Vitamin D receptor genotype BB is associated with higher serum osteocalcin in first pregnancy.

AIM: Serum osteocalcin was shown in a previous study on first trimester pregnant women to correlate with bone density and to distinguish between fast and slow bone losers. The objective of the present study is to examine whether serum osteocalcin is related to vitamin D receptor (VDR) BsmI polymorphism in pregnant women. STUDY DESIGN: We determined osteocalcin serum levels and VDR BsmI genotype in 97 healthy first trimester pregnant women consecutively recruited during six months. RESULTS: BB (21%), Bb (38%) and bb (41%) genotypes showed similar osteocalcin serum levels. However, in primigravidas (n=38) the BB genotype was significantly associated with higher mean osteocalcin level (9.67 ng/mL) than the Bb (8.07 ng/mL) and the bb genotype (8.14 ng/mL), respectively (P<0.05). The VDR genotype was the only independent parameter to correlate with serum osteocalcin (P<0.05). CONCLUSION: Only primigravidas show in the first trimester a relation between the bone formation parameter serum osteocalcin and the VDR genotype BB which indicates a higher risk of fractures. For further clinical applications serum osteocalcin and VDR genotype should be tested on a cohort of primigravidas including measurements of bone density.

Radioiodide treatment after sodium iodide symporter gene transfer is a highly effective therapy in neuroendocrine tumor cells.

This study evaluates the possibility of treating Bon1 and QGP pancreatic neuroendocrine tumor cells with radioactive iodide ((131)I) after stable transfection with the thyroid sodium iodide symporter (NIS). NIS expression was driven either by the strong viral cytomegalovirus promoter or by the tissue-specific chromogranin A promoter. Using either approach, NIS expression was confirmed by reverse transcription-PCR and Western blotting. Uptake of radioactive iodide was increased approximately 20-fold by chromogranin A promoter-driven NIS expression and approximately 50-fold by cytomegalovirus promoter-driven NIS expression. Maximal uptake was reached within 15 min in QGP cells and 30 min in Bon1 cells. Effective half-life was 5 min in QGP and 30 min in Bon1 cells. No evidence of organification was detected by high-performance liquid chromatography and gel filtration chromatography. (131)I was a highly effective treatment in NIS-expressing QGP and Bon1 cells, reducing clone formation by 99.83 and 98.75%, respectively, in the in vitro clonogenic assay. In contrast, clone formation was not reduced in QGP and Bon1 cells without NIS expression after incubation with the same activity concentration of (131)I as compared with mock treated cells. Absorbed doses to QGP and Bon1 cells are up to 150 and 30 Gy, respectively. In addition, a direct cytotoxic effect of radioiodide was demonstrated in NIS-expressing Bon1 cells after (131)I incubation. In conclusion, radioiodide treatment after NIS gene transfer appears to be a promising novel approach in the therapy of neuroendocrine tumors if its highly encouraging in vitro effectiveness can be transferred to the in vivo situation.

Peroxisome proliferator-activated receptor-gamma in thyroid eye disease: contraindication for thiazolidinedione use?

A male type-2 diabetic, treated with the peroxisome proliferator-activated receptor (PPAR) agonist, Pioglitazone, experienced exacerbation of his thyroid eye disease (TED), which had been stable and inactive for more then 2 yr. Expansion of the orbital fat developed, and we have investigated the effects of PPAR gamma agonists, including Pioglitazone and, subsequently, an antagonist on the adipogenesis of preadipocytes from TED orbits and Graves' neck fats. The percentage of differentiating cells, assessed by oil red O staining, morphological changes, and PPAR gamma transcript levels, was determined for preadipocytes in hormone/agonist-induced models of adipogenesis, supplemented or not with PPAR gamma agonists or antagonist. The PPAR gamma agonists resulted in a 2- to 13-fold increase, and a PPAR gamma antagonist produced a 2- to 7-fold reduction in adipogenesis in vitro. Effects were dose dependent and maximal at 1 or 10 micro M. We suggest that care should be exercised when selecting patients for treatment with PPAR gamma agonists and that such agonists may be contraindicated in individuals with a previous history of autoimmune thyroid or eye diseases. Our work also suggests that PPAR gamma antagonists could provide a novel therapy for TED patients in the active stage of disease.