Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Shiizaki, K. et al.

Shiizaki, Hayakawa, Imazeki, Hatamura, Okada, Negi, Sakaguchi, Shigematsu, Akizawa,

Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells.

BACKGROUND: Injection of maxacalcitol ( OCT) directly into the parathyroid gland (PTG) is a clinically safe and effective treatment for advanced secondary hyperparathyroidism (A-SHPT) resistant to conventional medical treatment. In the present study, the degree of nuclear localization of directly injected OCT in parathyroid cells ( PTC) was investigated by microautoradiography (mARG) in a model of A-SHPT. METHODS: The 5/6 nephrectomized Sprague-Dawley rats were fed a high-phosphate and low-calcium diet for 8 weeks and consequently the level of vitamin D receptor ( VDR) in their PTC severely decreased. The bilateral PTG were surgically exposed and only the left gland were directly injected with (3)H-OCT (DI-(3)H-OCT). The time course of the changes in both radioactivity and localization of (3)H-OCT in the bilateral glands was analysed using a bioimaging analyser system and mARG, respectively. A very high dose of unlabelled calcitriol was administered intravenously (IV-1,25D(3)) prior to DI-(3)H-OCT, as a competitive study. RESULTS: Peak radioactivity levels in the directly injected and intact PTG occured immediately and 1 h, respectively, after DI-(3)H-OCT, and the difference was about 50-fold higher in the treated gland. The of mARG showed a marked concentration of silver grains in the nuclei of PTC in the gland treated with DI-(3)H-OCT and that concentration was significantly suppressed by IV-1,25D(3). CONCLUSIONS: Direct injection of OCT into the PTG enables the administration of the highly concentrated drug for specific binding to nuclear vitamin D binding sites, including VDR of PTC, which markedly suppresses the parathyroid hormone, improves the response to calcium and vitamin D and induces apoptosis in PTC.[1]

References

Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells. Shiizaki, K., Hayakawa, N., Imazeki, I., Hatamura, I., Okada, T., Negi, S., Sakaguchi, T., Shigematsu, T., Akizawa, T. Nephrol. Dial. Transplant. (2007) [Pubmed]

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