Search PubMed⌕ Search

Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 343 records · Page 19Linked to original sources
PubMed1982

1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis.

We evaluated the effects of therapy with a small dose (0.5 microgram/day) of 1,25-dihydroxyvitamin D3 in 12 previously untreated patients with postmenopausal osteoporosis. Combined radiocalcium kinetic and balance studies showed that at base line, net calcium absorption (mean +/- SEM) was low (7 +/- 3%), calcium balance was negative (-59 +/- 22 mg/day), and bone resorption rate (297 +/- 40 mg/day) exceeded bone formation rate (239 +/- 36 mg/day). After short-term therapy (6-8 months), calcium absorption was normal (27 +/- 3%, P less than 0.001 for difference from base line), calcium balance had improved (+2 +/- 26 mg/day, P less than 0.05), and bone resorption rate (195 +/- 35 mg/day, P less than 0.01) had decreased more than bone formation rate (197 +/- 26 mg/day, NS). Compared with base-line values, after long-term therapy (2 years) the increased level of calcium absorption was maintained (27 +/- 3%, P less than 0.001), but calcium retention declined to a level intermediate (-27 +/- 24 mg/day, NS) between base-line and short-term treatment values, and both bone resorption rate (294 +/- 33 mg/day, NS) and bone formation rate (267 +/- 34 mg/day, NS) increased. Urinary hydroxyproline excretion was lower than before treatment (26.3 +/-2.0 mg/day) after both short-term (21.1 +/- 1.6 mg/day, P less than 0.001) and long-term (22.0 +/- 1.8 mg/day, P less than 0.01) treatments. Trabecular bone volume was 11.3 +/- 1.0% at base line and increased to 16.0 +/- 1.2% (P less than 0.01) after long-term treatment. By contrast, the eight patients studied before and after 6-8 months of placebo treatment had no significant change in any variable.

Bone and Bones↗
PubMed1982

Association between age, blood lead concentration, and serum 1,25-dihydroxycholecalciferol levels in children.

Serum levels of 1,25-dihydroxycholecalciferol (1,25-CC), the form of vitamin D active in stimulating intestinal absorption of calcium, phosphorus, and lead, were determined in 177 human subjects ages 1 to 16 yr. Significant negative association (r = -0.88) was observed between serum 1.25-CC levels and blood lead concentrations over the entire range of blood lead levels, 12 to 120 micrograms/dl. Adolescents ages 11 to 16 yr had serum 1,25-CC levels higher than those observed among children 10 yr old or younger. No effect of sex or season on serum 1,25-CC level was observed. When the 1,25-CC values for children with blood lead concentrations greater than 30 micrograms/dl were excluded from the analysis, no significant effect of geographic location on 1,25-CC levels was observed.

Adolescent↗
PubMed1982

Vitamin D of human milk: identification of biologically active forms.

Human milk has been found to contain 40 to 50 IU/l of vitamin D activity. This was determined by measuring stimulation of intestinal calcium transport in the rat, an assay not subject to the errors inherent in the rat line test or calcification assay. Five vitamin D metabolites were then isolated using a combination of conventional chromatography on Sephadex LH-20 and Lipidex 5000 followed by high-performance liquid chromatography. 24,25-Dihydroxyvitamin D and 1,25-dihydroxyvitamin D were measured using binding protein assays and were found to be present at very low levels. These dihydroxylated metabolites do not contribute significantly to the total vitamin D activity. Vitamins D2 and D3 were found to be present at concentrations of 338 and 41 ng/l, respectively. This is equivalent to 14 to 16 IU/l of vitamin D activity. Human milk contains 163 ng/l of 25-hydroxyvitamin D3, which gives about 33 IU/l of vitamin D activity. Thus 25-hydroxyvitamin D3 accounts for about 75% of the biological activity observed in the calcium transport assay. Vitamin D2, vitamin D3, and 25-hydroxyvitamin D3 are responsible for more than 90% of the total vitamin D activity present. This fails to support the idea that vitamin D-sulfate or any other unknown metabolites of vitamin D provide significant vitamin D activity in human milk.

