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Biomedical subjects

S Balsan

Publications and source records attributed to S Balsan.

At least 91 records · Page 5Linked to original sources
PubMed1977

The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks.

The metabolism of vitamin D3 was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [3H]25-(OH)D3, the production of 1,25-(OH)2D3 was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [3H]D3 (1220 pM/bird), the level of 1,25-(OH)2D3 was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)2D3 synthesis.

Acidosis↗
PubMed1977

Intestinal calcium-binding protein 3 months after massive small bowel resection in the piglet.

Changes in intestinal calcium-binding protein and calcium binding activity were studied at resection and 3 months after 90% small bowel resection in piglets and one adult pig. A calcium-binding protein (MW congruent to 11.000) with calcium-dependent eletrophoretic mobility was partially purified from mucosal extract of proximal jejunum, mid-gut, and ileum. The concentration of calcium-binding protein and the calcium-binding activity of the intact animals were found highest in the proximal jejunal segment, lowest in the ileal segment. After resection in the four surviving animals out of nine, a significant increase in calcium-binding activity was observed in the proximal jejunum and in the distal ileal segment. The change in calcium-binding activity was much more marked in the ileum than the jejunum. These data demonstrate that pig intestinal mucosa possesses an adaptive capacity to increase the synthesis of calcium-binding protein after massive small bowel resection.

Adaptation, Physiological↗
PubMed1977

Long-term therapy with 1alpha-hydroxyvitamin D3 in children with 'pseudo-deficiency' rickets.

This investigation confirms that 1alpha-hydroxyvitamin D3 (1alpha-OHD3) is a potent drug for the treatment of patients with pseudo-deficiency rickets (Balsan et al., 1975a; Reade et al., 1975; Prader et al., 1976). 1alpha-OHD3 corrects their intestinal malabsorption of calcium and phosphorus, normalizes their serum calcium and phosphate concentrations and promotes healing of skeletal lesions. This study also shows differences in the needs for 1alpha-OHD3 of children with PDR. Three factors appear to be of importance: familial sensitivity, severity of chronic secondary hyperparathyroidism, and periods of increased growth velocity. Tolerance to long-term 1alpha-OHD3 therapy, at doses varying from 0.5 to 2 microgram/d is excellent. Surveillance of patients should include regular measurements of 24 h urinary excretion of calcium, since hypercalciuria is the first signal of overdosage.

Adolescent↗
PubMed1977

Decreased bone sensitivity of thyroidectomized rats to the calcaemic effect of 1,25-dihydroxycholecalciferol.

The calcaemic response of thyroidectomized parathyroid transplanted rats to a single dose of biosynthetic 1,25-dihydroxycholecalciferol (50 ng) injected into a jugular vein, was evaluated. The animals were fed a vitamin D-free, low calcium diet. Compared to sham-operated and to thyroid-intact parathyroid transplanted rats thyroidectomized animals had a significantly reduced calcaemic response to 1,25-dihydroxycholecalciferol. Daily supplementation with d,1-thyroxine (100 mug/rat) during the experimental period restored a normal response. The increase in serum calcium concentration after 1,25-dihydroxycholecalciferol injection was a similar in thyroidectomized bilaterally nephrectomized animals, and in thyroidectomized kidney-intact rats. The results suggest that in thyroxine depleted rats, the sensitivity of bone to the calcaemic effect of 1,25-dihydroxycholecalciferol is decreased.

Animals↗
PubMed1976

1,25-Dihydroxycholecalciferol increases bone resorption in thyroparathyroidectomised mice.

Mice, 1 week old, prelabelled with 45Ca, were either thyroparathyroidectomised or sham-operated; 1 day later half of the mice of each group were injected with 1,25-dihydroxycholecalciferol (5 ng/g), and 20 h later all the mice were killed. Bone resorption in explants was then measured by an in vivo/in vitro technique previously published; compared with untreated mice it was found that 1,25-dihydroxycholecalciferol had increased resorption irrespective of whether the mice had been thyroparathyroidectomised or not. These data suggest that 1,25-dihydroxycholecalciferol is able to increase bone resorption independently of parathyroid hormone.

Animals↗
PubMed1976

Maintenance by cortisone of the calcemic response to parathyroid extract of rats on a diet without vitamin D and low in calcium.

