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Biomedical subjects

L Miravet

Publications and source records attributed to L Miravet.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effects of the calcium antagonist, diltiazem on in vitro and in vivo/in vitro bone resorption.

The effect of the calcium antagonist diltiazem on bone resorption in organ culture has been investigated. It was found that diltiazem was ineffective alone but that in concentrations above 5 mumol/l it reduced mineral and organic resorption induced in vitro by 1.25 dihydroxycholecalciferol (1.25 (OH)2D3). No additivity with calcitonin effects was observed. Diltiazem did not significantly affect bone resorbing activity stimulated by 24,25(OH)2D3. Bone resorption was measured by an in vivo/in vitro technique using 45Ca prelabelled mice. Compared with 1.25(OH)2D3 alone treated group (0.480 pmol/g), it was found that diltiazem (100 nmol/g) reduced bone resorption without effect on calcium and phosphorus plasmatic concentrations at death. These data suggest that such a calcium antagonist is able to inhibit 1.25-(OH)2D3-increased-bone resorption either in vitro or in vivo/in vitro.

Animals↗
PubMed1985

Vitamin D3 3 beta sulfate has less biological activity than free vitamin D3 during pregnancy in rats.

The biological activities of free (D3) and sulfoconjugated (SD3) vitamin D3 were compared after 6 weeks of oral administration to D-deficient (-D) female rats which were mated in the meantime. Mothers and pups were sacrificed 1-2 days following parturition and mineral and hormonal plasma status was determined in mothers and bone mineral determinations and bone histomorphometric studies performed. In newborns, plasma levels of Ca, P and 25-hydroxyvitamin D (25(OH)D) were measured. After parturition, -D mothers had decreased body weight (BW) as well as decreased plasma levels of Ca, P and 1,25-dihydroxyvitamin D (1,25(OH)2D) associated with undetectable levels of 25(OH)D. Plasma levels of immunoreactive calcitonin and parathormone, by contrast, were higher than in vitamin D-replete (+D) control mothers. Bone histomorphometric analysis showed osteomalacia and secondary hyperparathyroidism in -D mothers. After parturition, -D +SD mothers had reduced BW compared to D-treated mothers and the plasma parameters measured were abnormal. Almost all bone histomorphometric parameters were found to be intermediate between +D and -D groups without reaching values of +D mothers. By contrast, -D +D mothers had most of the bone formation parameters identical to those of +D mothers. However, bone resorption was still higher while plasma levels of P and 25(OH)D remained slightly, but significantly lower than in +D mothers. In pups, plasma Ca in both D3- and SD3-treated groups was similar to values in +D-treated rats. However, pups from SD3-treated mothers still showed plasma levels of P and 25(OH)D lower than in +D pups. In conclusion, treatment with SD3 in -D mother rats significantly improves the biochemical plasma parameters of pups, but complete normalization can be achieved only in the D3-treated group. Our results show that when administered at equal amounts, SD3 has a much lower biological activity than D3 in -D female rats and cannot therefore replace vitamin D3 particularly during pregnancy.

Animals↗
PubMed1985

Multifactorial low remodeling bone disease during cyclic total parenteral nutrition.

The physiopathology of metabolic bone disease described during long term total parenteral nutrition is poorly understood. We therefore prospectively assessed bone status of seven adult patients [mean age, 42 +/- 16 (SD) yr] treated with cyclic total parenteral nutrition for a period of 7 +/- 2 (SD) months. All patients had hypercalciuria (381 +/- 96 mg/day) associated with negative calcium balance in six of seven patients (-49 +/- 120 mg/day). A correlation was found (r = +0.74, P less than 0.01) between protein intake and calciuria. Two patients developed slight transient hypercalcemia. Serum magnesium and phosphate levels remained within the normal range. A high aluminum load due to the added phosphate solution (253 +/- 84 micrograms/day) was associated with increased serum aluminum levels (52 +/- 38 micrograms/liter). Normal serum levels of 25 hydroxyvitamin D (12 +/- 7 ng/ml) and low normal 1,25 dihydroxyvitamin D levels (21 +/- 8 pg/ml) were found. Serum PTH was normal in five and increased in two of the seven patients. However, in these two patients skeletal unresponsiveness to the action of PTH was found. A new histomorphometric picture of bone was observed; it consisted of a markedly reduced bone formation with subnormal osteoclastic activity leading to a low trabecular bone volume. No osteomalacia was found. The aluminum load may have played a role in these bone defects. The hypercalciuria with negative calcium balance was attributed to the cyclic amino-acid delivery during TPN.

