Abstract. The histogenesis and organogenesis of the human gonad in twelve embryos and six fetuses of ovulational ages 5 to 18 weeks was investigated by histological and ultrastructural examination, including observation of almost complete serial Epon-embedded sections of the entire gonads of 10 embryos. This investigation revealed that the main constituent cells of the gonads are derived from the mesonephros, and that the coelomic epithelium is not involved in the formation of the main component at any stage.

Abstract. Fullerene (C 60 ), a condensed ring aromatic compound with extended π systems, is a novel carbon allotrope. Because of its poor solubility in polar solvents, investigation of the biological and pharmacological properties of fullerene has been difficult. Recently, water-soluble fullerene derivatives have been synthesized, and we and others have found that they have potent and selective pharmacological effects on organs, cells, enzymes, and nucleic acids. In the presence of fullerene C 60 derivative (10 −5 M), endothelium-dependent relaxations induced by agonists in the vascular system were eliminated and acetylcholine-induced contractile response of smooth muscle was observed. Some investigators have reported free radical-scavenging activity and direct nitric oxide-quenching activity of fullerene derivatives. Knowledge of the chemical modifications, biological significance, and materials applications of functionalized fullerenes is growing rapidly; and these compounds are emerging as new tools in the field. The focus of this review is to introduce several pharmacological effects of fullerenes and to discuss the possible mechanisms of the pharmacological actions caused by previously synthesized fullerenes.

Abstract-Thyroid hormones have marked cardiovascular effects in vivo. However, their direct effects on vascular smooth muscle cells have been unclear. Because thyroid hormones play critical roles in bone remodeling, we hypothesized that they are also associated with vascular smooth muscle calcification, one of the pathological features of vascular sclerosis.To test this hypothesis, we examined the effects of 3Ј,3,5-triiodo-L-thyronine (T 3 ) on the expression of calcificationassociated genes in rat aortic smooth muscle cells (RAOSMCs). Quantitative RT-PCRs revealed that a physiological concentration of T 3 (15 pmol/L free T 3 ) increased mRNA level of matrix Gla protein (MGP), which acts as a potent inhibitor of vascular calcification in vivo, by 3-fold in RAOSMCs, as well as in cultured human coronary artery smooth muscle cells. In RAOSMCs transiently transfected with a luciferase reporter gene driven by the MGP promoter, T 3 significantly stimulated luciferase activity. In addition, RNA interference against thyroid hormone receptor-␣ gene diminished the effect of T 3 on MGP expression. Aortic smooth muscle tissues from methimazole-induced hypothyroid rats (400 mg/L drinking water; 4 weeks) also showed a 68% decrease in the MGP mRNA level, as well as a 33% increase in calcium content compared with that from the control euthyroid animals, whereas hyperthyroidism (0.2 mg T 3 /kg IP; 10 days) upregulated MGP mRNA by 4.5-fold and reduced calcium content by 11%. Our findings suggest that a physiological concentration of thyroid hormone directly facilitates MGP gene expression in smooth muscle cells via thyroid hormone nuclear receptors, leading to prevention of vascular calcification in vivo. (Circ Res. 2005;97:550-557.)Key Words: calcium Ⅲ gene expression Ⅲ nuclear receptors Ⅲ vascular smooth muscle Ⅲ thyroid hormone T hyroid hormone has marked effects on differentiation, development, and metabolic balance of virtually every body tissue. The action of thyroid hormone is mediated by highaffinity thyroid hormone nuclear receptors (TRs), which recognize specific response elements in the promoters of target genes and regulate their transcriptional activity in response to the hormone. Alterations in thyroid hormone levels have a profound impact on the cardiovascular system, which include changes in myocardial contractility, heart rate, and resistance of peripheral vasculature. Hyperthyroidism leads to positive inotropic, lusitropic, and chronotropic effects on the heart and low systemic vascular resistance, whereas the opposite is observed in hypothyroidism. In myocardium, the mechanisms for these changes are based on altered expression levels of several key proteins involved in the regulation of intracellular ion homeostasis. The effects of thyroid hormone on cardiac contractility as well as rates of contraction and relaxation are mainly mediated by increases in the levels of the sarcoplasmic reticulum Ca 2ϩ -ATPase and decreases in its inhibitor phospholamban in cardiomyocytes. 1 The positive chronotropic effect of th...

Fullerence (C60) was determined by high-performance liquid chromatography using both ultraviolet and mass spectrometric detection. The detection limit for each method was 0.05 and 2.0 ng (signal-to-noise ratio (S/N = 2)) per injection, respectively. Rat plasma spiked with C60 (10 micrograms/ml) was extracted using solid phase extraction with a recovery of 62.1% and the coefficient of variation (c.v., n = 5) between intra-day assays was 4.0%. The calibration curve for peak area and plasma C60 concentration with ultraviolet detection showed good linearity (r = 0.996) over the range 0.5-60 micrograms/ml. This newly developed method was applied to rat plasma samples after intravenous administration of C60 solubilized with polyvinylpyrrolidone.