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Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 505 records · Page 28Linked to original sources
PubMed1978

Direct C-1 hydroxylation of vitamin D compounds: convenient preparation of 1alpha-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3, and 1alpha-hydroxyvitamin D2.

An efficient procedure for the direct C-1 hydroxylation of vitamin D compounds has been developed. The method involves conversion of vitamin D3 tosylates to 3,5-cyclovitamin D derivatives, allylic oxidation with selenium dioxide, and acid-catalyzed solvolysis to the 1 alpha-hydroxyvitamin D analogs. When applied to vitamin D3,25-hydroxyvitamin D3, and vitamin D2, this sequence give the corresponding 1alpha-hydroxylated derivatives in 10-15% yield.

Cholecalciferol↗
PubMed1978

Identification of 5,8-oxyretinoic acid isolated from small intestine of vitamin A-deficient rats dosed with retinoic acid.

A retinoid was isolated by a multistep procedure from the small intestines of vitamin A-deficient rats given a single dose of retinoic acid. The compound, designated 8II, was pure, as demonstrated by four high-pressure liquid chromatographic procedures. It was positively identified as 5,8-oxyretinoic acid by ultraviolet spectrophotometry, mass spectrometry, and spectral and chromatographic comparison to known compounds. It is probable that 5,8-oxyretinoic acid was produced from 5,6-epoxyretinoic acid under the acidic conditions used in the isolation. It is highly probable, therefore, that the natural product is 5,6-epoxyretinoic acid.

Animals↗
PubMed1978

Stimulation of lead absorption by vitamin D administration.

Two methods for the determination of lead absorption have been developed using the rat as the test animal. One is an everted intestinal sac method in which the time course of 210Pb transport across intestinal wall can be followed in vitro; and the other, 210Pb absorption from the intestine following gastric intubation can be followed in vivo. By using these techniques it can be clearly demonstrated that vitamin D markedly enhances lead absorption. Both techniques provide evidence that the distal small intestine is the major site of lead absorption and the site of greatest vitamin D stimulation. Lead acetate is apparently absorbed to the extent of 45% as it passes through the small intestine at a concentration of 0.01 mM.

Animals↗
PubMed1978

Regulation of the vitamin D endocrine system located in the kidney.

During the past decade, it has been clearly established that the kidney is an endocrine organ which converts 25-hydroxyvitamin D to the active hormone 1,25-dihydroxyvitamin D. The kidney and intestine are the sites of an alternative hydroxylation which places an 24 hydroxyl in the R position on either 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D. The production of 1,25-dihydroxyvitamin D is stimulated by hypocalcemia through the parathyroid gland, hypophosphatemia, the sex hormones and the peptide hormones insulin and prolactin. This vitamin D based endocrine system is of central importance in regulating calcium and phosphorus metabolism and its disturbances result in a variety of pathological conditions.

Animals↗
PubMed1978

Synergistic effect of progesterone, testosterone, and estradiol in the stimulation of chick renal 25-hydroxyvitamin D3-1alpha-hydroxylase.

Castrate male chickens have low levels of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase (13 pmol 1,25-dihydroxyvitamin D3/200 mg tissue . 10 min). This activity is markedly increased by the administration of 5 mg/kg estradiol and 5-20 mg/kg testosterone 24 h before in vitro measurement of the enzyme. Both hormones are required for this stimulation. The testosterone, but not estradiol, requirement for the stimulation can also be satisfied by progesterone. Progesterone (12.5 mg/kg) given in addition to estradiol and testosterone stimulates even further the 25-hydroxyvitamin D3-1 alpha-hydroxylase activity to very high levels (388 pmol 1,25-dihydroxyvitamin D3/200 MG tissue . 10 min). This is accompanied by a 3-fold increase in plasma 1,25-dihydroxyvitamin D3 (from 55 to 170 pg/ml), which provides in vivo evidence for the stimulation of the 1 alpha-hydroxylase by sex hormones in birds.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1978

Metabolism and excretion of 3H-1,25-(OH)2-vitamin D3 in healthy adults.

The synthesis of very high specific activity 25-OH-vitamin D3 (78 Ci/mmol) has made possible the study of the metabolism and plasma disappearance of 3H after a single dose of 3H-1,25-(OH)2-D3 in quantities that are only 10-20% of the endogenous plasma pool. We studied seven healthy adults who were given doses of 1,25-(OH)2-D3 ranging from 30-2300 pmol. Plasma disappearance was rapid with only 14 +/- 2% of administered 3H remaining in the plasma pool 4 h after labeling. Plasma metabolite profiles during the first 4 h showed only 1,25-(OH)2-D3. Thereafter, significant amounts of other metabolites were detected. The 6-day cumulative excretion of 3H in urine and feces (virtually all associated with metabolites of 1,25-(OH)2-D3) averaged 16 +/- 3% and 49 +/- 11% of the dose, respectively. Compartmental analysis of the isotope data for two subjects who received the smallest doses of 1,25-(OH)2-D3 indicated that endogenous renal 1,25-(OH)2-D3 synthesis rates approximate 0.8-2.4 nmol/day (0.3-1.0 microgram/day).

Adult↗
PubMed1978

A bioassay capable of measuring 1 picogram of 1,25-dihydroxyvitamin D3.

