Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Calcitriol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol.

Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Plasma calcitriol in chickens producing strong and weak egg shells and the response of hens to exogenous calcitriol.

Calcitriol (CAL) regulates intestinal calcium transport by inducing an increase in membrane phosphatidylcholine (PC) and calbindin. A positive correlation has been reported between shell gland PC and egg shell strength. Three experiments were conducted to test the hypothesis that the improvement in egg shell strength associated with increased PC is mediated via changes in the concentration of CAL. Sera from aged laying hens, identified as either strong (SES) or weak (WES) egg shell producers, were obtained from blood samples collected at 16 h after oviposition and assayed for CAL. Laying hens were injected (i/m) with 1.0 or 0.4 micrograms CAL/d for 28 d. Serum CAL in the WES hens was 70% of that in the SES hens (P less than .05). Hens producing extremely weak shells did not respond to 0.4 micrograms CAL/d for 10 d. Administration of CAL did not improve egg shell strength nor was serum CAL increased when WES hens were molted and shell gland PC increased. The results show that serum CAL is lower in aged hens producing weak egg shells but shell strength is not responsive to exogenous CAL and increased shell gland PC in WES hens after molting is not associated with higher serum CAL.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Calcitriol metabolism in patients with chronic renal failure.

We studied calcitriol metabolism in white patients with chronic renal failure and in age- and sex-matched normal subjects. The plasma levels of calcitriol (21.9 +/- 1.6 pg/mL, n = 7, v control, 37.4 +/- 2.9 pg/mL, P less than 0.001), metabolic clearance rate (MCR) of calcitriol (0.45 +/- .01 mL/min/kg v control, 0.58 +/- .02 mL/min/kg, P less than 0.001), and production rate (PR) of calcitriol (14.2 +/- 1.0 ng/kg/d v control, 31.8 +/- 3.2 ng/kg/d, P less than 0.001) were significantly lower in patients with moderate renal failure (average creatinine clearance, 0.59 +/- 0.01 mL/s [35.1 +/- 6.1 mL/min]) when compared with the respective values of normal control subjects. The MCR of calcitriol was determined again in patients with renal failure after they received calcitriol, 1 microgram/d, for 1 week. The MCR remained unchanged (0.46 +/- .04 mL/min/kg, n = 7) and plasma levels of calcitriol were increased to 34.6 +/- 2.77 pg/mL. The mechanism by which the MCR of calcitriol decreases in renal failure is partly due to the presence of inhibitory factors of degradation enzymes in uremic plasma. When the ultrafiltrates of uremic plasma obtained from hemodialysis patients were infused to normal Sprague-Dawley rats, the MCRs of calcitriol (0.20 +/- .01 mL/min/kg, n = 6) were markedly suppressed in comparison to those of rats infused with the ultrafiltrates of normal plasma (0.37 +/- .01 mL/min/kg, n = 6, P less than 0.001). The uremic plasma also contained factors that inhibit the synthesis of calcitriol. We conclude that metabolic degradation of calcitriol is decreased in patients with renal failure, and uremic plasma contains inhibitory factors that suppress the synthesis and degradation of calcitriol.

Adult↗
PubMed1992

Stability and sorption of calcitriol in plastic tuberculin syringes.

The stability of commercially formulated calcitriol 1 and 2 micrograms/mL and calcitriol formulation subsequently diluted to 0.5 microgram/mL in 0.9% sodium chloride injection, 5% dextrose injection, or water for injection was evaluated after eight hours' storage in polypropylene syringes. The apparent affinities of calcitriol for polypropylene and polyvinyl chloride were also examined. Three calcitriol 0.5 microgram/mL solutions (diluted in 0.9% sodium chloride injection, 5% dextrose injection, or water for injection) and aqueous calcitriol formulations, 1 and 2 micrograms/mL, were placed in 1-mL polypropylene tuberculin syringes and assayed by high-performance liquid chromatography initially and after two, four, and eight hours' storage under room light at ambient temperature. Samples of calcitriol 2 micrograms/mL were also exposed to polypropylene or polyvinyl chloride at room temperature for 20 days. The remaining calcitriol concentrations were determined and apparent calcitriol polymer/water partition coefficients were calculated. Calcitriol concentrations did not change substantially during the eight-hour stability study. The mean apparent polymer/water partition coefficient for polyvinyl chloride was 66 times that for polypropylene, indicating that calcitriol has a definite affinity for polyvinyl chloride but no similar affinity for polypropylene. Aqueous calcitriol solution 1 or 2 micrograms/mL or 0.5 microgram/mL in 0.9% sodium chloride injection, 5% dextrose injection, or water for injection, when stored in polypropylene syringes exposed to ambient temperature and room light, appears to be stable for eight hours. Calcitriol appears to have greater affinity for polyvinyl chloride than for polypropylene.