Animals↗
PubMed1982

Vitamin D compounds in cows' milk.

The milk from cows fed normal levels of vitamin D has been found to contain approximately 40 IU per liter of vitamin D activity. A 14-fold increase in dietary vitamin D intake causes only a doubling of the amount of vitamin D in milk. This was determined by measuring stimulation of intestinal calcium transport in the vitamin D-deficient rat. Four vitamin D compounds were then isolated from cow's milk using a combination of conventional chromatography on Sephadex LH-20 and Lipidex 5000 followed by high-performance liquid chromatography. 24,25-Dihydroxycholecalciferol and 1,25-dihydroxycholecalciferol were measured using binding protein assays. One liter of milk contained 27 ng and 4.9 ng, respectively, of these two metabolites. Together these account for about 15% of the vitamin D activity. Cholecalciferol was found to be present at a concentration of 281 ng/liter or 11 IU/liter of biological activity. The milk contained 145 ng/liter 25-hydroxycholecalciferol or 29 IU/liter of activity. Therefore the known vitamin D compounds fully account for the biological activity observed in milk. It is therefore clear that no evidence could be found for the existence of a highly active water-soluble form of vitamin D in milk.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

A new vaginal smear assay for vitamin A in rats.

A method is described for measuring the relative activities of vitamin A active substances based on their direct effect on the cornified vaginal epithelium of vitamin A-deficient rats. The results obtained agree well with those found in the tracheal organ culture assay. The relative activities found for several test compounds were: all-trans-retinoyl-beta-glucuronide greater than all-trans-retinoic acid greater than all-trans retinol greater than all-trans-5,6-epoxyretinoic acid. The assay is simple and inexpensive to perform, and should find use in laboratories where the equipment and personnel required for the tracheal organ culture assay are not available.

Animals↗
PubMed1982

The biological activity of retinotaurine.

The ability of the biliary metabolite retinotaurine to reverse the cornification of vaginal epithelial cells induced by vitamin A deficiency was assessed using a vaginal smear assay. Retinotaurine activity was examined following the intravaginal administration of 10(-12) mol to 10(-8) mol of this compound per vagina. This metabolite exhibited no detectable activity at any dose tested. These results show that retinotaurine cannot be more than 1% as active as all-trans-retinoic acid since retinoic acid shows a response at concentrations of 10(-10) mol per vagina. The low biological activity of this recently identified biliary metabolite suggests that it represents an excretory form of retinoic acid.

Animals↗
PubMed1982

1,25-Dihydroxyvitamin C3-stimulated active uptake of phosphate by rat jejunum.

An assay system for measuring an active phosphate uptake in rat jejunal disks has been developed and used to study the rat's response to 1,25-dihydroxyvitamin D3. The active component of phosphate uptake is stimulated by added KCl, fructose, sodium, and CaCl2, but not MgCl2. Half-saturation values obtained with this assay are 0.08 mM (1,25-dihydroxyvitamin D3-treated) and 0.11 mM (D-deficient). The maximal velocities are 9.6 nmol . cm-2 . min-1 (D-deficient). Using a 5-min preincubation and a 15-min incubation, a dose-response curve for 1,25-dihydroxyvitamin D3 shows 6 pmol to be the lowest dose to give a significant response and 60 pmol to be the level at which the maximal response is reached. Measurement of phosphate uptake versus time after dosing with 1,25-dihydroxyvitamin D3 (300 pmol) revealed a biphasic response with peaks at 8 and 36 h and a trough at 20 h.

Animals↗
PubMed1982

1,25-dihydroxyvitamin D3-treated hypoparathyroidism: 35 patients years in 10 children.

