ABSTRACT
Recombinant human calcitonin (rh-CT) has been developed as an agent for patients with excessive bone resorption to replace calcitonins from animal species, which are associated with tolerance problems. In this study, inhibitory effects of rh-CT against bone resorption were examined in thyroparathyroidectomized (TPTX) rats, the animal model of accelerated bone resorption induced by administering a synthetic retinoid (arotinoid). The arotinoid-treated TPTX rats exhibited signs of stimulated bone resorption, such as hypercalcemia, reduced bone mineral density, and inferior bone strength. Significant improvements were seen in all of these changes after a daily treatment with rh-CT (30, 300 U/kg s.c.) for 1 week. A histomorphometrical analysis showed that the treatment with rh-CT markedly suppressed the reduction of trabecular bone volume and that of cortical thickness in the femur of arotinoid-treated TPTX rats. These results suggest that rh-CT may prevent osteopenia caused by accelerated bone resorption.
Subject(s)
Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/prevention & control , Calcitonin/pharmacology , Hypercalcemia/physiopathology , Parathyroidectomy , Retinoids/pharmacology , Thyroidectomy , Animals , Biomechanical Phenomena , Bone Density/drug effects , Bone Density/physiology , Bone Diseases, Metabolic/chemically induced , Calcium/urine , Disease Models, Animal , Humans , Rats , Rats, Wistar , Recombinant Proteins/pharmacologyABSTRACT
In order to examine whether 8-isopentenylnaringenin (1), which has been proven to possess estrogen agonist activity in in vitro tests, also produces in vivo estrogenic properties, the effects of 1 on uterus and on bone metabolism were determined in ovariectomized rats. Rats were ovariectomized and treated with 1 at 30 mg/kg/day subcutaneously for two weeks or 17 beta-estradiol at 0.01 mg/kg/day subcutaneously for two weeks. Ovariectomy resulted in an increase in urinary excretion of bone resorption markers (hydroxyproline, pyridinoline and deoxypyridinoline) and a decrease in bone mineral density of the proximal tibia as well as reduced uterine weight. Treatment with 1 or 17 beta-estradiol completely suppressed these ovariectomy-induced bone and uterine changes in a qualitatively similar manner. These results demonstrate that 1 acts as an estrogen agonist in the uterus as well as in bone in vivo.
Subject(s)
Bone Density/drug effects , Bone Resorption , Estrogens, Non-Steroidal/pharmacology , Isoflavones/pharmacology , Tibia/drug effects , Uterus/drug effects , Amino Acids/urine , Animals , Biomarkers/urine , Estradiol/pharmacology , Female , Hydroxyproline/urine , Organ Size/drug effects , Ovariectomy , Phytoestrogens , Plant Preparations , Rats , Rats, Sprague-Dawley , Tibia/physiology , Uterus/physiologyABSTRACT
Polyclonal anti-BSA antibodies were ractionated by stepwise elution from an immobilized BSA column by decreasing pH or increasing the concentration of NaSCN. The binding affinities of each fraction and original globulin under physiological conditions and their dependence on pH and ionic environments were compared. Fractions with high association constant under physiological conditions did not necessarily show antigen binding affinity over a wide pH range, but they retained a high affinity at higher ionic strength of NaSCN. Consequently, by combining these two fractionation procedures, a fraction with high affinity and which dissociated at moderate pH was obtained. It is clear that high affinity is not always incompatible with ease of dissociation accompanying a change in conditions.
