Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 595 records · Page 33Linked to original sources

PubMed1975

Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats.

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on Ca balance, 45Ca kinetics, and bone morphology has been studied in control rats and rats given disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), 10 mg P/kg sc per day. This large dose of EHDP is known to inhibit bone mineralization and intestinal calcium absorption and to depress the endogenous production of 1,25-(OH)2D3. In conctrol rats, 1,25-(OH)2D3 increased intestinal calcium absorption. However, in contrast to the enhanced calcium absorption that results from an augmentation of dietary calcium, the 1,25(OH)2D3-induced augmentation of calcium absorption does not lead to a rise in calcium retention, the intestinal effect being matched by an increased excretion of urinary calcium. The EHDP-induced decrease of intestinal calcium absorption could be completely prevented by the concomitant administration of 1,25-(OH)2D3 but not the inhibition of bone mineralization. Therefore, in contrast to the impairment of calcium absorption, that of bone mineralization brought about by large doses of EHDP cannot be merely attributed to a decreased production of 1,25-(OH)2D3.

Animals↗

PubMed1975

Phosphatemic action of 1,25-dihydroxyvitamin D3.

The action of a single intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was investigated in thyroparathyroidectomized (TPTX) vitamin D-deficient phosphate-depleted rats. After 14 h, plasma inorganic phosphorus (Pi) was significantly greater in animals receiving 1,25(OH)2D3 than in D-deficient controls, but urinary Pi excretion was very low in both groups and not significantly different in the rats given 1,25(OH)2D3. Clearance studies indicated that the D-deficient controls reabsorbed more than 99% of their filtered Pi. Avid Pi reabsorption continued even after the infusion of sufficient phosphate to raise the plasma and filtered Pi to approximately 3 times normal. Fractional calcium excretion (FECa) exceeded fractional sodium excretion (FENa) by severalfold, but FECa decreased strikingly during phosphate infusion. In animals that manifested a substantial elevation of plasma Pi after 1,25(OH)2D3, FECa was significantly less than in D-deficient controls. Therefore, the increase in plasma Pi following 1,25(OH)2D3 administration occurs independently of any effect on renal Pi reabsorption and may be responsible, at least in part, for the amelioration of hypercalciuria after 1,25(OH)2D3 treatment.

Animals↗

PubMed1975

Response to crystalline 1alpha-hydroxyvitamin D3 in vitamin D dependency.

The therapeutic response to chemically synthesized 1alpha-hydroxycholecalciferol (1alpha-OH-D3) was studied in three patients with autosomal recessive vitamin D dependency (ARVDD). The daily maintenance dose for vitamin D2, to prevent signs of vitamin D deficiency in these patients, was 40-54.4 mug/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D2 resulted in the ultimate reappearance of the vitamin D depletion syndrome in patients 1 and 2 (Figs. 1 and 2). The third patient presented with the deficiency syndrome despite adequate vitamin D nutrition and was recognized to have ARVDD. Treatment with 1alpha-OH-D3 by mouth in all three patients at dose levels of 1-3 mug/24 hr (80-100 ng/kg) corrected hypocalcemia and suppressed parathyroid hormone-dependent renal loss of amino acids (Figs. 1, 2, and 4). Rickets healed in 7-9 weeks on 1alpha-OH-D3 alone (Fig. 3). The therapeutic response was rapid. It was usually seen first in the rise of serum calcium (Figs. 5 and 6). Withdrawal of 1alpha-OH-D3 was followed first by a fall of serum phosphorus, then by a fall in serum calcium; the latter occurred within about 2 weeks of withdrawal. Because the synthesis of 1alpha-OH-D3 is simpler than for 1alpha,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal 1alpha-OH-D3 to be the agent of choice for treatment of this and analogous diseases.

Alkaline Phosphatase↗

PubMed1975

The mobilization of bone mineral by 1,25-dihydroxyvitamin D3 in hypophosphatemic rats.

Administration of 1,25-dihydroxyvitamin D3 to thyroparathyroidectomized, hypophosphatemic rats on a low-phosphorus diet increases serum inorganic phosphorus and calcium concentrations. Experiments utilizing such rats treated with 45Ca and 32P ten days before use revealed that the rise in serum phosphorus in response in 1,25-dihydroxy-vitamin D3 is derived at least in part from bone mineral. This suggests that under conditions of hypophosphatemia, 1,25-dihydroxyvitamin D3 can mobilize bone in the absence of parathyroid hormone.

Animals↗

PubMed1975

Calcium metabolism.

It is evident that in the past decade much new information has been gathered regarding calcium metabolism at the physiological and extracellular level. In addition, new information is becoming available regarding intracellular mechanisms of calcium transport and mobilization. Finally, during the past decade the hormone calcitonin has been introduced as well as a hormone derived from vitamin D, namely 1,25-(OH)2D3, has been discovered and demonstrated to play a central role in the regulation of calcium metabolism. The exciting developments will undoubtedly foster the revelation of new information during the next decade which hopefully will bring about an elucidation of the molecular mechanisms of calcium metabolism.

Animals↗

PubMed1975

High-pressure liquid chromatography: separation of the metabolites of vitamins D2 and D3 on small-particle silica columns.

The high-pressure liquid chromatographic separation of all of the known metabolites of vitamin D(2) and vitamin D(3) found in biological fluids has been achieved. This technique has been successfully applied to the analysis of vitamin D mixtures, purification of vitamin D metabolites, and identification of radioactive peaks. Some theoretical bases for the observed resolutions are suggested.

Cholecalciferol↗

PubMed1974

1alpha-Hydroxyvitamin D2: a potent synthetic analog of vitamin D2.

A hydroxy analog of vitamin D(2), 1alpha-hydroxyvitamin D(2), has been synthesized and tested for biological activity. This vitamin derivative is active in stimulating intestinal calcium transport and bone calcium mobilization in the rat and exhibits antirachitic activity. Its biopotency is comparable to that of the corresponding vitamin D(3) analog, 1alpha-hydroxyvitamin D(3).

Animals↗

PubMed1974