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H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 451 records · Page 25Linked to original sources
PubMed1979

Effect of ethane-1-hydroxy-1,1-diphosphonate and vitamin D on bone mineralization.

Administration of large quantities of ethane-1-hydroxy-1,1-diphosphonate to growing chicks resulted in a decrease in percent bone ash and an increase in percent osteoid. The degree of inhibition of bone mineral accumulation was a function of both duration and quantity of ethane-1-hydroxy-1,1-diphosphonic acid administration. The inhibition of bone mineral accumulation could be partially corrected with administration of 1,25-dihydroxyvitamin D3. Administration of high levels of ethane-1-hydroxy-1,1-diphosphonate also resulted in inhibition of intestinal calcium absorption. This could be reversed or prevented by the administration of 1,25-dihydroxyvitamin D3.

Animals↗
PubMed1979

Biological activity of 24,24-difluoro-25-hydroxyvitamin D3. Effect of blocking of 24-hydroxylation on the functions of vitamin D.

To examine the question of whether 24-hydroxylation plays and importance role in the physiological functions of vitamin D, the biological activity of 24,24-difluoro-25-hydroxyvitamin D was compared with that of 25-hydroxyvitamin D in vitamin D-deficient rats. These two compounds were found almost identically active in the stimulation of intestinal calcium transport, the mobilization of calcium from bone, the healing of rachitic epiphyseal plate cartilage, the elevation of serum inorganic phosphorus, the mineralization of rachitic bone, and in the prevention of rachitogenesis in rats. Little or no difference was detected in the time course of response of intestinal calcium transport or bone calcium mobilization to the two forms of vitamin D. Therefore, in the rat no support could be obtained for the idea that 24,25-dihydroxyvitamin D3 plays an important role in the known physiological responses to the vitamin.

Animals↗
PubMed1979

Metabolism and biological activity of 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol in the rat.

Three side-chain analogues of cholecalciferol (vitamin D3) modified at C-25, namely 25-fluorocholecalciferol, 24-dehydrocholecalciferol and 25-dehydrocholecalciferol, conceived as potential inhibitors of the cholecalciferol 25-hydroxylase have been prepared and tested in the rat. These compounds markedly diminish conversion in vivo of cholecalciferol into 25-hydroxycholecalciferol, but are not antagonists of vitamin D action, because they themselves possess significant biological activity in vivo. Each compound is capable of stimulating the intestinal transport of calcium and the mobilization of calcium from bone in vitamin D-deficient rats. Biological responses equivalent to those generated by a physiological dose of cholecalciferol (0.05 microgram) are produced, however, only when the analogues are administered at high doses (5-50 microgram). The biological activity of 24-dehydrocholecalciferol and 25-dehydrocholecalciferol is shown to result from conversion, in vivo, to the natural hormone, 1 alpha,25-dihydroxycholecalciferol, whereas 25-fluorocholecalciferol is metabolically activated in the rat by hydroxylation to 1 alpha-hydroxy-25-fluorocholecalciferol. This latter conversion is the first reported example of the 1 alpha-hydroxylation of a vitamin D compound lacking the 25-hydroxy group.

Animals↗
PubMed1979

Determination of vitamin D and its metabolites in plasma from normal and anephric man.

A multiple assay capable of reliably determining vitamins D(2) and D(3) (ergocalciferol and cholecalciferol), 25(OH)D(2) (25-hydroxyvitamin D(2)) and 25(OH)D(3) (25-hydroxyvitamin D(3)), 24,25(OH)(2)D (24,25-dihydroxyvitamin D), 25,26(OH)(2)D (25,26-dihydroxyvitamin D) and 1,25(OH)(2)D (1,25-dihydroxyvitamin D) in a single 3-5ml sample of human plasma was developed. The procedure involves methanol/methylene chloride extraction of plasma lipids followed by separation of the metabolites and purification from interfering contaminants by batch elution chromatography on Sephadex LH-20 and Lipidex 5000 and by h.p.l.c. (high-pressure liquid chromatography). Vitamins D(2) and D(3) and 25(OH)D(2) and 25(OH)D(3) are quantified by h.p.l.c. by using u.v. detection, comparing their peak heights with those of standards. 24,25(OH)(2)D and 25,26(OH)(2)D are measured by competitive protein-binding assay with diluted plasma from vitamin D-deficient rats. 1,25(OH)(2)D is measured by competitive protein-binding assay with diluted cytosol from vitamin D-deficient chick intestine. Values in normal human plasma samples taken in February are: vitamin D 3.5+/-2.5ng/ml; 25(OH)D 31.6+/-9.3ng/ml; 24,25(OH)(2)D 3.5+/-1.4ng/ml; 25,26(OH)(2)D 0.7+/-0.5ng/ml; 1,25(OH)(2)D 31+/-9pg/ml (means+/-s.d.). Values in two normal human plasma samples taken in February after 1 week of high sun exposure are: vitamin D 27.1+/-7.9ng/ml; 25(OH)D 56.8+/-4.2ng/ml; 24,25(OH)(2)D 4.3+/-1.6ng/ml; 25,26(OH)(2)D 0.5+/-0.2ng/ml. Values in anephric-human plasma are: vitamin D 2.7+/-0.8ng/ml; 25(OH)D 36.4+/-16.5ng/ml; 24,25(OH)(2)D 1.9+/-1.3ng/ml; 25,26(OH)(2)D 0.6+/-0.3ng/ml; 1,25(OH)(2)D was undetectable.

