Kazunao Suzuki

C1 esterase inhibitor activity in amniotic fluid embolism.

ObjectivesAmniotic fluid embolism exhibits activation of the complement system and the kallikrein-kinin and coagulofibrinolytic systems. C1 esterase inhibitor is a major inhibitor of C1 esterase and can inhibit plasma kallikrein and also factors XIIa and XIa. Its activity has been shown to be significantly lower in pregnancy and labor than in the nonpregnant state. The purpose of this study was to determine C1 esterase inhibitor activity levels in amniotic fluid embolism. DesignRetrospective study. SettingA single university-based center. PatientsOne hundred six cases with amniotic fluid embolism in a total of 194 singleton pregnant women between January 2010 and December 2011. InterventionsNone. Measurements and Main ResultsOne hundred six cases of amniotic fluid embolism had applied to the Japan amniotic fluid embolism registration center in Hamamatsu University School of Medicine between January 2010 and December 2011. In amniotic fluid embolism cases, 85 cases were nonfatal and 21 cases were fatal. Eighty-eight women who delivered without amniotic fluid embolism were regarded as a control. C1 esterase inhibitor activity levels were significantly lower in amniotic fluid embolism patients (30.0% ± 1.8%) than in control women (62.0% ± 2.0%) (p < 0.0001). C1 esterase inhibitor activity levels in fatal amniotic fluid embolism cases (22.5% ± 3.4%) were significantly lower than those in nonfatal amniotic fluid embolism cases (32.0% ± 2.1%) (p < 0.05). Conclusions:These results demonstrated that low C1 esterase inhibitor activity levels were closely associated with the pathogenesis of amniotic fluid embolism suggesting that C1 esterase inhibitor activity levels have potential as a prognosis factor of amniotic fluid embolism.

Angiomyofibroblastoma arising from the fallopian tube.

BACKGROUND Angiomyofibroblastoma is a rare tumor that occurs most commonly in the vulva and vagina. CASE A 28-year-old woman, gravida 1, para 1, presented with secondary infertility. Pelvic ultrasound showed a multicystic mass that further imaging found to be septated and extended to the umbilicus. At laparotomy, a 25 x 14 x 4 cm mass originating from the left fallopian tube and the tube were excised. Pathologic examination confirmed an angiomyofibroblastoma of the fallopian tube. CONCLUSION Angiomyofibroblastomas can occur in the fallopian tube and should be differentiated from more aggressive angiomyxoma.

Chorangiosis and placental oxygenation

Chorangiosis is a vascular hyperplasia in the terminal chorionic villi, usually diagnosed histologically using the criteria of Altshuler. Its true etiology has not been fully identified, but chorangiosis has been proposed to result from a longstanding, rather low‐grade hypoxia in the placental tissue. To clarify a possible association of placental oxygenation status with the development of chorangiosis, we measured placental tissue oxygen index (TOI) values using near‐infrared spectroscopy (NIRS) before delivery and retrospectively compared them to the detection of placental chorangiosis, in a total of 47 (46 singleton and one set of dichorionic diamniotic twins) pregnant women. Small for gestational age (SGA) and/or maternal complications were observed in all cases of placental chorangiosis. Placental TOI values were significantly elevated in cases of chorangiosis. This indicates high oxygen saturation in the intervillous spaces because placental TOI values are expected to represent the oxygenation of maternal blood in the placental tissue. A possible preceding low efficiency of oxygen transfer to the fetal circulation in the villi might not only augment the oxygen saturation of maternal blood in intervillous spaces, but also cause rather low oxygenation in the capillaries of the villi and result in chorangiosis.

Thrombomodulin release from umbilical endothelial cells initiated by preeclampsia plasma-induced neutrophil activation.

Objective To assess the capacity of neutrophils to release thrombomodulin from umbilical vein endothelial cells in vitro in response to plasma from normal gravidas and those with preeclampsia. Methods We collected venous plasma samples from 66 pregnant women: 18 women with severe preeclampsia, 18 women with mild preeclampsia, and 30 normotensive healthy women with singleton pregnancies in the third trimester. Neutrophils were isolated from venous blood obtained from healthy adult volunteers. Endothelial cells from normal umbilical veins were digested by collagenase and cultured. The effect of preeclampsia plasma on thrombomodulin release from endothelial cells was tested after incubating cultured cells with plasma from severe preeclampsia. Thrombomodulin and elastase levels were measured with specific immunoassays. Results Plasma thrombomodulin levels (mean ± standard error of the mean) were elevated in pregnant women with severe preeclampsia (62.5 ± 7.9 compared with 40.1 ± 3.3 [matched control] ng/mL; P = .02), and elastase levels correlated directly with thrombomodulin (r = .49; P < .05). Both coincubation of endothelial cells and neutrophils with preeclampsia plasma (16.3 ± 2.0 compared with 9.4 ± 1.2 [normotensive plasma] ng/mL; P < .05) and incubation of endothelial cells with neutrophils pretreated with preeclampsia plasma (13.9 ± 1.8 compared with 9.6 ± 0.9 [normotensive plasma] ng/mL; P < .05) significantly promoted thrombomodulin release from endothelial cells. Thrombomodulin can be released by the concerted action of preeclampsia plasma-stimulated neutrophils and endothelial cells. Conclusion In patients with severe preeclampsia oreclampsia, neutrophil activation occurs and the activated neutrophils induce vascular endothelial damage.

Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord

OBJECTIVE To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. STUDY DESIGN We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. RESULTS Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. CONCLUSIONS Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.

