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Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 271 records · Page 15Linked to original sources
PubMed1984

Effects of 1,25(OH)2D3 on bone tissue in the rabbit: studies on fracture healing, disuse osteoporosis, and prednisone osteoporosis.

A closed tibial fracture, which was controlled by an intramedullary stainless steel pin, was created in 16 rabbits. Eight rabbits were treated with 75 ng of 1,25(OH)2D3 daily as subcutaneous (s.c.) injections. After three weeks, the fractured tibia resisted a force of 101.7 +/- 21.0 Newtons in the control group and 57.3 +/- 8.0 Newtons in animals given 1,25(OH)2D3 (m +/- SE, P less than 0.05). In another group of eight rabbits, the left hindleg was immobilized in a plastic splint. Four rabbits were given 75 ng of 1,25(OH)2D3/day s.c. and the effect of immobilization was studied on the calcaneus. Bone ash/cm3 of the calcaneus on the immobilized side was decreased by 11 +/- 2% in control rabbits and by 20 +/- 2% in the group treated with 1,25(OH)2D3 indicating a more advanced immobilization osteoporosis (m +/- SE, P less than 0.05), which was also demonstrated by studies of bone density. Eighteen rabbits were used in a study of the effects of 1,25(OH)2D3 on the development of prednisolone osteoporosis. The dose of prednisolone was 2.5 mg per day, given by the oral route. After four months, the density of the femur was 1.53 +/- 0.02 g/cm2 in control rabbits and 1.42 +/- 0.01 in prednisolone-treated animals (P less than 0.01). In rabbits additionally given 1,25(OH)2D3, the mean value for bone density was further lowered (n.s.). It appears that 1,25(OH)2D3 exaggerates disuse osteoporosis and prednisolone osteoporosis and impairs fracture healing in rabbits. These results differ from what has been shown earlier with 1,25(OH)2D3 treatment in the rat.

Animals↗
PubMed1984

Metabolism of 25-hydroxyvitamin D3 by rat kidney cells in culture: isolation and identification of cis- and trans-19-nor-10-oxo-25-hydroxyvitamin D3.

A primary confluent culture of epithelial cells from rat kidney has been developed. These cells possess a 3.2-3.4 S high-affinity, low-capacity binding protein for 1,25-dihydroxyvitamin D3. They metabolize 25-hydroxyvitamin D3 to at least five metabolites. Two have been identified as 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. Two others have been identified by means of physical data and cochromatography as trans 19-nor-10-oxo-25-hydroxyvitamin D3 and the other as its cis isomer. These two "metabolites" have not been observed in vivo, but one of them (cis) comigrates with 1,25-dihydroxyvitamin D3 on straight-phase high-performance liquid chromatography. Thus, mere cochromatography on high-performance liquid chromatography is not sufficient to identify critical vitamin D metabolites.

Animals↗
PubMed1984

Renal tubular acidosis does not alter circulating values of calcitriol.

In 10 patients with renal tubular acidosis, seven with type I and three with Fanconi syndrome, simultaneous measurements of vitamin D metabolites and electrolytes were made. No marked abnormalities of calcidiol2, calcidiol3, 24,25(OH)2D, or calcitriol were found in these patients, whose mean serum HCO3 was 18 +/- 3 mM/L (SD). Further, no relationship between serum HCO3 and calcitriol could be found. These results suggest that either vitamin D deficiency may be required before any alterations in the production of calcitriol are seen, or that the effects of acidosis in animals may not be reflected in humans. Further, it appears less likely that the bone disease found in renal tubular acidosis is related to abnormalities in vitamin D metabolism resulting from systemic acidosis, but that bone disease is more likely related to the acidosis and hypercalcuria prevalent in this disorder.

Acidosis, Renal Tubular↗
PubMed1984

Subcellular distribution of DNA-binding and non-DNA-binding 1,25-dihydroxyvitamin D receptors in chicken intestine.

A comparison of 1,25-dihydroxyvitamin D3 receptor concentration and equilibrium dissociation constants of whole tissue, nuclear, and cytosol extracts of vitamin D-deficient chicken intestine has been carried out. The extracts had the following order of receptor concentration: nuclei greater than whole tissue greater than cytosol. The receptors in each preparation had identical equilibrium dissociation constants (Kd) for 1,25-dihydroxyvitamin D3. However, the receptor in the cytosol fraction did not bind to DNA-cellulose, while a large fraction of the receptor population in crude nuclear extract and whole tissue extract bound to DNA-cellulose and could be eluted with 0.22 M KCl, suggesting that the cytosolic form of the receptor does not possess a DNA binding site.