Weanling rats raised for 21 days on a vitamin D deprived, low Ca diet (0.02%), and given chronic cortisone administration (5 mg/kg/d), maintain responsiveness to the hypercalcemic effect of endogenous and exogenous parathyroid extract (PTE). The PTE action is a bone effect that does not require the presence of the kidneys, and is not related to a higher concentration of calcium or cortisone. Maintained sensitivity of D- Ca- Cort+ rats to PTE does not appear to be the consequence of a lesser degree of D-deficiency: the whole body vitamin D pool and its chloroform-soluble fraction in these animals are not different from those of their D- Ca- PTE- unresponsive controls. Repeated PTE injections for 4 days exhaust the sensitivity to the hypercalcemic action of PTE of D- Ca- Cort+ rats. The present data seem to indicate that cortisone-treated D- Ca- rats, responsive to the bone action of PTE, are characterized by a near normal bone calcium content and Ca/P ratio, and a significant increase in the number of osteoclasts.

Animals↗
PubMed1976

Effects of 25-hydroxycholecalciferol on bone lesions of children with terminal renal failure.

Quantitative histology was performed on serial iliac crest biopsies obtained from 14 children with terminal renal failure. A long-term study on the comparative effects of vitamin D2 and 25-hydroxycholecalciferol [25-(OH)D3], in five patients with severe lesions of osteomalacia and/or osteitis fibrosa, demonstrated the efficiency of 25 to 200 mug/day of 25-(OH)D3 and the lack of therapeutic action of 345 to 685 mug/day of vitamin D2. In nine subjects with normal roentgenograms or minimal skeletal alterations, the first biopsy taken at the beginning of intermittent hemodialysis showed evidence of defective mineralization and/or lesions of resorption. Four of these children were treated with 25-(OH)D3 (25 to 50 mug/day) and calcium supplementation orally (0.5 to 1.5 g/day); five children received calcium orally (0.5 to 0.75 g/day) alone. Aggravation of bone lesions during intermittent hemodialysis was observed in patients treated with calcium supplements alone. In subjects who were given 25-(OH)D3, mineralization improved and marrow fibrosis disappeared. However, as the two groups of patients were different in composition and in the manner in which they were treated, it is difficult to state whether the beneficial effects observed were solely attributable to 25-(OH)D3 administration. 25-(OH)D3 therapy induced severe intoxication in two patients. A rise in plasma calcium concentration to 11.0 to 11.5 mg/100 ml was observed in two other patients. It is concluded that: a) pharmacologic doses of 25-(OH)D3 are highly effective in healing bone lesions of children with terminal renal failure; b) such treatment requires strict clinical surveillance as 25-(OH)D3 intoxication may occur even in anephric patients.

Adolescent↗
PubMed1976

1,25-Dihydroxycholecalciferol effect on serum phosphorus homeostasis in rats.

It has recently been shown that 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) increases the serum phosphorus concentration of rats on a low-phosphorus diet. While studying the biological activity of 1,25(OH)2D3, we observed that under certain circumstances 1,25-(OH)2D3 would decrease the serum phosphorus concentration. The analysis of all data obtained in rat experiments during the past 3 years revealed highly significant linear correlations (P less than 0.001) between changes of serum phosphorus concentrations after the administration of 1,25-(OH)2-D3 (130 pmol/d for 1 or 5 days) and serum phosphorus or calcium levels in the animals before injection. Similar correlations could only be found with the higher dose of 25-hydroxycholecalciferol (130 pmol/d for 5 days). Another vitamin D3 metabolite, 24,25-dihydroxycholecalciferol, had no effect on serum phosphorus concentrations under our experimental conditions. The 1,25-(OH)2D3 effect on serum phosphorus concentration does not require the presence of circulating parathormone and/or calcitonin. We suggest that 1,25-(OH)2D3 might be an important factor in serum phosphorus homeostasis.

Animals↗
PubMed1975

Phosphorus depletion in children on long-term total parenteral nutrition.

The retention of nitrogen, calcium and phosphorus was studied in nine infants on total parenteral nutrition. The amounts of calcium, nitrogen and phosphorus were varied singly or simultaneously. The results demonstrate close interrelationships in the retention of these three elements. Not only the absolute amount of phosphorus perfused daily but also the amounts of nitrogen and/or calcium perfused simultaneously account for the phosphorus depletion that may lead to severe hypophosphatemia. The decrease in serum phosphorus concentration with a simultaneous fall of urinary phosphorus excretion to undetectable levels and a rise in urinary calcium output to 10 mg/kg/24 hours or more are warning symptoms of phosphorus depletion. Such a complication was observed in our first seven children on total parenteral nutrition. Phosphorus depletion can be prevented by using the following amounts of these elements in the perfusate: per 100 Kcal/kg/24 hours, 400 mg/kg/24 hours of nitrogen, 35 mg/kg/24 hours of calcium and 40 mg/kg/24 hours of phosphorus. With such a technique no phosphorus depletion was observed in any of the 63 subsequent patients whom we treated with total parenteral nutrition for periods varying from 20 days to 9 months.

