6-Fluoro-vitamin D3: a new antagonist of the biological actions of vitamin D3 and its metabolites which interacts with the intestinal receptor for 1 alpha,25(OH)2-vitamin D3

The biological activity and the binding affinity for the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] intestinal receptor of a new fluorine-containing vitamin D compound, namely 6-fluoro-vitamin D3 (6-F-D3), is reported. A significant interaction of 6-F-D3 with the 1,25(OH)2D3 receptor was found, with a relative competitive index (RCI) of 0.26 +/- 0.04, which is intermediate between 25-hydroxyvitamin D3 (0.14 +/- 0.01) and 1 alpha-hydroxyvitamin D3 (0.46 +/- 0.08), where the RCI of 1,25(OH)2D3 is defined to be 100. In contrast, vitamin D3 was unable to interact with the 1,25(OH)2D3 receptor. Also, the biological activity of 6-F-D3 was assessed in vivo in the vitamin D-deficient chick. 6-F-D3 at doses up to 130 nmol displayed no biological action on either intestinal calcium absorption (ICA) or bone calcium mobilization (BCM) over the time interval of 14-48 h after dosing. However, when 130 nmol 6-F-D3 was given 2 h before and 6 h after vitamin D3 (1.62 nmol), a significant inhibition of vitamin D-mediated ICA was noted. Also, a dose of 130 nmol 6-F-D3 given 2 h before and 6 h after 1,25(OH)2D3 (0.26 nmol) significantly inhibited ICA, as measured at 12 h. 6-F-D3 is the first vitamin D analog found which has an ability to both bind to the 1,25(OH)2D3 receptor and to antagonize the production of biological responses by 1,25(OH)2D3.     

Grayscale representation of infrared microscopy images by extended multiplicative signal correction for registration with histological images

Fourier‐transform infrared (FTIR) microspectroscopy is rounding the corner to become a label‐free routine method for cancer diagnosis. In order to build infrared‐spectral based classifiers, infrared images need to be registered with Hematoxylin and Eosin (H&E) stained histological images. While FTIR images have a deep spectral domain with thousands of channels carrying chemical and scatter information, the H&E images have only three color channels for each pixel and carry mainly morphological information. Therefore, image representations of infrared images are needed that match the morphological information in H&E images. In this paper, we propose a novel approach for representation of FTIR images based on extended multiplicative signal correction highlighting morphological features that showed to correlate well with morphological information in H&E images. Based on the obtained representations, we developed a strategy for global‐to‐local image registration for FTIR images and H&E stained histological images of parallel tissue sections.