Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the small intestine, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] stimulates both calcium (Ca) and inorganic phosphate (Pi) absorption. This is mediated through an increase in mucosal-to-serosal flux (Jms) whereas the serosal-to-mucosal flux (Jsm) remains unchanged. We now report that in rat proximal colon, 1,25(OH)(2)D(3) produces active Ca absorption without affecting Pi transport, and that this induced active Ca absorption is associated with alterations in kinetics of both Jms and Jsm so that both processes demonstrate saturable components. Vitamin D-deficient rats were given daily injections of solvent (-D) or 270 ng 1,25(OH)(2)D(3) (+D) for 3 d. (45)Ca and [(32)P]phosphate fluxes were measured employing the Ussing technique using a modified Krebs-Ringer-HCO(3) buffer ([Ca] 1.25, [Pi] 1.18, [glucose] 11 mM). In -D rats there was no net flux (Jnet) of either Ca or Pi. In +D rats net active Ca absorption was observed (-D = 3.3 nmol/cm(2) per h +/-3.4 (SEM); +D = 27.3 +/-3.8, n = 11, P < 0.001) whereas Pi transport was unchanged, i.e., still no Jnet. Pi Jms was not different from Pi Jsm measured at the following buffer [Pi]: 0.0118, 0.118, 1.18, and 2.36 mM. Ca saturation kinetics were estimated using buffer [Ca] from 0.0125 to 5.0 mM. Saturable processes were demonstrated for both Jms and Jsm. Jnet for Ca across colon from +D rats exhibited saturation at [Ca] > 3 mM, with an estimated V(max) of 44.0 nmol/cm(2) per h and a K(m) of 0.9 mM. This colonic model may provide a useful system for studying 1,25(OH)(2)D(3)-induced molecular events related to Ca but not Pi transport. The apparent action of 1,25(OH)(2)D(3) on Ca secretory process may furnish new insights into the mechanism of action of vitamin D.
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PMID:Calcium and inorganic phosphate transport in rat colon: dissociated response to 1,25-dihydroxyvitamin D3. 625 Nov 10

Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24,25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1,25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P less than 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 +/- 0.12 mmol/l GF, mean +/- SEM) and FHH (0.86 +/- 0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 +/- 16 mmol/l GF) which was significantly greater (P less than 0.0001) than the normal NcAMP (13.5 +/- 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium. It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.
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PMID:Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function. 631 24

The circulating concentrations of 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D are abnormally low in patients with chronic renal failure (CRF). To determine the importance of substrate (25-hydroxyvitamin D) concentration in this phenomenon, five patients with end stage renal disease treated with hemodialysis were given 25-hydroxyvitamin D3 (25-OH-D3) orally for 4 weeks. The serum concentration of 25-OH-D3 increased from a mean (+/- SEM) of 26 +/- 5 ng/ml immediately before therapy to a maximum of 108 +/- 5 ng/ml 4 weeks after beginning administration of 25-OH-D3. The concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), and 25,26-dihydroxyvitamin D3 (25,26(OH)2D3) increased from 6.6 +/- 0.8 pg/ml, 0.29 +/- 0.10 ng/ml, and 0.36 +/- 0.06 ng/ml, respectively, immediately before 25-OH-D3 administration to 21.7 +/- 2.2 pg/ml, 0.48 +/- 0.09 ng/ml; and 0.78 +/- 0.12 ng/ml, respectively, after 4 weeks of administration of 25-OH-D3. These results suggest that substrate availability may be an important determinant of the circulating concentrations of these metabolites in patients with CRF. It seems possible that the therapeutic effects of 25-OH-D3 administration to the CRF patient may be mediated through the normal actions of 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and perhaps other metabolites rather than through analog effects of 25-OH-D3.
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PMID:Plasma vitamin D metabolite concentrations in chronic renal failure: effect of oral administration of 25-hydroxyvitamin D3. 633 30

A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney.
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PMID:Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification. 637 96

Vitamin D and its metabolites were determined in cow's milk, infant formulas, and colostrum, transitional and mature breast milk by specific protein-binding assays following HPLC (high-pressure liquid chromatography). Cow's milk contains (mean +/- SEM) 50.4 +/- 4.1 pg/ml vitamin D (n = 10), 499 +/- 47 pg/ml 25-OH D (n = 10) and 9.7 +/- 1.0 pg/ml 1,25 (OH)2D (n = 3). 86.6% of the added vitamin D3 was recovered from infant formulas. The mean content (mean +/- SEM) of 25-OH D and 1,25(OH)2D of infant formulas are 299 +/- 35 pg/ml and 5.4 +/- 0.9 pg/ml (n = 9), respectively. Vitamin D concentration of colostrum and mature breast milk is 122 +/- 3.4 pg/ml (n = 7, mean +/- SEM) and 38 +/- 3.3 pg/ml (n = 9) respectively; the 25-OH D content increases from 294 +/- 50.6 pg/ml (n = 10) to 845 +/- 190 pg/ml (n = 14) during lactation. The increase of 1,25-(OH)2D from early to mature breast milk (3.2 +/- 0.6 pg/ml, n = 8 versus 5.3 +/- 0.7 pg/ml, n = 20) is still statistically significant.
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PMID:Vitamin D, 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D in cow's milk, infant formulas and breast milk during different stages of lactation. 654 30

