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)

High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
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PMID:Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. 136 Jul 44

We have developed a sensitive, specific solid-phase immunoradiometric assay (IRMA) of parathyroid hormone-related protein (PTH-RP) with use of affinity-purified polyclonal immunoglobulins. Antibodies recognizing PTH-RP(37-74) are immobilized to a polystyrene bead to "capture" analytes from the sample; antibodies to epitopes within the 1-36 amino acid region of PTH-RP are labeled with 125I. This IRMA recognizes PTH-RP(1-74) and PTH-RP(1-86) equivalently, but does not detect N-terminal or C-terminal fragments of PTH-RP, intact human parathyrin (PTH), or fragments of PTH. PTH-RP is not stable in plasma at 3-5 degrees C or room temperature, but a mixture of aprotinin (500 kallikrein units/L) and leupeptin (2.5 mg/L) improves PTH-RP stability in blood samples. In plasma collected in the presence of these protease inhibitors from normal volunteers and patients with various disorders of calcium metabolism, PTH-RP concentrations were above normal (greater than 1.5 pmol/L) in 91% (42 of 46) of patients with hypercalcemia associated with nonhematological malignancy. In plasma from patients with other hypercalcemic conditions (e.g., primary hyperparathyroidism, sarcoidosis, and vitamin D excess), PTH-RP was undetectable. Above-normal concentrations of PTH-RP and total calcium decreased to normal in a patient with an ovarian cyst adenocarcinoma after surgical removal of the tumor. We conclude that PTH-RP is related to and probably the causative agent of hypercalcemia in most patients with cancer, and that measurements of PTH-RP are useful in the diagnosis and management of patients with tumor-associated hypercalcemia.
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PMID:Modified immunoradiometric assay of parathyroid hormone-related protein: clinical application in the differential diagnosis of hypercalcemia. 154 Sep 98

Topical vitamin D analogues offer a new, effective, more convenient and generally well-tolerated option for the treatment of psoriasis. Only psoriasis vulgaris has been intensively studied, but other forms of the disease may also respond. Both calcitriol and calcipotriol have been shown to be effective in numerous clinical trials, and the latter has compared well with betamethasone valerate and short-contact dithranol in controlled studies. Their mechanism of action is not yet fully understood and may prove complex. The most important effect may be a direct regulation of keratinocyte proliferation and differentiation. However, these compounds also have potent immunological properties, and may act by inhibition of cytokine production by keratinocytes or lymphocytes. Topical application of vitamin D analogues appears generally to be remarkably safe, but hypercalcaemia and hypercalciuria may develop if large quantities are used.
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PMID:Vitamin D analogues and psoriasis. 139 Jan 59

In order to prevent aluminum toxicity induced by the association of aluminum phosphate binder with 1 alpha(OH) vitamin D3 derivatives and the use of deferoxamine with its own hazards to diagnose and treat this toxicity, we have shown in 1982 that it was possible to replace the iatrogenic association of aluminum phosphate binder with 1 alpha OH vitamin D derivatives by oral calcium carbonate taken with the meals in order to bind phosphate and correct the negative calcium balance. This led to the disappearance of the crippling aluminic osteomalacia and adynamic bone diseases in our center. The effectiveness of CaCO3 without 1 alpha(OH)D3 derivatives in the control of hyperparathyroidism in dialysis patients has been proven by the appearance in four patients of our dialysis population of an histological idiopathic adynamic bone disease associated with relative hypoparathyroidism, and by the finding that more than 50% of our dialysis population treated by this sole treatment have plasma concentration of intact PTH below twice the upper limit of normal (that is, the threshold above which only significant histological osteitis fibrosa is observed). Besides the compliance problem, the limit of CaCO3 is the occurrence of hypercalcemia which occurs in about 8% of the measurements. Since calcium acetate binds twice as much phosphate for the same dose of elemental calcium as CaCO3, its use has been recommended. However, clinical experience has shown that in spite of the fact that half the dose of calcium element given as acetate does actually control predialysis plasma phosphate as well as CaCO3, the incidence of hypercalcemia is not decreased, probably because calcium availability at the alkaline pH of the intestine is much greater with Ca acetate. When hypercalcemia is frequent (and not explained by autonomized hyperparathyroidism, adynamic bone disease, overtreatment with vitamin D, granulomatosis or neoplasia) it is necessary either to decrease the dose of calcium and complete the necessary binding of phosphate by adding small doses of Mg(OH)2 or Mg carbonate, provided the dialysate Mg is decreased to 0.2 to 0.35 mmol/liter to prevent hypermagnesemia or to decrease the dialysate calcium (DCa) concentration. The decrease of DCa can be made either just when hypercalcemia occurs or on a systemic basis according to the amount of CaCO3 used and to the necessity of associating 1 alpha(OH) vitamin D3 derivatives.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of alkaline calcium salts as phosphate binder in uremic patients. 140 82