Adsorption↗
PubMed1989

Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.

Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.

Animals↗
PubMed1992

Serum vitamin D metabolites and calcitriol receptor concentration in parathyroid tissue in primary hyperparathyroidism.

Vitamin D metabolites in serum and calcitriol receptor concentration in parathyroid tissue were examined in 52 patients operated on for primary hyperparathyroidism. The calcitriol receptor levels were not different in parathyroid adenomas (mean 224 fmol/mg of protein, range 29-509, N = 43), normal parathyroid tissue (mean 245, range 31-690, N = 20), and primary parathyroid hyperplasia (mean 172, range 46-477, N = 9). Preoperative serum levels of calcitriol concentration correlated inversely to the calcitriol receptor in normal parathyroid tissue in patients with adenoma (r = -0.57, N = 17, p = 0.017), but no such correlation was found in the corresponding adenomas (r = 0.14, p = 0.59). In 31 patients in whom both pre- and postoperative vitamin D metabolite analyses were carried out, 23 had lower calcitriol postoperative concentrations compared to preoperative values (p = 0.012, sign test). No change was found in the other vitamin D metabolites postoperatively. By multiple regression analysis calcitriol concentration in serum was inversely correlated to the serum concentration of urea and phosphate (p = 0.003). We conclude that calcitriol may influence calcitriol receptor expression in normal parathyroid tissue, but not in adenomatous parathyroid gland. Furthermore, serum calcitriol was correlated to the renal function, and phosphate level, and in most patients the calcitriol concentration was lower after the operation.

Adenoma↗
PubMed1991

Calcemic response to parathyroid hormone in renal failure: role of calcitriol and the effect of parathyroidectomy.

Hyperparathyroidism due to renal failure begins in the early stages of renal insufficiency and is in part secondary to skeletal resistance to the calcemic action of parathyroid hormone (PTH). Factors which have been reported to reduce the calcemic response to PTH include: decreased calcitriol levels, hyperphosphatemia and down regulation of PTH receptors in bone. While hyperphosphatemia may directly decrease the calcemic response to PTH, it may also act indirectly by a suppression of calcitriol synthesis. In this study, the effect of calcitriol on the calcemic response to PTH was evaluated in normal rats and in rats with moderate and advanced renal failure. To determine the combined effect of calcitriol and phosphorus on the calcemic response to PTH, rats receiving calcitriol were fed either a high (1.0%) or low (0.2%) phosphorus diet during a 48-hour PTH infusion. In advanced renal failure, calcitriol administration increased the calcemic response to PTH independent of the dietary phosphorus intake. During ingestion of a low phosphorus diet, a 48 hour PTH infusion resulted in a serum calcium level of 13.7 +/- 0.5 and 12.1 +/- 0.2 mg/dl (P less than 0.02) with and without calcitriol administration, respectively. In normal rats and in rats with moderate renal failure, calcitriol administration improved the calcemic response only during a high phosphorus intake. After a 48-hour PTH infusion in normal rats, the serum calcium levels with and without calcitriol were 16.1 +/- 0.9 and 14.8 +/- 0.6 mg/dl, P less than 0.01 respectively; in rats with moderate renal failure, calcitriol administration increased serum calcium, 13.2 +/- 0.5 versus 11.2 +/- 0.4 mg/dl, P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Calcitriol-mediated modulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-2.

