Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of one single injection of two new bisphosphonates, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate and 2-(2-pyridyl)ethylidene-1,1-bisphosphonate, and of dichloromethylenebisphosphonate on the hypercalcemia and hypercalciuria induced by the Walker carcinosarcoma 256/B in the thyroparathyroidectomized rat was evaluated. When given either before or after the development of hypercalcemia and hypercalciuria, 16.1 mumol/kg 4-amino-1-hydroxybutylidene-1,1-bisphosphonate or 2-(2-pyridyl)ethylidene-1,1-bisphosphonate totally inhibited hypercalciuria, whereas hypercalcemia was only partially reduced over the 14 days of the experiment. At 10 and 100 times lower doses, the effect was strongest the first days, but still partially present 14 days later. The difference of activity on calcemia and calciuria appears to be due to the fact that the tumor increased both bone resorption and renal reabsorption of calcium. Only the former was altered by the bisphosphonates. The two new compounds appeared to be of similar potency and more active than dichloromethylenebisphosphonate. These compounds could be promising for the treatment of malignant hypercalcemia and other conditions with increased bone resorption in humans, even when given only over short periods of time.
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PMID:Effect of a single injection of two new bisphosphonates on the hypercalcemia and hypercalciuria induced by Walker carcinosarcoma 256/B in thyroparathyroidectomized rats. 367 71

Advanced tumor osteopathy is characterized by abnormal bone turnover. Using a rat model of parathyroid hormone-related peptide (PTHrP)-mediated tumor osteolysis, the aim of the present study was to define the sequential changes in, and the association between, biochemical and histomorphometric indices of bone metabolism during the early stages of developing tumor osteopathy. Eight-month-old Wistar rats (n = 48) were subcutaneously inoculated with either 2 x 10(6) cells of the Walker carcinosarcoma 256, or saline on day 0, and treated with either saline or the bisphosphonate ibandronate until killing on day 8. Serum calcium (sCa), alkaline phosphatase (sTAP), and osteocalcin (sOC) and urinary calcium (uCa), deoxypyridinoline (uDPD), and pyridinoline (uPYD) were measured daily. In a second semilongitudinal experiment (n = 70), the number of osteoclasts and osteoblasts (N.Oc, N.Ob), trabecular bone volume (BV/TV), and osteoid volume (O.Ar) were assessed by histomorphometry. In untreated tumor-bearing animals, osteoclast numbers increased by 74% on day 3 (5.4 +/- 2.4 vs. 3.1 +/- 1.5/mm(2), p < 0.05), and trabecular bone volume fell by 24% on day 4 (12.5 +/- 2.0 vs. 15.8 +/- 1.2%, p < 0.05). Both time course and magnitude of these changes were closely reflected by an increase in uDPD (0.46 +/- 0.14 vs. 0. 31 +/- 0.15 nmol/12 h, p < 0.05) and uPYD on day 4 (1.44 +/- 0.25 vs. 1.03 +/- 0.3 nmol/12 h, p < 0.05), sCa (3.8 +/- 0.52 vs. 3.0 +/- 0. 13 mmol/L, p < 0.01), and uCa (0.13 +/- 0.08 vs. 0.03 +/- 0.01 mmol/12 h, p < 0.001) on day 6, and sTAP (254 +/- 127 vs. 120 +/- 40 U/L, p < 0.001) on day 7 (mean +/- SD), whereas sOC remained unchanged until day 8. When combining the results of the two experiments, a high correlation was found between the number of osteoclasts and the urinary excretion of PYD (r = 0.91) and DPD (r = 0.89). Treatment with ibandronate delayed hypercalcemia, abolished hypercalciuria, and accelerated bone resorption. We conclude that osteoclast activation is an early event in PTHrP-mediated osteolysis, which is closely reflected by the renal excretion of pyridinium cross-links of type I collagen. Therefore, specific biochemical markers of collagen breakdown may be useful as early indicators of developing tumor osteopathy.
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PMID:Association between histomorphometry and biochemical markers of bone turnover in a longitudinal rat model of parathyroid hormone-related peptide (PTHrP)-mediated tumor osteolysis. 1077 87