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Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 487 records · Page 27Linked to original sources

25-hydroxycholecalciferol for prevention of "milk fever" in dairy cows.

Intramuscular injections of 4 or 8 mg 25-hydroxycholecalciferol (25-OH D3) in 5 ml corn oil given three days before the predicted calving date and repeated at weekly intervals until calving effectively reduced the incidence of parturient paresis. Drug efficacy was improved in cows receiving low to normal recommended levels of dietary phosphorus prepartum. With proper management techniques, 25-OH D3 could prevent parturient paresis in dairy cattle.

Animals↗

1 alpha-hydroxy-25-fluorovitamin D3: a potent analogue of 1 alpha,25-dihydroxyvitamin D3.

Chemically synthesized 1 alpha-hydroxy-25-fluorovitamin D3 was compared to 1,25-dihydroxyvitamin D3 for potency in the chick intestinal cytosol-binding protein assay, induction of intestinal calcium transport, mobilization of calcium from bone, and epiphyseal plate calcification in the rat. The 25-fluorinated analogue causes 50% displacement of 1,25-dihydroxy[23,24-3H]D3 at 1.8 X 10(-8) M in the competitive protein-binding assay, whereas only 5.6 X 10(-11) M of unlabeled 1,25-dihydroxyvitamin D3 is needed for equal competition. This 315-fold difference between and 1 alpha-hydroxy-25-fluorovitamin D3 indicates that the fluoro analogue is about equipotent with 1 alpha-hydroxyvitamin D3 in the protein-binding assay. However, 1 alpha-hydroxy-25-fluorovitamin D3 is 1/50 as active as 1,25-dihydroxyvitamin D3 in vivo in the stimulation of intestinal calcium transport and bone calcium mobilization in vitamin D deficient rats on a low-calcium diet. Likewise, 1 alpha-hydroxy-25-fluorovitamin D3 is about 40 times less active than 1,25-dihydroxyvitamin D3 in inducing endochondrial calcification in rachitic rats. No selective actions of 1alpha-hydroxy-25-fluorovitamin D3 were noted. Since the 25 position of the analogue is blocked by a fluorine atom, it appears that 25-hydroxylation of 1 alpha-hydroxylated vitamin D compounds in vivo is not an obligatory requirement for appreciable vitamin D activity.

Animals↗

Rat intestinal 25-hydroxyvitamin D3- and 1alpha,25-dihydroxyvitamin D3-24-hydroxylase.

The 24-hydroxylation of 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 occurs in vitro in rat intestinal homogenates. 1alpha,24,25-Trihydroxyvitamin D3 obtained by incubating 1alpha,25-dihydroxyvitamin D3 with rat intestinal homogenates was isolated and then identified by co-chromatography of the biologically generated material with synthetic 1alpha,24R,25-trihydroxyvitamin D3 on a high pressure liquid chromatography system and by ultraviolet spectroscopy, periodate cleavage, and mass spectroscopy. 24,25-Dihydroxyvitamin D3 obtained by incubating 25-hydroxyvitamin D3 with intestinal homogenates was identified by co-chromatography of the biologically generated material with authentic 24R,25-dihydroxyvitamin D3 on a high pressure liquid chromatography system and by periodate cleavage. Tissue distribution studies indicate that the process occurs in rat intestinal homogenates but not in rat muscle, liver, or fetal calvaria homogenates. Nephrectomy does not diminish the production of 1alpha,24,25-trihydroxyvitamin D3 in vivo while it reduces markedly, but does not eliminate, production of 24,25-dihydroxyvitamin D3.

Animals↗

The essentiality of vitamin D metabolites for embryonic chick development.

Laying hens maintained on 1,25-dihydroxyvitamin D3 as their sole source of vitamin D produce eggs which appear normal but which produce embryos having a defective upper mandible and which die at 18 to 19 days of embryonic life. Hens maintained on 25-hydroxyvitamin D3, on the other hand, produce normal embryos. Hens fed a vitamin D deficient diet produce eggs which develop the same embryonic defect. Injection of the affected eggs from the 1,25-dihydroxyvitamin D3 fed hens with vitamin D3, 25-hydroxyvitamin D3, or 1,25-dihydroxyvitamin D3 greatly increases the percentage of normal embryos. It therefore appears that 1,25-dihydroxyvitamin D3 is not transferred from hen to egg in sufficient amounts to support embryonic development and that vitamin D or its metabolites, or both, are necessary for normal chick embryo development.

Animals↗

Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D.

Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II.

Adult↗

Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy.

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.

Administration, Oral↗

The synthesis and activity in vitro of 25-masked 1alpha-hydroxylated vitamin D3 analogs.

1alphaHydroxylated-25-masked-vitamin D3 and analogs were synthesized as probes to help evaluate the role of 25-hydroxyl group in hormone-receptor interactions of 1alpha,25-dihydroxyvitamin D3 (13a). Synthetic work on model systems showed that the steroidal 25-hydroxyl group could be easily fluorinated in high yield with diethylaminosulfur trifluoride. Treatment of 25-fluoro compound with acetic acid resulted in both elimination and displacement of fluorine by acetate. The desired 1alpha-hydroxy-25-fluoro-vitamin D3 (14b) was obtained efficiently by fluorination and subsequent deacetylation of 1alpha,25-dihydroxyvitamin D3 1,3-diacetate (13b). Also obtained was a mixture of 1alpha-hydroxyvitamin D3-24- and 25-enes (15b). Both 14b and 15b were 300-400 times less active than 13a in the chick intestinal cytosol protein binding assay, making these analogs similar in potency to 1alpha-hydroxyvitamin D3 in vitro. The essentially equivalent activity of 14b and 15b with 1alpha-hydroxyvitamin D3 indicates that in the absence of a 25-hydroxyl group some alterations to the side chain carbons of 13a may be tolerated without further weakening analog-protein interactions. The fluoroanalog 14b was also about 250 times less potent than 13a in stimulating bone resorption in vitro. These compounds should prove to be valuable tools in aiding understanding of the salient structural features of the vitamin D3 metabolites.

Animals↗