Chronic plaque psoriasis is by far the most frequent form of the disease and is usually amenable to home treatment. The therapeutic armamentarium for self-treatment of psoriasis has, until recently, been limited to emollients, tar, dithranol and topical corticosteroids. Although limited progress has been made in improving formulations and treatment regimes for these compounds, they still have significant drawbacks in terms of either unwanted effects or cosmetic acceptability. Topical vitamin D analogues offer a new, effective, convenient and safe option for self-treatment of psoriasis. Most research has been performed on calcipotriol. This has compared well to beta-methasone valerate and short-contact dithranol in controlled studies. Skin irritation is frequently noticed by patients, but rarely requires treatment to be discontinued. The mechanism of action appears most likely to be a direct regulation of keratinocyte proliferation and differentiation. Calcipotriol has relatively little effect on calcium metabolism and appears to be safe when used according to established guidelines but hypercalcaemia may develop if excessive quantities are used.
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PMID:Progress in self treatment for psoriasis vulgaris. 142 14

Clinical usefulness of calcium acetate (CAA) as phosphorus binder was assessed in 19 stable hemodialysis patients with persistent hyperphosphatemia. All were dialysed thrice weekly with a constant dialytic schedule and a dialysate calcium of 3.5 mEq/l. One month prior the study beginning all patients stopped assumption of Ca and vitamin D supplements. In the first period of the study CAA (mean daily doses 2.2 g) was administered for one month followed by 15 days of withdrawal. The mean serum phosphorus decreased from 7.6 +/- 1.4 to 5.8 +/- 0.8 mg% (p < 0.005). After 15 days of withdrawal mean serum phosphorus reached the pretreatment value. Then the patients entered a long term study with personalized doses of CAA (between 1 and 4 g/day) and administration in 8 of them of alpha-calcidol. After a mean follow-up period of 5.4 +/- 1.5 months serum phosphorus was reduced from 7.5 +/- 1.1 to 5.6 +/- 1.1 mg% (p < 0.0005) while calcemia increased from 9.0 +/- 0.7 to 9.6 +/- 0.6 mg% (p < 0.005). Only one patient developed mild hypercalcemia. We concluded that CAA is a safe alternative to calcium carbonate for the control of hyperphosphatemia of uraemic patients for the most efficient phosphorus binding and the lesser absorption of calcium.
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PMID:Treatment of uraemic hyperphosphatemia with calcium acetate: a safe alternative to calcium carbonate. 145 93

EB1089 is a novel vitamin D analogue which has been tested for its effects on breast cancer cell growth in vitro, using the established human breast cancer cell line MCF-7, and in vivo on the growth of established rat mammary tumours. Both EB1089 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited MCF-7 cell proliferation with the synthetic analogue being at least an order of magnitude more potent than the native hormone. In vivo anti-tumour effects were investigated using the N-methyl-nitrosourea-induced rat mammary tumour model. Oral treatment with EB1089 was tested at three doses. With the lower dose, significant inhibition of tumour growth was seen in the absence of a rise in serum calcium. The same dose of 1,25-(OH)2D3 had no effect on tumour growth but caused hypercalcaemia. With the higher dose of EB1089, striking tumour regression was seen although serum calcium rose. This report demonstrates that EB1089 possess enhanced anti-tumour activity coupled with reduced calcaemic effects relative to 1,25-(OH)2D3 and thus may have therapeutic potential as an anti-tumour agent.
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PMID:EB1089: a new vitamin D analogue that inhibits the growth of breast cancer cells in vivo and in vitro. 147 92

