著者
Junichiro Irie Emi Inagaki Masataka Fujita Hideaki Nakaya Masanori Mitsuishi Shintaro Yamaguchi Kazuya Yamashita Shuhei Shigaki Takashi Ono Hideo Yukioka Hideyuki Okano Yo-ichi Nabeshima Shin-ichiro Imai Masato Yasui Kazuo Tsubota Hiroshi Itoh
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ19-0313, (Released:2019-11-02)
被引用文献数
8 112

Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.
著者
Junichiro Irie Emi Inagaki Masataka Fujita Hideaki Nakaya Masanori Mitsuishi Shintaro Yamaguchi Kazuya Yamashita Shuhei Shigaki Takashi Ono Hideo Yukioka Hideyuki Okano Yo-ichi Nabeshima Shin-ichiro Imai Masato Yasui Kazuo Tsubota Hiroshi Itoh
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.67, no.2, pp.153-160, 2020 (Released:2020-02-28)
参考文献数
21
被引用文献数
22 112

Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.
著者
Yu-ki Nishimura Junya Komatsu Hiroki Sugane Hayato Hosoda Ryu-ichiro Imai Yoko Nakaoka Koji Nishida Shu-ichi Seki Toru Kubo Naohito Yamasaki Hiroaki Kitaoka Sho-ichi Kubokawa Kazuya Kawai Naohisa Hamashige Yoshinori Doi
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
vol.4, no.12, pp.571-578, 2022-12-09 (Released:2022-12-09)
参考文献数
16
被引用文献数
1

Background: Cardiogenic unilateral pulmonary edema (UPE) has been reported as an unusual condition and to occur in association with severe mitral regurgitation (MR). However, the prevalence of UPE in patients with severe MR remains unknown.Methods and Results: Among 143 consecutive patients with chordal rupture and significant MR, 38 patients with acute severe MR were studied. The prevalence of UPE was 50% (19 patients); all these patients had right-sided UPE. Eight (21%) patients had bilateral pulmonary edema (BPE). All 8 patients with BPE and 18 of 19 patients with UPE had chordal rupture of the posterior leaflet. All patients with UPE and BPE had severe MR with similar left atrial size. Chest radiographs taken ≤48 h from symptom onset diagnosed UPE in 15 of 19 (79%) patients and BPE in 3 of 8 (38%) patients (P=0.037). Chest radiographs taken >48 h from symptom onset diagnosed UPE in 4 (21%) patients and BPE in 5 (62%) patients (P=0.037).Conclusions: The prevalence of UPE was estimated as 50%; it was most frequently right sided and almost always associated with chordal rupture of the posterior leaflet. UPE is not rare, but common, particularly shortly after the development of acute severe MR caused by chordal rupture.