Calcitriol-induced differentiation of U937 mononuclear phagocytes is known to have divergent effects on the synthesis of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2). In this study, we sought to determine whether calcitriol affects the expression of these proteins by modulating intermediate signal transduction involving intracellular calcium and protein kinase C (PKC). U937 cells were stimulated with calcitriol (50 nM) for 6-72 hr, inducing a transient increase in specific binding of [3H]phorbol dibutyrate ([3H]PDBu), seen only after 24 hr. Staurosporine (2 nM), a PKC inhibitor, had no effect on calcitriol-induced secretion of plasminogen activator (PA) activity. However, staurosporine significantly (P less than 0.05) inhibited the ability of calcitriol to enhance phorbol myristate acetate (PMA)-induced secretion of PA inhibitor activity, indicating that this priming effect of calcitriol requires expression of PKC. The calcium ionophore A23187 (0.1 microM) induced a modest increase in secreted PA inhibitor activity, in contrast to the secretion of PA activity which is consistently seen in response to calcitriol. Northern blot analysis demonstrated that A23187 induced an increase in PAI-2 mRNA and a marked reduction in uPA mRNA, while calcitriol induced opposite changes in both mRNA species. We conclude that calcitriol modulates uPA and PAI-2 expression by multiple mechanisms that are both PKC dependent and PKC independent. Our studies also demonstrated that increased intracellular calcium alters the synthesis of both uPA and PAI-2 in a manner which favors expression of PA inhibitor activity.

Blotting, Northern↗
PubMed1989

Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis.

The effect of intravenous calcitriol on parathyroid function was evaluated in nine chronic hemodialysis patients with secondary hyperparathyroidism. Two micrograms of calcitriol were administered intravenously after dialysis thrice weekly for ten weeks. Parathyroid function was assessed by inducing hypo- and hypercalcemia with low calcium (1.0 mEq/liter) and high calcium (4.0 mEq/liter) dialyses before and after ten weeks of intravenous calcitriol therapy. To avoid hypercalcemia during calcitriol administration, the dialysate calcium was reduced to 2.5 mEq/liter. Parathyroid hormone (PTH) values (pg/ml) from dialysis-induced hypo- and hypercalcemia were plotted against serum ionized calcium, and the sigmoidal relationship between PTH and calcium was evaluated. Basal PTH levels fell from 902 +/- 126 pg/ml to 466 +/- 152 pg/ml (P less than 0.01) after therapy without a significant change in the serum total calcium concentration. The ionized calcium-PTH sigmoidal curve shifted to the left and downward after calcitriol therapy. The maximal PTH response during hypocalcemia decreased after calcitriol from 1661 +/- 485 pg/ml before calcitriol to 1031 +/- 280 pg/ml afterward (P less than 0.05). The PTH level at maximal inhibition due to hypercalcemia decreased from 281 +/- 76 pg/ml before calcitriol to 192 +/- 48 pg/ml afterward (P less than 0.05). The slope of the sigmoidal curve changed from -2125 +/- 487 to -1563 +/- 385 (P less than 0.05). The set point of ionized calcium (4.60 +/- .11 mg/dl before vs. 4.44 +/- .07 mg/dl after) did not change significantly with calcitriol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗
PubMed1990

Effect of physiological concentrations of calcitriol on lymphocyte proliferation in normal subjects and in patients with renal failure.

Specific receptors for calcitriol (1,25-dihydroxyvitamin D) have been found in immune cells, such as monocytes and activated lymphocytes, suggesting that calcitriol may play an immunoregulatory role. In fact, a marked increase in lymphocyte proliferation has been reported after treating hemodialyzed patients with 1 alpha-hydroxyvitamin D3, a precursor of calcitriol. We have studied in vitro the effect of calcitriol depletion and calcitriol addition on the phytohemagglutinin-induced mitogenesis of peripheral blood mononuclear cells from 14 healthy subjects and 8 hemodialyzed patients. The calcitriol depletion of culture medium did not modify cell proliferation. The addition of calcitriol in concentrations about the physiological range (10(-11) M) induced a small, marginally significant, 11% increase in the proliferation of lymphocytes from hemodialysis patients. Supraphysiological concentrations (10(-9)-10(-7) M) induced a marked inhibition (up to 60% of control values) of cell mitogenesis, both in patients and in healthy subjects. These results suggest that the increase in lymphocyte proliferation observed in vivo after treatment with calcitriol precursors is not mediated by a direct effect of calcitriol on circulating mononuclear cells.