Fetal rat bones in organ culture constitute a sensitive system for assay of the vitamin D metabolite, 1 alpha,25-dihydroxyvitamin D3. Significant bone resorption is obtained with as little as 2 pg 1,25-dihydroxyvitamin D3 after 48 h of culture and with 1 pg after 64 h of culture. In the current study, organ cultures of fetal rat bone are used as a bioassay for 1,25-dihydroxyvitamin D i normal human plasma, which was prepared for assay by extraction with dichloromethane, chromatography on Sephadex LH-20, and purification on silicic acid by high pressure liquid chromatography. The concentration of 1 alpha,25-dihydroxyvitamin D3 in normal adult human plasma was 24.8 +/- 2.0 pg/ml (n = 19) by this assay.

Animals↗
PubMed1978

A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D.

Typical features of hereditary vitamin D-dependent (pseudovitamin D-deficient) rickets were observed beginning at ages 20 and 5 months in a brother and sister. Both had calcium malabsorption correctable with high doses of 25-hydroxyvitamin D. During periods of hypocalcemia they both manifested secondary hyperparathyroidism with hypophosphatemia and high serum concentrations of endogenously produced 1,25-dihydroxyvitamin D. In each, normalization of serum calcium concentration and resolution of osteomalacia were obtained with continuous administration of high doses of ergocalciferol or high doses of 1,25-dihydroxycholecalciferol. Chemical features of vitamin D deficiency were corrected in the presence of high circulating concentrations of 1,25-dihydroxyvitamin D2, produced endogenously, or of 1,25-dihydroxyvitamin D3, administered by mouth. Serum concentrations of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal in five first degree relatives. We conclude that in these five first degree relatives. We conclude that in these siblings, rickets and osteomalacia resulted from a hereditary decreased sensitivity to 1,25-dihydroxyvitamin D at the intestine and perhaps other vitamin D target tissues.

Absorption↗
PubMed1978

Hypophosphatemic vitamin D-resistant rickets: metabolic balance studies in a child receiving 1,25 dihydroxyvitamin D3, phosphate, and ascorbic acid.

A child with hypophosphatemic vitamin D-resistant rickets was treated for three years with the conventional vitamin D-inorganic phosphate supplementation followed by a new therapeutic regimen consisting of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) and half of the previous phosphate supplementation. The effectiveness of the two treatment regimens was compared by calcium, phosphate, and magnesium balance techniques and by serial radiological examinations as well as careful height measurements. In addition, the lowering of the urinary pH with ascorbic acid supplementation seems to be associated with improvement in the renal tubular reabsorption of phosphate, but its distinct effect, separate from the rest of the treatment modalities, was not tested in this study. The conventional treatment did not correct the hypophosphatemia and alkaline phosphatase elevation, whereas the 1,25 (OH)2 D3-inorganic phosphate regimen is well tolerated and effective in achieving a sustained normalization of these variables. In addition, the improved growth and healing of rickets further attest to the efficacy of the new treatment.

Alkaline Phosphatase↗
PubMed1978

A syndrome of osteoporosis, increased serum immunoreactive parathyroid hormone, and inappropriately low serum 1,25-dihydroxyvitamin D.

Although most patients with postmenopausal osteoporosis have normal or low values for serum immunoreactive parathyroid hormone (iPTH), we have reported previously that a small subset (about 10% of the total group) have increased values. We studied three patients representative of this latter group. Serum iPTH was two to three times higher than the age-adjusted normal mean, serum ionized calcium and total calcium were in the lower half of the normal range, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was in the low-normal range. Six months of treatment of one patient with 0.5 microgram/day of synthetic 1,25(OH)2D improved calcium absorption and balance; however, serum iPTH remained high. After surgical removal of 1,010 mg of hyperplastic parathyroid tissue, serum iPTH decreased to normal. These and other data suggest that increased serum iPTH in these patients was caused by secondary hyperparathyroidism, possibly because of inadequate conversion of 25-OH-D to 1,25(OH)2D.

Aged↗
PubMed1977

A specific high-affinity binding macromolecule for 1,25-dihydroxyvitamin D3 in fetal bone.

Cytosol fractions were prepared from fetal rat or embryonic chick calvaria and analyzed for binding of vitamin D3 metabolites on sucrose density gradients. Both cytosol fractions contain a 3.5S macromolecule which specifically binds 1,25-dihydroxy-[3H]vitamin D3 and in addition, a 5 to 6S macromolecule which binds 25-hydroxy-[3H]vitamin D3. In rat calvaria cytosol, 1,25-dihydroxy-[3H]vitamin D3 also binds to the 5 to 6S macromolecule but appears to have greater affinity for the 3.5S component.

Animals↗
PubMed1977

Specific cytosol-binding protein for 1,25-dihydroxyvitamin D3 in rat intestine.

Cytosol prepared from intestinal homogenates of vitamin D3-deficient rats demonstrate a 3.2 S protein having high affinity and low capacity for 1,25-dihydroxyvitamin D3. Appearance of the protein is dependent upon the presence of 0.3 M potassium chloride and dithiothreitol in the homogenization buffer. A 6 S protein having greater affinity for 25-hydroxyvitamin D3 than 1,25-dihydroxyvitamin D3 is observed using all conditions and is increased by the addition of rat serum to cytosol. The 3.2 S protein is neither a serum contaminant nor a component of the 6 S protein and is probably not a consituent of tissues which which are not responsive to vitamin D3.

Animals↗