Three cases of hypercalcaemia secondary to acute adrenocortical insufficiency are described; all the patients had moderate to severe renal impairment, one being on chronic dialysis treatment with no residual diuresis. Parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D] were low, indicating a suppressed PTH-vitamin D axis. In the two patients with partial renal impairment, urine Ca excretion was increased, indicating increased load of the cation into the extracellular fluid (ECF), most probably from bone. Saline infusion, to correct any ECF depletion and to increase urine Ca excretion, could not fully correct the hypercalcaemia. Complete correction of plasma Ca levels was observed shortly after the institution of hormonal substitutive therapy. Despite the evidence of increased Ca mobilization from bone, bone biopsies in two patients did not show any signs of cell-mediated bone resorption; instead, bone cell activity appeared to be suppressed. Thus, glucocorticoid deficiency appears to induce Ca mobilization from bone stores by mechanism(s) unrelated to bone remodelling processes.
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PMID:Hypercalcaemia in Addison's disease: calciotropic hormone profile and bone histology. 147 63

The effect of intravenous 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on circulating levels of intact parathyroid hormone (PTH 1-84) and COOH-terminal immunoreactive PTH(PTH 53-84) was examined in 13 patients on chronic hemodialysis. Thirteen patients were treated for 300 days (10 months), 9 patients for 520 days (14 months) and 6 patients for 720 days (2 years) with increasing doses of 1 alpha(OH)D3 intravenously under careful control of plasma Ca2+. Blood samples were obtained 1 week before start of treatment and then at every 2nd week. None of the patients had previously been treated with oral vitamin D metabolites. Intact PTH levels were maximally suppressed after 27-33 weeks of treatment by approximately 73%. At the end of the study periods, PTH 1-84 was still suppressed by 78 +/- 4.3% after 300 days, 78 +/- 8.8% after 520 days and 85 +/- 6.5% after 720 days. Plasma Ca2+ was kept within normal levels, but showed an initial increase from 1.14 +/- 0.03 to 1.27 +/- 0.15 mmol/l, and an adjustment of the doses of 1 alpha(OH)D3 was necessary. The present investigation demonstrated (1) that intravenous administration of the 1-hydroxylated vitamin D metabolite 1 alpha(OH)D3 induced a significant decrease in circulating levels of biologically active intact PTH, and (2) that it was possible to maintain the marked suppression of PTH secretion by intravenous treatment of 1 alpha (OH)D3 for up to 2 years. Hypercalcemia could be avoided by careful monitoring of plasma Ca2+ and adjustment of the doses of 1 alpha(OH)D3.
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PMID:Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis. 148 99

The recent advances in molecular biology and cytogenetics have made it possible to localize, clone and characterize some of the genetic abnormalities which result in disorders of phosphate and calcium homeostasis. Thus, the genes causing X-linked hypophosphataemic rickets, Lowe syndrome, X-linked recessive hypoparathyroidism, Di George syndrome, multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and vitamin D-dependent rickets type I have been mapped. In addition the genes involved in the pathogenesis of the humoral hypercalcaemia of malignancy, vitamin D-dependent rickets type II, pseudohypoparathyroidism, and some of the autosomal forms of hypoparathyroidism have been cloned and the mutations characterized. The molecular and genetic studies which have mapped and identified these disease genes are described and the implications of these developments in clinical practice and in further elucidation of the mineral metabolic defects are discussed.
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PMID:Molecular genetics of mineral metabolic disorders. 152 19


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