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H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 577 records · Page 32Linked to original sources
PubMed1975

Importance of the stereochemical position of the 24-hydroxyl to biological activity of 24-hydroxyvitamin D3.

Both stereoisomers of 24-hydroxyvitamin D3, i.e. 24(S)-hydroxyvitamin D3 and 24(R)-hydroxyvitamin D3, stimulate intestinal calcium transport almost equally well in the rat. The duration of effect is somewhat shorter for the 24(S)-hydroxyvitamin D3 than for the 24(R)-hydroxyvitamin D3. However, the 24(S)-hydroxyvitamin D3 has little or no activity in the mobilization of calcium from bone, in the growth of rats on a low calcium diet, in the elevation of serum phosphorus of rachitic rats, or in the calcification of bone. On the other hand, the 24(R)-hydroxyvitamin D3 is almost as active as 25-hydroxyvitamin D3 in all of these systems, although its activity is not always of equal duration to that of 25-hydroxyvitamin D3. The selectivity of these systems for only one of the 24-hydroxy stereoisomers supports the idea that in vivo 24-hydroxylation of vitamin D compounds is of functional importance.

Animals↗
PubMed1975

Isolation and identification of 1,25-dihydroxyvitamin D2.

The chemical synthesis of [3alpha-3H]vitamin D2 of high specific activity has been described. With the use of this radioactive material, the existence of a polar metabolite believed to be the active form of vitamin D2 in the rat and chick has been demonstrated. It has been isolated in pure form from an in vitro chick kidney mitochondrial system and identified as 1,25-dihydroxyvitamin D2 by means of mass spectrometry, ultraviolet absorption spectrophotometry, and specific derivative synthesis. Its antirachitic activity equals that of 1,25-dihydroxyvitamin D3 in the rat.

Animals↗
PubMed1975

Effect of I,25-dihydroxycholecalciferol in renal osteodystrophy.

A 23-year-old man with medullary cystic disease had been undergoing hemodialysis for 5 years and had become confined to a wheelchair because of renal osteodystrophy. He was treated with 125-dihydroxycholecalciferol, 2.0 mug (later 1.0 mug) three times a week, administered by way of the venous end of the dialysis machine. Within 1 month bone pain lessened and his ability to stand and walk improved. By 3 months he was walking short distances and by 5 months, long distances. Calcium balance was near zero before treatment and was strongly positive during treatment. Bone mineral content in the lower femur, measured by photon absorptiometry, increased at a rate of 32.2% per year. In contrast, 26 other patients on long-term hemodialysis had a mean loss of bone mineral content of 14.0% per year. Radiographs taken during treatment showed a decrease in subperiosteal bone resorption and healing of a pseudofracture. A significant decrease in the mean serum alkaline phosphatase value was noted during treatment, but no significant changes in mean serum calcium or phosphorus values were seen.

Adult↗
PubMed1975

Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity.

27-nor-25-Hydroxyvitamin D3, 26,27-bisnor-25-hydroxyvitamin D3, and 22-27-hexanor-20-hydroxyvitamin D3 and the corresponding 5,6-trans isomers have been synthesized. All compounds were tested for their ability to induce intestinal calcium transport and bone calcium mobilization in normal and anephric rats. The 27-nor- and 26,27-bisnor-25-hydroxyvitamin D3 analog are capable of stimulating intestinal calcium transport and bone calcium mobilization in normal rats but are 10 to 100 times less active than 25-hydroxyvitamin D3. Although these analogs are inactive in anephric rats, their corresponding 5,6-trans isomer are capable of stimulating both intestine and bone activity in these animals. The 22-27-hexanor-20-hydroxyvitamin D3 and its corresponding 5,6-trans isomer are incapable of stimulating either intestinal calcium transport or bone calcium mobilization. These results suggest that minor alterations in the side chain significantly decrease the biopotency of 25-hydroxyvitamin D3. Since these analogs are biologically active in normal but not in anephric animals, it appears that the kidney 1alpha-hydroxylation is necessary for activity. Since 22-27-hexanor=20-hydroxyvitamin D3 and its corresponding 5,6-trans analog are biologically inactive, it is likely that at least part of the side chain is necessary for 25-hydroxyvitamin D3 to stimulate intestinal calcium transport and bone calcium mobilization.

Animals↗
PubMed1975

Long-term therapy of viramin D-resistant richets with 25-hydroxycholecalciferol.

The long-term effects of the vitamin D metabolite, 25-hydroxycholecalciferol (25-HCC), were evaluated in 2 children with hypophosphatemic vitamin D-resistant rickets. Serial total balance studies demonstrated an apparent lack of correlation between the effects of the vitamin on intestinal absorption of calcium and phosphorus and both the onset of healing in 1 of the 2 patients treated with 5,000 to 7,500 u of the metabolite and the absence of demonstrable radiologic improvement in another patient in whom the final dosage was 20,000 u. per day. At first, the metabolite induced a positive calcium balance in both patients resulting largely from a reduction in intestinal calcium excretion. Despite a continued positive calcium balance, 1 of the 2 patients did not demonstrate further healing, while in the other patient healing was noted even when total calcium balance was negative. Serum phosphate levels did not return to normal in either patient, nor was phosphate excretion altered by 25-HCC. Serum alkaline phosphatase remained elevated in both. Serum immunoassayable parathyroid hormone levels were consistently normal to high-normal in the 2 patients throughout more than 24 months of observation. No instances of hypercalcemia and only occasional hypercalciuric episodes were noted.

Alkaline Phosphatase↗
PubMed1975

The kidney as an endocrine organ involved in the function of vitamin D.

