Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the mechanism of action of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP, formerly APD) on bone metabolism, we have studied the influence of low doses of AHPrBP on bone resorption and formation in the mouse. Thirty-five-day-old mice were given daily injections of 0.16, 1.6, or 16 mumol/kg BW per day of AHPrBP for 10 days. At sacrifice biochemical parameters were measured in serum and bone ash, and histomorphometric parameters of bone formation and resorption were determined on undecalcified sections of caudal vertebrae after double 3H-proline and double tetracycline labelings. Serum calcium and 1,25-dihydroxyvitamin D levels remained normal at all dosage levels. Compared to controls, AHPrBP at doses of 1.6 and 16 mumol/kg per day increased the number of osteoclasts and the number of nuclei per osteoclast but markedly decreased the number of acid phosphatase-stained osteoclasts. Thus, AHPrBP appears to inhibit osteoclastic activity in vivo in part through reduction of acid phosphatase activity. At doses of 1.6 and 16 mumol/kg per day AHPrBP reduced serum alkaline phosphatase and the osteoblastic surface and decreased the endosteal osteoid surface and thickness. Both the matrix apposition rate and the mineral apposition rate were progressively reduced at the endosteal level, although they were not significantly changed at the periosteal level. Greater inhibition of bone resorption than bone formation resulted in increased endosteal bone density and bone mineral content. AHPrBP at a dose of 0.16 mumol/kg per day did not alter either the osteoclastic bone resorption or the mineral and matrix apposition rates.
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PMID:Inhibition of bone matrix apposition by (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) in the mouse. 402 97

Bisphosphonates are potent inhibitors of bone resorption, and are therefore used for the treatment of various bone diseases including osteoporosis. We examined whether cyclic therapy with bisphosphonates in oophorectomized osteoporotic rats had any advantage over continuous treatment. We therefore treated intact and oophorectomized young female rats for 8 weeks with 1 and 5 mg/kg/day of pamidronate. The 8-week treatment was given continuously for 6 days/week or intermittently, i.e. 6 days of pamidronate (APD) and 3 weeks off, for 2 cycles. We found an increase in tibial wet and ash weight and in the mineral content in oophorectomized rats treated continuously or intermittently with APD in comparison to nontreated oophorectomized animals. Histomorphometric analysis showed an increase in the volume of metaphyseal cartilage and bone. No changes were found in the volume of epiphyseal or diaphyseal bone. Pamidronate had very little effect on the bone of intact rats. Pamidronate seems to be more effective in inhibiting bone resorption in bone that undergoes rapid turnover (i.e. in oophorectomized animals) when compared to bone with low turnover (intact rats). Although the results of cyclic treatment were similar to those of continuous treatment, we have to remember that cyclic therapy may be more advantageous since animals receiving cyclic therapy received only 25% of the dose of rats continuously treated.
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PMID:Effects of continuous or cyclic administration of pamidronate on the skeleton in intact and oophorectomized young rats. 952 96

In connection with the known inhibitive action of bisphosphonates on bone resorption we were interested in their possible influence on bone blood flow (BBF). We determined BBF (85Sr-microsphere uptake in the tibia, distal femur and diaphysis of femur), cardiac output, density and ash weight of the tibia, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. Pamidronate (Aredia, CIBA-Geigy, Switzerland) was administered to sham-operated or oophorectomized (OOX) female rats in doses of 0.6 mg i.p. 2 days a week for 4 weeks. 85Sr-microsphere uptake was increased after OOX in the tibia and distal femur, simultaneous pamidronate administration significantly suppressed this increase below the control level. In addition, pamidronate inhibited the 24-h incorporation of 45Ca and 3H-proline in sham-operated females and suppressed the incorporation of 3H-proline that was increased after OOX. Bone density and ash weight were significantly increased after pamidronate administration in both sham-operated and OOX rats. The results of both experiments showing a significant effect of pamidronate on BBF and incorporation of 45Ca and 3H-proline require further verification and elucidation.
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PMID:Effect of pamidronate on bone blood flow in oophorectomized rats. 980 69

So far it is not known whether the growth hormone (GH) has an effect on the local blood circulation in bones. Using male rats we studied the local blood circulation in the tibia and the distal end of the femur (by means of the uptake of 85Sr-microspheres), the density and ash weight of the tibia, the urinary excretion of pyridinoline (PD) and deoxypyridinoline (DPD) as an indicator of bone resorption and the blood levels of IGF-I after the administration of human GH (4 mg/kg s.c. daily for 4 weeks) and/or bisphosphonate pamidronate (Aredia, CIBA-Geigy, administered in the dose of 3 mg/kg i.p. on day 1, 2, 9 and 10). The rats were divided into four groups: 1. controls, 2. GH, 3. pamidronate, 4. GH plus pamidronate. After the administration of GH, we observed a significant increase in bone blood flow (and in the uptake of 85Sr-microspheres), a decrease in the density and ash weight of the tibia and increased urinary excretion of PD and DPD; IGF-I levels in the blood were non-significantly elevated. Simultaneously administered pamidronate inhibited all significant effects of GH and it also decreased the IGF-I levels in rats treated with GH. After the administration of pamidronate itself the bone density and ash weight of the tibia were increased and urinary DPD excretion was decreased. In view of the known vascular effects of IGF-I, we assume that the increase in bone blood flow after the administration of GH and its reduction after simultaneous administration of pamidronate could be mediated by the changes of IGF-I blood levels, although the effect of pamidronate on IGF-I is still not clear. Regarding the role of blood circulation in rat bones, we consider that our present results are further evidence for the relationship between the blood circulation in bones and bone resorption, although these results do not show how active is bone blood circulation in the regulation of bone tissue metabolism.
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PMID:Effect of growth hormone and pamidronate on bone blood flow, bone mineral and IGF-I levels in the rat. 1098 78