The involvement of platelet-activating factor in thrombocytopenia and follicular rupture during gonadotropin-induced superovulation in immature rats.

To investigate whether the platelets in the ovaries are activated by the action of platelet-activating factor (PAF) during gonadotropin-induced ovulation, we examined the changes in the platelet count in immature rats after administration of PMSG followed 48 h later by human CG (hCG). The platelet count in the inferior vena cava was significantly decreased 48 h after PMSG administration and was further decreased after hCG administration. When both ovaries of rats were extirpated, the administration of PMSG and hCG did not decrease the platelet count. Subcutaneous administration of a PAF antagonist, Y24180 (0.5-5 mg/kg.6 h), after PMSG injection decreased the number of ova shed in a dose-dependent manner. The decrease in the platelet count induced by the administration of PMSG and hCG was reversed to the level of the untreated control group by Y24180 (2.5 mg/kg.6 h). This inhibitory activity of Y24180 on ovulation and thrombocytopenia was completely reversed by the ip injection of synthetic PAF. Subcutaneous administration of indomethacin (IDM) also reduced the number of ova shed in a dose-dependent manner. However, thrombocytopenia was not reversed by IDM. Moreover, the inhibition of ovulation by IDM was not reversed by synthetic PAF. The present study suggests that: 1) platelets are activated by PAF during gonadotropin-induced ovulation in immature rats; 2) PAF is also involved in the rupture of follicles; 3) the presence of the ovary is indispensable for the generation of PAF in gonadotropin-stimulated immature rats; and 4) the mechanism of PAF action on ovulation may be different from that of prostaglandins.

Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells.

The presence and biochemical characteristics of human brain natriuretic peptide (hBNP) in the amniotic fluid at various gestational ages were investigated. The hBNP-like immunoreactivity (hBNP-LI) levels in amniotic fluid, determined by RIA, were 118.7 +/- 57.6 pmol/L (mean +/- SEM; n = 5) and 107.7 +/- 8.7 pmol/L (n = 9) in the first and second trimesters of pregnancy, respectively; it was significantly decreased to 28.4 +/- 5.1 pmol/L (n = 9) in the third trimester. However, human atrial natriuretic peptide-like immunoreactivity (hANP-LI) was not detected (< 0.3 pmol/L) in any of these samples. Northern blot analysis demonstrated hBNP mRNA in human amnion tissue. Moreover, cultured amnion cells secreted a significant amount of hBNP-LI (100-200 fmol/10(6) cells/day), but not hANP-LI, into the culture medium. The synthesis of hBNP in cultured amnion cells was further confirmed using the polymerase chain reaction. High performance gel permeation chromatography of hBNP-LI extracted from human amniotic fluid and the culture medium of amnion cells revealed that the predominant molecular form of hBNP-LI in both samples was the hBNP precursor, with an approximate mol wt of 12 kilodaltons. These findings indicate that hBNP is present in the human amniotic fluid, and that amnion cells synthesize hBNP and secrete it into the amniotic cavity.

Case report: pregnant woman with a ventriculoperitoneal shunt to treat hydrocephalus.

A pregnant woman with hydrocephalus who required multiple revisions of a ventriculoperitoneal shunt is discussed. Her symptoms improved after the replacement of the ventriculoperitoneal (VP) shunt with a ventriculoatrial (VA) shunt, suggesting the benefits of ventriculoatrial shunting during pregnancy.

Lupus anticoagulant (LAC) and its relation to pregnancy outcome: a report of five cases.

We examined the relation between the spontaneous remission and prednisolone-induced suppression of lupus anticoagulant (LAC) or anticardiolipin antibody (ACA) and pregnancy outcome in 5 LAC-positive women. Two women showed a spontaneous remission of LAC and ACA during the observation period. One of these 2 women became pregnant and delivered healthy twin infants at 36 weeks of pregnancy without any therapy. The other woman became LAC positive again after 1 year of remission, and experienced 2 more fetal losses. Two of the remaining LAC-positive women received prednisolone and aspirin. Only 1 woman, whose ACA was suppressed by medication, delivered a healthy newborn. The pregnancy of the other woman, whose LAC and ACA remained positive in spite of medication, terminated in an IUFD. These results suggest that the administration of prednisolone and aspirin is the first choice of therapy for LAC-positive women, and that encouraging such women to become pregnant while LAC is negative might be an alternative therapy.

Clinical application of pulsatility index of flow volume to detect the hemodynamic changes in IUGR fetus.

We attempted to assess feto-placental circulation in fetuses with intrauterine growth retardation (IUGR) by calculating the pulsatility index of flow volume (PIQ) based on the quantitative measurement of blood flow. Doppler sound was processed by an analog to digital converter and a frequency analyzer. Multiplication of frequency and signal strength of the Doppler sound at a certain time theoretically represents a value proportional to flow volume. Using this value, we calculated PIQ of the descending aorta, umbilical artery, and middle cerebral artery in normal fetuses, IUGR fetuses, and distressed fetuses during 24-41 weeks gestation. The PIQ of the fetal descending aorta in the IUGR fetus was significantly higher than that of the normal fetus. When cutoff value was set to mean +1 SD, abnormal PIQ was observed in 88% of IUGR fetuses. In contrast, the abnormal pulsatility index of maximal flow velocity (PIV) of the descending aorta was observed in only 62% of IUGR fetuses. In the distressed fetuses, both PIQ and PIV of the umbilical artery increased, and these indices of the middle cerebral artery markedly decreased. It is suggested that the increased PIQ of the descending aorta is an early indicator of changes in the fetal circulation in IUGR fetuses.

