Showing papers by "Rajesh Kumar published in 1980"
TL;DR: It is concluded that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)2D in humans, and other mechanisms must be postulated to explain satisfactorily the abnormalities of bone structure and intestinal calcium absorption that may occur after chronic glucoc Corticoid therapy.
Abstract: The decreased intestinal absorption of calcium and accelerated bone loss associated with chronic glucocorticoid excess may be mediated by changes in vitamin D metabolism, leading to decreased availability of circulating 1,25-dihydroxyvitamin D. This hypothesis was examined in 14 patients with either endogenous or exogenous glucocorticoid excess. Analysis of paired serum samples (mean +/- SE) in 13 patients during euglucocorticoidism and during hyperglucocorticoidism showed that glucocorticoid excess resulted in small decreases of plasma 25-hydroxy-vitamin D concentrations (22 +/- 2- 18 +/- 2 ng/ml; P < 0.05) but no significant changes in plasma 1,25-dihydroxyvitamin D (32 +/- 8- 23 +/- 6 pg/ml) or serum immunoreactive parathyroid hormone (21 +/- 2- 18 +/- 2 muleq/ml). Additionally, we studied plasma kinetics of [3H]1,25-dihydroxyvitamin D3 after intravenous bolus administration in 10 hyperglucocorticoid patients and in 14 normal controls. Assessment with a three-compartment model showed no significant abnormalities in production rates (hyperglucocorticoid patients 1.2 +/- 0.3 micrograms/d, controls 1.5 +/- 0.2 micrograms/d) or metabolic clearance rates (hyperglucocorticoid patients, 18 +/- 2%; controls, 14 +/- 2%) or feces (hyperglucocorticoid patients, 60 +/- 9%, controls, 54 +/- 6%). We conclude that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)2D in humans. Thus, other mechanisms must be postulated to explain satisfactorily the abnormalities of bone structure and intestinal calcium absorption that may occur after chronic glucocorticoid therapy.
170 citations
TL;DR: There is a quantitatively important enterophepatic circulation of the products of 1,25-dihydroxyvitamin D3 in the rat and one of the metabolites was transformed into a less polar compound.
Abstract: After intravenous administration of radiolabeled 1,25-dihydroxyvitamin D3 to rats, approximately 25% of the administered radioactivity appeared in the bile within 24 h. Instillation of the biliary radioactivity into the duodena of other rats was followed by recovery of 15% of the radioactivity in newly secreted bile within 24 h. The process by which products of 1,25-dihydroxyvitamin D3 were excreted in bile was not saturable in the dose range tested (0.275-650 ng). The metabolites of 1,25-dihydroxyvitamin D3 present in bile were found to be much more polar than 1,25-dihydroxyvitamin D3 and were resolved into three fractions on high performance liquid chromatography. 60% of the radioactivity present in bile was retained selectively by DEAE-cellulose; the radioactive material could be eluted from the gel at a low pH or at high salt concentrations. When bile containing the radiolabeled metabolites was incubated at 37 degrees C and pH 5 with beta-glucuronidase, there was an increase in the amount of radioactivity comigrating with 1,25-dihydroxyvitamin D3. Treatment of the products of radiolabeled 1,25-dihydroxyvitamin D3 in bile with diazomethane, an agent which converts acids into methyl esters, transformed one of the metabolites into a less polar compound. These results demonstrate that there is a quantitatively important enterophepatic circulation of the products of 1,25-dihydroxyvitamin D3 in the rat.
87 citations
TL;DR: Well before the major fetal ossification of late pregnancy, intestinal absorption of calcium is enhanced in the mother and her bone mass increases, a unique event in .
Abstract: There is no time of life, and there are few diseases, in which such massive shifts in calcium occur so regularly as during pregnancy. Fetal bone formation demands that 25 to 30 g of calcium be depo...
45 citations
TL;DR: The data demonstrate that vitamin D(3) 3beta-glucosiduronate is biologically active in vivo and that the observed activity is due to hydrolysis of the conjugate to vitaminD(3), and suggest the existence of a mechanism for reutilization of the biliary products of vitamin D (3).
