Disease relevance of Alfarol

• 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 [1].
• Treatment with 1alpha-hydroxyvitamin D3 (1alpha(OH)D3; an active form of vitamin D) was evaluated for maintaining bone mass and reducing the incidence of hip and other nonvertebral fractures in patients with Parkinson's disease [2].
• Bone histomorphometry in patients with chronic renal failure: effect of 1alpha-hydroxyvitamin D3 [3].
• Correlation of clinical, biochemical and skeletal responses to 1alpha-hydroxyvitamin D3 in renal bone disease [4].
• During treatment of renal osteodystrophy with 1alpha-hydroxyvitamin D3 in eleven patients, regional changes in the skeleton have been compared with long-term calcium balance as assessed by whole-body calcium [5].

High impact information on Alfarol

• One alpha chain was the product of the alpha transgene, whereas the other was derived by endogenous rearrangement [6].
• Treatment of these patients for 1 wk within 2 mug/day of 1alpha-hydroxycholecalciferol [1alpha-(OH)-D3] restored net calcium absorption and unidirectional calcium flux out of the lumen to normal values in the jejunum; in the ileum, 1alpha-(OH)-D3 increased calcium absorption 60-83% of normal at the various luminal calcium concentrations [7].
• Direct C-1 hydroxylation of vitamin D compounds: convenient preparation of 1alpha-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3, and 1alpha-hydroxyvitamin D2 [8].
• The effect of 1alpha-hydroxyvitamin D3 administration on calcium transport in chick intestine brush border membrane vesicles [9].
• The maximal accumulation of 1alpha,25-dihydroxy[6-3H]vitamin D3 in intestine precedes the intestinal absorption response to 1alpha-hydroxyvitamin D3 by at least 2 hours [10].

Chemical compound and disease context of Alfarol

• We conclude that alpha-calcidol is more toxic than calcitriol in the mouse and suggest that the degree of toxicity is correlated to the degree of hypercalcemia and to the vitamin D metabolite used [11].
• Toxicologic studies of the hormonal form of vitamin D3: acute and subacute toxicity of 1alpha-hydroxycholecalciferol [12].
• The lack of a GH-induced increase in 1,25-dihydroxyvitamin D levels, probably due to treatment with alpha-calcidol, might be linked to the absence of a response in BMD during GH treatment in children with chronic renal failure [13].
• Pamidronate was given to 10 patients with end stage renal failure who had become symptomatically hypercalcaemic due to the use of calcium based phosphate binders and alphacalcidol [14].
• We evaluated intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis, with special reference to bone mineral density (BMD) and prevention of spinal fracture [15].

Biological context of Alfarol

• 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 [1].
• In a recent study evaluating 145 patients suffering from diseases requiring long-term treatment with high doses of corticosteroids, we have demonstrated a significant benefit of alphacalcidol (1 microg/day) over placebo in terms of changes in bone mineral density of the lumbar spine [16].
• Hypertension in primary hyperparathyroidism--reduction of blood pressure by long-term treatment with vitamin D (alphacalcidol). A double-blind, placebo-controlled study [17].
• One alpha B- and three different beta-crystallin cDNA clones were isolated from a chicken lens cDNA library by using anti-crystallin antibodies [18].
• A total of 79 Japanese women who were within 5 years of menopause were randomly assigned 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] 1.0 microg/day, conjugated estrogens 0.625 mg/day, a combination of both, or control (no treatment) [19].

Anatomical context of Alfarol

• Changes in intestinal calcium absorption, calcium deposition into egg shell, and intestinal, renal and uterine calcium-binding protein (CaBP) in laying hens were related to changes in 25 hydroxycholecalciferol-1-hydroxylase activity (1-hydroxylase), or to the supplementation of 1alpha-hydroxycholecalciferol (1alpha-OH-CC) [20].
• One alpha subunit mRNA increased in abundance at the early blastocyst stage [21].
• Both 14b and 15b were 300-400 times less active than 13a in the chick intestinal cytosol protein binding assay, making these analogs similar in potency to 1alpha-hydroxyvitamin D3 in vitro [22].
• In ovariectomized rat model for osteoporosis, ED-71 caused an increase bone mass at the lumbar vertebra to a greater extent than 1alpha-hydroxyvitamin D3 (alfacalcidol), while enhancing calcium absorption and decreasing serum parathyroid hormone levels to the same degree as alfacalcidol [23].
• Additional intake of alpha-calcidol [25(OH) vitamin D(3)] or calcitriol, despite normal serum levels, reduces persistent hyperparathyroidism after kidney transplantation, improves intestinal calcium absorption and activates osteoblasts [24].

Associations of Alfarol with other chemical compounds

• MATERIALS AND METHODS: Sixteen major hepatic microsomal recombinant enzymes derived from cytochrome P450 cDNAs expressed in baculovirus-infected insect cells were screened for 25-hydroxylase activity with 1alpha-hydroxyvitamin D2 [1alpha(OH)D2], 1alpha-hydroxyvitamin D3 [1alpha(OH)D3], vitamin D2, and vitamin D3 as substrates [25].
• Using Sephadex LH-20 and high-pressure liquid chromatography, it was clearly demonstrated that 1alpha-hydroxycholecalciferol rapidly disappears from the blood and is metabolized to 1alpha,25-dihydroxycholecalciferol [26].
• We carried out a cross-sectional study during the month of September in an Algerian dialysis center of 113 patients who were not taking supplements of alphacalcidol or calcitriol [27].
• Dihydrotachysterol and 1alpha-hydroxyvitamin D3 had significant practical advantages over vitamin D in their rapid onset of action and their relatively short biological half-life [28].
• Subsequently, injectable vitamin D3 was discontinued and all patients received their previous dose of oral One-Alpha for a period of 1 month [29].

Gene context of Alfarol

• Daily oral treatment with 1alpha-hydroxyvitamin D3 (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated the bone loss in the db/db mice [30].
• Interestingly, 1alpha(OH)D derivatives (1alpha-hydroxyvitamin D3, D2, D4 and D7) effectively induced the differentiation of monoblastic leukaemia U937, P39/TSU and P31/FUJ cells [31].
• The management of hypoparathyroidism with 1alpha-hydroxyvitamin D3 [28].
• One alpha 4 transfectant, which exhibited a tight human alpha 4/mouse beta 1 association, could be induced, but only after PMA activation, to bind strongly to VCAM [32].
• Serum PTH increased in both groups after 4 weeks of glucocorticoid treatment and was reduced in group A, but not in group B, after 6 weeks on alphacalcidol [33].

Analytical, diagnostic and therapeutic context of Alfarol

• During the next 14 days each patient received 0.25 microgram Etalpha orally, after which a third OGTT was performed [34].
• Prophylactic administration of calcium carbonate and alphacalcidol after cardiac transplantation reduces bone loss and seems to decrease osteoporotic complications [35].
• Six months after transplantation, however, patients receiving alphacalcidol had a significant reduction in bone loss at the level of the lumbar spine (P=0.047) and at the level of the femoral neck (P=0.043) [35].
• Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. The Liver Transplant Group, Groningen [36].
• The use of 1alpha-hydroxyvitamin D3 in the management of patients undergoing parathyroidectomy [37].

References