Amino Acids↗
PubMed1975

1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance.

This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1alpha-hydroxyvitamin D3 (1alpha-OH-D3) on children with nutritional rickets, "pseudodeficiency" rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1alpha-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5 mug/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal le lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1alpha-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1974

Metabolism of 25-hydroxyvitamin D3 in anephric rats: a new active metabolite.

After the injection of radioactive 25-hydroxyvitamin D(3) into rats given a normal diet, two metabolites can be detected on Sephadex LH-20 chromatography modified to reveal polar metabolites. The first is designated peak Va, which by means of periodate cleavage has been identified as 24,25-dihydroxyvitamin D(3). The second more polar metabolite has been designated peak X(1) and is only partially sensitive to periodate. This metabolite appears in serum, bone, intestine, and liver and does not chromatograph on any system like any of the previously identified metabolites. Nephrectomy, especially in the animals given large doses of 25-hydroxyvitamin D(3), does not abolish production of either peak Va or X(1), revealing that both metabolites can be made in extra-renal tissue. Peak X(1) has marked ability to elevate serum calcium of rats on a vitamin D-deficient, low calcium diet, but requires the presence of kidneys to carry out this function.

Animals↗
PubMed1973

Calcium-mobilizing effect of large doses of 25-hydroxycholecalciferol in anephric rats.

The effect of high doses of 25-hydroxycholecalciferol on plasma calcium concentration was studied in rats receiving a low-calcium normal vitamin D diet. In bilaterally nephrectomized animals, as in sham-operated controls, 62.5 nmol of 25-hyroxycholecalciferol did not produce a rise of plasma calcium concentration. In contrast, the administration of 125 or 625 nmol, doses 1,000-5,000 times the minimal active dose in D-deficient rats, was followed in both groups of animals by a significant increase of plasma calcium concentration. Removal of either parathyroids alone or parathyroid and thyroid glands did not suppress this effect. These data suggest that when large doses are used in vivo, the renal conversion of 25-hydroxycholecalciferol to more polar metabolites is not an obligatory step for its calcium-mobilizing action. The present study does not elucidate, however, the exact mechanism(s) of this effect.

Animals↗
PubMed1972

25-Hydroxycholecalciferol. A comparative study in deficiency rickets and different types of resistant rickets.

The effects of 25-hydroxycholecalciferol were studied in 4 children with deficiency rickets and 22 children with D-resistant rickets, including patients with hereditary hypophosphatemic D-resistant rickets, "pseudo-deficiency" rickets, and rickets secondary to cystinosis or to tyrosinosis. Three protocols were used. (a) 8 days after a single oral dose of 16,000 IU of 25-hydroxycholecalciferol, normalization of all biological parameters was observed in all cases of deficiency rickets. A complete lack of response was observed in the different types of resistant rickets. (b) Under prolonged administration of 2,640 IU/day for 2 months, clinical-biological symptoms and X-ray lesions disappeared, and a catch-up growth pattern was observed in deficiency rickets; no relapse of rickets occurred up to 5 months after therapy was stopped. The same dose had no significant effect in 10 patients with hereditary hypophosphatemic D-resistant rickets. A bone biopsy performed in one case showed the persistence of characteristic lesions. (c) With increasing doses of 25-hydroxycholecalciferol varying from 6,000 to 30,000 IU/day and a follow-up of 6 months up to 2 yr duration, clinical-biological-radiologic recovery and catch-up growht was obtained in all cases of "pseudo-deficiency" rickets. In hypophosphatemic hereditary D-resistant rickets, 5 out of 13 patients' serum concentration of phosphorus reached at least 30 mg/liter, but a catch-up growth pattern was not observed. These results indicate that (a) 25-hydroxycholecalciferol is highly active in deficiency rickets; (b) a defect in the conversion of vitamin D(3) to its active 25-hydroxy metabolite is probably not the metabolic defect in any of the different types of vitamin D-resistant rickets studied.

Administration, Oral↗