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Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 361 records · Page 20Linked to original sources
PubMed1981

The effect of inhibitors of protein and RNA synthesis on 1 alpha,25-dihydroxyvitamin D3-dependent calcium uptake in cultured embryonic chick duodenum.

To determine whether 1 alpha, 25-dihydroxyvitamin D3-dependent increases in intestinal calcium uptake require de novo protein and RNA synthesis, the effects of several inhibitors of these processes have been re-examined in vitro using cultured embryonic chick duodenum. To minimize the contributions of antibiotic toxicity to the interpretation of results, care was taken to examine inhibitor effects at early times after the onset of the 1 alpha, 25-dihydroxyvitamin D3 response. Cycloheximide at a concentration of 5 microM blocked hormone-dependent calcium uptake at all times examined (6 to 24 h). Actinomycin D was similarly effective at 6 to 12 h. The effects of cycloheximide were totally reversible while actinomycin D inhibition was only partially reversible. These compounds inhibited protein or RNA synthesis by 68.4 +/- 1.4 and 51.4 +/- 1.1%, respectively. Anisomycin, another inhibitor of polypeptide chain elongation and alpha-amanitin, an inhibitor of RNA polymerase I, also blocked 1 alpha, 25-dihydroxyvitamin D3-dependent calcium uptake after 12 h in culture. These results further strengthen the hypothesis that 1 alpha, 25-dihydroxyvitamin D3 stimulates intestinal calcium transport via a nuclear mechanism involving new gene expression.

Amanitins↗
PubMed1981

Isolation of identification of 24(R)-hydroxyvitamin D3 from chicks give large doses of vitamin D3.

A new metabolite of vitamin D was isolated from the blood plasma of chicks given large doses of vitamin D3. The isolation involved methanol-chloroform extraction and four column chromatographic steps. The metabolite was identified by high- and low-resolution mass spectroscopy, chemical derivatization, an comigration with authentic standard as 3 beta, 24(R)-dihydroxy-9,10-seco-5,7,10(19)-cholestatriene [24(R)-hydroxyvitamin D3]. No detectable 24-(R)-hydroxyvitamin D3 was recovered from 16 L of plasma from chicks receiving physiologic levels of vitamin D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

The metabolism of retinoic acid to 5,6-epoxyretinoic acid, retinoyl-beta-glucuronide, and other polar metabolites.

A description of the enzyme that produces 5,6-epoxyretinoic acid from all-trans-retinoic acid has been presented. This enzyme system is found in highest concentrations in the kidney followed by intestine, liver and spleen. The enzyme requires molecular oxygen, magnesium ions, ATP, and NADPH. In the kidney, it is found in the mitochondrial and microsomal fractions and has a Michaelis constant of 3.2 X 10(-6) M and 3.7 X 10(-6) M for 13-cis and all-trans-retinoic acid, respectively. The resultant product, 5,6-epoxyretinoic acid, has minimal activity in supporting growth of vitamin A-deficient rats, its activity estimated to be 0.5% that of retinoic acid. An investigation of the biliary excretion products of tritiated retinoic acid has revealed several unknown metabolites. A glucuronidase sensitive metabolite from these products has been isolated and identified as retinoyl-beta-glucuronide by ultraviolet absorption spectrometry and mass spectrometry. The retinoyl-beta-glucuronide originally discovered by Olson and collaborators accounts for only 12% of the total excreted biliary products of retinoic acid. At least four to six major unknown retinoic acid metabolites, in addition to retinoyl-beta-glucuronide, have been detected and will shortly be identified.

Animals↗
PubMed1981

Synthesis and biological activity of vitamin D3-sulfate.

Vitamin D3-3 beta-sulfate has been synthesized using pyridine sulfur trioxide as the sulfate donor. It has been shown to be pure by high performance liquid chromatography and spectral methods. Unlike previous reports, the product has been identified unambiguously as the 3 beta-sulfate ester of vitamin D3 by its ultraviolet, nuclear magnetic resonance, infrared, and mass spectra. The biological activity of vitamin D3-sulfate was then determined in vitamin D-deficient rats. Vitamin D3-sulfate has less than 5% of the activity of vitamin D3 to mobilize calcium from bone and approximately 1% of the ability of vitamin D3 to stimulate calcium transport, elevate serum phosphorus, or support bone calcification. These results disprove previous claims that vitamin D3-sulfate has potent biological activity, and they further do not support the contention that vitamin D-sulfate represents a potent water-soluble form of vitamin D in milk.