Animals↗
PubMed1984

Activation and fusion induced by 1 alpha,25-dihydroxyvitamin D3 and their relation in alveolar macrophages.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] induces fusion of murine alveolar macrophages. This effect was observed in growth medium containing 5% human serum but not in the medium with 5% fetal bovine serum. Unlike 1 alpha,25-(OH)2D3, bacterial lipopolysaccharides (LPS) did not induce fusion of alveolar macrophages. However, both 1 alpha,25-(OH)2D3 and LPS activated alveolar macrophages, as measured by glucose consumption, increase in Fc receptors, and induction of cytotoxicity. The number of Fc receptors on the surface of multinucleated giant cells induced by 1 alpha,25-(OH)2D3 was much smaller than that on the surface of mononuclear macrophages treated with the hormone. These results indicate that 1 alpha,25-(OH)2D3 induces both fusion and activation of alveolar macrophages, whereas LPS elicits activation only.

Animals↗
PubMed1984

Complex carbohydrate diets are not capable of maintaining normal plasma calcium and phosphorus levels in vitamin D-deficient rats.

Substitution of Cerelose (glucose monohydrate) for complex carbohydrate (whole wheat flour) does not alter plasma calcium levels in vitamin D-deficient rats, contrary to a previous report. It is suspected that whole wheat flour may contain traces of vitamin D that result in a slower rate of depletion than found with Cerelose diets. Vitamin D-deficient rats showing low plasma 1,25-dihydroxyvitamin D3 levels and no detectable 25-hydroxyvitamin D3 levels in their blood show a hypocalcemia (5.6 mg/dl) and normal phosphatemia whether fed whole wheat or Cerelose diets.

Animals↗
PubMed1984

Antirachitic activity of 1 alpha-hydroxyergocalciferol and 1 alpha-hydroxycholecalciferol in rats.

Weanling vitamin D-deficient rats fed a high calcium, low phosphate diet were injected daily with 1 alpha-hydroxyergocalciferol or 1 alpha-hydroxycholecalciferol at doses of 2.5, 25 or 250 ng. Intestinal calcium and phosphate transport, serum phosphorus level, epiphyseal plate calcification, and percent femur ash increased as a function of the dose. Both compounds were equally effective in eliciting these responses demonstrating their equivalency as antirachitic compounds.

Animals↗
PubMed1984

Hydroxylation of carbon-24 of 25-hydroxycholecalciferol is not necessary for normal embryonic development in chickens.

Laying hens fed 25-hydroxycholecalciferol, 24,24-difluoro-25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol or 24,25-dihydroxycholecalciferol were used to investigate whether hydroxylation of C-24 of cholecalciferol is necessary for normal embryonic development in chickens. Laying hens were fed a rachitogenic diet and 25-hydroxycholecalciferol from hatching until normal egg production, fertility and hatchability were achieved. When the hens were 40 weeks old, 25-hydroxycholecalciferol was withdrawn and egg production ceased in 4 weeks. The hens were divided into 6 groups of 5 and dosed daily for 19 weeks with either 2.0 micrograms of 25-hydroxycholecalciferol, 2.0 micrograms of 24,24-difluoro-25-hydroxycholecalciferol, 0.4 microgram of 1,25-dihydroxycholecalciferol, 2.0 micrograms of 24,25-dihydroxycholecalciferol, both 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol or vehicle only. Egg production during this period was high for all hens fed the cholecalciferol compounds. Egg production of 3% occurred in hens given vehicle only. Fertility was over 90% for all groups of cholecalciferol compound-fed hens. Hatchability of over 90% was achieved with the eggs from hens given 25-hydroxycholecalciferol or 24,24-difluoro-25-hydroxycholecalciferol and 6% with eggs from hens fed both 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol. No eggs from hens fed 1,25-dihydroxycholecalciferol or 24,25-dihydroxycholecalciferol alone hatched (over 140 eggs in each group.

24,25-Dihydroxyvitamin D 3↗
PubMed1984

Self-selection of a high calcium diet by vitamin D-deficient lactating rats increases food consumption and milk production.

