Changes in blood and urinary cadmium levels and bone mineral density according to osteoporosis medication in individuals with an increased cadmium body burden.

The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.

NMR investigation of echinomycin binding to d(ACGTTAACGT)2: Hoogsteen versus Watson-Crick A.T base pairing between echinomycin binding sites.

The structure of the echinomycin complex with the self-complementary DNA decamer d(ACGTTAACGT)2 has been investigated in solution by proton NMR spectroscopy. Echinomycin binds as a bisintercalator at the CpG steps. An analysis of the intermolecular NOE patterns defined the position and orientation of the bound drug molecule. The terminal A.T base pairs are Hoogsteen base-paired, whereas the central four A.T base pairs are clearly Watson-Crick base-paired. Thus, the presence of the extra A.T base pairs between the binding sites appears to prevent the formation of Hoogsteen base pairs immediately adjacent to the binding site. All four central A.T base pairs are destabilized relative to those in the free DNA. Because there is no evidence for unwinding of the DNA duplex in the complex relative to the free DNA, we conclude that the hypersensitivity to DNA cleavage reagents distal to echinomycin binding sites might be due to the destabilization of DNA structure induced by the drug binding.