Earlier studies have shown that an oral sodium (Na) load may induce hypercalciuria in previously normocalciuric subjects and may also increase intestinal calcium (Ca) absorption. To probe the cause of the increased intestinal Ca absorption, we simultaneously measured parathyroid function, serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], and fractional intestinal 47Ca absorption before and after a salt load. Eleven normal subjects and two patients with postsurgical hypoparathyroidism were placed on a 10 meq Na, 400 mg Ca per day diet for 10 days, followed by another 10-day period in which the same diet was supplemented by 240 meq Na daily. Measurements were performed on the final 3 days of each phase. In the normal subjects, urinary Na excretion increased from 7 +/- 2 to 226 +/- 8 meq/day (mean +/- SEM), urinary Ca rose from 110 +/- 14 to 167 +/- 16 mg/day, serum parathyroid hormone (PTH) increased from 20 +/- 1 to 22 +/- 1 muleq/ml, serum 1,25-(OH)2D rose from 38 +/- 4 to 51 +/- 7 pg/ml, and fractional intestinal 47Ca absorption increased from 0.39 +/- 0.03 to 0.49 +/- 0.03 (P less than 0.05 for all changes). Serum Ca corrected for total protein did not change (9.9 +/- 0.1 to 9.8 +/- 0.1 mg/dl). The patients with hypoparathyroidism who were maintained on vitamin D therapy also showed increases in urinary Na (20 +/- 12 to 245 +/- 11 meq/day) and urinary Ca (271 +/- 48 to 305 +/- 43; P less than 0.05). However, there were no increases in serum PTH (13 +/- 1 to 11 +/- 1 muleq/ml), serum 1,25-(OH)2D (44 +/- 1 to 40 +/- 6 pg/ml), or intestinal Ca absorption (0.41 +/- 0.03 to 0.42 +/- 0.05). Corrected serum Ca decreased from 9.4 +/- 0.2 to 8.6 +/- 0.2 mg/dl. We conclude that in normal subjects, Na-induced renal hypercalciuria is accompanied by increased 1,25-(OH)2D synthesis and enhanced intestinal Ca absorption. Since this adaptive mechanism did not occur in two patients with hypoparathyroidism, mediation by PTH is suggested.
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PMID:The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism. 689 38

The effects of continuous ambulatory peritoneal dialysis on parathyroid hormone (PTH) and mineral metabolism were evaluated in ten patients. Utilizing a PTH radioimmunoassay, which measures both intact hormone and carboxyl-terminal PTH fragments, it was found that the mean clearance of immunoreactive parathyroid hormone was 1.5 +/- 0.73 ml/min (SEM) yielding a daily net removal of 13.6 +/- 3.2% of estimated total extracellular parathyroid hormone. Gel electrophoresis of the dialysate revealed the presence of both intact parathyroid hormone and fragments in a similar pattern to that of peripheral plasma. Normal levels of 25-(OH) vitamin D and vitamin D binding protein were observed prior to the initiation of continuous ambulatory peritoneal dialysis and following 6 months of treatment. Timed dialysate collections (N = 93) demonstrated a daily calcium influx of only 9.9 +/- 9.7 mg. The daily removal of phosphorus was 308.4 +/- 15.5 mg. Despite elevated serum magnesium levels in all patients, the net daily removal was inadequate (31.2 +/- 15.5 mg). It was concluded that: (1) Unlike chronic hemodialysis, continuous ambulatory peritoneal dialysis removes significant amounts of parathyroid hormone. (2) Normal 25-(OH) vitamin D and vitamin D binding protein levels are maintained with continuous ambulatory peritoneal dialysis despite large protein losses. (3) Substantial amounts of phosphorus are removed with continuous ambulatory peritoneal dialysis but not to an extent that precludes use of phosphorus binders. (4) Dialysate containing lower magnesium and possibly higher calcium concentrations should be made available to improve mineral homeostasis.
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PMID:Minerals, vitamin D, and parathyroid hormone in continuous ambulatory peritoneal dialysis. 689 87

