Metabolic effects of diphosphonate in primary hyperparathyroidism.

Six patients with primary hyperparathyroidism (PHPT) and one with squamous cell carcinoma of the esophagus with parathyroid hormone excess received disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at a daily dose of 20 mg/kg orally. During treatment, the decrease in urinary calcium, total urinary hydroxyproline, and fasting urinary calcium suggested an inhibition of bone resorption. Serum calcium intestinal absorption of calcium and urinary cyclic adenosine monophosphate (cAMP) did not change significantly.

Experimental diabetes reduces circulating 1,25-dihydroxyvitamin D in the rat.

Duodenal calcium absorption and a vitamin D-dependent duodenal calcium-binding protein are depressed in rats with alloxan- or streptozotocin-induced diabetes. To test for possible abnormal vitamin D metabolism in diabetes we measured serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in control, streptozotocin diabetic, and insulin-treated diabetic rats. The serum concentration of 1,25-dihydroxyvitamin D was depressed in untreated diabetic rats to one-eighth of the level in controls and was restored to control levels by insulin treatment.

The role of 1 alpha, 25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria.

The cuase for the intestinal hyperabsorptionof calcium (Ca) in various forms of hypercalciurias was explored by a careful measurement of plasma 1 alpha, 25-dihydroxycholecalciferol [1 alpha, 25-(OH)I D] and by an assessment of intestinal Ca absorption and of parathyroid function. In 18 cases of primary hyperparathyroidism (PHPT), the mean plasma concentration of 1 alpha, 25-(OH)2D was significantly increased (4.9 +/- 2.

Plasma 1,25-dihydroxyvitamin D levels in patients receiving anticonvulsant drugs.

Recent evidence has linked altered plasma vitamin D metabolite levels to the reported occurrence of hypocalcemia and other metabolic abnormalities in patients receiving anticonvulsant drugs. We have measured plasma levels of 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) in institutionalized patients on diphenylhydantoin (Dilantin) and/or phenobarbital therapy. Values were compared with those obtained in institutionalized patients receiving no drugs and with normal ambulatory subjects.

Influence of dietary vitamin D3 on the circulating concentration of its active metabolites in the chick and rat.

Plasma concentrations of 25-hydroxyvitamin D3 (25-OHD3) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) in growing chicks and weanling rats were measured by a new radioreceptor assay to determine the effects of varying dietary levels of vitamin D3. The plasma concentration of 25-OHD3 fell from 14.1 ng/ml in 1-day-old chicks to undetectable levels after 3 weeks on a rachitogenic diet.

Calcinogenic factor in Solanum malacoxylon: evidence that it is 1,25-dihydroxyvitamin D3-glycoside.

After glycosidic cleavage of the water-soluble vitamin D-like principle of the calcinogenic plant Solanum malacoxylon, the active lipophilic portion was purified by column chromatography and analyzed by combined gas chromatography and mass spectrometry. It was identified as 1,25-dihydroxyvitamin D3, the active form of vitamin D. Thus this active metabolite of vitamin D exists in the plant world, and its presence probably accounts for pathologic calcification in grazing animals ingesting Solanum malacoxylon.

Radioligand receptor assay for 25-hydroxyvitamin D2/D3 and 1 alpha, 25-dihydroxyvitamin D2/D3.

A competitive protein binding assay for measurement of the plasma concentration of 1 alpha, 25-dihydroxyvitamin D3 [1alpha, 25-(OH)2D3] has been extended to include the immediate precursor of this hormone, 25-hydroxyvitamin D3 (25-OHD3). In addition, the assay system is capable of measuring the two metabolic products of ergocalciferol, namely. 25-hydroxyvitamin D2 (25-OHD2) and 1alpha, 25-dihydroxyvitamin D2 [1alpha, 25-(OH)2D2].

Increased intestinal chromatin template activity. Influence of 1alpha,25-dihydroxyvitamin D3 and hormone-receptor complexes.

1alpha,25-Dihydroxyvitamin D3 administration to rachitic chicks results in an increase in the chromatin template activity of intestinal target tissue assayed in vitro using Escherichia coli RNA polymerase. The maximum stimulation of template capacity was 12 to 20% over control values and occurred 2 hours after administration of the sterol. This rapid effect preceded the biologic response to 1alpha,25-dihydroxyvitamin D3 in the intestine and was not observed in other tissues such as liver or kidney.

Studies on the 1alpha, 25-dihydroxycholecalciferol-like activity in a calcinogenic plant. Cestrum diurnum, in the chick.

Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick.

1,25-Dihydroxycholecalciferol deficiency: the probable cause of hypocalcemia and metabolic bone disease in pseudohypoparathyroidism.

Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells.

The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels.

A sensitive radioreceptor assay for 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) is utilized to quantitate the circulating concentration of this sterol in experimental animals and humans. When weanling rats are grown for 2 weeks on low calcium or low phosphate diets, limited availability of either ion elicits a five-fold increase in the plasma level of 1alpha,25-(OH)2D3. The enhancement of 1alpha,25-(OH)2D3 in calcium deficiency is dependent upon the presence of the parathyroid and/or thyroid glands, which is consistent with parathyroid hormone (PTH) mediation of this effect.

Cytoplasmic and nuclear binding components for 1alpha25-dihydroxyvitamin D3 in chick parathyroid glands.

Specific binding of 1 alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3] to macromolecular components in the cytoplasm and nucleus is demonstrated in parathyroid glands of vitamin-D-deficient chicks. The interaction of 1alpha,25-(OH)2D3 with the cytoplasmic binding component is of high affinity (Kd = 3.2 X 10(-10) M) and high specificity [1alpha,25-(OH)2D3 greater than 25-hydroxyvitamin D3 greater than 1alpha-hydroxyvitamin D3 greater than vitamin D3 in competing with radioactive 1alpha,25-(OH)2D3].

Effect of oral contraceptives on plasma clearance.

The effects of chronic steroid contraceptive therapy on drug clearance from plasma were studied by using plasma antipyrine, phenylbutazone, and cholecalciferol half-lives in women. After 3 mo of oral steroid therapy (Norinyl, 2 mg; norethindrone + mestranol), the antipyrine half-life was increased in 3 of 6 subjects, phenylbutazone half-life was not consistently altered, and vitamin D3 half-life was increased in 3 of 4 patients. After 1 to 7 yr of oral steroid theraphy, the antipyrine half-life was longer while taking the contraceptive than when the contraceptive treatment was discontinued in 4 of 6 subjects, whereas that of phenylbutazone was not consistently altered.

Specific binding of 1alpha,25-dihydroxycholecalciferol to nuclear components of chick intestine.

Specific binding of 1alpha,25-dihydroxycholecalciferol to macromolecular components of small intestinal mucosa nuclei is demonstrated in vitamin D-deficient chicks. The nuclear 1alpha,25-dihydroxycholecalciferol-macromolecule complex was isolated on sucrose density gradients and sediments at 3.7 S in the presence of 0.

Rapid enhancement of chick intestinal DNA-dependent RNA polymerase II activity by 1 alpha, 25-dihydroxyvitamin D3, in vivo.

1alpha,25-dihydroxyvitamin D(3) was examined for its ability to affect the DNA-dependent RNA polymerases (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.