Morphologic characteristics of the placental basal plate in in vitro fertilization pregnancies: a possible association with the amount of bleeding in delivery.

The aim of the present study was to investigate the relationship between assisted reproductive technology procedures, the morphology of the basal plate of placentas, and amount of bleeding in deliveries. Fifty-five whole placentas (fresh-embryo transfer in the in vitro fertilization cycle [n = 6], frozen-thawed embryo transfer in the natural cycle [n = 13] or in the hormonal cycle [n = 10], and age-matched spontaneously conceived pregnancies [n = 26]) were retrospectively enrolled and histologically analyzed. The whole placentas were stored in our pathological division among 512 singleton pregnancies with vaginal deliveries (34-41 weeks of gestation) at Hamamatsu University Hospital. The morphology of the placental basal plate was examined using Azan staining. A total of 20 digital images (each 0.53 mm(2)) of microscopic fields were analyzed per placenta to measure the mean values of the vertical maximum thickness of Rohr and Nitabuch fibrinoid layers and % loss of decidua. The thickness of Rohr fibrinoid layer and % loss of decidua were significantly higher in the frozen-thawed embryo transfer in the hormonal cycle group than in the frozen-thawed embryo transfer in the natural cycle and spontaneously conceived pregnancy groups (each P < .01). The z scores for both the thickness of Rohr fibrinoid layer and % loss of decidua positively correlated with those for the amount of bleeding in deliveries (P < .05 each). Assisted reproductive technology procedures changed the morphology of the placental basal plate, suggesting a possible association with an increase in the amount of bleeding in deliveries.

Comparison between placental gene expression of 11β-hydroxysteroid dehydrogenases and infantile growth at 10 months of age.

The local expression of two isoenzymes of 11β‐hydroxysteroid dehydrogenase, type 1 (11βHSD‐1) and type 2 (11βHSD‐2), regulates the access of glucocorticoid hormones to their target cells. Reports on the association between the placental expression of 11βHSD and infantile growth are limited. The aim of the present study was to investigate if the placental gene expression of 11βHSD affects infantile growth at 10 months of age.

Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero.

Rapid growth in infancy considerably increases the risk of obesity and metabolic disorders in adulthood especially among neonates born small. To investigate the mechanism involved, we developed an animal model of undernourishment in utero by maternal caloric restriction, in which the Z scores of body weight at weaning (19.5 days) positively correlated with parameters of obesity, metabolic disorders, and remodeling of subcutaneous adipose tissue, such as numbers of macrophages in adipose tissue, the ratio of inflammatory M1 to anti-inflammatory M2 macrophages, estimated by gene expression of specific antigens, and the relative ratio of small adipocytes less than 30 μm in diameter, on a high-fat diet at 17 weeks of age. To our knowledge, this is the first report of a possible connection between infantile body weight and adipose tissue remodeling in obesity after undernourishment in utero.

Cerebral oxygen saturation evaluated by near-infrared time-resolved spectroscopy (TRS) in pregnant women during caesarean section – a promising new method of maternal monitoring

Time‐resolved spectroscopy (TRS‐20) measures tissue oxygen saturation (%) by evaluating the absolute concentrations of oxygenated, deoxygenated and total haemoglobin based on measurement of the transit time of individual photons through a tissue of interest. We measured tissue oxygen saturation in the prefrontal lobes of the brain by TRS‐20 in eighteen pregnant women during caesarean section. In a case of placenta previa, massive bleeding immediately decreased cerebral oxygen saturation from 67·2% to 54·2%, but did not alter peripheral tissue oxygenation as measured by pulse oximetry. Four cases of pre‐eclampsia revealed chronic changes in elevated base levels of cerebral oxygen saturation, though peripheral oxygen saturation was similar to that in normotensive pregnant women. Average cerebral oxygen saturation in the cases of pre‐eclampsia before the introduction of anaesthesia was 73·6 ± 4·4 (SD)% (n = 4), significantly higher than in normotensive pregnant women, 67·2 ± 4·3% (n = 13, P<0·05). Z‐scores of cerebral oxygen saturation prior to anaesthesia positively correlated with those of systolic or diastolic blood pressure. TRS‐20 could detect acute as well as chronic changes in brain oxygen saturation in response to pregnancy‐associated complications.

Zinc and magnesium ions synergistically inhibit superoxide generation by cultured human neutrophils--a promising candidate formulation for amnioinfusion fluid.

Oligohydramnios is often caused by the premature rupturing of membranes and subsequent intrauterine infections, such as chorioamnionitis, in which event oxidative stress is hypothesized to be closely associated with the damage to the fetal organs. The clinical efficiency of amnioinfusion using warmed saline in cases of premature rupture of membranes is still controversial, especially concerning the prognosis for the fetus. In the present study, we found that human amniotic fluid per se suppresses the release of superoxide from cultured human neutrophils, suggesting an acute or chronic shortage of amniotic fluid in cases of premature rupture of membranes can affect the shielding of intrauterine organs from oxidative stress. The aim of this study was to propose a formula of zinc and magnesium ions in saline for amnioinfusion, by assessing antioxidative activities. A combination of 5 microM zinc and 5mM magnesium in saline synergistically inhibited superoxide production by cultured human neutrophils, equivalent to human amniotic fluid. The intraperitoneal administration of this formula significantly improved the survival rate in a rat model of peritonitis compared to the saline control (46.7% vs. 10%). The combination of these metals with saline may thus be a promising formula for an amnioinfusion fluid with the capacity to protect fetal organs from oxidative stress.