Hideki Kamegai

Role of extracellular signal-regulated kinase and AKT cascades in regulating hypoxia-induced angiogenic factors produced by a trophoblast-derived cell line

During human pregnancy, trophoblasts play an important role in embryo implantation and placental development. Cytotrophoblast cells invade the uterine spiral arteries and differentiate into extravillous trophoblasts, resulting in the remodeling of the uterine vessels and fetoplacental vasculature. During early pregnancy, a physiologically hypoxic environment induces the production of angiogenic factors, such as vascular endothelial growth factor (VEGF), which are suggested to locally control the vascular remodeling. Endoglin, a cell-surface coreceptor for transforming growth factor-beta1, is highly expressed in endothelial cells and syncytiotrophoblasts, and can be associated with endothelial nitric oxide synthase and vascular homeostasis. Several studies have recently suggested that some pregnancy-related complications, such as preeclampsia, have their origins early in pregnancy as a result of abnormalities in implantation and placental development. Although angiogenic factors are recognized as key molecules in placental development, little is known about the mechanism(s) of their regulation in trophoblasts. In this study, we elucidated the mechanisms underlying the regulation of VEGF and endoglin production under hypoxic conditions in the trophoblast-derived cell line, BeWo. We evaluated the role of the AKT-MTOR cascade and ERK kinase in the expression of VEGF and endoglin in response to hypoxia using various kinase inhibitors and small interfering RNA targeted against hypoxia-inducible factor (HIF)-1alpha (listed as HIF1A in Hugo Database). Our results suggest that both the phosphatidylinositol 3-kinase-AKT-MTOR-HIF-1alpha and ERK-HIF-1alpha signaling pathways are crucial for increasing VEGF and endoglin expression in response to hypoxia in BeWo cells.

Associations between the pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in Japanese women.

To examine the associations between the pre‐pregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Japanese women.

Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Traditional Herbal Medicine, Stimulates Lactation with Increase in Secretion of Prolactin but not Oxytocin in the Postpartum Period

The aim of the present investigation was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin, a traditional Japanese herbal medicine, in stimulating lactation in the postpartum period. We enrolled 82 women who had a normal delivery in Osaka Medical College Hospital, and randomly assigned them to the following two groups: a group of 41 women who received Xiong-gui-tiao-xue-yin at a dose of 6.0 g/day (Group X), and a group of 41 women who received ergometrine (methylergometrine maleate) at a dose of 0.375 mg/day (Group E). Volume of lactation was determined daily until Day 6 postpartum. Plasma prolactin and oxytocin concentration were measured at Days 1 and 6 postpartum. The results showed that volume of lactation was significantly higher in Group X than in Group E at Days 4 (p = 0.042), 5 (p = 0.038), and 6 (p = 0.046). Significant differences between Groups X and E were noted in plasma prolactin concentration at Days 1 (157.9 +/- 78.2 ng/ml and 129.1 +/- 64.8 ng/ml; p = 0.037) and 6 (167.5 +/- 95.4 ng/ml and 117.1 +/- 53.6 ng/ml; p = 0.0042) postpartum. On the other hand, at Day 1, oxytocin concentration was significantly higher in Group E than in Group X (p = 0.0024). No adverse effects were observed in this study. The results of our study demonstrate the beneficial effects of Xiong-gui-tiao-xue-yin on lactation, with increase in prolactin level without increase in oxytocin level in the postpartum period. Therefore, Xiong-gui-tiao-xue-yin can be expected to improve lactation in women in the postpartum period. Further detailed bio-pharmacological studies and clinical trials to investigate the properties of this drug are warranted.

A case of a methotrexate-resistant ectopic pregnancy in which dactinomycin was effective as a second-line chemotherapy

OBJECTIVE To report a case of a methotrexate (MTX)-resistant heterotopic interstitial pregnancy in which dactinomycin was necessary as a second-line chemotherapy. DESIGN Case report. SETTING Medical college-affiliated hospital. PATIENT(S) A 39-year-old woman with vaginal bleeding after the transfer of two thawed 8-cell embryos. INTERVENTION(S) MTX 50 mg/m(2) was given to the patient to treat a concomitant pregnancy in which an interstitial pregnancy and an intrauterine blighted ovum were identified. However, the patients hCG level rose despite two MTX administrations. As a result, dactinomycin was then administered as a second-line chemotherapy. The patients serum hCG level declined to a normal range after two administrations of dactinomycin. CONCLUSION(S) Dactinomycin could be an alternative in cases for which MTX is not effective and persistently high hCG levels exist.

