Impact of Gestational Age at Delivery on Fetal Heart Rate Monitoring During the Second Stage of Labor

Objective: To clarify whether gestational age at delivery affects the interpretation level of fetal heart rate (FHR) tracings in the second stage of labor in primiparous and singleton pregnancies.Methods: The database at one tertiary hospital in Japan was retrospectively reviewed for women with singleton fetuses in cephalic presentation and vaginal labor at ≥37+0 gestational weeks between June 1, 2011, and March 31, 2013. Continuous FHR tracings in the second stage of labor were subdivided into 10-minute intervals, each of which we called a window, from the beginning through delivery, and were assessed according to the five-tier classification proposed by the Japan Society of Obstetrics and Gynecology, in which level 1 is normal, level 2 is subnormal, and levels 3-5 are abnormal patterns. Subjects were divided into two groups, including early term (37 0/7 to 38 6/7 weeks) and full term (39 0/7 to 41 6/7 weeks), according to the delivery age.Results: In total, 914 parturient women were eligible for the study protocol, including 228 and 686 women in early and full term, respectively. Vacuum extraction was more often observed in full term than in early term (P=0.007). Although the maximal level, number of level-5 windows, number of level-4 windows, and number of level-3 and level-4 windows were similar between the groups, the summation of level-4 windows ≥3 was significantly higher in full term than in early term (P=0.004).Conclusion: Full term delivery has a higher risk than does early term delivery from the standpoint of FHR monitoring

Bovine lactoferrin action on angiogenesis

Lactoferrin (LF) exerts a variety of biological effects, including the promotion of angiogenesis by increasing the expression of angiogenesis-related genes and reducing blood pressure via a nitric oxide-dependent mechanism. In the present study, we investigated the effects of LF on angiogenesis using C57BL/6J mice that received daily unilateral treatment with or without bovine milk-derived LF (bLF) following unilateral hindlimb surgery. The analysis of laser speckle blood flow showed that bLF treatment promoted blood flow recovery in response to ischemic hindlimb. The capillary density of ischemic adductor muscles, as well as the phosphorylation of Src, Akt, and endothelial nitric oxide synthase (eNOS) was also significantly higher in bLF-treated mice than in vehicle-treated mice. Furthermore, bLF increased the phosphorylation levels of Src, Akt, and eNOS in in vitro experiments using human aortic endothelial cells (HAECs). The action of bLF on eNOS phosphorylation was abolished by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and PP2, a Src inhibitor. Similarly, bLF-induced acceleration of tube formation, cell proliferation, and cell migration in HAECs were inhibited by LY294002 or PP2. Thus, bLF promotes vascular endothelial cell function via an Src-Akt-eNOS dependent pathway, thereby contributing to revascularization in response to ischemia

Bilirubin action on angiogenesis

Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as anti-oxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthesis (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner

Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells

Summary Our previous study demonstrated that tyrosine phosphorylation of p145met/β-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD) serve as a structural platform for signaling events involving p145met, EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa), an urothelium-specific protein. Results obtained so far revealed: 1) UPIIIa undergoes partial proteolysis in serum-starved cells; 2) a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3) knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP), inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells