Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We investigated the effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) on cultured fibroblasts and keratinocytes from patients with psoriasis and treated 17 patients with psoriasis with orally or topically administered 1,25-(OH)2-D3. Cultured fibroblasts from three of five patients showed a normal response to the antiproliferative activity of a physiologic dose of 1,25-(OH)2-D3, whereas fibroblasts from the other two had a partial resistance to the drug. Cultured keratinocytes from two patients with psoriasis possessed nuclear receptors for 1,25-(OH)2-D3 and the drug caused a dose-dependent inhibition of proliferation and induction of terminal differentiation of these cells similar to effects in normal cultured keratinocytes. Ten of 14 patients with moderate to severe psoriasis who received oral 1,25-(OH)2-D3 showed significant clearing of their hyperkeratotic plaques. Three patients had complete clearing that was sustained with maintenance therapy, but four patients received little or no benefit from the therapy. By the administration of 1,25-(OH)2-D3 as a single oral dose at bedtime, larger doses of the drug could be tolerated without evidence of hypercalciuria or hypercalcemia. Three patients who received topical 1,25-(OH)2-D3 showed a rapid response with complete clearing after 6 weeks of therapy. Therefore, these preliminary findings suggest that orally or topically administered 1,25-(OH)2-D3 may be a safe and effective alternative therapy for the treatment of psoriasis.
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PMID:A novel approach for the evaluation and treatment of psoriasis. Oral or topical use of 1,25-dihydroxyvitamin D3 can be a safe and effective therapy for psoriasis. 245 66

MC 903 is a novel vitamin D analogue which has been tested for its effects on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation MC 903 was compared to the natural metabolite of vitamin D3, 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] and to its synthetic analogue 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3]. MC 903 was found to be a potent inducer of cell differentiation and to inhibit cell proliferation and DNA-synthesis in concentrations comparable to those observed with 1,25(OH)2D3. 1 alpha (OH)D3, which is only active after metabolic conversion to 1,25(OH)2D3, was more than 100 times less potent. Oral or intraperitoneal administration of MC 903 to rats showed that the compound was at least 100 times less active than 1,25(OH)2D3 and 1 alpha (OH)D3 in causing hypercalciuria, hypercalcemia and bone calcium mobilisation. The low vitamin D activity of MC 903 was further confirmed by administration of the compound to rachitic rats. The strong direct effects of MC 903 on cell proliferation and cell differentiation, coupled with its decreased activity as a classical vitamin D makes this compound an interesting candidate for studies in human proliferative disorders such as psoriasis.
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PMID:Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo. 283 Aug 85

It is now recognized that it is casual exposure to sunlight that provides most humans with their vitamin D requirement. During exposure to sunlight, the high energy ultraviolet B photons (290-315 mm) photolyzes cutaneous stores of 7-dehydrocholesterol to previtamin D3. Once formed, previtamin D3 undergoes a thermal isomerization that results in the formation of vitamin D3. Vitamin D3 is biologically inert and requires successive hydroxylations in the liver and kidney to form its biologically active hormone 1,25-dihydroxyvitamin D3. The major physiologic function of 1,25-dihydroxy-vitamin D3 is to maintain blood calcium in the normal range. It accomplishes this by increasing the efficiency of intestinal calcium absorption and mobilizing stem cells to become osteoclasts which, in turn, remove calcium from the bone. It is now recognized that there are a variety of calcium metabolic disorders that are related to defects in the synthesis and metabolism of vitamin D. Chronic granulomatous disorders are often associated with hypercalciuria and hypercalcemia. The mechanism by which this occurs is that activated macrophages within granulomatous tissue, in an unregulated manner, convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Besides its calcemic activity 1,25-dihydroxyvitamin D3 is a potent antiproliferative factor for cells and tissues that possess its vitamin D receptor. This has clinical utility in that 1,25-dihydroxyvitamin D3 and its analogs have been successfully used for the treatment of the hyperproliferative skin disease psoriasis.
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PMID:Defects in the synthesis and metabolism of vitamin D. 758 27

Vitamin D topical analogues are now considered an excellent adjunct to the therapy of psoriasis. Systemic vitamin D3 treatment has been used occasionally, especially in case of associated hypocalcemia. We report five patients (aged 6, 16, 36, 58 and 79 years) successfully treated with vitamin D3 per os. Four had erythrodermic and/or pustulous psoriasis, and two of these had concomitant hypocalcemia. The fifth patient was a girl with pseudohypoparathyroidism and psoriasis vulgaris. The association of hypocalcemia and severe psoriasis is classical and was an incentive to try vitamin D treatment. A review of the literature showed that vitamin D can also be reported as a treatment of psoriasis vulgaris. Hypercalciuria and hypercalcemia are limiting risks. However calcium toxicity seems to be minor when vitamin D is given once a day at bedtime in doses lower than 2 micrograms/24 h. Double blind studies should be performed to determine the real efficacy of this treatment.
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PMID:[Treatment of psoriasis by oral calcitriol. A study of 5 cases and review of the literature]. 783 59