Early diagnosis of postpartum acute myocardial infarction with combined use of troponin T and heart‐type fatty acid‐binding protein rapid assay

Acute myocardial infarction (AMI) during pregnancy or in the early postpartum period is a rare event but may cause perinatal morbidity and mortality. Early diagnosis of AMI is critical for appropriate treatment. We report a case of postpartum AMI in a 40‐year‐old multiparous woman with varicose veins. On postpartum day 3, the patient suffered severe chest pain. She had been administered oral methylergometrine. In addition to ST‐segment elevation in her electrocardiogram, the patient presented with a positive result on whole blood rapid panel tests for troponin T and heart‐type fatty acid‐binding protein (H‐FABP). These findings indicated AMI in the anterolateral wall. The chest pain disappeared with the prompt administration of intravenous pentazocine hydrochloride and sublingual nitroglycerin spray. Angiography did not reveal any signs of coronary stenosis. To our knowledge, this is the first report of postpartum AMI diagnosed rapidly with combined use of troponin T and H‐FABP qualitative panel tests.

Local injection of vasopressin reduces the blood loss during cesarean section in placenta previa.

The aim of this study was to evaluate the effect of local injection of vasopressin on blood loss and secondary impact on complications during cesarean section in patients with placenta previa.

Efficacy of the Kampo medicine Xiong-gui-jiao-ai-tang, a traditional herbal medicine, in the treatment of threatened abortion in early pregnancy.

This study was carried out to evaluate the clinical efficacy of Xiong-gui-jiao-ai-tang (Kyuki-kyogai-to), a traditional Chinese herbal medicine, in the treatment of threatened abortion in early pregnancy. We enrolled 72 women diagnosed with threatened abortion at Osaka Medical College Hospital and assigned them at random to the following two groups: a group of 36 women who received Xiong-gui-jiao-ai-tang at a dose of 7.5 g/day and another group of 36 women who received human chorionic gonadotropin (hCG)(control group). We found that in the Xiong-gui-jiao-ai-tang group (2.9 + or - 3.5 days), the number of days required before hemostasis was reached in the uterus was significantly shorter than in the control group (10.8 + or - 8.2 days, p < 0.0001). Furthermore, the number of days required for retroplacental hematoma in the vicinity of the gestational sac to disappear was significantly shorter in the Xiong-gui-jiao-ai-tang group (9.9 + or - 7.1 days) than in the control group (23.2 + or - 12.8 days) (p < 0.0001). In retroplacental hematoma size, significant rates of reduction were obtained in both major and minor axis measurements at the 7th day of treatment for the Xiong-gui-jiao-ai-tang group compared to the control group (control vs Xiong-gui-jiao-ai-tang: major axis: 7.5 + or - 3.8% vs 42.3 + or - 10.5%; minor axis: 15.3 + or - 16.8% vs 71.5 + or - 48.2%)(p < 0.0001, each case). The results of this study demonstrated the beneficial effects of Xiong-gui-jiao-ai-tang in stabilizing early pregnancy. Xiong-gui-jiao-ai-tang can be expected to improve unstable early pregnancy with uterine bleeding and to prevent abortion.

expression and epigenetic change of the AR and FsHR Genes in the Granulosa cells of endometriosis patients

Background Endometriosis is one of the most common gynecological diseases associated with infertility. Endometriosis may affect the androgen receptor (AR) mRNA expression in human granulosa cells and the methylation of the promoter region of AR. We investigated 28 patients with endometriosis and 47 subjects without endometriosis undertaking IVF treatment. Methods Granulosa cells were obtained from 28 patients with endometriosis and 47 subjects without endometriosis as a control. Expressions of AR and FSHR mRNA were then evaluated by OneStep real-time PCR analysis, and the level of methylation of the promoter region was qualified by methylation-specified PCR (MSP). Results The expression of AR mRNA in the endometriosis group was statistically lower than that in the control group. As well, FSHR mRNA expression in the control group showed a positive correlation with AR mRNA expression; however, there was no such correlation in endometriosis patients. In the control group, AR mRNA expression was statistically higher in pregnant subjects compared with non-pregnant subjects; however, in the endometriosis group, no significant difference was identified. The promoter of AR was heavily methylated in all endometriosis cases; however, only 5 (45.4%) were methylated in the control group. Conclusion Lower AR mRNA expression and methylation of the AR promoter region might affect the expression of AR and FSHR the presence of endometriosis, thus leading to a disturbance in the regulation of AR and FSHR.

Efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma

Myomectomy for cervical myoma is problematic because cervical myomas are very close to neighboring structures, such as the ureters, uterine artery, bladder and rectum. There are a few reports on laparoscopic myomectomy for cervical myomas to avoid blood loss, such as occlusion of iliac arteries and clipping of the uterine artery. We evaluated the efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma.