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1.  Discovery of DS-8108b, a Novel Orally Bioavailable Renin Inhibitor 
ACS Medicinal Chemistry Letters  2012;3(9):754-758.
A novel orally bioavailable renin inhibitor, DS-8108b (5), showing potent renin inhibitory activity and excellent in vivo efficacy is described. We report herein the synthesis and pharmacological effects of 5 including renin inhibitory activity in vitro, suppressive effects of ex vivo plasma renin activity (PRA) in cynomolgus monkey, pharmacokinetic data, and blood pressure-lowering effects in an animal model. Compound 5 demonstrated inhibitory activities toward human renin (IC50 = 0.9 nM) and human and monkey PRA (IC50 = 1.9 and 6.3 nM, respectively). Oral administration of single doses of 3 and 10 mg/kg of 5 in cynomolgus monkey on pretreatment with furosemide led to dose-dependent significant reductions in ex vivo PRA and sustained lowering of mean arterial blood pressure for more than 12 h.
PMCID: PMC4025657  PMID: 24900544
renin inhibitor; hypertension; plasma renin activity; 4-aminoadamantan-1-ol
2.  Absorption of Radionuclides from the Fukushima Nuclear Accident by a Novel Algal Strain 
PLoS ONE  2012;7(9):e44200.
Large quantities of radionuclides have leaked from the Fukushima Daiichi Nuclear Power Plant into the surrounding environment. Effective prevention of health hazards resulting from radiation exposure will require the development of efficient and economical methods for decontaminating radioactive wastewater and aquatic ecosystems. Here we describe the accumulation of water-soluble radionuclides released by nuclear reactors by a novel strain of alga. The newly discovered green microalgae, Parachlorella sp. binos (Binos) has a thick alginate-containing extracellular matrix and abundant chloroplasts. When this strain was cultured with radioiodine, a light-dependent uptake of radioiodine was observed. In dark conditions, radioiodine uptake was induced by addition of hydrogen superoxide. High-resolution secondary ion mass spectrometry (SIMS) showed a localization of accumulated iodine in the cytosol. This alga also exhibited highly efficient incorporation of the radioactive isotopes strontium and cesium in a light-independent manner. SIMS analysis showed that strontium was distributed in the extracellular matrix of Binos. Finally we also showed the ability of this strain to accumulate radioactive nuclides from water and soil samples collected from a heavily contaminated area in Fukushima. Our results demonstrate that Binos could be applied to the decontamination of iodine, strontium and cesium radioisotopes, which are most commonly encountered after nuclear reactor accidents.
PMCID: PMC3440386  PMID: 22984475
3.  Effects of Prenatal Exposure to Polychlorinated Biphenyls and Dioxins on Mental and Motor Development in Japanese Children at 6 Months of Age 
Environmental Health Perspectives  2005;114(5):773-778.
Several studies have shown that prenatal and/or postnatal background-level exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs) and dioxins, induces adverse effects on the neurodevelopment of children. However, other studies have not detected any harmful influences on neurodevelopment. Furthermore, except in western countries, no developmental tests have been carried out in relation to detailed assessment of exposure to PCBs and dioxins. In this study (the Hokkaido Study on Environment and Children’s Health), the effect of prenatal exposure to background levels of PCBs and dioxins on infant neurodevelopment in Japan/Sapporo was elucidated. The associations between the total or individual isomer level of PCBs and dioxins in 134 Japanese pregnant women’s peripheral blood and the mental or motor development of their 6-month-old infants were evaluated using the second edition of the Bayley Scales of Infant Development. The mean level of total toxicity equivalency quantity (TEQ) was 18.8 (4.0–51.2) pg/g lipid in blood of 134 mothers. After adjustment for potential confounding variables, the total TEQ value was shown not to be significantly associated with mental developmental index (MDI) or psychomotor developmental index (PDI). However, the levels of one polychlorinated dibenzo-p-dioxin (PCDD) isomer, total PCDDs, and total PCDDs/polychlorinated dibenzofurans (PCDFs) were significantly negatively associated with MDI, and the levels of two PCDD isomers and three PCDF isomers were significantly negatively associated with the PDI. In conclusion, the background-level exposure of several isomers of dioxins during the prenatal period probably affects the motor development of 6-month-old infants more than it does their mental development.
PMCID: PMC1459935  PMID: 16675436
dioxins; infant development; maternal blood; polychlorinated biphenyls (PCBs); prenatal exposure

Results 1-3 (3)