Disease relevance of Rocaltrol

• Short-term episodes of hypercalcemia were easily controlled by changes in calcitriol dosage [1].
• Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure [2].
• We administered high doses of calcitriol (up to 32 micrograms per day) to an infant with malignant osteopetrosis, in an attempt to stimulate bone resorption [3].
• Regression of parathyroid hyperplasia by calcitriol-pulse therapy in patients on long-term dialysis [4].
• The prevalence of bone aluminum deposition in renal osteodystrophy and its relation to the response to calcitriol therapy [5].

Psychiatry related information on Rocaltrol

• Based on a literature implicating altered calcium homeostasis in brain aging and Alzheimer's Disease (AD) and evidence of decreased vitamin D action in AD subjects, the possibility was tested that calcitriol (1,25(OH)2 vitamin D3), the active form of vitamin D3, might reduce markers of brain aging in rats [6].
• Calcitriol showed an association with physical activity in the hospital group (r = -.19, P < .05), and with fall last month in the home group (r = -.22, P < .05) [7].
• These findings suggest IV calcitriol treatment has a superior effect on bone remodeling by influencing the levels of bone-resorptive cytokines as compared to the oral therapy group, beyond its suppressive effect on iPTH [8].
• Medical management with calcitriol, dietary modifications, and administration of phosphate binders continues to be the best treatment for most patients [9].
• Serum levels of the important hormone 1,25-dihydroxyvitamin D (1,25-diOHD, calcitriol) have not been extensively evaluated in patients with cystic fibrosis (CF) during the critical period of skeletal growth and development [10].

High impact information on Rocaltrol

• Treatment of postmenopausal osteoporosis with calcitriol or calcium [11].
• After transplantation, the mean serum concentrations of parathyroid hormone, phosphorus, and alkaline phosphatase decreased and the serum calcitriol concentration increased [12].
• Therapy with calcitriol and phosphate may increase the growth of children with X-linked hypophosphatemic rickets [13].
• Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia [2].
• Before therapy, the patient's monocytes were incapable of in vitro bone resorption, but after calcitriol, their resorptive capacity was increased to 3.3 times control levels [3].

Chemical compound and disease context of Rocaltrol

• The aim of this study was to compare the anti-proliferative activity of a new vitamin D3 analogue, 22-oxa-1,25-dihydroxyvitamin D3 (22-oxa-calcitriol), on pancreatic cancer cells lines with that of 1,25-dihydroxyvitamin D3 (calcitriol) with analysis of vitamin D receptor status [14].
• Elevated levels of calcitriol, an active vitamin D metabolite, occurred in the presence of significant renal impairment (creatinine clearance, 8 to 19 mL/min) and relative parathyroid suppression (serum immunoreactive parathyroid hormone, 17 to 39 microL-eq/mL; mean value in end-stage renal disease, 182 +/- 39 microL-eq/mL) [15].
• Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer [16].
• The data also showed that only a PLC beta1 linked to a Pertussis toxin-insensitive G-protein and a PLC beta2 coupled to a Pertussis toxin-sensitive G-protein are involved in the effects of calcitriol and 17beta estradiol on the mobilization of Ca2+ from intracellular Ca2+ stores [17].
• In less-advanced renal insufficiency (CCr, 25 to 60 ml/min), the active vitamin D sterols calcitriol or alfacalcidol [1 alpha-hydroxyvitamin D3] have been shown to ameliorate the skeletal lesions of renal osteodystrophy [18].

Biological context of Rocaltrol

• We conclude that aluminum deposition is associated with impaired bone formation or mineralization and with a poor response to calcitriol therapy [5].
• Increasing dosage of calcitriol were needed during the last trimester with a prompt decrease in the requirement after delivery [19].
• Lastly, the suppressive effect of calcitriol on cellular proliferation was partially reversed by the addition of saturating amounts of purified IL-2 [20].
• Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins [21].
• In addition, uremic ultrafiltrate blocked calcitriol-induced reporter gene activity in transfected JEG-3 cells [21].

Anatomical context of Rocaltrol

• These data indicate that calcitriol regulated proteins associated with T cell activation at the transcriptional level and that these effects were mediated in a specific, coordinate fashion [22].
• Discovery of cytosolic receptors for vitamin D in human peripheral blood monocytes and lectin-stimulated lymphocytes prompted us to study the effects of 1,25-dihydroxyvitamin D3 (calcitriol), the most biologically active metabolite of vitamin D, upon phytohemagglutinin (PHA)-induced lymphocyte blast transformation [20].
• RESULTS: In vitro, 22-oxa-calcitriol and calcitriol markedly inhibited the proliferation (3 of 9 cell lines) and caused a G1 phase cell cycle arrest by appearance of numerous domes [14].
• In mutant fibroblasts VDR pattern changes after calcitriol were absent or severely disturbed at selected steps [23].
• We found similar rapid effects of calcitriol on VDRs in various other types of cultured cells [23].

Associations of Rocaltrol with other chemical compounds

• No significant changes in the plasma levels of parathyroid hormone, calcitonin, or calcitriol were observed after the estrogen-induced increases in vitamin D-binding protein had been taken into account [24].
• Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role [25].
• We report that sarcoid lymph node homogenate metabolized calcifediol to a substance indistinguishable from calcitriol, whereas six nonsarcoid lymph nodes failed to produce this compound [26].
• Since 1 alpha,25-dihydroxyvitamin D3, calcitriol, also transforms JB6 cells and, in other cell types, regulates osteopontin synthesis, we hypothesized that calcitriol-mediated transformation of JB6 cells would also cause induction of osteopontin synthesis and secretion [27].
• When, prior to injecting 1 X 120 mg/kg cyclophosphamide i.p., 0.2 microg calcitriol or vehicle alone were administered topically to the back skin of C57BL/6 mice with all hair follicles in anagen, no significant macroscopic differences in the onset and severity of CIA were seen [28].

Gene context of Rocaltrol

• Calcitonin stimulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in hypophosphatemic mice. Evidence that the regulation of calcitriol production is not universally abnormal in X-linked hypophosphatemia [29].
• Calcitriol significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme [30].
• Exogenous IL-1 or IL-6 did not overcome the impaired costimulatory activity of calcitriol-treated monocytes [31].
• Calcitriol was used to induce a high level of CD14 expression in the human monocyte-like cell line THP-1, resulting in enhanced responses of these cells to LPS-LBP complexes manifested by enhanced binding of LPS and a decrease in the amount of LPS needed to induce IL-8 release [32].
• By contrast, GST-Msx2 has no effect on calcitriol-regulated DNA-protein interactions at the VDRE [33].

Analytical, diagnostic and therapeutic context of Rocaltrol

• Patients whose osteitis fibrosa is refractory to oral calcitriol and who are candidates for parathyroidectomy should be considered first for intravenous calcitriol therapy [2].
• To evaluate the efficacy and safety of calcitriol (1,25-dihydroxyvitamin D3) in the treatment of postmenopausal osteoporosis, we conducted a three-year prospective, multicenter, single-blind study in 622 women who had one or more vertebral compression fractures [11].
• These complications were reversible with kidney transplantation or treatment with 0.25 to 2 microgram/day of calcitriol for four to 20 weeks [34].
• Calcitriol was fully active with respect to each of the indices listed when given in a manner resembling its continuous endogenous production by the kidney, suggesting that previous reports of incomplete skeletal response to calcitriol result from its rapid clearance and infrequent oral administration [35].
• In this study we employed an animal model to evaluate the single and combined effects of parathyroid hormone and calcitriol on bone aluminum accumulation [36].

References