Lactating and nonlactating rats, both deficient and replete in cholecalciferol, were allowed a free selection among three diets containing 0.47% Ca, 0.3% P (normal Ca, normal P diet); 2.0% Ca, 0.3% P (high Ca diet); and 0.47% Ca, 1.0% P (high P diet). An additional group of vitamin D-deficient lactating rats was fed only the normal Ca, normal P diet. Vitamin D-deficient rats showed a strong selection preference for the high Ca diet but avoided the high P diet, whereas cholecalciferol-replete rats consumed the normal Ca, normal P diet predominantly. Compared to the nonselecting rats, the selection of the high Ca diet by the lactating rats deficient in vitamin D resulted in an increase in plasma calcium levels, hypophosphatemia, a doubling of food consumption, a reduction in maternal body weight loss and a stimulation of milk production as indicated by pup growth. These results demonstrate that vitamin D-deficient rats select a high Ca diet and that the decrease in milk production found in vitamin D deficiency results from a decrease in food consumption and that this anorexia is at least partially dependent on the hypocalcemia normally occurring in vitamin D deficiency.

Animals↗
PubMed1984

Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation.

The effects of thyroparathyroidectomy, parathyroid hormone, 1,25-dihydroxyvitamin D3, dietary calcium, dietary phosphorus, age, and sex on the renal 25-hydroxyvitamin D3 1- and 24-hydroxylases measured in vitro in rats have been studied. Thyroparathyroidectomy of vitamin D-deficient rats abolishes 25-hydroxyvitamin D3 1-hydroxylase activity, and administration of bovine parathyroid extract to the thyroparathyroidectomized rat restores diminished 1-hydroxylase activity. Both suppression and restoration of the enzyme activities require many hours (18-24 h) independent of rapid changes in serum calcium and inorganic phosphorus levels in response to these manipulations. Administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats suppresses 25-hydroxyvitamin D3 1-hydroxylase activity and stimulates 25-hydroxyvitamin D3 24-hydroxylase activity within 48 h. Rats maintained on a low-calcium or a low-phosphorus diet with a daily supplement of 20 IU vitamin D3 show high 25-hydroxyvitamin D3 1-hydroxylase activity and low 24-hydroxylase activity as compared with rats similarly treated but fed a diet containing adequate calcium or adequate phosphorus. When vitamin D-sufficient rats having suppressed renal 25-hydroxyvitamin D3 1-hydroxylase activity are placed on a low-calcium vitamin D-deficient diet for 7 days, the 1-hydroxylase activity is greatly stimulated in 6-wk-old rats but much less so in rats with advancing age.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1984

A maternal defect is responsible for growth failure in vitamin D-deficient rat pups.

Vitamin D deficiency was induced in lactating rats and their pups by placing female rats on a vitamin D-deficient diet immediately after mating. Evidence of vitamin D deficiency included undetectable plasma levels of 25-hydroxyvitamin D3 in the dams, maternal hypocalcemia, the lack of pup growth, and pup hypocalcemia following starvation. This method of producing vitamin D-deficient pups was then used to determine whether the failure of vitamin D-deficient pups to grow properly results from a maternal or neonatal defect. Vitamin D-deficient dams and pups were injected with either vitamin D3 or the ethanol vehicle, and pup growth was monitored over the subsequent 6 days. Providing vitamin D3 to the pups directly had no effect on their growth, but administering vitamin D3 to the dams resulted in a tripling of the pup growth rate. The failure of vitamin D3 to promote pup growth when given directly to the pups was not the result of their inability to metabolize the vitamin because these pups converted [3H]-vitamin D3 to 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 as determined by comigration with standards on both straight and reverse phase high-performance liquid chromatography systems. These results demonstrate that a maternal defect is responsible for the growth failure observed in vitamin D-deficient rat pups.

Animals↗
PubMed1984

Vitamin D-deficient rats produce reduced quantities of a nutritionally adequate milk.