Urine calcium excretion is a very sensitive method of detecting vitamin D intoxication, and may rise in the absence of any apparent change in the serum level. Little attention has been paid to urine calcium levels during the large trials performed to assess the efficacy and safety of calcipotriol in psoriasis vulgaris. There are some urine calcium data from short-term studies of average dose rates of calcipotriol. However, there are no published data on long-term usage, nor on the use of dose rates at the upper end of the licensed range (100 g/week). In a group of 20 patients, who were using typical quantities of calcipotriol ointment (50 micrograms/g) to treat psoriasis vulgaris, urine calcium excretion was measured prior to treatment, and then monthly for 12 months. There was no significant change in urine calcium over the year. In a separate group of 10 patients, who were using calcipotriol in the same concentration, at the maximum recommended rate of 100 g/week, urine calcium was measured at baseline, and after 2 and 4 weeks. There was a statistically significant rise in calcium excretion. This is the first trial to demonstrate that topical calcipotriol affects calcium homeostasis when used within the recommended dose range. Further studies are necessary to determine more precisely the magnitude and variability of this effect in a large group of individuals. For the present, caution is required when prescribing calcipotriol for any patient with known hypercalciuria or a history of renal stone formation. Consideration should be given to monitoring urine calcium excretion during prolonged use at dose rates approaching the recommended maximum.
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PMID:Urine calcium excretion during treatment of psoriasis with topical calcipotriol. 821 55

Tacalcitol is a vitamin D3 analogue which is available in Japan as a 2 micrograms/g ointment for twice daily application and in Western markets as a 4 micrograms/g ointment for once daily application. Tacalcitol inhibits proliferation, and induces the differentiation, of keratinocytes. In addition, it appears to modulate inflammatory and immunological mediators in the skin which may be involved in the aetiology of psoriasis. No significant systemic drug absorption occurs after application of tacalcitol to the skin. Results of clinical trials indicate that topical tacalcitol is effective in the management of stable plaque psoriasis (and possibly pustular forms of the disease), and has a similar efficacy to topical betamethasone valerate in this setting. Application of tacalcitol ointment 4 micrograms/g once daily for up to 8 weeks did not cause hypercalcaemia or hypercalciuria. Mild local skin irritation has been reported in a variable proportion of patients (< or = 12%).
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PMID:Tacalcitol. 925 82

Although topical vitamin D3 derivatives have been used in the treatment of patients with psoriasis for the past 15 years, questions remain about the indications and limitations of application. Extensive personal experience gained during the development of calcitriol (1alpha25-dihydroxyvitamin D3) is therefore reviewed. Three double-blind, vehicle-controlled trials have revealed that calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories) has very good clinical efficacy. In a left-right comparison with vehicle ointment, complete clearance of psoriatic lesions was achieved in 48% of sites treated with calcitriol and a further 41% showed considerable or definite improvement. The clinical response to calcitriol in another study was as good as, or even better than, that achieved with betamethasone valerate 0.1% ointment. A preparation containing calcitriol 15 microg g(-1) did not show any clinical superiority to the lower dose but was associated with a higher risk of hypercalciuria, particularly when applied to extensive skin lesions. These results suggest that calcitriol 3 microg g(-1) ointment is an effective and safe treatment for chronic plaque psoriasis.
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PMID:Efficacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment: a review of our experience in Poland. 1150 7

Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of inflammatory skin diseases such as psoriasis. Hypercalcemia has not been previously reported during treatment with topical tacalcitol. We experienced a male patient with psoriasis and hypertension whose conditions were treated with tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and urinary excretion of calcium increased gradually. On day 28 of the treatment, his serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was terminated, seven days later, the serum calcium level had returned to the reference range without any specific treatment. The present case is the first report of hypercalcemia induced by vitamin D3 ointment and thiazide simultaneously.
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PMID:Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with thiazide diuretics in a case of psoriasis. 1468 37

1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an important hormone that regulates metabolism of calcium and phosphorus in small intestine, kidney, and bone, and its physiological action is expressed as ligand-dependent transcription activity mediated by vitamin D receptor (VDR). The VDR is found in various organs and cells including small intestine, kidney, and bone. In addition to the regulation of calcium metabolism, 1,25(OH)2D3 is involved in various biological reactions such as differentiation induction, antiproliferative effect, immunomodulatory effect, and regulation of cytokine and parathyroid hormone secretion. Thus, 1,25(OH)2D3 is expected to become a therapeutic drug for various related diseases. At present, a number of vitamin D derivatives are clinically applied to psoriasis, secondary hyperparathyroidism and osteoporosis but hypercalcemia and hypercalciuria are major concerns. Therefore, the current focus is directed toward new vitamin D derivatives with weak calcemic effects and a wide therapeutic window. In this summary, recent developments of new vitamin D derivatives for application in clinical treatment are described.
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PMID:Vitamin D receptor agonists: opportunities and challenges in drug discovery. 1684 44


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