Animals↗
PubMed1981

Oxygen-dependent 1,25-dihydroxycholecalciferol-induced calcium ion transport in rat intestine.

O2-dependent CA2+ uptake by rat duodenal discs has been characterized and used in a revised assay for 1,25-dihydroxycholecalciferol-induced intestinal Ca2+ transport. Although both muscle and mucosal surfaces are exposed in this free-floating-disc assay, the Ca2+ influx across the muscle surface is small, not O2- or vitamin D-dependent, and can be subtracted out. Depriving the animals of food for 9-14 h before assay increases the O2-dependent uptake by about 75%. Half-saturation values for O2-dependent Ca2+ uptake as determined with this assay are: 0.8mM-Ca2+ (fed) and 0.5mM-Ca2+ (food-deprived) for vitamin D-deficient rats, and 0.9mM-Ca2+ (fed) and 1.5mM-Ca2+ (food-deprived) for rats dosed with 1,25-dihydroxycholecalciferol. The maximum velocity of uptake varies from 6.7nmol of Ca2+ per cm2/min (fed) to 7.0nmol of Ca2+ per cm2/min (food-deprived) for vitamin D-deficient rats and 16.7nmol of Ca2+ per cm2/min (fed) to 29 nmol of Ca2+ per cm2/min (food-deprived) for 1,25-dihydroxycholecalciferol-treated rats. By using a 5 min preincubation and 15 min incubation with 1.0mM-Ca2+, duodenal tissue taken from vitamin D-treated rats shows about a 3-fold increase in O2-dependent Ca2+ uptake when compared with tissue taken from vitamin D-deficient animals. The calcium ionophore A23187, depending on concentration, either has no significant effect on or inhibits the O2-dependent uptake, rather than increasing it. Actinomycin D, at a dose of 2 micrograms/g, inhibits the O2-dependent uptake in intestinal discs from both vitamin D-deficient and vitamin D-treated rats by 58 and 80% respectively, when administered in vivo 3 1/2 h before assay.

Animals↗
PubMed1981

Isolation and identification of 25-hydroxyvitamin D2 25-glucuronide: a biliary metabolite of vitamin D2 in the chick.

The biliary metabolites of vitamin D2 obtained from chickens dosed with 3H-labeled vitamin D2 were investigated. Most of the biliary radioactivity migrated as charged compounds on diethylaminoethyl-Sephadex chromatography, and the charged fraction could be resolved into several components by reversed-phase high pressure liquid chromatography. A major charged metabolite was further purified by reversed-phase high-pressure liquid chromatography. This compound was found to be beta-glucuronidase sensitive and to yield 25-hydroxyvitamin D2 upon mild acid hydrolysis. The metabolite was converted first to the methyl ester and then to silylated and acetylated derivatives, which were subjected to mass spectrometry. The structure of the original metabolite was established as 25-hydroxyvitamin D2 25-beta-D-glucuronic acid. This 25-hydroxyvitamin D2 25-beta-glucuronide is a major biliary metabolite of vitamin D2 in the chick and may play a role in the chick's discrimination against vitamin D2.

25-Hydroxyvitamin D 2↗
PubMed1981

Lactose facilitates the intestinal absorption of lead in weanling rats.

The milk sugar lactose is known to facilitate calcium absorption and has been shown to enhance the uptake of essential trace metals from the intestines as well. Its physiological role as the major carbohydrate source for suckling mammals is thus complemented by its ability to facilitate the absorption of necessary minerals. The studies reported here show that the intestinal absorption of lead and its uptake into blood, liver, kidney, and bone are also increased by lactose in young weanling rats. These data extend the known range of lactose facilitation of mineral absorption to a nonessential, toxic element, confirming the nonspecificity of its action on the gut. In addition, they suggest an explanation for some of the conflicting evidence regarding the prophylactic efficacy of milk in lead poisoning.

Age Factors↗
PubMed1981

Rickets of prematurity. Supranormal levels of serum 1,25-dihydroxyvitamin D.

