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)

Vitamin D3 metabolites and iPTH were measured in 26 patients at various times after renal transplantation. Hypercalcaemia (serum Ca greater than 2.62 mmol/L, 14 patients) was associated with hyperparathyroidism (p less than 0.02) and raised 1,25(OH)2D3 (p less than 0.05) but raised 1,25(OH)2D3 was also found in most patients in the normocalcaemic group. Lower 25(OH)D3 concentrations were found in the group with normal 1,25(OH)2D3 compared to the group with elevated 1,25(OH)2D3 (p less than 0.05). Low values of 24,25(OH)2D3 were found in both the normocalcaemic and hypercalcaemic patients (p less than 0.002). Impaired creatinine clearance (less than or equal to 55 ml/min, mean: 38 ml/min) was not associated with reduced 1,25(OH)2D3. No difference in D3 metabolites was found between hypophosphataemic and normophosphataemic patients.
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PMID:Vitamin D3 metabolites in hypercalcaemic adults after kidney transplantation. 631 19

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 D3 and its metabolites, particularly 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3), have received increasing attention as potential anticarcinogens in the prevention of cancers in a number of organs, including the colon. These agents, however, have the potential to induce hypercalcemia, thus limiting their practical use for these purposes. In the present studies it was, therefore, of interest to determine whether dietary supplementation with 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (RO24-5531), a recently synthesized apparently noncalcemic analogue of 1 alpha,25(OH)2D3, inhibited colon cancer induced by azoxymethane (AOM). Rats were placed on a standard diet or fed this diet with supplemental RO24-5531 (2.5 nmol/kg feed) before and during (initiation arm), or after AOM or vehicle administration (postinitiation arm). After 34 weeks of study, animals in each group were sacrificed, and their colons were removed and examined macroscopically and microscopically for the presence of tumors. At the time of sacrifice, the animals' serum calcium, phosphorus, 25-hydroxyvitamin D3 and 1 alpha,25(OH)2D3 levels were also analyzed. The results of these studies demonstrated that dietary RO24-5531 supplementation during the initiation arm of these experiments significantly reduced (by 70%) the incidence of AOM-induced colonic tumors compared to rats on the standard diet without RO24-5531. Moreover, this dietary regimen abolished the development of adenocarcinomas in this model. Although there was also a trend for dietary RO24-5531 supplementation during the postinitiation arm of this study to reduce the incidence of colon tumors, this did not reach statistical significance (P > 0.05). In addition, neither dietary RO24-5531 supplementation regimen significantly influenced the animals' rates of growth or their serum levels of calcium, phosphorus, or 25-hydroxyvitamin D3. These studies, therefore, demonstrate for the first time that supplemental dietary RO24-5531 is a chemopreventive agent in the AOM model of experimental colonic carcinogenesis. They also suggest that this agent may ultimately prove useful in clinical colon cancer chemopreventive trials.
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PMID:1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol, a noncalcemic analogue of 1 alpha,25-dihydroxyvitamin D3, inhibits azoxymethane-induced colonic tumorigenesis. 760 26

Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby protect against colorectal cancer. Cell turnover is increased in ulcerative proctocolitis, which might therefore respond to vitamin D3 metabolites. This study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis. Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M). After 15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest, and CCPR was determined by linear regression analysis of accumulated metaphases. Compared with values in 17 controls with incidental anal conditions, median rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80 (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22) cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition.
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PMID:Calcipotriol inhibits rectal epithelial cell proliferation in ulcerative proctocolitis. 782 8

We report a male newborn with typical clinical signs of idiopathic infantile hypercalcemia (IIH); that is, hypercalcemia, hypercalciuria, an elfin face and nephrocalcinosis without giving Vitamin D3 supplementation to the patient. He had been treated with a vitamin D-free, low calcium milk and rectal administration of exogenous calcitonin (elcatonin). The latter seemed to be more effective as a treatment for IIH. The serum calcium level came within the normal range and the serum 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) level decreased from 101.5 to 75.6 pg/mL with the treatments mentioned above. These results suggest that a high serum concentration of 1,25(OH)2D3 is part of the pathogenesis of IIH. However, we were not able to clarify the pathogenesis of the high serum concentration of 1,25(OH)2D3.
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PMID:Idiopathic infantile hypercalcemia discovered in the newborn period. 787 92

1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxicity is hypercalcaemia. The cellular action of 1,25(OH)2D3 is mediated by binding to an intracellular protein, the vitamin D receptor (VDR). We have evaluated the activity of 1,25(OH)2D3 and its non-calcaemogenic analogue MC903 in the SU-DHL4 and SU-DUL5 B cell lines which carry the 14;18 translocation characteristic of follicular NHL, and also the expression of the VDR in a range of B cell NHLs. Both agents induced differentiation and had an antiproliferative effect on the SU-DHL4 and SU-DUL5 cell lines. However this occurred at a relatively high concentration (10(-7) M) which exceeds the physiological concentration of 1,25(OH)2D3 by approximately 10(3)-10(4)-fold. Expression of the VDR was low in each cell line and in the low grade lymphoma tumour samples. To account for the observed clinical response to 1 alpha OHD3 (alpha-calcidol) in follicular NHL a network is suggested whereby 1,25(OH)2D3 modulates the activity of CD4+T cells which have previously been shown to promote follicle centre cell proliferation. Vitamin D3 analogues may enable serum levels to be achieved which produce a direct action on follicular lymphoma cells without disturbing calcium metabolism.
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PMID:The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma. 839 90

