Treatment of Predialysis Renal Bone Disease with 1a-(OH) Vitamin D3 and 1.25-(OH)2 Vitamin D3. Initial Results of Balance Studies and the Effect on Intestinal Calcium Absorption, Serum PTH and Calcitonin Levels

1979 ◽  
pp. 861-864
Keyword(s):  
Vitamin D3 ◽  
Bone Disease ◽  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Renal Bone Disease ◽  
Serum Pth ◽  
Initial Results

scholarly journals Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 82-93 ◽  
Author(s):  
JY Zhou ◽  
AW Norman ◽  
M Lubbert ◽  
ED Collins ◽  
MR Uskokovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mechanism Of Action ◽  
Vitamin D3 ◽  
Clonal Growth ◽  
Calcium Absorption ◽  
Active Form ◽  
Intestinal Calcium Absorption ◽  
Leukemic Cells ◽  
Binding Studies ◽  
Vitamin D Analogs

Abstract Induction of terminal differentiation of leukemic and preleukemic cells is a therapeutic approach to leukemia and preleukemia. The 1 alpha, 25- dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form of vitamin D3, can induce differentiation and inhibit proliferation of leukemia cells, but concentrations required to achieve these effects cause life-threatening hypercalcemia. Seven new analogs of 1,25(OH)2D3 were discovered to be either equivalent or more potent than 1,25(OH)2D3 as assessed by: (a) inhibition of clonal proliferation of HL-60, EM-2, U937, and patients' myeloid leukemic cells: and (b) induction of differentiation of HL-60 promyelocytes. Furthermore, these analogs stimulated clonal growth of normal human myeloid stem cells. The most potent analog, 1,25-dihydroxy-16ene-23yne-vitamin D3, was about fourfold more potent than 1,25(OH)2D3. This analog decreased clonal growth and expression of c-myc oncogene in HL-60 cells by 50% within ten hours of exposure. Effects on calcium metabolism of these novel analogs in vivo was assessed by intestinal calcium absorption (ICA) and bone calcium mobilization (BCM). Each of the analogs mediated markedly less (10 to 200-fold) ICA and BCM as compared with 1,25(OH)2D3. To gain insight into the possible mechanism of action of these new analogs, receptor binding studies were done with 1,25(OH)2–16ene-23yne-D3 and showed that it competed only about 60% as effectively as 1,25(OH)2D3 for 1,25(OH)2D3 receptors present in HL-60 cells and 98% as effective as 1,25(OH)2D3 for receptors present in chick intestinal cells. In summary, we have discovered seven novel vitamin D analogs that are more potent than the physiologic 1,25(OH)2D3 as measured by a variety of hematopoietic assays. In contrast, these compounds appear to have the potential to be markedly less toxic (induction of hypercalcemia). These novel vitamin D compounds may be superior to 1,25(OH)2D3 in a number of clinical situations including leukemia/preleukemia; they will provide a tool to dissect the mechanism of action of vitamin D seco-steroids in promoting cellular differentiation.

scholarly journals Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 82-93 ◽  
Author(s):  
JY Zhou ◽  
AW Norman ◽  
M Lubbert ◽  
ED Collins ◽  
MR Uskokovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mechanism Of Action ◽  
Vitamin D3 ◽  
Clonal Growth ◽  
Calcium Absorption ◽  
Active Form ◽  
Intestinal Calcium Absorption ◽  
Leukemic Cells ◽  
Binding Studies ◽  
Vitamin D Analogs

Induction of terminal differentiation of leukemic and preleukemic cells is a therapeutic approach to leukemia and preleukemia. The 1 alpha, 25- dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form of vitamin D3, can induce differentiation and inhibit proliferation of leukemia cells, but concentrations required to achieve these effects cause life-threatening hypercalcemia. Seven new analogs of 1,25(OH)2D3 were discovered to be either equivalent or more potent than 1,25(OH)2D3 as assessed by: (a) inhibition of clonal proliferation of HL-60, EM-2, U937, and patients' myeloid leukemic cells: and (b) induction of differentiation of HL-60 promyelocytes. Furthermore, these analogs stimulated clonal growth of normal human myeloid stem cells. The most potent analog, 1,25-dihydroxy-16ene-23yne-vitamin D3, was about fourfold more potent than 1,25(OH)2D3. This analog decreased clonal growth and expression of c-myc oncogene in HL-60 cells by 50% within ten hours of exposure. Effects on calcium metabolism of these novel analogs in vivo was assessed by intestinal calcium absorption (ICA) and bone calcium mobilization (BCM). Each of the analogs mediated markedly less (10 to 200-fold) ICA and BCM as compared with 1,25(OH)2D3. To gain insight into the possible mechanism of action of these new analogs, receptor binding studies were done with 1,25(OH)2–16ene-23yne-D3 and showed that it competed only about 60% as effectively as 1,25(OH)2D3 for 1,25(OH)2D3 receptors present in HL-60 cells and 98% as effective as 1,25(OH)2D3 for receptors present in chick intestinal cells. In summary, we have discovered seven novel vitamin D analogs that are more potent than the physiologic 1,25(OH)2D3 as measured by a variety of hematopoietic assays. In contrast, these compounds appear to have the potential to be markedly less toxic (induction of hypercalcemia). These novel vitamin D compounds may be superior to 1,25(OH)2D3 in a number of clinical situations including leukemia/preleukemia; they will provide a tool to dissect the mechanism of action of vitamin D seco-steroids in promoting cellular differentiation.

scholarly journals Renal bone disease in pediatric and young adult patients on hemodialysis in a children's hospital.

