A B S T R A C T The development of a vitamin D-resistant state in the course of renal failure may be responsible for reduced intestinal absorption of calcium and an impaired response of skeletal tissue. Moreover, the kidney has been shown to carry out the conversion of 25-hydroxycholecalciferol (25-OH-CC) to a highly biologically active metabolite, 1,25-dihydroxycholecalciferol (1,25-diOH-CC). In the present studies, vitamin D-deficient rats, made acutely uremic by either bilateral nephrectomy or urethral ligation, received physiological doses of cholecalciferol (vitamin D3) (CC), 25-OH-CC or 1,25-diOH-CC; 24 hr later intestinal calcium transport, in vitro, and bone calcium mobilization, in vivo, were assessed. Whereas CC and 25-OH-CC stimulated calcium transport in sham-operated controls, they were without effect in the uremic animals. In contrast, administration of 1,25-diOH-CC stimulated calcium transport in both groups of uremic animals. Administration of 1,25-diOH-CC also stimulated calcium mobilization from bone in each group of animals. However, CC and 25-OH-CC were only effective in the sham controls and the uremic group produced by urethral ligation and had little or no effect in animals without kidneys. These results indicate that renal conversion of calciferol to a
A B S T R A C T Studies were carried out to evaluate the mechanism of hypocalcemia in magnesium depletion. Day old chicks fed a magnesium deficient diet developed marked hypocalcemia, with a direct relation between serum calcium (y) and magnesium (x): y = 2.68 x + 4.24, r = 0.84 (both in mg/100 ml). Injections of parathyroid extract that increased serum calcium 2-3 mg/100 ml in normals had no effect in Mg-depleted birds. Very large dietary supplements of calcium or vitamin D3 increased mean serum calcium only from 5.3 to 7.7 and 7.8 mg/100 ml, respectively, while a normal magnesium diet for 3 days increased calcium from 5.3 to 9.9 mg/100 ml despite absence of dietary calcium. Intestinal calcium transport, studied in vitro, and the calcium concentration of the carcass was significantly increased in magnesium-depleted chicks, making it unlikely that reduced intestinal absorption of calcium caused the hypocalcemia. In magnesium-deficient chicks, the bone content of magnesium was decreased by 74%, the calcium content was unchanged, and the cortical thickness of bone was markedly increased. After 3 days of magnesium-repletion, cortical thickness was reduced with increased endosteal resorption. There INTRODUCTIONHypocalcemia has been reported to be associated with magnesium depletion in a number of species, including rats fed a low calcium diet (1, 2), sheep (3), pigs (4), calves (5, 6), dogs (7,8), monkeys (9), and man (10)(11)(12)(13)(14) In the present study, a model of experimental magnesium depletion in the chick is described, and various factors which might be involved in the development of hypocalcemia were evaluated. METHODS White leghorn cockerels obtained 1 day after hatching (through courtesy of H & N Hatchery, Inc., Riverside, Calif.) were housed in electric brooders. Chicks were chosen as experimental models because their diet can be controlled immediately after hatching, permitting the rapid development of magnesium depletion. In addition, chickens are known to be sensitive to parathyroid extract (15), thus providing a suitable model to evaluate responsiveness to the hormone. Furthermore, considerable information is available concerning calcium homeostasis in this species.They received a synthetic diet, modified from that of Fox and Briggs (16), and distilled water ad libitum. The diet, as originally described, contained 0.060% magnesium, an amount considered the optimal quantity needed by growing chicks (16,17). With deletion of supplemental magnesium and calcium salts, the basic diet was found by analysis to contain 0.004% magnesium and 0.005% calcium. In preparation of certain diets discussed below, magnesium sulfate was added providing 0.010, 0.020, or 0.060% magnesium.Unless noted otherwise, the diets were supplemented to contain 1.2% calcium, an amount higher than the 0.7-0.8% usually provided, 0.8% phosphorus, and 80 IU of vitamin D3 (cholecalciferol) /100 g.For purposes of establishing the appropriate dietary magnesium for studying magnesium depletion in the fowl, preliminary experiments were ...
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