dihydrotachysterol and Chronic-Disease

Dihydrotachysterol which was developed already 50 years ago is above all used in the substitution therapy of hypoparathyroidism. Its parathyreomimetic effectivity has led to an enlargement of the spectrum of indication during the last years; it allows the prophylactic use of dihydrotachysterol in chronic nephropathy in order to prevent by this means the risk of reactive hyperparathyroidism as well as its sequelae. On the basis of own experimental results the pathophysiologic prerequisites of this new form of treatment are discussed.

Topics: Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Hyperparathyroidism; Parathyroid Glands

The hypothesis that endogenous PGE2 mediates defective thick ascending limb (TAL) Cl reabsorption (percent delivered load: FRCl%) in rats with vitamin D-induced chronic hypercalcemia (HC) was tested by measuring FRCl% in loop segments microperfused in vivo in HC and control rats treated acutely with indomethacin (Indo) or its vehicle, and obtaining the corresponding outer medullary [PGE2]. Microperfusion conditions were developed in which FRCl% was exclusively furosemide sensitive. To determine the cellular mechanism, tubules were perfused acutely with forskolin (FSK), cAMP, or the protein kinase C inhibitor staurosporine (SSP). Outer medullary [PGE2] in HC rats was 9 to 10 times greater than control and could be normalized by Indo. FRCl% was 20% lower in HC rats infused with vehicle, and Indo, FSK, and cAMP returned FRCl% to normal despite sustained HC. Indo or FSK had no effect on FRCl% in control rats and Indo did not prevent inhibition of FRCl% by luminal PGE2 (1 microM). Luminal SSP (10(-7), 10(-8) M) in HC did not return FRCl% to control values. We conclude that impaired TAL FRCl% in HC occurs at a pre-cAMP site and is due to endogenous PGE2 and not to HC.

Topics: Alkaloids; Animals; Biological Transport, Active; Chlorides; Chronic Disease; Colforsin; Cyclic AMP; Dihydrotachysterol; Dinoprostone; Furosemide; Hypercalcemia; In Vitro Techniques; Indomethacin; Kidney Medulla; Kidney Tubules, Collecting; Male; Perfusion; Rats; Rats, Sprague-Dawley; Staurosporine

The reported coincidence of primary hyperparathyroidism and cholelithiasis led us to investigate the effects of acute and chronic hypercalcemia on bile secretion in cats. Acute hypercalcemia (6-7 mmol/liter) was induced by an intravenous calcium infusion. Chronic hypercalcemia (3-4 mmol/liter) was induced and maintained for 8-10 weeks by treatment with subcutaneous vitamin D3, oral dihydrotachysterol, and feeding a calcium-rich diet. Bile secretion was then studied in acute experiments. We found that calcium concentrations in serum and hepatic bile were similar during all experimental normo- or hypercalcemic conditions (y = 1.12x - 0.85; r = 0.76). Biliary volume outputs were significantly decreased during both acute (P less than 0.002) and chronic (P less than 0.05) hypercalcemia compared with normocalcemic controls. Acute hypercalcemia also decreased total bile acid outputs (P less than 0.05), but had no effect on biliary bile acid concentrations. The inhibitory effect of acute hypercalcemia on biliary fluid and bile acid secretion was dose dependent and not antagonized by atropine. These findings suggest that calcium is secreted in hepatic bile at similar concentrations as present in the serum and that elevations of serum calcium concentration inhibit biliary volume and bile acid secretion in cats. Similar effects of hypercalcemia on bile composition in humans might promote calcium salt precipitation in bile.

Topics: Acute Disease; Animals; Bile; Bile Acids and Salts; Calcium; Calcium, Dietary; Cats; Cholecalciferol; Chronic Disease; Dihydrotachysterol; Female; Hypercalcemia; Male

A 31-year-old man developed chronic secondary hypoparathyroidism after removal of goitre. Asymmetric cerebral oedema occured and a classical picture of pseudo-brain tumour with severe cerebral involvement developed which regressed merely on administration of calcium ions. The patient has remained well for over a year on dihydrotachysterol maintenance.

Topics: Adult; Brain Edema; Calcium; Chronic Disease; Dihydrotachysterol; Humans; Hypoparathyroidism; Male; Postoperative Complications; Pseudotumor Cerebri; Thyroidectomy; Time Factors

Topics: Alkaline Phosphatase; Biopsy; Bone Resorption; Calcium; Calcium Isotopes; Chronic Disease; Dihydrotachysterol; Ergocalciferols; Glomerulonephritis; Humans; Hyperparathyroidism, Secondary; Intestinal Absorption; Nephritis; Osteitis Fibrosa Cystica; Renal Dialysis

Topics: Adult; Calcium; Chronic Disease; Dihydrotachysterol; Humans; Hypoparathyroidism; Male; Phosphates