Defined nephron segments were microdissected from the kidney of vitamin D-deficient rats, normal rats, and normal rats treated with 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3]. Tubule segments were incubated with 3H]labeled 25-hydroxyvitamin D3 and the rates of production of 3H]labeled 1 alpha, 25-(OH)2D3 and 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] were determined. Nephron segments tested include the glomerulus, proximal convoluted tubules (PCT), proximal straight tubules (PST), medullary and cortical thick ascending limbs of Henle's loop, distal tubules, and collecting tubules. Production of 1 alpha, 25-(OH)2D3 was detected only in PCT of vitamin D-deficient rats (mean +/- SEM, 0.70 +/- 0.05 fmol/mm per hr); the value decreased to 0.11 +/- 0.05 after parathyroidectomy. By contrast, significant 24,25-(OH)2D3 production occurred in PCT of normal rats (0.23 +/- 0.05 fmol/mm per hr). After administration of 1 alpha, 25-(OH)2D3 to normal rats, the rate of production of 24,25-(OH)2D3 in PCT increased to 0.64 +/- 0.06 fmol/mm per hr and also became apparent in PST (1.07 +/- 0.21). The rates of production of 1 alpha, 25-(OH)2D3 and 24,25-(OH)2D3 in these nephron segments were linear with tubule length over a wide range of lengths per incubation and with the incubation time. The results define the localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron: PCT is capable of producing both 1 alpha, 25-(OH)2D3 and 24,25-(OH)2D3 and PST can produce 24,25-(OH)2D3. the use of defined nephron segments may be useful for study of the distribution and regulation of 25-hydroxyvitamin D3 hydroxylases in the kidney.
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PMID:Localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron. 694 Jan 35

We studied the effects of glucocorticoid excess on calcium and phosphorus homeostasis in relation to vitamin D metabolites and parathyroid hormone (PTH) in seven patients with spontaneous ACTH-dependent Cushing's syndrome. Remission of hypercortisolism resulted in a significant increase in tubular reabsorption of phosphate [from 76 +/- 4% to 89 +/- 2% (mean +/- SEM); P less than 0.01] and serum phosphorus (from 3.1 +/- 0.1 to 4.2 +/- 0.2 mg/dl; P less than 0.005). Serum calcium did not change, although there was a reduction in daily urinary calcium excretion from 0.23 +/- 0.02 to 0.107 +/- 0.02 mg calcium/mg creatinine. Serum immunoreactive PTH (iPTH) levels were normal during Cushing's syndrome (34 +/- 5 microleq/ml), but fell significantly after remission to 22 +/- 2 microleq/ml (P less than 0.05). This small decrease in iPTH did not correlate with the improvement of phosphate homeostasis. Plasma 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH2)D] concentrations in Cushing's syndrome did not differ from measurements in 97 normal subjects. After treatment, 25OHD did not change, but 1,25-(OH)2D fell in each patient from a mean of 44 to 22 pg/ml (P less than 0.02). 1,25-(OH)2D was inversely correlated with serum phosphorus (r = 0.59; P less than 0.01), but did not correlate with iPTH. The known impairment of intestinal calcium absorption in Cushing's syndrome cannot be attributed to a decrease in the circulating levels of 1,25-(OH)2D. Endogenous hypercortisolism decreases tubular phosphate reabsorption and serum phosphorus, increase tubular phosphate reabsorption and serum phosphorus, increases iPTH, and results in an increase in 1,25-(OH)2D. These events may contribute to the severe loss of bone mass in such patients and may account for the calciuria and phosphaturia of Cushing's syndrome.
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PMID:Vitamin D metabolites and parathyroid hormone in Cushing's syndrome: relationship to calcium and phosphorus homeostasis. 697 49

This study was carried out to evaluate the effects of an iv injection of parathyroid extract on serum levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D3] in elderly osteopenic patients and age-matched nonosteopenic controls. Serum concentrations of 1,25-(OH)2D were reduced in elderly osteopenic subjects (mean +/- SEM, 20 +/- 3 pg/ml) compared with values in age-matched nonosteopenic controls (35 +/- 3 pg/ml), whereas no differences were found in serum 24,25-dihydroxyvitamin D levels (1.5 +/- 0.3 and 2.2 +/- 0.5 ng/ml, respectively). An iv injection of parathyroid extract was followed by a significant increase in serum 1,25-(OH)2D levels in both osteopenic patients (16 +/- 6 pg/ml) and controls (15 +/- 5 pg/ml). The mean 4-h increases in serum 1,25-(OH)2D of 11-18 pg/ml were not significantly different in the two groups. The results indicate that the reduced 1,25-(OH)2D concentrations in the osteopenic patients are secondary to changes in factors that normally stimulate this enzyme system.
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PMID:Acute effects of parathyroid hormone on vitamin D metabolism in patients with the bone loss of aging. 697 88


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