Adult↗
PubMed1985

Influence of vitamin D on mineral metabolism, hormonal status and bone histology in lactating rats and their pups.

Mineral, hormonal and skeletal changes were determined in vitamin D-deficient (-D) and vitamin D-replete (+D) mother rats and in their litters on day 20 of lactation. These results were compared with those obtained in -D mothers and pups, after giving the mothers an oral supplement (10 i.u. vitamin D3/day) during the period of lactation (20 days). Compared to +D animals, both -D lactating mothers and their pups exhibited extremely low plasma levels of 25-hydroxyvitamin D3 (25-OH-D3), diminished 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and increased levels of immunoreactive parathyroid hormone (iPTH). Vitamin D-deficient mothers also had higher levels of calcitonin and lower levels of prolactin than +D mothers. All -D animals (mothers and pups) showed increased osteoclastic bone resorption and severe osteomalacia as shown by decreased bone ash, decreased calcification rate and increased endosteal osteoid surface, volume and thickness. In mothers treated with vitamin D3 during lactation, nearly all the plasma variables measured, as well as bone histomorphometric features, were normal. In contrast, their pups still showed rickets and osteomalacia, despite normal levels of 25-OH-D3 and calcium in the plasma. These pups had raised plasma levels of 1,25(OH)2D3 and iPTH associated with persistent stimulation of bone resorption. This study showed that (1) severe vitamin D deficiency in lactating rats produced marked osteomalacia and secondary hyperparathyroidism in both mothers and pups, and (2) vitamin D treatment of -D mother rats during lactation (10 i.u. vitamin D3/day) reversed the mineral, hormonal and skeletal abnormalities in mothers but not in pups.

Animal Population Groups↗
PubMed1985

Effect of low doses of stable strontium on bone metabolism in rats.

The effects of low doses of oral stable strontium (0.19-0.40% of strontium chloride) on mineral and bone metabolism were examined in normal rats using biochemical and histomorphometrical methods. The strontium levels in serum and bone rose according to the intake of the element. Oral strontium supplementation did not produce deleterious effects on body growth or on mineral homeostasis except a transitory slight decrease in serum calcium. At the dosage level of 0.40% however, strontium induced a slight defective bone mineralization. At lower levels, treated rats showed stimulated bone formation evidenced by increased amount of osteoid and increased extent of tetracycline double-labelled surface while the mineralization lag time remained normal. The osteoclastic surface and the number of acid phosphatase-stained chondroclasts and osteoclasts remained unchanged. Stimulation of bone formation without apparent change in bone resorption resulted in a 10% increase in the trabecular calcified bone volume. The strontium-induced increased osteogenesis was not associated with changes in circulating levels of 1,25(OH)2 vitamin D or in parathyroid hormone effects. The results show that small doses of oral strontium may stimulate bone formation without altering bone resorption in the rat.

Animals↗
PubMed1984

[Treatment of hypercalcemia in osteolytic metastases with oral amino-hydroxypropylidene-diphosphonate].

Twelve patients with malignant hypercalcemia were treated with amino-hydroxypropylidene-diphosphonate (APD), a potent inhibitor of osteoclast-mediated bone resorption. The mean serum calcium levels fell from 3,48 +/- 0,27 mmol/l before treatment to 2,66 +/- 0,31 after 10 days of oral APD (10 to 15 mg/kg/d) as the sole agent (p less than 0,001). The molar calcium/creatine ratio in the 24-h urine was significantly reduced from 2,11 +/- 0,73 to 0,70 +/- 0,52 after ten days of treatment (p less than 0,001). Serum phosphorus and urine hydroxyproline did not change significantly. Tolerance was good except for two patients with hiatal hernia who developed oesophagitis. Ours results confirm that oral APD is an effective and simple treatment of malignant hypercalcemia.

Administration, Oral↗
PubMed1984

Effects of iron overload on bone remodeling in pigs.