Vitamin D3 must be metabilically altered first in the liver to 25-hydroxyvitamin D3 (25 OH-D3) and subsequently in the kidney to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) before it can function. Because 1,25-(OH)2D3 is formed in the kidney and acts in intestine and bone to elevate serum calcium and phosphate concentrations, it can be considered a hormone. The production of 1,25-(OH)2D3 is feedback regulated either directly or indirectly by serum calcium and serum phosphate concentrations. The hypocalcemic regulation is mediated by the parathyroid glands. The hypophosphatemic stimulus, however, does not involve either the parathyroid or thyroid glands. Under conditions whereby the synthesis of 1,25-(OH)2D3 is repressed, 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3 is formed. This metabolite can be converted further to 1,24,25-trihydroxyvitamin D3 (1,24,25-(OH)3D3), which stimulate intestinal calcium transport but not bone calcium mobilization or phosphate transport reactions. A number of vitamin D-resistant bone diseases may be related to defective vitamin D metabolism. For example, bone disease related to choric renal failure likely results from defective formation of 1,25-(OH)2D3 in the kidney. Treatment of this disease with intravenously administered 1,25-(OH)2D3 is effective in correcting the bone lesions. 1Alpha-hydroxyvitamin D3 (1alpha-OH-D3), a new synthetic analog of 1,25-(OH)2D3 which is less expensive to produce than 1,25-(OH)2D3, is effective in anephric animals and may have several advantages over 1,25-(OH)2D3 in treating bone diseases.

Biological Transport↗
PubMed1975

Effects of 1alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 on calcium and phosphorus metabolism in hypoparathyroidism.

The effects of 1alpha-OH D3 or 1,25-(OH)2D3 on calcium and phosphorus metabolism have been evaluated in five hypoparathyroid patients to establish the direct effects of these compounds in adult humans, uncomplicated by compensatory changes in parathyroid hormone secretion. Doses of 1-2.5 mug/day in four patients (5 mug/day in a fifth patient on diphenylhydantoin and phenobarbital) caused a marked increase in serum calcium concentration and urinary calcium excretion, without significant changes in renal calcium clearance or urinary hydroxyproline excretion. These results suggest that the correction of hypocalcemia involved primarily a stimulation of intestinal calcium absorption rather than a stimulation of skeletal calcium resorption. Simultaneously, there were increases in urinary phosphorus excretion and variable changes in serum inorganic phosphate concentration. These effects were produced by doses of 1alpha-OH D3 and 1,25-(OH)2D3 which approach the dose needed to prevent rickets, in contrast to the very large doses of vitamin D or 25-OH D3 required for comparable effects in hypoparathyroid patients. The increased relative effectiveness of these one-hydroxylated forms of vitamin D reveals a deficiency of vitamin D one-hydroxylation in hypoparathyroidism. The rapidity of action of 1alpha-OH D3 and 1,25-(OH)2D3 was also striking. Apart from its physiologic implications, the potency of the one-hydroxylated forms of vitamin D offers significant therapeutic advantages in some patients whose hypoparathyroidism is difficult to control with vitamin D itself.

Adult↗
PubMed1975

Structural analogs of 1alpha,25-dihydroxycholecalciferol: preparation and biological assay of 1alpha-hydroxypregnacalciferol.

The synthesis of 1alpha-hydroxypregnacalciferol, a side chain analog of 1alpha,25-dihydroxycholecalciferol (1alpha,25-dihydroxyvitamin D3), is described. Pregnenolone acetate was converted in five steps to 5-pregnen-1alpha,3beta-diol. Conversion of the diol to pregna-5,7-diene-1alpha,3beta diol diacetate followed by ultraviolet irradiation gave the corresponding previtamin derivative. Thermal isomerization, hydrolysis and chromatography then furnished the desired analog, 1alpha-hydroxypregnacalciferol. The compound was tested in vivo for its effect on intestinal calcium transport, serum calcium and phosphate levels and bone calcification, and in vitro for its effect on bone resorption. When given to intact rats, either as a single dose or in repeated daily doses, the analog even at high dose levels, exhibited no biological activity. The compound stimulated bone resorption in vitro, but only at high concentrations.

Animals↗
PubMed1975

Vitamin D today.

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Bone Diseases↗
PubMed1975

Synthesis and biological activity of 25xi,26-dihydroxycholecalciferol.

25xi,26-Dihydroxycholecalciferol (25xi,26-dihydroxyvitamin D3), a metabolite of vitamin D3 preferentially active on intestine has been synthesized. This compound was prepared by converting 3beta-hydroxy-27-norcholest-5-en-25-one to 25xi,26-epoxy-5-cholesten--3beta-ol and base-catalyzed hydrolysis of the latter to 5-cholestene-3beta,25xi,26-triol; allylic bromination of the corresponding triacetate, and dehydrobromination gave the required 5,7-diene which yielded the vitamin derivative upon photolysis (Figure 3). The synthetic product shows the same activity pattern as the natural metabolite: at dose levels of 0.25 mug, the compound stimulates intestinal calcium transport, but has no effect on bone calcium mobilization in rats maintained on a vitamin D-deficient, low calcium diet. Higher doses (2.5 mug) elicit a more pronounced intestinal calcium transport response, but also have no significant effect on the bone mobilization system. The compound exhibits no biologial activity in nephrectomized animals.

Animals↗
PubMed1975

Function of the fat-soluble vitamins.

Much has been learned about the function of the fat-soluble vitamins in recent years. Their mechanisms are divergent ranging from a role in transcription of DNA or differentiation to a direct enzymatic activation of the gamma-carboxylation of glutamate residues of a preexisting protein. Thus the only resemblance so far among these physiologically active agents is their lipid solubility. However, in general the fat-soluble vitamins play important roles in specialized functions carried out by highly differentiated organisms.

Animals↗