Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The measurement of calciotropic hormones may be useful in metabolic bone disease. Assays of intact parathyroid hormone are essential to differentiate between primary hyperparathyroidism and nonparathyroid-mediated hypercalcemia. Vitamin D status is best assessed by measuring serum 25(OH)D. Concentrations of calciotropic hormones should be measured in osteoporotic patients if the degree of osteopenia does not correlate with the risk factors. The decrease in circulating parathyroid hormone in osteoporotic patients treated with vitamin D reflects the success of the vitamin D treatment. Parathyroid hormone is also a potential anabolic agent.
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PMID:Diagnostic and therapeutic aspects of calciotropic hormones. 922 85

Hypercalcemia occurs in children of all ages. A serum calcium level over 15 mg/dL can be life-threatening. The association between familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NHPT) has been discussed. FHH is characterized by a high serum calcium concentration, relatively low urine calcium excretion, and an inappropriately normal parathyroid hormone (PTH) concentration. On the other hand, NHPT is a rare disease characterized by markedly increased serum calcium (15 mg/dL) and PTH concentrations, and is fatal without parathyroidectomy early in life. Recently, a complementary DNA encoding an extracellular calcium-sensing receptor has been isolated. Furthermore, three mutations in the receptor gene in FHH and NHPT individuals have been described. Thus, heterozygotes and homozygotes of FHH may have an intermittent hypercalcemia and NHPT, respectively. Vitamin D-related hypercalcemia, and vitamin D intoxication and immobilization are also discussed.
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PMID:Hypercalcemia in children: an overview. 931 97

Vitamin D intoxication developed in Vietnamese Pot-Bellied Pigs (Sus scrofa) fed 2 commercially available swine rations. Pronounced hypercalcemia and a history incompatible with other causes of hypercalcemia led to confirmation of this diagnosis by plasma vitamin D metabolite analysis in 2 affected animals as compared to a control animal. Feed sample analysis suggested the diet as the likely source of toxicity.
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PMID:Dietary vitamin D toxicity in a household of pot-bellied pigs (Sus scrofa). 950 59

Vitamin D is required for the normal development of teeth and bones. When there is excess vitamin D, systemic and dental changes may occur. This is a case report of a girl who experienced hypercalcemia secondary to excess vitamin D derived from the consumption of milk that was incorrectly fortified. The changes in the permanent dentition to date are enamel hypoplasia and focal pulp calcification. These changes correspond to the timing of the toxemia caused by hypervitaminosis D.
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PMID:Dental changes in hypervitaminosis D. 957 50

Vitamin D compounds induce differentiation of human leukemic cells and have potential for the treatment of leukemia. In this review we summarize some of the basic mechanisms underlying the action of vitamin D compounds. A variety of vitamin D analogues were synthesized until now, some of which have enhanced antileukemic activity and a decreased propensity to cause hypercalcemia. Most actions of vitamin D compounds are mediated by nuclear receptors. In vivo, vitamin D binding protein interacts with free vitamin D compounds. Both in normal and leukemic cells, vitamin D compounds cause a differentiation to monocytes and macrophages. A variety of genes are regulated by vitamin D compounds. Recently, the cell cycle inhibitory gene p21/WAF-1/CIP-1 was characterized. The expression de novo of WAF-1 in blasts of acute myelogenous leukemia is an independent factor of unfavorable prognosis. In HL-60 leukemic cells treated with vitamin D analogs, WAF-1 can be induced by nano- or picomolar concentrations of vitamin D analogs and correlates with the induction of a differentiated phenotype. When vitamin D analogs are combined in-vitro with retinoids, an irreversible differentiation is observed. Clinical trials of vitamin D analogs are indicated in the situation of minimal residual disease and in combination with standard chemotherapy.
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PMID:Vitamin D analogs, leukemia and WAF1. 986 91

Impaired calcitriol synthesis is one of the major factors contributing to the development of secondary hyperparathyroidism in patients with chronic renal failure. Vitamin D therapy, particularly 1alpha-hydroxyvitamin D3, even in low doses, has been shown to be effective in the treatment of secondary hyperparathyroidism in patients with mild-to-moderate chronic renal failure. Complications associated with calcitriol and alfacalcidol therapy, which include hypercalcemia and progressive deterioration of renal function, have been reported in some patients. The majority of the studies reviewed, however, demonstrated that daily calcitriol and alfacalcidol doses below 0.25 microg are rarely associated with hypercalcemia, hyperphosphatemia, or progressive decline in renal function. In addition, these complications usually resolve with the reduction in dose or discontinuation of the medication. Thus, vitamin D therapy may be valuable in the treatment of patients with mild-to-moderate chronic renal failure who may be at high risk of developing secondary hyperparathyroidism.
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PMID:Prevention of renal osteodystrophy in predialysis patients. 1037 40