Adult↗
PubMed2025

Transcriptomic profile induced by calcitriol in CaSki human cervical cancer cell line.

The vitamin D endocrine system, primarily mediated by its main metabolite calcitriol and the vitamin D receptor (VDR), plays a critical role in numerous human physiological processes, ranging from calcium metabolism to the prevention of various tumors, including cervical cancer. In this study, we comprehensively investigated the genomic regulatory effects of calcitriol in a cervical cancer model. We examined the transcriptional changes induced by calcitriol in CaSki cells, a cervical cell line harboring multiple copies of HPV16, the primary causal agent of cervical cancer. Our microarray findings, revealed that calcitriol regulated over 1000 protein-coding genes, exhibiting a predominantly repressive effect on the CaSki cell transcriptome by suppressing twice as many genes as it induced. Calcitriol decreased EPHA2 and RARA expression while inducing KLK6 and CYP4F3 expression in CaSki cells, as validated by qPCR and Western blot. Functional analysis demonstrated that calcitriol effectively inhibited key processes involved in cancer progression, including cell proliferation and migration. This was further supported by the significant downregulation of MMP7 and MMP13 mRNA levels. Our microarray results also showed that, in addition to its effects on protein-coding genes, calcitriol significantly regulates non-coding RNAs, altering the expression of approximately 400 non-coding RNAs, including 111 microRNA precursors and 29 mature microRNAs, of which 17 were upregulated and 12 downregulated. Notably, among these calcitriol-regulated microRNAs are some involved in cervical cancer biology, such as miR-6129, miR-382, miR-655, miR-211, miR-590, miR-130a, miR-301a, and miR-1252. Collectively, these findings suggest that calcitriol exhibits a significant antitumor effect in this advanced cervical cancer model by blocking critical processes for tumor progression, underscoring the importance of maintaining adequate vitamin D nutritional status.

Humans↗
PubMed1991

The effect of long-term intravenous calcitriol administration on parathyroid function in hemodialysis patients.

Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium.

Adult↗
PubMed1991

Renal adaptation to dietary phosphate restriction in rats. Interactions with insulin and calcitriol.

Insulin may contribute to the increase in tubular reabsorption of phosphate during dietary phosphate restriction. Moreover, insulin is required for the stimulation of calcitriol under this experimental condition. To evaluate whether calcitriol plays a role in the antiphosphaturic effect of insulin during phosphate restriction, phosphate uptake was measured in brush border membrane vesicles (BBMVs) obtained from the following six experimental groups of rats: normal (0.8%)-phosphate diet for 1 wk, low (0.03%)-phosphate diet for 1 wk, normal-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low-phosphate diet and streptozocin and exogenous insulin, and low-phosphate diet and streptozocin and exogenous calcitriol. BBMV phosphate uptake was higher in the nondiabetic rats on a low-phosphate diet than in the controls on a normal-phosphate diet. BBMV phosphate uptake was not different between diabetic rats on a normal-phosphate diet than in nondiabetic controls on the same diet. In contrast, BBMV was significantly lower in diabetic rats on a low-phosphate diet than in nondiabetic controls on the same diet. Exogenous insulin but not calcitriol restored the increase in BBMV phosphate uptake in diabetic rats on a low-phosphate diet. Plasma calcitriol levels were increased threefold in nondiabetic rats fed a low-phosphate diet. Streptozocin-induced diabetes abolished the adaptive increase in plasma calcitriol. Exogenous insulin and calcitriol administration to diabetic rats on a low-phosphate diet resulted in similar increases in plasma calcitriol levels. These results suggest that, during dietary phosphate restriction, insulin stimulates renal phosphate retention independently of its effect on calcitriol.

