Ipriflavone inhibits bone resorption in intact and ovariectomized rats

The aim of this study was to investigate the possible inhibitory effect of ipriflavone on bone resorption in rats. For this purpose, 10-week-old, intact and ovariectomized (OVX) rats, prelabeled from birth with [3H]tetracycline, were used. Bone resorption was monitored by measuring the urinary excretion of [3H]. The animals were fed a purified diet devoid of naturally occurring flavonoids. In the intact rats, the daily meal was given either as a single portion or divided into four portions, a procedure known to lead by itself to a decrease in bone resorption. Ipriflavone, given 7 days after OVX at the dose of 400 mg/kg B.W. daily mixed with the food, led within 2-3 days to a significant decrease in bone resorption equivalent to that of 27.2 μg/kg S.C. of 17β-estradiol. The inhibition was sustained for the length of the experiment, up to 21 days. Ipriflavone given 7 days before OVX prevented the increase in bone resorption induced by castration, the effect being dose-dependent between 50 and 400 mg/kg B.W. In contrast to 17β-estradiol, a 5-week treatment with ipriflavone failed to prevent the OVX-induced uterine atrophy. Significant inhibition of bone resorption was also seen in intact animals, provided they rapidly ingested the daily meal. Actually, the decrease in bone resorption induced by portioning the daily food masked the inhibitory effect of ipriflavone in intact animals. In conclusion, ipriflavone can decrease bone resorption in both intact and OVX animals given a purified diet as a single daily meal. In the OVX model, ipriflavone mimics the osteoprotective effect of estrogen. However, the lack of a uterotropic effect suggests that the compound can discriminate between bone and reproductive tissue

The role of bisphosphonates in breast cancer: Development of bisphosphonates

Bisphosphonates are synthetic compounds characterized by a P–C–P group, and are thus analogs of inorganic pyrophosphate. They are used in medicine mainly to inhibit bone resorption in diseases like osteoporosis, Paget's disease and tumor bone disease. They have been used for over a century in industry, and only in 1968 was it shown that bisphosphonates have biological effects. These effects consist mainly of an inhibition of bone resorption and, when given in large amounts, an inhibition of ectopic and normal calcification. While the latter effect is the consequence of a physical-chemical inhibition of calcium phosphate crystal formation, the former is due to a cellular effect involving both apoptosis of the osteoclasts and a destruction of the osteoclastic cytoskeleton, inducing a decrease in osteoclast activity. The biochemical basis of these effects for the nitrogen-containing compounds is an inhibition of the mevalonate pathway caused by the inhibition of farnesylpyrophosphate synthase, which leads to a decrease of the formation of isoprenoid lipids such as farnesylpyrophosphate and geranylgeranylpyrophosphate. The other bisphosphonates are incorporated into the phosphate chain of ATP-containing compounds so that they become non-hydrolyzable. The new P–C–P-containing ATP analogs inhibit cell function and may lead to apoptosis and death of osteoclasts

THERMAL ALTERATION IN RECEPTOR ACTIVITY OF THE RAT FUNDAL STRIP1'2

ABSTRACT FLEISCH, JERo rs H. AND S. EHRENPREIS

Effects of Partial and Complete Ablation of the Slow Pathway on Fast Pathway Properties in Patients with Atrioventricular Nodal Reentrant Tachycardia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73520/1/j.1540-8167.1994.tb01187.x.pd