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)

A 22-year-old man was given 70-75 million I.U. vitamin A by mouth for 38 days as a treatment for psoriasis. But it had to be stopped because of the appearance of typical signs of vitamin A poisoning. Acute renal failure set in nine days later, after hospital admission for cerebral signs. In addition to conventional conservative treatment, seven haemodialyses were undertaken, with complete restitution to normal within 12 days. The skin disease and the cerebral signs predominated, in addition to later anaemia, hypercalcaemia, bone pain, and acute renal failure, the latter confirmed by renal biopsy. There were no histological changes in the liver.
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PMID:[Renal tubular failure after treatment with high dose of vitamin A (author's transl)]. 124 99

The naturally occurring 1,25(OH)2 vitamin D3 and the two synthetic derivatives 1,24(OH)2 vitamin D3 and calcipotriol (Calcipotriol, INN, Calcipotriene, USAN) have a profound effect on keratinocyte proliferation and differentiation. Clinical trials have shown an effect of all three derivatives in psoriasis. The limiting factor for the use of 1,25(OH)2 vitamin D3 is the risk of hypercalcemia, which is 100 to 200 times less for calcipotriol and that may be less also for 1,24(OH)2 vitamin D3. Presently, calcipotriol in an ointment base has been marketed in a number of countries and represents an alternative to treatment with topical glucocorticoids and dithranol.
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PMID:Psoriasis treatment with vitamin D derivatives. 133 62

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

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

Calcipotriol is a non-calcaemic vitamin D3 analogue. In short-term studies, topically applied calcipotriol is both efficacious and safe for the treatment of psoriasis vulgaris. The purpose of the present study was to determine the efficacy and safety of calcipotriol ointment in patients treated for approximately 6 months. Fifteen patients with plaque-type psoriasis were treated daily with calcipotriol ointment 50 micrograms/g. After treatment for 6 weeks there was a significant alleviation of erythema, infiltration and scaling. This degree of improvement was maintained throughout the study, except in one patient, who was withdrawn at week 15 because of minimal improvement. At the end of treatment, 80% of the patients showed a moderate improvement at least. Local adverse events occurred in 3 patients. These were mild and transient. Hypercalcaemia or other laboratory abnormalities did not develop in any patient. Morphometric examination of biopsies taken from perilesional skin (i.e. skin exposed to calcipotriol) at the end of treatment did not show signs of epidermal or dermal atrophy compared with uninvolved psoriatic skin. Although only a limited number of patients participated in the study, these results indicate that calcipotriol ointment 50 mu/g is both efficacious and safe for the long-term treatment of psoriasis.
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PMID:Long-term efficacy and tolerability of topical calcipotriol in psoriasis. Results of an open study. 168 28

1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to be a hormonally active form of vitamin D3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 alpha,24(R)-dihydroxyvitamin D3 (1,24(OH)2D3), a novel synthetic derivative of vitamin D3, is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH)2D3 had the same affinity as 1,25(OH)2D3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH)2D3 induced their differentiation in a time- and dose-dependent manner, as determined by the formation of a cornified envelope and an increase in the activity of transglutaminase. 1,24(OH)2D3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH)2D3 were similar to, or rather more than, those of physiologically active 1,25(OH)2D3. However, 1,24(OH)2D3 was found to cause less hypercalcemia than 1,25(OH)2D3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.
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PMID:1,24(R)-dihydroxyvitamin D3, a novel active form of vitamin D3 with high activity for inducing epidermal differentiation but decreased hypercalcemic activity. 216 63

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

Possible new indications for the use of octreotide are discussed. In October 1988, octreotide received FDA-approved labeling for use in the management of carcinoid syndrome and vipomas. Since that time, research results and clinical experience have accumulated that suggest a potentially much broader therapeutic role for octreotide. Reports continue to be published on the use of octreotide for treating pituitary tumors, gastroenteropancreatic tumors, diabetes mellitus, AIDS-associated diarrhea, autonomic neuropathy, pancreatitis, pancreatic pseudocysts and ascites, complications of pancreatic surgery and transplantation, ileostomy-associated diarrhea, enterocutaneous fistulas, pancreatic fistulas, dumping syndrome, short bowel syndrome, and gastrointestinal bleeding. Other emerging indications for the use of octreotide include psoriasis, hypercalcemia, cancer-related pain, polycystic ovary syndrome, and certain cancers. In children, octreotide has been studied for use in treating hyperinsulinemic hypoglycemia of infancy. Along with the common adverse effects of octreotide, such as pain at the injection site and nausea, less frequent effects, such as cholelithiasis, gallbladder hypercontractility, and gastritis have now been described. Much of what has been learned is based on small uncontrolled studies and case reports, since the rarity of many of the conditions for which octreotide has shown promise has tended to preclude larger studies. As clinical experience with octreotide accumulates and better-designed trials are completed where possible, a broader therapeutic role for octreotide is likely to be recognized.
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PMID:Emerging indications for octreotide therapy, Part 1. 804 37


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