N. Furuhashi

The Behavior of Endometrial Hyperplasia: A Prospective Study

Objective: To clarify the behavior of endometrial hyperplasia in a prospective study.

Brain Natriuretic Peptide and Atrial Natriuretic Peptide Levels in Normal Pregnancy and Preeclampsia

Brain natriuretic peptide (BNP) was increased in many hypertensive subjects. In this study, we have evaluated maternal, umbilical plasma and amniotic fluid BNP and atrial natriuretic peptide (ANP) in 19 normotensive pregnant women and in 35 preeclamptic patients. The maternal plasma and umbilical cord plasma ANP (p < 0.05) and BNP (p < 0.005) levels were significantly higher than those in normal pregnancy. There was no significant correlation among ANP level, BNP level, clinical symptoms and laboratory examinations. It is suggested that ANP and BNP may be rather a sequel to preeclamptic pathophysiological changes, and may not play an important role as the etiological factor of preeclampsia.

Maternal plasma endothelin levels and fetal status in normal and preeclamptic pregnancies

Endothelin (ET) is a potent vasoconstrictor peptide. In this study, we investigated maternal venous plasma ET levels measured by Sandwich-enzyme immunoassay within a week before the onset of labor, and measured plasma renin activity and plasma aldosterone concentration by radioimmunoassay in normal and severely preeclamptic pregnancies. Also, we determined umbilical cord blood pH and gas concentrations after spontaneous vaginal deliveries and cesarean sections. There was a significant (p < 0.01) negative correlation between maternal ET levels within 1 week before the onset of labor and birth weights. There was no significant correlation between maternal ET levels and umbilical gas concentrations. These data suggest that the correlation is the result of decreasing uteroplacental blood flow. We speculate that increased maternal ET expresses not only maternal renal vascular endothelial injury but also other vascular endothelial injuries. These vascular injuries may occur at least 1 week before the clinical manifestation in the preeclamptic mothers and their fetuses.

Serum Collagen IV and Laminin Levels in Preeclampsia

Collagen IV is the main collagenous component localized in the trophoblast and glomerular basement membrane. Serum collagen V reflects degradation of basement membrane collagen. In this study, we measured collagen IV levels in maternal serum, umbilical cord serum and amniotic fluid, both from preeclamptic and normal pregnant women, by radioimmunoassay. The serum collagen IV levels in the preeclamptic group were significantly (p < 0.05) higher than those in the normal pregnant group. The amniotic fluid collagen IV level at term was found to be higher than maternal serum collagen IV. We postulate that collagen IV may have an important role in the maintenance of pregnancy. There was a significant positive correlation between maternal serum collagen IV levels and serum laminin levels. There was no significant correlation between maternal serum collagen IV level and blood pressure, urinary protein concentration, or any other laboratory data. These results suggest that there is early damage of endothelial cells in preeclampsia.

Effects of Nifedipine on Normotensive Rat Placental Blood Flow, Placental Weight and Fetal Weight

Recently, nifedipine (Ca antagonist) has been used for the treatment of preeclampsia. In this study, we investigated the effects of nifedipine on the normotensive Wistar Kyoto rats placental blood flow, fetal weight and placental weight. We measured the rats placental blood flow using clearance of hydrogen gas generated by electrolysis. The placental blood flow, placental and fetal weights of nifedipine-treated rats (5, 10 and 25 mg/kg) were significantly (p less than 0.05) reduced compared with normal pregnant rats. These data suggest that nifedipine might have some reducing effects on placental blood flow, fetal weight and placental weight.

Serum Cortisol Levels of Maternal Vein, Umbilical Artery, and Umbilical Vein Classified by Mode of Delivery

We measured maternal venous (MV), umbilical arterial (UA), and umbilical venous (UV) cortisol levels of 180 pregnancies at term. The cortisol level of MV was higher than that of UA and UV in all deliveries. The cortisol levels of three samples had no difference between the induced labor group and the spontaneous onset of labor group regardless of delivery mode. In spontaneous vaginal delivery the cortisol levels of three individual samples were significantly higher in primipara than in multipara. The positive correlations were observed in any modes of deliveries between the cortisol levels of MV and UA, and MV and UA and UV. These data suggest that the fetus may produce cortisol by itself and maternal cortisol may inflow to the fetus.

Serum Laminin Levels in Normal Pregnancy and Preeclampsia

Laminin is a large noncollagenous glycoprotein localized in the trophoblast and glomerular basement membrane. We measured laminin levels in maternal serum, umbilical cord serum and amniotic fluid, both from preeclamptic and normal pregnant women, by enzyme immunoassay. The serum laminin levels in the preeclamptic group were significantly (p < 0.05 to p < 0.01) higher than those in the normal pregnant group. It has been suggested that laminin plays an important role in implantation of the placenta during early pregnancy. In this study, the amniotic-fluid laminin level at term was found to be lower than maternal serum laminin. We postulate that laminin may not have an important role in the maintenance of late pregnancy. There was a significant positive correlation between maternal serum laminin levels and serum uric acid levels. There was no significant correlation between maternal serum laminin level and blood pressure, urinary protein concentration, or any other laboratory data. These results suggest that there is damage of glomerular and placental spiral arteries in preeclampsia.

Antithromboxane Drug in the Treatment of Preeclampsia

In this study, we present our initial trials in the treatment of 6 cases of severe preeclampsia with thromboxane synthetase inhibitor (OKY-046). Following the treatment with OKY-046, maternal systolic blood pressure decreased significantly and umbilical artery waveforms were normalized. These data suggest that thromboxane synthetase inhibition might have a beneficial effect on preeclampsia.

Plasma β-Endorphin Levels in Pregnancy Induced Hypertension Patients

We measured the plasma β-endorphin (β-EP) levels in 11 normal pregnant women at term, 5 severe pregnancy induced hypertension (PIH) patients at term, 11 normal and 5 severe PIH mothers at labor, 11 fetuses who were delivered from normal mothers and 5 fetuses who were delivered from severe PIH mothers. There was a significant(p<0.05) difference in the maternal plasma β-EP at labor between the group without PIH (n=11, 186.9 ± 21.9 pg/ml, mean ± S.E.) and PIH patients (n=5, 108.5 ± 16.4 pg/ml). These data suggests that β-endorphin have a depressor role of a eodogenous cardiovascular regulatory factor in PIH patients during labor.

Effects of Thromboxane Synthetase Inhibitor (OKY-046) on Placental Blood Flow, Placental Weight and Fetal Weight in Normotensive and Spontaneously Hypertensive Rats

Recently, thromboxane synthetase inhibitor has been used for the treatment of preeclampsia. In this study, we investigated the effects of thromboxane synthetase inhibitor (OKY-046) on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The systolic blood pressure of OKY-046-treated SHR (1, 4 and 8 mg/kg) decreased significantly (p < 0.05); however, the systolic blood pressure of WKY did not decrease. The placental blood flow of both OKY-046-treated WKY and SHR did not decrease. We found that OKY-046 has no reducing effect on placental blood flow in rats, and systolic blood pressure of SHR decreases. These data suggest that thromboxane synthetase inhibitor might have a beneficial effect on preeclampsia.