Ten hormone-deficient hypoparathyroid children have been successfully treated with orally administered 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] within a dose range of 0.01--0.10 microgram/kg . day for a total of 35 patient yr. Resistance to 1,25-(OH)2D3 therapy was not observed. By monitoring the blood ionized calcium level (normal range, 4.05--5.14 mg/dl) at monthly intervals, 8 hypercalcemic and 10 hypocalcemic episodes were recognized during the entire treatment experience, though the patients were asymptomatic. In the former cases, cessation of treatment for 3 days resulted in normocalcemia; in the latter, half of the episodes were transient and related to intercurrent febrile illnesses. The remaining hypocalcemic occurrences responded to an increase in the dosage of 1,25-(OH)2D3. During 1,25-(OH)2D3 treatment, the mean ionized calcium level for individual patients ranged from 4.04--4.39 mg/dl. Urinary Ca excretion, expressed as a ratio of calcium to creatinine, ranged from 0.177--0.244. Twenty-four-hour mean levels of serum 1,25-(OH)2D did not correlate with the blood ionized calcium concentration in 4 patients who underwent sequential blood sampling every 1--2 h for a total of 59 time points (r = 0.05; P greater tha 0.10). To elucidate the temporal relationship between hormonal and mineral responses to exogenous PTH, we administered bovine PTH to four untreated hypoparathyroid children. Serum concentrations of PTH increased before the rise in ionized calcium, which in turn preceded the elevation in circulating 1,25-(OH)2D. This order was followed also in the fall in serum concentrations of these blood constituents to pre-PTH infusion values. These results indicate responsiveness of the l alpha-hydroxylase enzyme to exogenous PTH in hormone-deficient hypoparathyroid children.

Adolescent↗
PubMed1982

Molecular events involved in 1,25-dihydroxyvitamin D3 stimulation of intestinal calcium transport.

There is a biphasic response of intestinal calcium transport to 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). The first or rapid response is by existng mature villus cells, whereas the slow second response is by maturing crypt cells. For both responses, [3H]1,25-(OH)2-D3 localizes in the nucleus before initiating the transport events. This localization is brought about by a specific cytoplasmic receptor, which has a molecular weight of 67,000, is highly specific for 1,25-(OH)2-D3, and has a Kd of 5 X 10(-11) M. Its essentiality for intestinal calcium transport response to 1,25-(OH)2-D3 can be demonstrated in neonatal rat pups. In cultured chick intestinal duodena calcium transport begins to appear within 4 h after the addition of 1,25-(OH)2-D3. The response of this calcium transport system to 1,25-(OH)2-D3 is totally blocked by cycloheximide in a reversible manner. Similarly, it is blocked by actinomycin D in a partially reversible manner. These results make it obvious that the rapid calcium transport response to 1,25-(OH)2-D3 involves nuclear activity and transcription of DNA into functional proteins. The exact nature of the transport proteins remains largely unknown except for the calcium-binding protein originally discovered by Wasserman and colleagues. The transport proteins are believed to operate at the brush border membrane surface to facilitate the transfer of calcium and phosphorus into the absorption cells.

Animals↗
PubMed1982

New developments in the vitamin D endocrine system.

Vitamin D must be altered first by 25-hydroxylation in the liver and subsequently by 1-hydroxylation in the kidney in order to stimulate intestinal calcium transport, bone calcium mobilization, intestinal phosphate transport, and renal tubular reabsorption of calcium. Other pathways of vitamin D metabolism are described, and evidence is presented which indicates that only 25- and 1-hydroxylation pathways are activation mechanisms. The 1 alpha-hydroxylation step is regulated by the need for calcium and the need for phosphorus. The vitamin D hormone, 1,25-dihydroxyvitamin D3, appears to act in target tissues by virtue of interacting with a receptor appearing in the nucleus and eliciting transcription of specific genetic information that codes for calcium and phosphorus transport proteins. Diseases of calcium and phosphorus metabolism in which there is a disturbance of the vitamin D endocrine system and the use of the vitamin D metabolites are discussed.