Brain natriuretic peptide levels in the umbilical venous plasma are elevated in fetal distress.

We measured, by a specific radioimmunoassay, brain-natriuretic-peptide-like immunoreactive (BNP-LI) levels in the umbilical venous and arterial plasma of normal and distressed newborns. The indicated BNP-LI level in umbilical arterial plasma of normal newborns (3.5 +/- 0.9 fmol/ml, mean +/- SEM, n = 10) was significantly higher than that in umbilical venous plasma of the same newborns (2.2 +/- 0.5 fmol/ml). In the distressed newborns at term, the indicated BNP-LI level in umbilical venous plasma was 62.2 +/- 25.7 fmol/ml (n = 4), which was 19-fold higher than that of elective cesarean section cases (3.2 +/- 0.3 fmol/ml, n = 6; p < 0.05). The findings demonstrated that BNP was present in the human fetal circulation and that the plasma BNP level was elevated under fetal distress conditions.

[Levels of CA130 in maternal sera and amniotic fluid at various gestational ages].

We examined the CA130 concentration in the amniotic fluid, maternal sera, amnion, chorion, decidua and placenta. CA130 in the maternal sera showed an initial increase during early pregnancy, remained low from the 15th weeks of pregnancy until delivery, and then increased after term delivery (249u/ml, mean, n = 27) or mid-trimester abortions (844u/ml, n = 22). The CA130, concentration in the amniotic fluid was high in the mid-trimester and remarkably low at term. Among the tissues examined, amnion and decidua contained a relatively high concentration of CA130. Immunohistochemical examination also demonstrated abundant CA130 in the cytosol of amnion and decidua tissues. The pattern of changes in CA130 in amniotic fluid was similar to that in the amnion and decidua tissue. The results suggest that the amnion cells are the source of CA130 in the amniotic fluid and that the high concentration of CA130 in maternal serum after delivery originates in decidua tissue affected by the separation of the placenta.

Concentrations of endothelin-1 in human amniotic fluid at various stages of pregnancy.

To examine the possible role of endothelin in the initiation of parturition, endothelin-1-like immunoreactivity (ET-1-LI) in the amniotic fluid (AF) was determined by a sensitive radioimmunoassay (RIA) system. The concentrations of ET-1-LI in AF were 24.7 +/- 6.1 pg/ml (mean +/- SD, n = 6) at the second trimester and were significantly increased to 40.4 +/- 15.1 pg/ml (n = 6) at term. These ET-1-LI concentrations are about three- to fourfold higher than those observed in the maternal plasma. The gel permeation chromatography (GPC) profile of ET-1-LI extracted from second-trimester AF indicated that the ET-1-LI consisted of only one component of 6kET, the molecular weight of which was 6,000, larger than big ET-1. In contrast, ET-1-LI in the AF at term consisted of two components, ET-1 and 6kET. These findings suggest that the level of biologically active ET-1 in the AF increases markedly from second trimester toward term. A significant amount of ET-1-LI was also detected in the supernatant of amnion cell culture. The level of ET-1-LI in the culture medium after 12 h of incubation was almost comparable with that in AF at term. Thus, it is suggested that amnion tissue may be the major source of ET-1-LI in the AF. Together with the fact that ET-1 increases cytoplasmic calcium ion in the target cell, the results of present study raise the possibility that endothelin plays an important role in the initiation of parturition by triggering the production of prostaglandins in fetal membranes.

Concentrations of endothelin-1 in maternal and umbilical cord blood at various stages of pregnancy.

To examine the role of endothelin (ET) in the maternal and fetal circulation, the levels of endothelin-1-like immunoreactivity (ET-1-LI) in the plasma of maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) were determined by a sensitive radioimmunoassay (RIA). Levels of ET-1-LI in MV did not show any significant change (9.9 +/- 1.5 pg/ml, n = 26) throughout normal pregnancy and were similar to those of normal nonpregnant women (10.7 +/- 2.5 pg/ml, n = 5). Levels of ET-1-LI in UV and UA obtained at normal deliveries at term were about three times higher than those in MV. In the patients with mild and severe pre-eclampsia, the levels of plasma ET-1-LI were significantly higher than those of normal pregnancy (14.3 +/- 2.2 pg/ml, n = 5 and 27.2 +/- 8.6 pg/ml, n = 5, respectively). However, in pregnant women with chronic hypertension, the levels of ET-1-LI did not increase when the hypertension did not worsen during pregnancy (11.4 +/- 1.6 pg/ml, n = 7). Moreover, in two pregnant women with abnormally stimulated coagulation, such as acute or subacute DIC, the levels of ET-1-LI were extremely high and returned gradually to those of normal nonpregnant women after the coagulation was normalized by treatment. These results suggest the possibility that ET-1 plays an important role in the pathophysiology of preeclampsia.