Creation of Potent Vitamin D Receptor Agonists and Antagonists with 2α-(ω-Hydroxyalkylation) Concept to the seco-Steroid Skeleton.

2α-modification on the vitamin D skeleton with a 2α-(ω-hydroxyalkyl) or 2α-(ω-hydroxyalkoxy) group improves vitamin D receptor (VDR) binding affinity, lengthens the half-life in target cells because of increased resistance to CYP24A1 metabolism, and enhances biological activity. The introduced terminal hydroxy group forms an additional hydrogen bond to Arg274, which is the most important amino acid residue for recognizing the ligand hormone 1α,25-dihydroxyvitamin D₃ of human VDR. According to our 2α-functionalization concept, we synthesized several hundred vitamin D analogs, and some had selective potent biological activity, such as bone formation (by AH-1) or anticancer activity (by MART-10), without the side-effects of vitamin D such as hypercalcemia.

Effort-reward imbalance and its association with health among permanent and fixed-term workers.

Background: In the past decade, the changing labor market seems to have rejected the traditional standards employment and has begun to support a variety of non-standard forms of work in their place. The purpose of our study was to compare the degree of job stress, sources of job stress, and association of high job stress with health among permanent and fixed-term workers.

Methods: Our study subjects were 709 male workers aged 30 to 49 years in a suburb of Tokyo, Japan.