Synthesis of N-Aminated Salts of Aliphatic tert-Amines, (Trialkyl)amidines, and (Pentaalkyl)guanidines by Electrophilic Amination in an Ethereal Solvent.

The electrophilic amination of nitrogen-based nucleophiles, including strong organic bases, was conducted in an Et2O solvent using O-(mesitylenesulfonyl)hydroxylamine. Aliphatic tert-amines and N,N,N'-(trialkyl)amidines rapidly formed precipitates of the corresponding aminated salts in high yields. The amination of the highly basic and sterically hindered N,N,N',N',N″-(pentaalkyl)guanidines was achieved under modified conditions, although the yields were moderate because of a competing side reaction caused by the acid-base equilibrium.

Placental abruption in each hypertensive disorders of pregnancy phenotype: a retrospective cohort study using a national inpatient database in Japan.

We designed a retrospective cohort study using the Diagnosis Procedure Combination database, a national inpatient database for acute-care inpatients in Japan, to examine whether recent global diagnostic criteria for preeclampsia, phenotypes of hypertensive disorders of pregnancy (HDP) and features of the disease are useful as predictors of placental abruption and whether other risk factors are associated with the onset of placental abruption. A total of 85,858 hospitalized patients with a diagnosis of HDP who gave birth during hospitalization between July 2010 and March 2018 were included in this study. We examined the associations between the occurrence of placental abruption after hospitalization and several factors, including gestational age (GA) at placental abruption onset, HDP subtypes, GA on admission, maternal age, body mass index, smoking, multiple pregnancy, prelabor rupture of membranes, diabetes mellitus, emergency admission by ambulance, and consciousness, using a multivariate logistic regression analysis. Placental abruption occurred in 541 patients (0.63%) after hospital admission, and the occurrence increased acutely after 32 weeks GA. A decrease in abruption was significantly associated with maternal BMI on admission (≥30 kg/m2; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41-0.70) and multiple pregnancy (OR, 0.29; 95% CI, 0.18-0.46). An increase in abruption was associated with earlier GA on admission (<34 weeks' GA; OR, 3.77; 95% CI, 3.13-4.53) and emergency admission by ambulance (OR, 1.34; 95% CI, 1.09-1.65). Individual features of severe PE showed no significant associations with the occurrence of abruption. In conclusion, HDP at an earlier GA was suggested to be a risk factor for placental abruption, and we recommend hospitalization and careful management of such patients to improve their prognosis.

Impact of the Great East Japan Earthquake on Regional Obstetrical Care in Miyagi Prefecture.

OBJECTIVES: The authors report the results of surveys on the emergency transport or evacuation status of obstetric patients conducted in Miyagi prefecture, one of the major disaster areas of the Great East Japan Earthquake and tsunami. METHODS: The surveys examined the damages to maternity institutions, evacuation status and transport of pregnant women, and prehospital childbirths and were conducted in 50 maternity institutions and 12 fire departments in Miyagi. RESULTS: Two coastal institutions were destroyed completely, and four institutions were destroyed partially by the tsunami, forcing them to stop medical services. In the two-month period after the disaster, 217 pregnant women received hospital transport or gave birth after evacuation. Satisfactory perinatal outcomes were maintained. Emergency obstetric transport increased to approximately 1.4 fold the number before the disaster. Twenty-three women had prehospital childbirths, indicating a marked increase to approximately three times the number of the previous year. CONCLUSION: In the acute phase of the tsunami disaster, maternity institutions were damaged severely and perinatal transport was not possible; as a result, pregnant women inevitably gave birth in unplanned institutions, and the number of prehospital births was increased extremely. To obtain satisfactory obstetric outcomes, it is necessary to construct a future disaster management system and to re-recognize pregnant women as people with special needs in disaster situations. Sugawara J , Hoshiai T , Sato K , Tokunaga H , Nishigori H , Arai T , Okamura K , Yaegashi N . Impact of the Great East Japan Earthquake on regional obstetrical care in Miyagi Prefecture. Prehosp Disaster Med. 2016;31(3):255- 258.

Efficacy of oral administration of Lentinula eododes mycelia extract for breast cancer patients undergoing postoperative hormone therapy.

Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.

Conjugates of 3α-methoxyserrat-14-en-21ß-ol (PJ-1) and 3ß-methoxyserrat-14-en-21ß-ol (PJ-2) as cancer chemopreventive agents.

3α-Methoxyserrat-14-en-21ß-ol (PJ-1) and 3ß-methoxyserrat-14-en-21ß-ol (PJ-2) were conjugated with well-known phenolic compounds, narigenin, hesperetin, genistein, and daidzein (1-8). Other conjugates of PJ-2-3,5-dihydroxy-4-methoxybenzoic acid (9), PJ-2-pyrogallol (10), and derivatives of PJ-1, PJ-2-3,3-dimethyl-succinates (11, 12), PJ-1, PJ-2-succinates (13, 14), PJ-2-glycine (15), PJ-2-piperidine acetic acid (16), and PJ-1 epoxy-3,3-dimethyl-succinate (17) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 11 (IC(50) = 251), 12 (IC(50) = 248), and 17 (IC(50) = 230 mol ratio/32 pmol/TPA), were 2-fold stronger than those of the other compounds such as oleanolic acid (IC(50) = 449). Compounds 10, 11, and 17 inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse-skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

Cytotoxic effect of the red beetroot (Beta vulgaris L.) extract compared to doxorubicin (Adriamycin) in the human prostate (PC-3) and breast (MCF-7) cancer cell lines.