Animals↗
PubMed1979

25-Azavitamin D3, an inhibitor of vitamin D metabolism and action.

25-Azavitamin D3 inhibited both the bone calcium mobilization and intestinal calcium transport responses of rats to vitamin D3 but not to 25-hydroxyvitamin D3. Although 25-azavitamin D3 had no effect on the response of bone to 1alpha,25-dihydroxyvitamin D3, it did diminish the response of the intestine to that metabolite. 25-Azavitamin D3 increased liver vitamin D content and reduced the concentration of 25-hydroxyvitamin D3 required to inhibit the metabolism of vitamin D3 (75 and 200 microgram) were similar to the doses of 25-azavitamin D3 required to inhibit the action of vitamin D3 in vivo (50 and 150 microgram). 25-Azavitamin D3 is thus a vitamin D antagonist, acting for the most part via inhibition of the liver 25-hydroxylation of vitamin D3.

Animals↗
PubMed1979

Vitamin D deficiency and reproduction in rats.

Female weanling rats from a colony maintained on a diet low in vitamin D were raised on a diet that was deficient in vitamin D but was otherwise adequate. Vitamin D deficiency was confirmed in the rats by hypocalcemia and the absence of vitamin D metabolites in blood. These females gave birth to litters that were slightly smaller than control litters from females maintained on a vitamin D-containing diet. The pups from the vitamin D-deficient mothers appeared normal throughout lactation, and at weaning had normal concentrations of calcium and phosphate in the plasma. These results indicate that vitamin D and its metabolites are not necessary for reproduction and fetal development in the rat.

Animals↗
PubMed1979

Rickets with alopecia: an inborn error of vitamin D metabolism.

Rickets with alopecia, an inborn error of vitamin D metabolism, is described in two sisters. The rachitic disorder began during the first year of life and was refractory to 50,000 IU of vitamin D2/day. Surprisingly, both children had marked elevations in serum concentrations of 1,25-(OH)2D. Although the molecular basis for this disorder is not evident to date, intestinal end-organ unresponsiveness to exceedingly high levels of 1,25-(OH)2D was present, in addition to hyporesponsiveness of bone to these high levels of the hormone, since normocalcemia was maintained despite elevated serum levels of PTH. Therapy with oral 1,25-(OH)2D3 failed to reverse the disorder, but oral phosphorus supplements resulted in significant radiographic and clinical improvement.

Alopecia↗
PubMed1979

1,25-Dihydroxyvitamin D3 in childhood hepatic osteodystrophy.

Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.

Bile Ducts↗
PubMed1979

In vitro production of 1,25-dihydroxyvitamin D3 by rat placental tissue.

Weanling female rats were fed a vitamin D-deficient diet for 4 months until they reached maturity. They were mated with normal, vitamin D-replete male rats and, at 20 days of pregnancy, the female rats were killed and their placentae were removed, homogenzied, and incubated with 25-hydroxyvitamin D3. The incubation mixtures were extracted and the extracts were subjected to Sephadex LH-20 column chromatography followed by high-pressure liquid chromatography. The 1,25-dihydroxyvitamin D3 region of the high-pressure liquid chromatogram was recycled to purity and the structure of the product was identified as 1,25-dihydroxyvitamin D3 by ultraviolet absorption spectrophotometry and by mass spectrometry. Thus it is now evident that placenta, in addition to renal tissue, is capable of converting 25-hydroxyvitamin D3 to the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3.

Animals↗