Bone Diseases, Metabolic↗
PubMed1981

23,24,25-Trihydroxyvitamin D3, 24,25,26-trihydroxyvitamin D3, 24-keto-25-hydroxyvitamin D3, and 23-dehydro-25-hydroxyvitamin D3: new in vivo metabolites of vitamin D3.

Four new in vivo metabolites of vitamin D3 were isolated from the blood plasma of chicks given large doses of vitamin D3. The metabolites were isolated by methanol-chloroform extraction and a series of chromatographic procedures. By use of mass spectrometry, ultraviolet absorption spectrophotometry, and specific chemical reactions, the metabolites were identified as 23,24,25-trihydroxyvitamin D3, 24,25,26-trihydroxyvitamin D3, 24-keto-25-hydroxyvitamin D3 and 23-dehydro-25-hydroxyvitamin D3.

Animals↗
PubMed1981

Stimulation of intestinal calcium transport and bone calcium mobilization by prolactin in vitamin D-deficient rats.

In vitamin D-deficient rats intestinal calcium transport increased significantly 4 hours after an injection of prolactin, reached a maximum after 8 hours, and declined to preinjection levels after 24 hours. Similarly, in vitamin D-deficient rats fed a diet low in calcium or phosphorus prolactin stimulated an increase in serum calcium in both groups and an increase in serum phosphorus in the rats fed the diet low in phosphorus. Thus it appears that prolactin affects organs involved in calcium regulation in a manner that is independent of the vitamin D endocrine system.

Animals↗
PubMed1981

Appearance of the intestinal cytosolic receptor for 1,25-dihydroxyvitamin D3 during neonatal development in the rat.

During the early suckling period in the rat, active calcium uptake by the intestine is refractory to stimulation by 1,25-dihydroxyvitamin D3. To determine the role that the specific cytosolic receptor for 1,25-dihydroxyvitamin D3 plays in this refractory state, the concentration of the receptor and its binding characteristics were measured during the neonatal period. From Scatchard analysis, the concentration of receptor in the adult intestine was 563 +/- 64 fmol/mg of protein. At 28 and 21 days postpartum, receptor concentrations were 711 +/- 129 and 251 +/- 36 fmol/mg of protein, respectively. Estimates from sucrose density gradient profiles and Scatchard analyses indicated that, at 14 and 7 days postpartum, receptor concentrations were less than 50 fmol/mg of protein. Equilibrium dissociation constants were similar at all times measured and ranged from 0.38 to 0.52 nM. These results suggest that the lack of response observed in the early neonatal intestine to 1,25-dihydroxyvitamin D3 may stem, at least in part, from the relative absence of receptors for 1,25-dihydroxyvitamin D3. Furthermore, the appearance of the receptor may be the determining factor in the initiation of active calcium absorption in the intestine and its regulation.

Aging↗
PubMed1981

Isolation and identification of 23,25-dihydroxyvitamin D3, an in vivo metabolite of vitamin D3.

Vitamin D supplemented rats produce a metabolite of 25-hydroxy[3 alpha-3H]vitamin D3 that is easily separated from known metabolites by using high-performance liquid chromatography. The production of this metabolite in vivo as well as 1,25-dihydroxyvitamin D3, 24(R),25-dihydroxyvitamin D3, and 25-hydroxyvitamin D3 26,23-lactone is largely if not totally eliminated by nephrectomy. Kidney homogenates from vitamin D supplemented chickens incubated with 25-hydroxyvitamin D3 produce significant quantities of the new, unknown metabolite. This metabolite was isolated in pure form from such incubation mixtures by using both straight-phase and reversed-phase high-performance liquid chromatography. This metabolite has been positively identified as 23,25-dihydroxyvitamin D3 by ultraviolet absorption spectrophotometry, mass spectrometry, and derivatization. This structure was confirmed by chemical synthesis of both C-23 stereoisomers. Although the natural product exactly comigrates with one of the synthetic isomers, the exact stereochemistry of the natural product remains unknown. It is possible that this new metabolite is an intermediate in the biosynthesis of 25-hydroxyvitamin D3 26,23-lactone.

Animals↗