Previous cancer chemoprevention studies from our laboratories and by other investigators have demonstrated that the extract of red beetroot (Beta vulgaris L.), the FDA approved red food color E162, can be effective in suppressing the development of multi-organ tumors in experimental animals. To further explore this finding, we have compared the cytotoxic effect of the red beetroot extract with anticancer drug, doxorubicin (adriamycin) in the androgen-independent human prostate cancer cells (PC-3) and in the well-established estrogen receptor-positive human breast cancer cells (MCF-7). This red colored anticancer antibiotic was selected for comparative cytotoxic study because its chemical structure with a planar configuration of an aromatic chromophore attached to a sugar molecule is remarkably similar to that of betanin, the beetroot extract constituent primarily responsible for its red color. Both doxorubicin and the beetroot extract exhibited a dose-dependent cytotoxic effect in the two cancer cell lines tested. Although the cytotoxicity of the beetroot extract was significantly lower when compared to doxorubicin, it continued to decrease the growth rate of the PC-3 cells (3.7% in 3 days vs. 12.5% in 7 days) when tested at the concentration of 29 µg/ml. In contrast, doxorubicin, at the same concentration level, completely inhibited the growth of the PC-3 cells in three days. Similarly, comparative studies in the normal human skin FC and liver HC cell lines showed that the beetroot extract had significantly lower cytotoxic effect than doxorubicin (8.6% vs. 100%, respectively, at 29 µg/ml concentration of each, three-day test period). The results suggest that betanin, the major betacyanin constituent, may play an important role in the cytotoxicity exhibited by the red beetroot extract. Further studies are needed to evaluate the chemopreventive potentials of the beetroot extract when used alone or in combination with doxorubicin to mitigate the toxic side-effects of the latter.

Antitumor-promoting effects and cytotoxic activities of dammar resin triterpenoids and their derivatives.

Nineteen known triterpenoids, 1-19, and one known sesquiterpenoid, 20, were isolated from dammar resin obtained from Shorea javanica K. & V. (Dipterocarpaceae). One of the acidic triterpenoids, dammarenolic acid (1), was converted to fourteen derivatives, namely, an alcohol, 21, an aldehyde, 22, and twelve L-amino acid conjugates, 23-34. Compounds 1-34 were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, a known primary screening test for antitumor promoters. All of the compounds tested, except for compounds 4, 5, 12-14, 16, and 17, showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of beta-carotene, a known natural antitumor promoter. In addition, (20S)-20-hydroxy-3,4-secodammara-4(28),24-dien-3-al (22) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Furthermore, evaluation of the cytotoxic activities of compounds 1-34 against human cancer cell lines showed that reduction (i.e., 21 and 22) or conjugation with L-amino acids (i.e., 23-34) of compound 1 enhanced the cytotoxicity against human melanoma cell line CRL1579.

2-O-beta-d-glucopyranosyl-sn-glycerol based analogues of sulfoquinovosyldiacylglycerols (SQDG) and their role in inhibiting Epstein-Barr virus early antigen activation.

New sulfoquinovosyldiacylglycerols derived from 2-O-beta-d-glucopyranosyl-sn-glycerol, carrying acyl chains of various length on the glycerol moiety, were prepared through a convenient synthetic procedure in which a sulfonate is introduced at the C-6 position of glucose by oxidation of a thioacetate in the presence of the unprotected secondary hydroxyl groups, and tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation. Our study has allowed to ascertain the role of the 6'-sulfonate group and the need of a free hydroxyl group on the glycerol moiety in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA).

Immunohistochemical analysis of an ectopic endometriosis in the uterine round ligament.

A rare case of the inguinal endometriosis was reported with immunohistochemical analysis. A 28-year-old woman had a thumb-sized tumor in the right groin for two years with a gradual increase in size and pain. An operation revealed an elastic hard tumor with an unclear margin and adhesion to the uterine round ligament. The histology showed irregular proliferation of the endometrial glands and stroma. The glandular epithelium stained weakly positive against CD125 antibody and the stromal matrix stained strongly positive against CD10 antibody. The nucleus in both the epithelial and stromal cells stained strongly positive against progesterone and estrogen receptor antibodies, and the cytoplasm in both types of cells stained moderately positive against COX-2 (cyclooxygenase-2) antibody. In conclusion, the combination of estrogen or progesterone receptor antibody for the nucleus and CD10 or COX-2 antibody for the cytoplasm could enhance the accuracy of diagnosis for ectopic endometriosis.