For study of the effects of an iron overload on bone remodeling, 5 control pigs were compared with 5 pigs given a total dose of 10.8 g of parenteral iron in 36 days. Treated pigs developed an iron tissue overload demonstrated by a marked increase in bone and liver iron. Except for a modest increase in SGOT, there was no biochemical or histologic sign of liver damage. Serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were unchanged in the treated pigs. There was no accumulation of iron in the parathyroid glands and the serum immunoreactive parathyroid hormone level was unchanged in the treated animals. Bone histomorphometry after double tetracycline labeling showed that in the treated pigs osteoblast cell surfaces, double and total labeled surfaces, appositional rate, and formation at tissue level were significantly decreased, and reversal surfaces were increased. Mineralization was not impaired because the osteoid thickness was unchanged. From the morphometric measurements it was concluded that osteoblast recruitment and the collagen synthesis rate were decreased. Mean wall thickness, which indicates the amount of bone synthesized, was also lowered. In contrast, the osteoclastic resorption surfaces and the depth of lacunae resulting from osteoclast resorption were unchanged by treatment. Despite this imbalance between formation and resorption, trabecular bone mass estimated on trabecular bone volume and bone ash was unchanged after 36 days' treatment. Perls' stain revealed that iron deposits were present in osteoblast and osteoclast cells and also inside the bone matrix, because there was a linear deposit along the trabecular surfaces, cement line, and osteoid-mineralized bone interface. Therefore, because treatment induced no modification of the major humoral regulators of bone metabolism, it is suggested that iron, which was present in bone cells and matrix, could play a role in bone remodeling.

Alanine Transaminase↗
PubMed1984

[Cellular aspects of the aging of the articular cartilage. II. Condylar cartilage with fissured surface taken from normal and arthritic knees].

The authors studied the cellular density (number of cells per mm2) of cartilage taken from the femoral condyles of 46 cadavers (73 knees). In each case, the cartilage was taken from the summit of the condyle and, in 46 joints (27 subjects), a sample was also taken from the posterior surface (non weight-bearing zones). The fragments of non-calcified cartilage were sectioned with a cryostat and the sections (10 micrometers) were stained with hematein-eosin and solid red-Alcian blue. This study demonstrates: 1) a decrease in the cellular density of fissured cartilage compared to normal cartilage; this decrease appears to be proportional to the degree of fibrillation; 2) a decrease in the cellular density of apparently normal cartilage from arthrotic joints compared with normal cartilage from healthy joints; 3) with the age of the subjects, an increase in the density of the clones (number of clones per mm2) and the density of clonal cells (number of clonal cells per mm2) together with a decrease in the mean number of chondrocytes per clone. In fissured cartilage, the density of the clones, the density of the clonal cells and the number of chondrocytes per clone are slightly higher on the posterior surface of the condyles than on the summit of the condyles. These results emphasise the importance of the role that might be played by cellular phenomena in the mechanisms of deterioration of cartilage with aging and with arthrosis.

Adult↗
PubMed1983

[Role of calcitonin in pregnant rats : interaction with 1,25-dihydroxycholecalciferol on fetal bone resorption in vivo/in vitro].

We studied in pregnant Rat the effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) alone or associated with calcitonin on fetal bone resorption measured by organ culture. 1,25(OH)2D3 (0.1 microgram per day) reduced fetal weight and increased fetal bone resorption. Calcitonin (30 mU/hr.) alone had no significant effects but, associated with 1,25(OH)2D3, it protected mother and foetus against the effect of the vitamin D3 metabolite.

Animals↗
PubMed1983

Effect of 1 alpha, 24 R,25-trihydroxycholecalciferol on isolated parathyroid cells secretion.

In this work we have studied the action of the trihydroxylated vitamin D metabolite (1 alpha, 24 R,25(OH)3D3) on parathyrin secretion by isolated parathyroid cells. In contrast with the results obtained with mono and dihydroxylated vitamin D, 1 alpha, 24 R,25(OH)3D3 increased the secretion of parathyrin. The effective concentration of this metabolite was 1.54 X 10(-9)M for cells rat and 1.54 X 10(-10)M for human cells.

Animals↗
PubMed1983

Effect of calcitonin in pregnant rats on bone resorption in fetuses.