Vitamin D has been discovered at the beginning of this century. 7-Dehydrocholesterol is converted to vitamin D3 in the skin and after several hydroxylations it is further converted to the active hormonal form, 1 alpha,25-(OH)2D3. Vitamin D stimulates the absorption of calcium and phosphate and is an essential link in bone resorption and formation and calcium metabolism. 1 alpha,25-(OH)2D3 acts through a vitamin D receptor. These receptors are not only present in clinical target organs (kidney, gut, liver) but can also be found in a wide variety of "non-classical" tissues (keratinocytes, cells belonging to the immune system). Moreover, numerous cells (keratinocytes, macrophages) can locally synthetize or can be induced to synthetize 1 alpha,25-(OH)2D3 and these cells are responsive to its action. When these data are combined, a possible paracrine function of 1 alpha,25-(OH)2D3 can be suspected. Via this paracrine function 1 alpha,25-(OH)2D3 can suppress the cellular and humoral immunity. Based on the discovery of these effects on immune cells in vitro it became clear that 1 alpha,25-(OH)2D3 might be an interesting molecule to prevent autoimmune diseases and organ transplantation. This has already been shown in several animal models (Heymann nephritis, diabetes mellitus, experimental allergic-encephalomyelitis, lupus). 1 alpha,25-(OH)2D3 demonstrates however some side-effects (hypercalciuria, hypercalcemia, bone resorption) and for this reason 1 alpha,25-(OH)2D3-analogs are developed with dissociated effects i.e. an activity profile that allows a specific action on non-classical tissues without calcemic effects. Some chemical modifications of the side chain, A and/or CD-ring results in "superanalogs" with 10 to 100-fold more activity on cell differentiation and the immune system then 1 alpha,25-(OH)2D3 but with less calcemic activity in vivo. These biological effects can be explained by differences in pharmacokinetics (low affinity for the plasma vitamin D-binding protein and short extracellular half-life) and increased intracellular activation and gen transactivation. Preclinical research must still be done to select the most potent superanalogs and to find the exact protocols for the prevention and treatment of autoimmune diseases and rejection of transplanted organs.
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PMID:[Immune modulation by vitamin D analogs in the prevention of autoimmune diseases]. 857 69

Vitamin D3 (650 pmol and 6.50 nmol/100 g body wt), 25-hydroxyvitamin D (650 pmol and 6.50 nmol/100 g body wt), and 1,25-dihydroxyvitamin D (65 pmol and 650 pmol/100 g body wt) were administered daily to the freshwater snake Natrix piscator for 15 days. Both serum calcium and inorganic phosphate levels were increased significantly in all of the treated groups. This is the first report of hypercalcemia and hyperphosphatemia in reptiles induced by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.
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PMID:Effect of various vitamin D metabolites on serum calcium and inorganic phosphate in the freshwater snake Natrix piscator. 857 58

Vitamin D3 (50 I.U./100 g body wt) was injected daily intraperitoneally to the fish H. fossilis maintained in artificial freshwater, calcium-rich freshwater and calcium deficient freshwater. The animals were killed on day 1, 3, 5, and 10. The serum calcium levels were estimated and CS were fixed for histological studies. Administration of vitamin D3 induced hypercalcemia in the fish kept in all the three different media. The AF-positive cells of CS of vitamin D3 treated specimens kept in artificial freshwater, calcium-rich freshwater and calcium-deficient freshwater depict hyperactivity which is expressed by their degranulation and increased nuclear volume. The AF-negative cells of CS of vitamin D3-treated fish kept in artificial freshwater have not shown any change, however, the AF-negative cells of the fish treated with vitamin D3 and maintained in calcium-rich freshwater and calcium-deficient freshwater exhibit a decrease in their nuclear volume.
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PMID:Vitamin D3- induced histological changes in the corpuscles of stannius of a freshwater catfish, Heteropneustes fossilis kept either in artificial freshwater, calcium-rich freshwater or calcium-deficient freshwater. 887 Apr 68

Myelodysplastic syndromes (MDS) are a group of clonal disturbances with defective cellular differentiation. Vitamin D3 (VD) analogues can act on the differentiation and maturity of different cell lines. We studied the effects of VD on a series of patients with MDS in an open-design trial. Nineteen patients, 12 men and seven women, with MDS were included. Patients were 74.8 +/- 5.6 years (mean +/- SD), seven had refractory anaemia with ringed sideroblasts, five had refractory anaemia, one had refractory anaemia with excess of blasts and six had chronic myelomonocytic leukaemia. All the patients were in a low to intermediate risk group. Mean follow-up period was 26.21 months, range 9-75. Responders were defined as follows: granulocyte or platelet count increase by 50%, or haemoglobin increase of 1.5 g/dl or transfusion needs decrease by 50%. The first five patients received 266 microg of calcifediol three times a week and the other 14 received calcitriol (0.25-0.75 microg/d). Response was observed in 11 patients. In the calcifediol-treated group, one case responded, three were nonresponders, and one showed progression. In the calcitriol group, 10 were responders (two with major response), and four were non-responders. No correlation was observed between baseline levels of vitamin D metabolites and the presence of response. No hypercalcaemia was observed. Treatment with vitamin D3 metabolites could induce a long-standing response of the haematological disturbance in some low-intermediate risk MDS patients without inducing hypercalcaemia.
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PMID:Vitamin D treatment in myelodysplastic syndromes. 1046 Jun 27


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