Dihydrotachysterol: a calcium active steroid not dependent upon kidney metabolism.
(17/33)
The activity of dihydrotachysterol and cholecalciferol was determined in nephrectomized or sham-operated vitamin D-depleted rats using in vitro transport of calcium and phosphate by everted intestinal preparations as the index of physiologic response. The activity of dihydrotachysterol was not reduced by absence of the kidneys whereas that of cholecalciferol was markedly inhibited so that at least a 10-fold greater dose of the latter was necessary to produce an equivalent effect in the nephrectomized rat as in the control. Dihydrotachysterol is therefore equipotent with cholecalciferol in the anephric rat although much less active in the intact animal. (+info)
Vitamin D: concerning the relationship between molecular topology and biological function.
(18/33)
Structure-function relationships for vitamin D, its metabolites, and analogs are discussed with particular emphasis on the A-ring conformation. It is emphasized that the A-ring of these seco-steroids consists of a pair of rapidly equilibrating chair conformers. As a consequence, different chair conformations produce different orientations of substituent groups in the A-ring. It is proposed that the 1alpha-hydroxyl of 1alpha,25-dihydroxyvitamin D(3) or its geometric equivalent in analogs must occupy the equatorial, as opposed to the axial, orientation for optimization of biological activity. This proposal is discussed in relation to existing published data on structure-function relationships and the steroid hormone model of action for the biologically active form of vitamin D. This three-dimensional topological model suggests the synthesis of other vitamin D analogs. (+info)
Metabolism of dihydrotachysterol and 5,6-trans-cholecalciferol in the chick and the rat.
(19/33)
Dihydrotachysterol and 5,6-trans-cholecalciferol are biologically active analogues of cholecalciferol (vitamin D) with a similarity in steric structure to 1,25-dihydroxycholecalciferol, the active form of the vitamin. The question arises as to the nature of the active form of these analogues. High specific radioactivity (14)C- and (3)H-labelled forms of dihydrotachysterol and 5,6-trans-cholecalciferol and its 25-hydroxy derivative were synthesized and their metabolism was studied in chicks and rats. All these steroids were very rapidly metabolized compared with cholecalciferol; 20% of the dihydrotachysterol dose was excreted in bile in the first 24h, about 50% as a carboxylic acid derivative. Although polar metabolites were detected in tissues, no 1-hydroxy form was observed. Larger proportions of the parent steroid and its 25-hydroxy metabolite were detected in tissues compared with cholecalciferol, but no single metabolite was detected at the intracellular site of action of cholecalciferol. It is suggested that analogues of cholecalciferol will be biologically active if they possess a hydroxyl group in the same steric position as that at C-1 of cholecalciferol, with the greatest activity shown by those that also have a C-25 hydroxyl group. The implication of these findings for the chemical features necessary for binding to receptor proteins are briefly discussed. (+info)
Bone disease in hemodialysis patients with particular reference to the effect of fluoride.
(20/33)
Forty-one patients on our chronic hemodialysis program were assessed for the degree of progression of bone disease over an average period of 46 months. Seven patients were using a fluoridated dialysate. Four of these seven patients developed a marked increase in osteoid as judged by bone biopsy, while in the nonfluoridated group the amount of osteoid remained within normal limits.In the absence of fluoride, although osteitis fibrosa occurred, it was reversible in 10 out of 12 cases by dihydrotachysterol treatment, and overall there was no evidence of progression of bone disease at the end of the study period. (+info)
Calcium metabolism in bone disease: effects of treatment with microcrystalline calcium hydroxyapatite compound and dihydrotachysterol.
(21/33)
Microcrystalline calcium hydroxyapatite compound (MCHC) was given orally together with small doses of dihydrotachysterol (DHT) to a number of patients with osteogenesis imperfecta (OI). Serial calcium and phosphate balances in three patients representing wide variations in severity of OI are presented over periods from eight months to two years. The combination of MCHC and DHT resulted in an immediate positive calcium balance which was maintained throughout the period of assessment in 2 cases. However, no radiological improvement could be demonstrated. Substituting calcium gluconate for MCHC resulted in a reduction of positive balance. No adverse effects were noted. The reasons why MCHC with DHT should result in increased calcium retention are discussed. This combination of MCHC and DHT could be of benefit in many common situations of bone demineralization, such as osteoporosis. (+info)
Effect of oral administration of calcium carbonate, aluminum hydroxide gel and dihydrotachysterol on renal acidosis.
(22/33)
The effects of oral administration of calcium carbonate, aluminum hydroxide gel, dihydrotachysterol (DHT) and sodium bicarbonate on metabolic acidosis and plasma calcium and phosphate were studied in 7 patients with chronic renal failure. Single administration of calcium carbonate alleviated the acidosis and increased the urinary bicarbonate excretion. These effects were potentiated when aluminum hydroxide gel was administered in combination with calcium carbonate. The plasma calcium was increased by this combination therapy. The effects of these two agents on acidosis and plasma calcium were further enhanced by the additional administration of DHT. Urinary bicarbonate excretion was less during the treatment with aluminum hydroxide gel and calcium carbonate than with aluminum hydroxide gel and sodium bicarbonate, when the excretions were compared at the similar concentrations of plasma bicarbonate. Aluminum hydroxide gel and DHT are likely to enhance the effect of calcium carbonate, which works as an alkalinizing salt on acidosis, probably through increasing calcium absorption in the intestine. And the three agents suppress the leak of bicarbonate into the urine contributing to the improvement of acidosis. (+info)
Hypercalcaemia due to dihydrotachysterol treatment in patients with hypothyroidism after thyroidectomy.
(23/33)
Hypercalcaemia is a recognised complication of hypothyroidism. We describe three patients who developed hypercalcaemia after thyroidectomy when thyroid supplements were discontinued. They were treated with thyroxine, dihydrotachysterol, and calcium after operation, and in all three cases serum calcium concentrations remained constant during combined treatment. Thyroxine treatment was discontinued several weeks before a radioiodine scan was performed; dihydrotachysterol and calcium were continued throughout. Serum calcium concentrations rose to hypercalcaemic levels in all cases. Elimination of dihydrotachysterol from plasma may be delayed in hypothyroidism, resulting in hypervitaminosis D. It is advisable to reduce the dose of dihydrotachysterol and to check serum calcium concentrations regularly in patients whose thyroid treatment is interrupted. (+info)
Rate of reversal of hypercalcaemia and hypercalciuria induced by vitamin D and its 1alpha-hydroxylated derivatives.
(24/33)
The rate of reversal of hypercalcaemia or hypercalciuria induced by calciferol, dihydrotachysterol, 1-alpha-hydroxycholecalciferol (1-alpha-OHD3), or 1-alpha, 25-dihydroxycholecalciferol (1-alpha, 25-(OH)2D3) was measured in three normal subjects, two patients with osteoporosis, and 14 patients with disorders resistant to vitamin D. The half time for reversal after stopping 1-alpha, 25 (OH)2D3 was less than that after stopping 1-alpha-OHD3, calciferol, or dihydrotachysterol. The differences observed were independent of the dose given or length of treatment. When 1-alpha-OHD3 or 1-alpha-25-(OH)2D3 was stopped patients with vitamin D resistant states (hypoparathyroidism, renal tubular hypophosphataemia, or chronic renal failure) showed less rapid reversal of hypercalcaemia and hypercalciuria than did normal subjects. These studies show one potential advantage of 1-alpha-25-(OH)2D3 over vitamin D, and possibly over 1-alpha-OHD3, in the management of vitamin D resistant states. (+info)