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Biomedical subjects

J M Hock

Publications and source records attributed to J M Hock.

61 records · Page 4Linked to original sources

Stimulation of undermineralized matrix formation by 1,25 dihydroxyvitamin D3 in long bones of rats.

We previously reported that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) given for 2-3 days, inhibited osteoblastic collagen synthesis in young rats. In this study, we tested the effects of 5, 25, and 125 ng of 1,25(OH)2D3 injected subcutaneously into 6-week-old rats for 12 or 18 days. In rats given 125 ng, cortical bone of distal half femurs exhibited decreased calcium (Ca) content but dry weight and hydroxyproline (Hyp) content were no different from control. Trabecular bone Ca was not different from control but dry weight and Hyp were increased. When cortical and trabecular bone were combined, there was a decrease in Ca, an increase in Hyp, and a 50% decrease in Ca:Hyp. Fluorescent labels given after 8 days of treatment were either diffuse or absent in calcified sections from rats given 125 ng, indicating impaired mineralization. The 25 and 125 ng doses produced hypercalcemia with normal serum phosphate. There was a dose-related increase in serum immunoreactive bone gla protein (BGP) and serum 1,25(OH)2D3 and a decrease in serum 25(OH)D3. At the 5 ng dose, no adverse effects were seen on body growth. With 25 ng and 125 ng, growth was inhibited. Increased serum urea nitrogen and histologic evidence of nephrocalcinosis occurred at the 125 ng dose. When 125 ng was given for 12 days and then withdrawn for 6 days, systemic toxicity decreased and bone Hyp and Ca increased so that Ca:Hyp remained low and comparable to that of rats treated with 1,25(OH)2D3 continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dental management of patients with hereditary angioedema: report of case.

Dental management and treatment of a patient with hereditary angioedema can be accomplished safely and satisfactorily in an outpatient setting by a dentist in collaboration with a physician. However, as acute attacks can occur as a complication of treatment, we recommend that dental treatment be provided in a hospital environment with adequate medical emergency resources.

Adult↗

Increased trabecular bone mass in rats treated with human synthetic parathyroid hormone.

Although PTH inhibits bone collagen synthesis acutely, prolonged administration of PTH increases trabecular bone mass. The objectives of this study were to develop a simple method to quantitate the anabolic response of cortical and trabecular bone, to determine if the trabecular bone response is at the expense of cortical bone, and to correlate the bone response with changes in serum calcium or phosphate. Subcutaneous injections of 2 to 16 micrograms/100 g body weight hPTH(1-34) were given daily to weanling rats for 12 days. The trabecular and cortical bone were manually separated from the distal femur, and calcium, hydroxyproline, and extracted dry weight were measured. Growth and renal function were not impaired. Serum calcium (range: 8.9-9.5 mg%) and serum phosphate (range: 7.7-8.5 mg%) did not differ significantly from control serum calcium, 9.1 mg%, or serum phosphate, 8.1 mg%. A dose-related anabolic response was observed in calcium, hydroxyproline, and dry weight of trabecular bone. At the highest dose of hPTH for 12 days, these values were increased above control by 26%, 33%, and 26%, respectively (P less than .01). While cortical bone values increased over 12 days, only the dry weight increase was significant (P less than .01). Our method showed an increase in trabecular bone mass after daily subcutaneous injections of hPTH (1-34) at doses that were neither toxic nor hypercalcemic. Although the absolute change of cortical bone mass was greater than that of trabecular bone, it was more variable and not statistically significant. Nevertheless, these results indicate that trabecular bone mass did not increase at the expense of cortical bone.

Animals↗

DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones.

Osteoclasts, the principal cells mediating bone resorption, are believed to increase their size, number, and resorbing activity in response to parathyroid hormone (PTH) through mechanisms dependent upon the fusion of specific mononuclear precursor cells into either new or existing multinucleated osteoclasts. To address the question of whether these actions of PTH are dependent on the replication of osteoclast precursor cells, we examined the ability of an inhibitor of DNA synthesis, hydroxyurea (HU), to alter bone resorption, osteoclast formation, and DNA synthesis in cultured fetal rat bones treated with PTH. We found that HU significantly reduced [3H]thymidine incorporation into the bones and labeling of osteoclast nuclei by greater than 90%, but did not prevent PTH from stimulating bone resorption, measured as the release of 45Ca, or from increasing the number of osteoclasts in the bones. In bones cultured without PTH, HU decreased the rate of bone resorption, but not the number of osteoclasts per bone. We conclude that in fetal rat bone cultures, PTH can increase osteoclast number and stimulate bone resorption by affecting existing osteoclasts and osteoclast precursors, and that replication of osteoclast precursor cells is not necessary for PTH to stimulate a resorptive response. In unstimulated cultures it appears that HU inhibits bone resorption by affecting mechanisms that are independent of changes in osteoclast number and that may be influenced by cell replication or other unknown factors.

Animals↗

Use of osmotic minipumps for delivery of parathyroid hormone.

To determine if osmotic minipumps can be used for the local delivery of parathyroid hormone (PTH), we examined the bone resorbing activity of PTH in minipumps, either removed and assayed in bone organ cultures or released over rat calvaria. Biological activity of PTH was maintained for up to 6 days when the hormone solution contained serum and the minipumps and tubing were siliconized and flushed with diluent prior to use. Addition of cysteine did not enhance activity.

Animals↗

Autoradiographic study of the effect of 1,25-dihydroxyvitamin D3 on bone matrix synthesis in vitamin D replete rats.

An autoradiographic technique using pulse labels of [3H]proline was developed to assess the early effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on bone matrix synthesis in vitamin D replete rats. Rats, 7 days old, were given 0.25 2.5, or 25 ng of 1,25(OH)2D3 for vehicle alone subcutaneously on days 1, 3, and 5 of the experiment. Rats received a subcutaneous injection of 100 microCi [3H]proline on days 2 and 6 and were killed on day 7. Calvaria and tibia were processed for autoradiography, and morphometric methods were developed to measure the rate and amount of bone matrix formed during the experimental period. When compared to control values, the amount and rate of formation of new bone matrix were both signifIcantly decreased in rats receiving 25 ng of 1,25(OH)2D3 and slightly, but not significantly, decreased in rats receiving 2.5 ng. We conclude that administration of pharmacologic doses of 1,25(OH)2D3 to vitamin D replete rat pups impairs the formation of collagenous bone matrix.

Animals↗