Potency of Tokishakuyakusan in treating preeclampsia: Drug repositioning method by in vitro screening of the Kampo library.

INTRODUCTION: Preeclampsia therapy has not been established, except for the termination of pregnancy. The aim of this study was to identify a potential therapeutic agent from traditional Japanese medicine (Kampo) using the drug repositioning method. MATERIALS AND METHODS: We screened a library of 74 Kampo to identify potential drugs for the treatment of preeclampsia. We investigated the angiogenic effects of these drugs using human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were performed to measure the levels of placental growth factor (PlGF) in conditioned media treated with 100 µg/mL of each drug. We assessed whether the screened drugs affected cell viability. We performed tube formation assays to evaluate the angiogenic effects of PlGF-inducing drugs. PlGF was measured after administering 10, 50, 100, and 200 µg/mL of the candidate drug in the dose correlation experiment, and at 1, 2, 3, 6, 12, and 24 h in the time course experiment. We also performed tube formation assays with the candidate drug and 100 ng/mL of soluble fms-like tyrosine kinase 1 (sFlt1). PlGF production by the candidate drug was measured in trophoblastic cells (BeWo and HTR-8/SVneo). The Mann-Whitney U test or one-way analyses of variance followed by the Newman-Keuls post-hoc test were performed. P-values < 0.05 were considered significant. RESULTS: Of the 7 drugs that induced PlGF, Tokishakuyakusan (TS), Shoseiryuto, and Shofusan did not reduce cell viability. TS significantly facilitated tube formation (P = 0.017). TS administration increased PlGF expression in a dose- and time-dependent manner. TS significantly improved tube formation, which was inhibited by sFlt1 (P = 0.033). TS also increased PlGF production in BeWo (P = 0.001) but not HTR-8/SVneo cells (P = 0.33). CONCLUSIONS: By using the drug repositioning method in the in vitro screening of the Kampo library, we identified that TS may have a therapeutic potential for preeclampsia. Its newly found mechanisms involve the increase in PlGF production, and improvement of the antiangiogenic state.

Obstetric outcomes and acceptance of alternative therapies to blood transfusion by Jehovah's Witnesses in Japan: a single-center study.

We sought to investigate obstetric outcomes and acceptance rates for blood products or types of autotransfusion by Jehovah's Witnesses (JWs) at a single institution in Japan. We retrospectively reviewed cases of 84 pregnant JW patients and 95 deliveries from April 2001 to August 2017. We examined the acceptance rates of blood transfusions, blood products, and autotransfusion types in patients who experienced postpartum hemorrhage (PPH), and investigated estimated hemorrhage volume at delivery and PPH treatments. Of the 84 JW patients, none accepted blood transfusion; however, 75 patients (89.3%) accepted blood products, 57 (67.9%) accepted autotransfusion using intraoperative cell salvage, and four (4.8%) refused all alternatives to blood transfusion. Furthermore, PPH > 1000 mL occurred in 18 of the 95 (18.9%) deliveries. Of these 18 patients, four (22.2%) required blood products and three (16.7%) required supracervical hysterectomy to control PPH. No maternal deaths occurred. Approximately 95% of the patients observed accepted all or some alternatives to blood transfusion. To treat JW patients in a safer manner, understanding their individual acceptance of alternatives to blood transfusion is important for the strategic use of such alternatives.