Vitamin D is a steroid hormone best known for its activity in regulating calcium and bone metabolism. Epidemiological evidence suggests that vitamin D may play a role in inhibiting the development of colon and prostate cancer. Vitamin D receptors are expressed in many types of malignant cells; in vitro and in vivo vitamin D and vitamin D analogues are active in suppressing the development and inhibiting the growth of numerous human and animal tumors. The major toxicity of the active form of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol), is the induction of hypercalcemia. There are no data indicating the maximum tolerated dose of calcitriol administered every other day (QOD) s.c. We hypothesized that this route and schedule would permit administration of higher doses of calcitriol, which might have anticancer activity. We conducted a Phase I trial of calcitriol given s.c. QOD in patients with advanced solid tumors. Thirty-six patients were entered at doses ranging from 2 to 10 microg QOD; dose-limiting toxicity (hypercalcemia) occurred in three of three patients entered at the 10-microg QOD dose. Hypercalciuria occurred at all dose levels examined. No other toxicity was seen. Assessment of serum calcitriol concentrations by a RIA revealed a decrease in concentration-time curves on day 7 compared to day 1 of therapy. A dose-dependent increase in peak serum level and estimated area under the concentration-time curve was seen. The maximum serum levels occurred at the 10-microg QOD dose: 288 +/- 74 and 321 +/- 36 pg/ml at days 1 and 7, respectively. The normal range of calcitriol serum concentration, determined using this assay, is 16-56 pg/ml. Serum calcitriol levels were maintained at near peak concentrations for at least 8 h following s.c. injection. This study indicates that substantial doses of calcitriol can be administered via this route with tolerable toxicity. Studies to explore approaches to ameliorate the hypercalcemia induced by calcitriol and to explore alternative schedules and interactions with other agents are warranted.
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PMID:A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. 1038 17

Vitamin D therapy is widely used for the treatment of secondary hyperparathyroidism associated with chronic renal failure. However, administration of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or its precursor 1alpha(OH)D(3), especially in combination with calcium-based phosphate binders, often produces hypercalcemia. Several vitamin D analogs have been developed that retain the direct suppressive action of 1,25(OH)(2)D(3) on the parathyroid glands but have less calcemic activity. These analogs offer a safer and more effective means of controlling secondary hyperparathyroidism. 22-Oxa-1,25(OH)(2)D(3) (22-oxacalcitriol or OCT), 19-nor-1, 25(OH)(2)D(2) (19-norD(2)) and 1alpha(OH)D(2) have been tested in animal models of uremia and in clinical trials. Intravenous 19-norD(2) and oral 1alpha(OH)D(2) have been approved for use in the United States; OCT is currently under review. The mechanisms by which these analogs exert their selective actions on the parathyroid glands are under investigation. The low calcemic activity of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression. The selectivity of 19-norD(2) and 1alpha(OH)D(2) is achieved by a distinct mechanism(s). Knowledge of how these compounds exert their selective actions on the parathyroid glands may allow the design of more effective analogs in the future.
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PMID:Vitamin D analogs: perspectives for treatment. 1068 62

Vitamin D, parathyroid hormone (PTH), and parathyroid hormone-related peptide (PTHrP) are major regulators of calcium metabolism and vitamin D can also reduce the growth of normal cells and tumor cells. PTHrP and PTH act via a common membrane receptor (PTHR). The mouse PTHR is regulated by a kidney-selective upstream promoter P(1) and ubiquitous downstream promoter P(2). In vitro and in vivo 1,25(OH)(2)D can inhibit PTHR expression in bone but not cartilage by downregulating transcription via P(2). Gene transcription of PTHrP per se can also be downregulated by 1,25(OH)(2)D and by low calcemic vitamin D analogs. This inhibitory effect may reduce the hypercalcemia caused by overproduction of PTHrP by tumor cells. In a malignant keratinoctye cell line, phosphorylation of the retinoid X receptor alpha occurs through the activated Ras-MAP kinase pathway and results in attenuated trans-activation by the vitamin D receptor, its heterodimeric partner. This decreases the growth-inhibitory efficacy of 1,25(OH)(2)D. Studies of the capacity of vitamin D to alter PTHrP production and action and of its anti-proliferative effects can, therefore, shed important light on basic mechanisms controlling these events, and may also have major implications for clinical medicine and therapeutics.
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PMID:Studies of the effects of 1,25-dihydroxyvitamin D on skeletal and calcium homeostasis and on inhibition of tumor cell growth. 1138 62

Vitamin D(3) affects the immuno response and improves experimental autoimmune diseases. We investigated the effect of 1,25-dihydroxycholecalciferol (1,25[OH](2)D(3)) Rocaltrol as a single immunosuppressive agent and in combination with low-dose cyclosporin A (CsA) in vascularized liver allografts in rats in a high-responder strain combination (ACI-->Lewis). Recipients were placed on a low-calcium diet 7 days before transplantation and were treated with 0.1 or 1 microg/kg/d 1,25(OH)(2)D(3) intraperitoneally beginning 3 days before transplantation. Treatment combining 1,25(OH)(2)D(3) with CsA (2 mg/kg/d) was also tested. Graft function and survival, histologic rejection, and concentrations of interleukin (IL)-2, -4, -10, and -12 in serum and in grafts were measured. 1,25(OH)(2)D(3) increased allograft survival in a dose-dependent manner when compared with controls (P <.05 for both groups). Serum bilirubin, aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities were significantly lower in 1,25(OH)(2)D(3)-treated animals. Vitamin D reduced the concentration of IL-2 and IL-12 in serum and in grafts, and increased IL-4 and IL-10 in the grafts. The rejection activity index 10 days after transplantation was significantly lower in low- and high-dose 1,25(OH)(2)D(3)-treated rats compared with vehicle-treated controls (P <.0001 for both groups). The combination of either low-dose or high-dose vitamin D(3) and CsA prolonged graft survival when compared with low-dose CsA only (P <.05 for both groups). After 3 weeks, hypercalcemia developed in high-dose 1,25(OH)(2)D(3)-treated rats. It is concluded that 1,25(OH)(2)D(3) prolongs survival of liver allografts in rats by decreasing the severity of acute rejection. Analogues of vitamin D with fewer hypercalcemic effects may have potential as immunosuppressive drugs in liver transplantation.
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PMID:1 alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts. 1167 63


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