1993 ◽  
Vol 3 (12) ◽  
pp. 1938-1946
Author(s):  
R Mathias ◽  
I Salusky ◽  
W Harman ◽  
A Paredes ◽  
J Emans ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Serum Calcium ◽  
Bone Disease ◽  
Adult Patients ◽  
Osteitis Fibrosa ◽  
Assay Method ◽  
Children's Hospital ◽  
Children’S Hospital ◽  
Renal Bone Disease ◽  
Serum Pth

Renal bone disease has been well defined in adult patients receiving chronic dialysis and in children on peritoneal dialysis/continuous ambulatory peritoneal dialysis. However, little is known about the histologic features in patients undergoing chronic hemodialysis in a children's hospital center. Twenty one patients, aged 17.5 +/- 1.5 yr, on hemodialysis for 35 +/- 6 months underwent iliac crest bone biopsies and deferoxamine infusion tests. Nineteen of 21 patients were receiving oral calcitriol. The 21 patients were classified by histomorphometry as follows: osteitis fibrosa, 5; mild hyperparathyroidism, 3; normal histology, 3; aplastic, 6; and mixed lesions, 4. Four of 21 patients were surface positive for aluminum, and seven other patients stained positive for iron in bone. Serum parathyroid hormone (PTH) levels correlated directly with the bone formation rate (r = 0.84) and with eroded bone perimeter (r = 0.67). Eight of the nine patients with serum PTH levels above 125 pg/mL had marrow fibrosis. All patients with serum calcium levels < 10.0 mg/dL and serum PTH levels > 125 pg/mL had either osteitis fibrosa or mixed bone lesions--a group of patients that might benefit from aggressive vitamin D therapy. In contrast, an examination of patients with serum calcium levels > 10.0 mg/dL and serum PTH levels < 65 pg/mL correctly identified three out of three patients with aluminum-related bone disease. These findings suggest that measurements of serum intact PTH levels by the immunoradiometric assay method may be valuable in distinguishing high-turnover lesions from normal or low-turnover skeletal lesions in this population.

scholarly journals The Effect of Vitamin D2 and Vitamin D3 on Intestinal Calcium Absorption in Nigerian Children with Rickets

2009 ◽  
Vol 94 (9) ◽  
pp. 3314-3321 ◽  
Author(s):  
Tom D. Thacher ◽  
Michael O. Obadofin ◽  
Kimberly O. O'Brien ◽  
Steven A. Abrams
Keyword(s):  
Vitamin D3 ◽  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Vitamin D2 ◽  
Nigerian Children

Effect of vitamin D3 (cholecalciferol) on plasma calcium and intestinal 45calcium absorption in goldfish, Carassius auratus L.

1984 ◽  
Vol 62 (1) ◽  
pp. 34-36 ◽  
Author(s):  
James C. Fenwick
Keyword(s):  
Vitamin D ◽  
Food Deprivation ◽  
Vitamin D3 ◽  
Carassius Auratus ◽  
Calcium Absorption ◽  
Plasma Calcium ◽  
Intestinal Calcium Absorption ◽  
Total Calcium ◽  
Goldfish Carassius Auratus

Goldfish that were fed as well as not fed for 2 weeks had similar plasma total calcium levels, and vitamin D3 injections during the last 6 days had no significant effect on this parameter. When fish were fed for 1 day after 13 days of food deprivation, plasma calcium increased significantly and this increase was augmented by vitamin D3 injections. This latter group also showed a chlorpromazine-sensitive increase in 45calcium absorption from perfused everted gut sacs when compared with the controls. It was concluded that vitamin D3 stimulates intestinal calcium absorption in the goldfish.

Comparison of Dihydrotachysterol and 5,6-trans Vitamin D3 on Intestinal Calcium Absorption in Patients with Chronic Renal Failure

1974 ◽  
Vol 52 (2) ◽  
pp. 272-274 ◽  
Author(s):  
R. Gagnon ◽  
G. W. Ogden ◽  
G. Just ◽  
M. Kaye
Keyword(s):  
Vitamin D ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Vitamin D3 ◽  
Calcium Absorption ◽  
Intestinal Calcium Absorption ◽  
Vitamin D Analogue

The effect of dihydrotachysterol2 and of 5,6-trans vitamin D3 on calcium absorption in patients with severe chronic renal failure were compared. Dihydrotachysterol appeared to be more effective than the vitamin D analogue.

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