Acclimatization↗
PubMed1989

Calcitriol inhibits the PHA-induced production of IL-2 and IFN-gamma and the proliferation of human peripheral blood leukocytes while enhancing the surface expression of HLA class II molecules.

1 alpha-dihydroxivitamin D3 [calcitriol; 1,25-(OH)2D3], the most biologically active metabolite of vitamin D3, exerts several effects on peripheral blood mononuclear cells (PBMC). We report here the effects of calcitriol on PBMC proliferation and on the expression of some lymphocyte surface differentiation markers, as well as its action on lymphokine production. Calcitriol inhibited the proliferation of PHA-activated PBMC in a dose-dependent manner, with peak activity at 10(-8) M. Exposure of PHA-stimulated PBMC to 10(-8) M calcitriol for 3 days tended to increase the percent of CD4- and CD8-positive cells, though statistical significance was not reached. A more striking effect of calcitriol was seen on the expression of the non-polymorphic determinants of HLA class II DR molecules; in cultures stimulated with PHA for 3 or 4 days; 10(-8) calcitriol doubled the percent of DR-positive cells as compared to controls treated with PHA alone. This activity peaked at 10(-9) M, a supra-physiologic dose. After 3 days in culture, 10(-8) M calcitriol strongly inhibited the production of both IL-2 and IFN-gamma. This effect was evident at different PHA concentrations (0.5, 1.5 and 3.0 micrograms/ml), and almost disappeared at 10(-10) M. These results underline the immunoregulatory role of calcitriol, but well defined experimental models in vitro are needed for elucidating the relevance of this compound in physiology and, possibly, in therapeutics.

Antigens, Differentiation↗
PubMed1992

Effect of calcitriol on the secretion of prostaglandin E2, interleukin 1, and tumor necrosis factor alpha by human monocytes.

Cells of the monocyte/macrophage lineage express specific receptors for calcitriol (1,25-dihydroxyvitamin D3) and secrete prostaglandins and several cytokines with potent effects on bone metabolism. The aim of this study was to determine the effect of calcitriol on the secretion of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and tumor necrosis factor (TNF alpha). Monocyte-enriched peripheral blood mononuclear cells (PBMC) from healthy subjects were cultured in the presence or absence of calcitriol (10(-11)-10(-7) M) and several stimulating agents. After 24 h, PGE2, IL-1, and TNF alpha were measured in the culture supernatants or lysates with specific immunoassays. Calcitriol induced a biphasic effect on PGE2 production by unstimulated cells and increased PGE2 synthesis by cells stimulated with either endotoxin or tau-interferon (IFN-tau). On the other hand, calcitriol inhibited the production of TNF alpha by monocytes stimulated with either IFN-tau or phorbol esters. This effect was not prevented by the addition of indomethacin, IL-1, or IL-2. Under the conditions used, we observed no effect of calcitriol on IL-1 alpha or IL-1 beta production. These results indicate that calcitriol induces in vitro marked changes in the secretion of monocyte products with known activity on bone cells. Further studies are needed to elucidate whether some effects of calcitriol on bone metabolism are mediated by the interaction of the sterol with cells of the immune system.

Calcitriol↗
PubMed1990

Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients.