Abstract: Evidence has been presented suggesting the presence of vitamin D(3) 3beta-glucosiduronate and 1,25-dihydroxyvitamin D(3) glucosiduronate in rat bile. To evaluate the role of vitamin D glucosiduronates in calcium and phosphorus homeostasis, we synthesized vitamin D(3) 3beta-glucosiduronate and tested its biological activity in calcium- and vitamin D-deficient rats. After the intravenous administration of vitamin D(3) 3beta-glucosiduronate to rats maintained on a low calcium diet, there was an increase in duodenal calcium transport and an increase in serum calcium. Vitamin D(3) 3beta-glucosiduronate, however, was less active than equimolar amounts of vitamin D(3). At doses of less than 0.65-1 nmol per rat, the conjugate exhibited no activity. When vitamin D(3) 3beta-glucosiduronate was administered to vitamin D-deficient rats, 25-hydroxyvitamin D was detected in the serum; the increase in serum 25-hydroxyvitamin D levels was less than that observed after the administration of an equimolar amount of vitamin D(3). Vitamin D(3) 3beta-glucosiduronate showed no detectable activity in the induction of calcium binding protein in chick embryonic duodena, a system in which no endogenous steroid beta-glucuronidase activity is detectable. These data demonstrate that vitamin D(3) 3beta-glucosiduronate is biologically active in vivo and that the observed activity is due to hydrolysis of the conjugate to vitamin D(3). As vitamin D(3) 3beta-glucosiduronate is excreted in the bile of rats, it is possible that this conjugate is reutilized in vivo after hydrolysis to free vitamin D(3). These results suggest the existence of a mechanism for reutilization of the biliary products of vitamin D(3).
35 citations
TL;DR: In this paper, the production and decay of a D0 have been observed in a nuclear emulsion exposed to a photon beam from the CERN super proton synchroton in conjunction with the Omega spectrometer.
17 citations
TL;DR: The rapid decline in the fecal excretion after 2nd day suggests that bulk of /sup 115m/Cd is absorbed and distributed to the tissues of the body by 2 second day, which strengthens the idea that over-all absorption of orally ingested /Sup 115m /Cd from the digestive tract is markedly low.
Abstract: The present studies on the fecal excretion of /sup 115m/Cd in male albino rats further strengthen the idea that over-all absorption of orally ingested /sup 115m/Cd from the digestive tract is markedly low. More than 70% of the total isotope administration passed out within the first five days. However, there occurred a sharp decrease in the rate of fecal excretion till the 7th day, whereafter it levelled off. The rate of excretion was the highest on the second day. The rapid decline in the fecal excretion after 2nd day suggests that bulk of /sup 115m/Cd is absorbed and distributed to the tissues of the body by 2nd day. Poor absorption of orally ingested cadmium have been observed by others too.
5 citations
01 Jan 1980
TL;DR: Thedecreasedl intestinal absorption of calcium and Accelerated l)onelossassociate(l with chronic glucocorticoid excess may beemediated by changes invitamin Dmetabolism, leading tocreased availability of circulating 1,25-dihydroxyvitamin D.
Abstract: Thedecreasedl intestinal absorption of calcium andaccelerated l)onelossassociate(l with chronic glucocorticoid excess maybemediated by changes invitamin Dmetabolism, leading todlecreased availability ofcirculating 1,25-dihydroxyvitamin D. Thishypothesis wasexamined in14patients with either endogenous orexogenous glucocorticoid excess. Analysis ofpaired serumsamples (mean±SE)in13pa- tients duiring euglucocorticoidlisml- anddutring hyper- glucocorticoidism showedthatglucocorticoid excess resulted insmalldecreases ofplasma25-hydroxy- vitaminD concentrations (22+2-18±2ng/ml;P < 0.05) lbut no significant chaniges inplasmiia 1,25- dihydroxyvitamini