Rickets, hypocalcemia, hypophosphatemia, and hyperparathyroidism were found in a low-birth-weight premature infant. The concentration of plasma calcitriol (1,25-dihydroxyvitamin D) was 145 pg/mL. With additional exogenous calcitriol (37.5 ng/kg/24 hr) given for eight weeks, the biochemical abnormalities were corrected and healing of rickets was evident. Three months later, while receiving only 400 IU of ergocalciferal daily, the patient had normal levels of serum calcium, phosphate, and alkaline phosphatase with a serum calcitriol concentration of 36 pg/mL. These observations suggest that rickets of prematurity may involve a malabsorption of calcium and phosphorus with an elevated calcitriol level needed to overcome this inadequate absorption. Additional doses of calcitriol may be of benefit in these infants, although it must be given carefully. Furthermore, the role of phosphate supplementation in these infants requires consideration.

Alkaline Phosphatase↗
PubMed1981

Vitamin D metabolite concentrations in vitamin D deficiency. Are calcitriol levels normal.

The levels of vitamin D metabolites were measured in three children with a decreased dietary intake of calcium and vitamin D and sun exposure. All three children had hypocalcemia, hypophosphatemia, and elevated alkaline phosphatase activities. Two children had rickets, aminoaciduria, and elevated immunoreactive parathyroid hormone (iPTH) concentrations. The concentrations of vitamins D2 and D3, 25-hydroxyvitamins D2 and D3 (25-OH-D2 and 25-OH-D3), and 24,25-dihydroxyvitamin D (24,25-[OH]2D) were reduced. Nonetheless, the levels of calcitriol (1,25-[OH]2D) were normal. The combination of hypocalcemia, hypophosphatemia, and increased iPTH concentrations should result in supranormal calcitriol concentrations. Moreover, the ratio of PTH to calcitriol is significantly higher than in normal subjects. Accordingly, in patients with vitamin D deficiency and "normal" calcitriol values, the synthesis of this compound may be reduced. The evaluation of vitamin D deficiency should include the measurement of all metabolites.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Subcellular mechanisms involving vitamin D.

During the past 15 years a vitamin D endocrine system has been demonstrated in which vitamin D produced normally in the skin is activated first by conversion in the liver and subsequently in the kidney to a hormonal form, 1,25-(OH)2D3. The production of the hormonal form of vitamin D3, is regulated, and much has been learned regarding the molecular mechanism of the hydroxylations of vitamin D and regarding the physiologic regulators of the 25-OH-D-1-hydroxylase. Much remains to be learned regarding the mechanism whereby the 1-hydroxylase is modulated. 1,25-(OH)2D3 appears to function in the target organs of bone, intestine, kidney, and elsewhere by a nucleus-mediated process. Receptors for 1,25-(OH)2D3 have been clearly demonstrated and characterized in crude form. How the receptor and ligand interact with the nucleus is not clear, nor are the gene products that result from this interaction known. One product, a calcium binding protein, is known but its role in calcium transport is in debate. Although much has been learned in the last decade and a half, much remains to be learned regarding the molecular mechanisms whereby vitamin D brings about its remarkable changes in mineral metabolism.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1981

Autoradiographic studies with 3H 1,25 (OH)2 vitamin D2 and 3H 25 (OH) vitamin D3 in rat parathyroid glands.

After injection of radiolabeled 1,35 (OH)s vitamin D3, nuclear concentration of radioactivity is observed in parenchymal cells o hte parathyroid gland in pregnant, adult male, and 10-day male neonatal rats. In competition studies with unlabeled 1,25 (OH)2 vitamin D3, but not with 25 (OH) vitamin D3, in contrast to 3H 1,25 (OH)2 vitamin D3, do not show nuclear concentration in cells of te parathyroid. The results of te autoradiographic studies suggest the presence of receptors for a direct effect of 1,35 (OH)2 vitamin D3 on the parathyroid gland for modulation of parathyroid hormone secretion.

Aging↗
PubMed1981

Role of the hypophysis in the regulation of vitamin D metabolism.

Hypophysectomy of animals given maintenance levels of vitamin D and adequate levels of dietary calcium and phosphorus brings about a marked reduction in plasma 1,25-dihydroxyvitamin D3 levels and a significant elevation in plasma 24,25-dihydroxyvitamin D3 levels. The hypophysectomy, as expected, results in reduced growth and lowered plasma levels of inorganic phosphorus. The injection of growth hormone markedly increases plasma levels of 1,25-dihydroxyvitamin D3 in hypophysectomized animals while bringing about a reduction in 24,25-dihydroxyvitamin D3 levels. These results support the idea that the hypophysis plays a role in the regulation of vitamin D metabolism and that growth hormone either directly or indirectly is one of the hypophyseal factors bringing about this regulation.

24,25-Dihydroxyvitamin D 3↗