Faculty Profiles - NAKATSUKA Mikiya

Clinical experience of long-term transdermal treatment with nitric oxide donor for women with preeclampsia

Mikiya Nakatsuka, Katsuhiko Tada, Yoshihiro Kimura, Kazuo Asagiri, Yasuhiko Kamada, Masayo Takata, Takakimi Nakata, Nanako Inoue, Takafumi Kudo

Gynecologic and Obstetric Investigation 47 ( 1 ) 13 - 19 1999

Language：English

Isosorbide dinitrate (ISDN), a nitric oxide donor, was applied transdermally for 4-16 days to 4 preeclamptic women with oligohydramnios, intrauterine fetal growth retardation (IUGR), and elevated resistance of blood flow in the uterine arteries. Pulsed Doppler ultrasonography revealed immediate and drastic improvement of pulsatility index (PI) of uterine arteries following treatment with ISDN. The average PI in uterine arteries of the 4 patients was reduced to approximately 67% of that of the untreated state. In 2 patients the amniotic fluid gradually increased over a few days which suggested improvement of fetoplacental circulation during administration of ISDN. This study suggests that long-term transdermal ISDN is an effective therapy, at least in a portion of preeclamptic women, to avoid maternal hypertension, fetal distress, oligohydramnios, and IUGR, and consequentially to prolong the gestational period.

DOI： 10.1159/000010055

Generation of peroxynitrite and apoptosis in placenta of patients with chorioamnionitis: Possible implications in placental abruption

Mikiya Nakatsuka, Kazuo Asagiri, Yoshihiro Kimura, Yasuhiko Kamada, Katsuhiko Tada, Takafumi Kudo

Human Reproduction 14 ( 4 ) 1101 - 1106 1999

Language：English

The reaction of nitric oxide (NO) and superoxide results in the formation of peroxynitrite, a potent and relatively long-lived oxidant. In infectious diseases, these molecules are not only bactericidal but also toxic to host cells. Chorioamnionitis is often complicated by premature rupture of membranes and can be associated with placental abruption. These diseases are significant causes of premature low-birth-weight deliveries and consequently the morbidity and mortality of neonates. Lipopolysaccharide, bacterial endotoxin, is known to be elevated in the amniotic fluid of patients with chorioamnionitis. Lipopolysaccharide is known to induce the formation of NO and superoxide. We report here that nitrite/nitrate, stable metabolites of NO, were increased in serum from patients with chorioamnionitis. Immunohistochemical studies demonstrated enhanced expression of inducible NO synthase and formation of nitrotyrosine, a footprint of peroxynitrite, in the placentae from patients with chorioamnionitis and also in patients with placental abruption. Furthermore, apoptotic cell death was also increased in the placentae from patients with both diseases. These results suggest that chorioamnionitis and a portion of placental abruption may share a common cascade of placental injury. Nitric oxide and its metabolites may play an important role in this cascade.

Clinical experience of long-term transdermal treatment with nitric oxide donor for women with preeclampsia

Mikiya Nakatsuka, Katsuhiko Tada, Yoshihiro Kimura, Kazuo Asagiri, Yasuhiko Kamada, Masayo Takata, Takakimi Nakata, Nanako Inoue, Takafumi Kudo

Gynecologic and Obstetric Investigation 47 ( 1 ) 13 - 19 1999

Language：English

DOI： 10.1159/000010055