Oral calcitriol is commonly used for the treatment of secondary hyperparathyroidism in patients undergoing long-term dialysis, but it has been suggested that intravenous (IV) or intraperitoneal (IP) administration enhances the therapeutic efficacy of the sterol. To examine potential mechanisms for this difference, the bioavailability of calcitriol was evaluated after single oral (PO), IV, and IP doses of 60 ng/kg in each of six adolescent patients with osteitis fibrosa undergoing continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD). Serum calcitriol levels were 3.6 +/- 4.3, 8.2 +/- 7.5, and 2.5 +/- 3.0 pg/mL, respectively, before IV, PO, and IP doses of the sterol; these values increased to similar levels at 24 hours: 55.6 +/- 14.6 pg/mL after PO, 56.4 +/- 17.6 pg/mL after IV, and 53.8 +/- 20.1 pg/mL after IP. Serum calcitriol levels were higher 1, 3, and 6 hours after IV injections than after PO or IP doses; values thereafter did not differ among groups. The bioavailability of calcitriol, determined from the 24-hour area under the curve (AUC0-24) for the increase in serum calcitriol concentration above baseline values was 50% to 60% greater after IV, 2,340 +/- 523 pg.mL-1.h-1, than after PO, 1,442 +/- 467 pg.mL-1.h-1, or IP, 1,562 +/- 477 pg.mL-1.h1, dosages, P less than 0.05. These differences were due to higher values for AUC during the first 6 hours after calcitriol administration. Although IP calcitriol did not increase sterol bioavailability, radioisotope tracer studies indicated that 35% to 40% of the hormone adheres to plastic components of the peritoneal dialysate delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: preliminary observations.

A direct effect of calcitriol on the regulation of the secretion of parathyroid hormone (PTH) has been shown in vitro and in vivo. In patients with renal failure on maintenance hemodialysis, it has been shown that intravenous (IV) administration of calcitriol appears to be superior to continuous oral administration. This may be due to the higher levels of calcitriol obtained in blood with consequent improved delivery of calcitriol to peripheral target tissues including the parathyroid glands. However, IV administration of calcitriol, is not practical for patients with end-stage renal disease (ESRD) who are maintained on continuous ambulatory peritoneal dialysis (CAPD). The present studies were designed to investigate whether intermittent administration of large doses of calcitriol orally ("pulse therapy") could mimic the effects of IV calcitriol in hemodialysis patients and achieve suppression of PTH secretion. Studies were performed in five patients who had been maintained on CAPD for more than 6 months. After basal determinations of calcium, phosphorus, and PTH, therapy was begun with calcitriol administered orally in a dose of 5 micrograms given twice per week. Calcium carbonate was continued as a phosphate binder. Dialysate calcium concentration was 1.75 mmol/L (3.5 mEq/L). With this therapy, PTH levels decreased rapidly, and, after 4 to 6 weeks of therapy, reached values 60% lower than pretreatment values. Mean values for serum calcium did not change significantly (2.29 +/- 0.12 mmol/L [9.6 +/- 0.5 mg/dL] before treatment compared with 2.32 +/- 0.08 mmol/L [9.7 +/- 0.25 mg/dL] after therapy). Mean serum phosphorus was also unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Subfractions in uremic plasma ultrafiltrate inhibit calcitriol metabolism.

Previous study from our laboratory has demonstrated that uremic plasma ultrafiltrate suppresses both the production rate (PR) and metabolic clearance rate (MCR) of calcitriol in normal rats. To characterize the the substances responsible for the suppression of the synthesis and degradation of calcitriol, we fractionated 20 ml uremic plasma ultrafiltrates into 13 fractions using high-performance liquid chromatography (HPLC) and studied the effect of each fraction on calcitriol metabolism. We measured the MCR and PR of calcitriol in normal rats after they were infused for 20 hours with each fraction dissolved in 20 ml normal saline. Using a UV absorption and fluorescence emission technique, several known uremic compounds were identified as individual peaks corresponding to the fractions. We found that fractions 4, and 6 to 13 markedly reduced the MCR of calcitriol. The patterns of the MCR suppression by the HPLC fractions suggest that there were at least two groups of chemically distinguishable compounds. Infusion of a solution containing all 13 fractions of the uremic ultrafiltrate also inhibited the calcitriol synthesis. One of the 13 fractions (fraction 4, containing uric acid, xanthine, and hypoxanthine) was further fractionated into eight subfractions. Infusion of subfractions 4 to 7 markedly reduced both the PR and MCR of calcitriol. We conclude that uremic plasma ultrafiltrate contains factors that inhibit calcitriol synthesis and degradation. These substances have molecular weight less than 2,000 Daltons.

Animals↗