Discovery of a Tamoxifen-related compound that suppresses glial l-glutamate transport activity without interaction with estrogen receptors.

We recently found that tamoxifen suppresses l-glutamate transport activity of cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter-inhibitory activity from the estrogen receptor-mediated genomic effects, we synthesized several compounds structurally related to tamoxifen. Among them, we identified two compounds, 1 (YAK01) and 3 (YAK037), which potently inhibited l-glutamate transporter activity.

Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats.

The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on fetal brain growth and neurobehavioral development in early developmental stages were investigated using rat offspring. TCDD in corn-oil (0.1microg/kg) was orally administrated to the dams from the 9th to 19th gestational day.

Urinary cadmium and mortality among inhabitants of a cadmium-polluted area in Japan.

The influence of cadmium (Cd) body burden on mortality remains controversial. Excess mortality and the dose-response relationship between mortality and urinary cadmium excretion were investigated in this study among environmentally exposed subjects. A 15-year follow-up study was carried out on 3119 inhabitants (1403 men and 1716 women) of the Cd-polluted Kakehashi River basin, whose urinary Cd concentration was examined in a 1981-1982 health impact survey.

Effects of cadmium exposure during pregnancy on trace elements in fetal rat liver and kidney.

Female rats were exposed by intragastric administration with a cannula 1mg/kg/day or 10mg/kg/day CdCl2 for the 11 days from the 9th to 19th day of pregnancy, and the effects of Cd exposure on eight elements, Na, K, Ca, Mg, P, Fe, Zn, and Cu in fetal liver, kidney, brain, fetal membrane and placenta then examined. We found that: (1) although Cd was not detected in fetal kidney and brain, significant Cd accumulation was found in fetal liver, fetal membrane and placenta in the 10 mg/kg Cd group, (2) the Zn and Fe concentrations in fetal liver in the 10 mg/kg Cd group were significantly lower than those in the control group, but no difference was found in the placenta, (3) the Cu concentrations in the placenta, fetal membrane and liver in the 10 mg Cd groups were significantly lower than those in the control group, (4) Na/K ratio in the placenta and fetal kidney and the Ca concentration in the placenta in the 10 mg/kg Cd group were lower than those in the controls. These results suggest that Cd exposure inhibits Zn and Fe transportation from the placenta to fetus, as well as Cu, Ca, Na and K uptake and transportation across the placenta, possibly influencing fetal growth and metabolism.

Mortality in a cadmium polluted area in Japan.

A 15-year follow-up study of 3178 inhabitants (1424 men and 1754 women) living in the cadmium (Cd) polluted Kakehashi River basin was conducted. The results clarified effects on mortality of renal dysfunction induced by Cd indicated by urinary beta-2-microglobulin (beta2-MG), total protein, glucose, and total amino acids. This study used Cox's proportional hazard model.

Comparison of brain activity between dopamine D2 receptor-knockout and wild mice in response to dopamine agonist and antagonist assessed by fMRI.

It has been reported that antipsychotic dopamine-D2-receptor (D2R) antagonists affected other neurotransmitter systems. In the present study, the effects of a D2R agonist, bromocriptine, and a D2R antagonist, spiperone, on brain activity were investigated using wild-type mice (WT) with intact D2Rs, and D2R-knockout mice (D2R-KO) lacking D2Rs by functional magnetic resonance imaging. In the WT, flow-weighted signal intensity significantly increased after administration of bromocriptine in the hippocampal formation.

Cadmium and nutritional intake in pregnant Japanese women.

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women.