Pups raised by lactating rats deficient in vitamin D do not grow normally, and we have shown previously that this growth failure results from a maternal rather than a neonatal defect. This result indicates that vitamin D-deficient rats produce reduced amounts of milk and/or the milk they do produce is nutritionally incomplete. To examine the first of these possibilities, 3H2O and 42K in separate experiments were given to lactating rats at 13 days postpartum, and the amount of isotope transferred to their pups during the next 24 h was determined. The amount of milk produced during this period was calculated from the measured concentrations of 3H2O and 42K in milk. The specific activity of 3H2O in maternal plasma was kept constant by providing 3H2O in the drinking water of the dams. Vitamin D-deficient rats were found to produce only 19.5 +/- 1.8% determined by the 3H2O method and 23.2 +/- 1.1% by the 42K method (means +/- SD) of the amount of milk produced by vitamin D-replete rats. The composition of milk from vitamin D-deficient rats was examined to determine its nutritional value. Vitamin D-deficient milk contains elevated levels of fat, and the skim fraction contains more protein, potassium, calcium, and inorganic phosphorus but less carbohydrate than normal milk. When vitamin D-deficient dams were given two pups to nurse rather than the eight usually provided, pup growth was equivalent to that of vitamin D-replete pups. Furthermore, femur dry weights and degree of mineralization were similar in vitamin D-deficient and -replete pups of equivalent body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1984

1,25-Dihydroxyvitamin D3 normalizes maternal food consumption and pup growth in rats.

Maternal food consumption, maternal body weight loss, and pup growth were studied in the following six groups of rats: vitamin D-deficient, vitamin D3-replete, vitamin D3-replete but pair-fed with the vitamin D-deficient rats and rats given either 50, 150, or 450 pmol/day of 1,25-dihydroxyvitamin D3 as their sole source of vitamin D by continuous infusion from an Alzet osmotic minipump. As expected, vitamin D-deficient rats were hypocalcemic and lost body weight, and their pups stopped growing at 1 wk of age. Food consumption by the vitamin D-deficient rats was one-third that of the vitamin D3-replete rats. Although normalization of plasma calcium levels was not perfect, 1,25-dihydroxyvitamin D3 treatment led to normal maternal food consumption, prevented maternal body weight loss, and promoted normal pup growth. Pups from the vitamin D3-replete rats pair-fed with the vitamin D-deficient rats did not grow properly and their dams lost body weight. These data indicate that 1,25-dihydroxyvitamin D3 is fully capable of replacing vitamin D3 in promoting maternal food consumption in lactating rats and that maintaining adequate food consumption is a major factor in the stimulatory effect of vitamin D3 on pup growth and hence milk production. The anorexia and reduced milk production of vitamin D-deficient lactating rats did not result from changes in plasma glucose or triglyceride levels.

Animals↗
PubMed1984

Vitamin D is not directly necessary for bone growth and mineralization.

To determine whether vitamin D has a direct action on bone growth and mineralization, severely vitamin D-deficient rats were infused continuously for 10 days with calcium and phosphorus solutions intrajugularly to maintain plasma calcium and phosphorus levels equal to those in rats on the same diet given vitamin D. Rats from the same litters identically treated were given 75 IU of vitamin D3 every 3 days and infused with saline for the 10-day period for comparison. Infusion of calcium and phosphorus to the vitamin D-deficient rats induces bone growth and mineralization equal to that of the rats given vitamin D as revealed by femur length, femur weight, total femur ash, percent femur ash, and epiphyseal plate width. The mineral deposited had a calcium-to-phosphorus ratio of 1.6 identical to the mineral deposited in the rats given vitamin D and unlike controls maintained in the vitamin D-deficient state without infusions. The vitamin D-deficient rats infused with calcium and phosphorus had greater amounts of mineral and matrix in their femurs than did those treated with vitamin D. This result demonstrates that some form of vitamin D does have a direct effect on bone. The most likely possibility is that bone resorption in relation to modeling or calcium mobilization for calcium homeostasis or both are compromised in extreme vitamin D deficiency. The above results strongly support the concept that vitamin D is not necessary for and does not stimulate directly bone growth and mineralization. Vitamin D therefore supports bone growth and mineralization indirectly by elevating plasma calcium and phosphorus levels.

Animals↗
PubMed1984

Bone histomorphometry in vitamin D-deficient rats infused with calcium and phosphorus.