Fetal bone resorption was measured by an organ culture technique using fetuses from intact or thyroparathyroidectomized pregnant rats. These experiments were performed to investigate the effects of 1,25-dihydroxycholecalciferol (1,25-DHCC) and salmon calcitonin (SCT) in pregnant rats, on both fetal growth and fetal bone resorption. Pregnant rats were given 0.1-0.5 microgram 1,25-DHCC per day from day 17 of gestation: in intact rats bone resorption was increased and fetal growth decreased; 1,25-DHCC probably modified fetal bone resorption in the absence of fetal parathyroid secretion. Infusion of SCT in minipumps (30 mu./h) did not modify plasma calcium levels in either the mother or fetuses, neither was bone resorption altered. In 1,25-DHCC-treated rats, SCT infusion resulted in an increase in fetal weight and a decrease in fetal bone resorption. On the other hand, SCT infusion was found to facilitate phosphate accumulation in fetuses. At the end of the SCT infusion the SCT concentration was 450 ng/l in maternal plasma and 553 +/- 60 ng/l in fetal plasma. Salmon calcitonin was shown to cross the placental barrier in the rats; it may interact with the effects of 1,25-DHCC in the fetus.

Animals↗
PubMed1983

Evidence for defective osteoblastic function. A role for alcohol and tobacco consumption in osteoporosis in middle-aged men.

In a group of 11 men ranging in age from 35 to 50 years with idiopathic osteoporosis, most were mild alcoholics and heavy smokers. Two had absorptive hypercalciuria. Histomorphometry showed that the patients had low trabecular bone volume and mean trabecular thickness when compared with age-matched control subjects. Mean wall thickness was also markedly reduced in patients as compared with control subjects. The quantity of resorbed bone was extrapolated from the calculated mean interstitial bone thickness. Resorption was not significantly different in patients and control subjects. Consequently, in this group of patients with severe osteoporosis, the pathogenesis was characterized by markedly decreased bone formation.

Adult↗
PubMed1982

Nonosteomalacic osteopathy associated with chronic hypophosphatemia.

We studied bone histomorphometry in 19 patients with chronic hypophosphatemia related to an idiopathic renal phosphate wasting and without histological osteomalacia. Nine patients had renal lithiasis (group 1), three had radiological osteoporosis (group 2), and seven had lumbar pain (group 3). In the whole group of 19 patients, serum phosphate levels were low (24.9 +/- 2.1 mg/l), calcium in blood was normal, calcium in urine was increased, and iPTH was low. Histomorphometric data showed decreased osteoblastic surfaces with normal resorption surfaces, normal osteoid volume and calcification front. There was no correlation between serum phosphate level and histomorphometric parameters. There was no statistical difference between the data of the 3 groups of hypophosphatemic patients. We concluded that chronic hypophosphatemia in the adult doses not always lead to osteomalacia but to an unusual osteopathy characterized by an osteopenia due to an isolated decrease in bone formation. The respective importance of phosphate deficiency and of decreased iPTH level in the pathogenesis of this osteopathy is uncertain.

Adult↗
PubMed1982

Comparative effects of some hydroxylated vitamin D metabolites on parathyrin secretion by dispersed rat parathyroid cells in vitro.

We have previously discussed the action of 1 alpha,25-(OH)2D3, (24R) 24,25-(OH)2 D3 and (25S) 25,26-(OH)2D3 on parathyrin secretion by isolated rat parathyroid cells. In this work, we have compared these effects with those obtained with 1 alpha-OH D3, 25-OH D3 and 1 alpha-OH D2. In decreasing order, the activities were: 1 alpha,25-(OH)2D3 greater than 1 alpha-OH D3 greater than (24R) 24,25-(OH)2D3 greater than 25-OH D3 greater than (25S) 25,26(OH)2D3 greater than 1 alpha-OH D2. The presence of two hydroxyl groups with one hydroxyl group in alpha position seems to have the higher activity to inhibit the parathyroid secretion. At least, the nature of the side chain conformation also plays a part upon the effect of PTH release.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

Cholecalciferol sulfate identification in human milk by HPLC.

Synthetic vitamin D3 sulfate was prepared by reacting cholecalciferol with sulfamic acid in pyridine. Vitamin D3 sulfate ammonium salt was purified by crystallisation and transformed in sulfate sodium salt. Homogeneity was controlled by reverse phase high pressure liquid chromatography (HPLC). Purified synthetic vitamin D3 sulfate sodium salt was used as a reference. Milk whey was obtained after protein precipitation by adding ethanol. Vitamin D3 sulfoconjugate was identified in supernatant (lyophylized) after purification by Sephadex LH 20 and HPLC. Milk whey purified fraction obtained exhibited the same ultra-violet absorption (UV) as synthetic vitamin D3 sulfate; after solvolysis, cholecalciferol was liberated from natural and synthetic sulfoconjugate. The results confirmed that vitamin D3 sulfate was present in human milk.

Cholecalciferol↗