ABSTRACT
[Purpose] In this study, we aimed to determine the components of activities of daily living that decline easily during hospitalization. [Participants and Methods] We performed a prospective cohort study of 2,819 inpatients who were hospitalized and discharged. We prospectively evaluated the Barthel Index at admission and discharge, age, length of hospital stay, clinical department, and rehabilitation type. We divided the inpatients into two groups based on the Barthel Index score at admission and compared the items of the index at admission and discharge to analyze the characteristics of decline in activities of daily living. [Results] Forty-nine inpatients (2.0%) had declined in activities of daily living. There were no significant between-group differences in age, length of hospital stay, clinical department, or ratio of individual rehabilitation. However, transfer and toilet use remarkably decreased in the group with Barthel Index scores at admission <85, and bathing and ascending/descending remarkably decreased in the group with Barthel Index at admission ≥85. [Conclusion] The characteristics of decrease in each activity of daily living vary, and our results suggested the components that easily declined when inpatients were divided based on their performance of activities of daily living at admission.
ABSTRACT
The Δ(16) structure as a vitamin D analog enhanced vitamin D receptor (VDR) binding affinity and induced significant cell differentiation, whereas its relative calcemic activity was reduced compared to 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)). Methodologies available to introduce a double bond at C16-C17 of the D-ring on the seco-steroidal skeleton were limited; therefore, a new synthetic strategy was developed to obtain not only the Δ(16) structure, but also a new C15-functional group. Since C15-functionalization was unprecedented in vitamin D analog studies, the hybrid structure of Δ(16) and the C15-OH group at the D-ring may provide important information on the structure-activity relationship with vitamin D analogs. The synthesized 16-ene-2α-methyl-1α,15α,25-trihydroxyvitamin D(3) showed almost 3-times higher VDR binding affinity and an equipotent level of osteocalcin promoter transactivation activity in human osteosarcoma cells as compared to 1α,25(OH)(2)D(3).
Subject(s)
Cell Differentiation/drug effects , Hydroxycholecalciferols/pharmacology , Osteocalcin/genetics , Receptors, Calcitriol/metabolism , Vitamin D/analogs & derivatives , Vitamin D/pharmacology , Bone Neoplasms/drug therapy , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Humans , Osteosarcoma/drug therapy , Osteosarcoma/metabolism , Osteosarcoma/pathology , Promoter Regions, Genetic , Structure-Activity Relationship , Transcriptional Activation , Tumor Cells, CulturedABSTRACT
C15-Substituted 1α,25-dihydroxyvitamin D(3) analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 Å shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.