Defective mineralization of bone and cartilage is the classical histological finding in vitamin D deficiency. Whether this represents a direct effect on mineral deposition or is a consequence of the decreased calcium and phosphorus levels that result from impaired intestinal absorption is not clear. A method has been developed in which vitamin D-deficient rats have plasma calcium and phosphorus levels maintained in the normal range by continuous infusion. Histomorphometric analysis of undecalcified tibiae from these animals was compared with that of rats given vitamin D. Epiphyseal growth plate thickness, trabecular osteoid volume, and mean osteoid seam width were not increased. Moreover, the administration of two time-spaced courses of tetracycline revealed that the mineralization rate and the time interval between apposition and subsequent mineralization of osteoid (mineralization lag time) were identical to those in rats treated with vitamin D. Trabecular bone volume was increased (osteosclerosis) in the vitamin D-deficient rats. In vitamin D-deficient controls without infusions, the osteosclerosis was mostly osteoid, whereas the excess bone was well mineralized in the vitamin D-deficient rats infused with calcium and phosphorus. Osteosclerosis in vitamin D-deficient animals may result from both decreased bone resorption and increased osteoid apposition. This study provides firm evidence that vitamin D is not essential for mineralization in young growing rats. Decreased availability of calcium and phosphorus thus may be the sole basis of the mineralization defect seen in vitamin D deficiency.

Animals↗
PubMed1984

Placental transport of calcium and phosphorus is not regulated by vitamin D.

The role of 1,25-dihydroxyvitamin D3 in regulating the maternal-to-fetal transfer of calcium and phosphorus across the placenta was examined by measuring maternal and fetal plasma levels of these elements in vitamin D-replete and -deficient rats. Pregnant rats in their 20th day of gestation and their fetuses were studied. Two diets with different calcium and phosphorus contents were used to produce either hypocalcemia or hypophosphatemia in the vitamin D-deficient rats. Calcium and phosphorus levels in fetal plasma were always higher than maternal values, and in vitamin D deficiency a twofold gradient of calcium and a fivefold gradient of phosphorus concentrations across the placenta were observed. Since protein levels in fetal plasma were approximately fivefold lower than maternal values, protein binding does not account for the higher fetal than maternal concentrations of plasma calcium. These results, together with previous data showing normal calcium content of vitamin D-deficient fetuses, indicate that 1,25-dihydroxyvitamin D3 and other vitamin D3 metabolites are not involved in the active transport of calcium and phosphorus across the placenta in the rat.

Animals↗
PubMed1984

Calcitriol but no other metabolite of vitamin D is essential for normal bone growth and development in the rat.

To determine the relative importance of different metabolites of vitamin D in bone growth and development, weanling male rat pups suckled by vitamin D-deficient mothers were given either calcitriol (1,25-dihydroxycholecalciferol) by continuous subcutaneous infusion, oral calcidiol (25-hydroxycholecalciferol), or oral 24,24-difluoro-25-hydroxycholecalciferol, a synthetic compound that can undergo 1-hydroxylation but not 24-hydroxylation, as their sole source of vitamin D for 40 d. Pups raised in the same manner, but given no vitamin D, served as controls. The three metabolites compared were given in doses that restored normal plasma calcium levels and normal increments in body weight. After in vivo double tetracycline labeling, bone histomorphometry by standard methods was performed on one femur and one tail vertebra. There were no significant differences between the three metabolite-treated groups in length, periosteal or endosteal diameter, cortical cross-sectional area, cortical porosity, osteoid thickness and volume, appositional rate and bone formation rate in the femur, or in qualitative and quantitative indices of endochondral ossification in the tail vertebra. All three groups differed markedly from the untreated controls with respect to all measurements. Collectively, the data indicate that neither calcidiol nor any 24-hydroxylated metabolite of calcidiol is needed in the rat (other than as a precursor) for longitudinal or transverse bone growth, for normal endochondral ossification, or for normal periosteal and endosteal formation, mineralization, and resorption of bone. Calcitriol was fully active with respect to each of the indices listed when given in a manner resembling its continuous endogenous production by the kidney, suggesting that previous reports of incomplete skeletal response to calcitriol result from its rapid clearance and infrequent oral administration. We demonstrated that calcitriol is the only metabolite that is both necessary and sufficient for normal bone growth and development in the rat, but our data do not indicate the extent to which its beneficial skeletal effects were mediated by direct action on bone, either of calcitriol itself or of some metabolite thereof, or by restoration of normal plasma levels of calcium and phosphate.

Animals↗