in parallel with the experiments.
- 著者
- Mutsuo Yamaya Hidekazu Nishimura Xue Deng Akiko Kikuchi Ryoichi Nagatomi
- 出版者
- Tohoku University Medical Press
- 雑誌
- The Tohoku Journal of Experimental Medicine (ISSN:00408727)
- 巻号頁・発行日
- vol.251, no.1, pp.27-30, 2020 (Released:2020-05-22)
- 参考文献数
- 24
- 被引用文献数
- 14
The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 μg/mL) or nafamostat (0.01-1 μg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.
- 著者
- Hiroyuki Arai Mutsuo Yamaya Takashi Ohrui Satoru Ebihara Takae Ebihara Kazushi Nakajo Hidetada Sasaki
- 出版者
- The Japan Society of Logopedics and Phoniatrics
- 雑誌
- The Japan Journal of Logopedics and Phoniatrics (ISSN:00302813)
- 巻号頁・発行日
- vol.43, no.4, pp.467-472, 2002-10-20 (Released:2010-06-22)
- 参考文献数
- 19
- 被引用文献数
- 1 2
誤嚥性肺炎を発症する高齢者では, 高率に脳血管障害, 特に大脳基底核領域に脳梗塞が見出される.この場合の脳梗塞は, 新しいものであっても陳旧性のものであっても, また症候性であっても無症候性であっても構わない.このような患者では, 嚥下反射と咳反射の両者の低下により, 誤嚥特に夜間の不顕性誤嚥により肺炎の成立にいたると考えられる.嚥下反射と咳反射は, 少なくとも2つの神経伝達物質, すなわちドーパミンとサブスタンス-Pによって支えられている.進行したアルツハイマー病患者も大脳基底核障害などにより誤嚥性肺炎を発症する.進行したアルツハイマー病患者において, major tranquilizerの使用と無症候性脳梗塞の合併は誤嚥性肺炎を誘発する危険因子であるため問題行動に対するmajor tranquilizerの使用には細心の注意が要求される.塩酸アマンタジン, ACE阻害薬, 抗血小板剤の使用また歯ブラシなどによる簡便な口腔ケアは肺炎の予防に役立つばかりでなく高齢者医療費削減にも貢献すると思われる.